Genome-wide association study for ketosis in US Jerseys using producer-recorded data.

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Parker Gaddis, K L; Megonigal, J H; Clay, J S; Wolfe, C W

2018-01-01

Ketosis is one of the most frequently reported metabolic health events in dairy herds. Several genetic analyses of ketosis in dairy cattle have been conducted; however, few have focused specifically on Jersey cattle. The objectives of this research included estimating variance components for susceptibility to ketosis and identification of genomic regions associated with ketosis in Jersey cattle. Voluntary producer-recorded health event data related to ketosis were available from Dairy Records Management Systems (Raleigh, NC). Standardization was implemented to account for the various acronyms used by producers to designate an incidence of ketosis. Events were restricted to the first reported incidence within 60 d after calving in first through fifth parities. After editing, there were a total of 42,233 records from 23,865 cows. A total of 1,750 genotyped animals were used for genomic analyses using 60,671 markers. Because of the binary nature of the trait, a threshold animal model was fitted using THRGIBBS1F90 (version 2.110) using only pedigree information, and genomic information was incorporated using a single-step genomic BLUP approach. Individual single nucleotide polymorphism (SNP) effects and the proportion of variance explained by 10-SNP windows were calculated using postGSf90 (version 1.38). Heritability of susceptibility to ketosis was 0.083 [standard deviation (SD) = 0.021] and 0.078 (SD = 0.018) in pedigree-based and genomic analyses, respectively. The marker with the largest associated effect was located on chromosome 10 at 66.3 Mbp. The 10-SNP window explaining the largest proportion of variance (0.70%) was located on chromosome 6 beginning at 56.1 Mbp. Gene Ontology (GO) and Medical Subject Heading (MeSH) enrichment analyses identified several overrepresented processes and terms related to immune function. Our results indicate that there is a genetic component related to ketosis susceptibility in Jersey cattle and, as such, genetic selection for

Valproate effect on ketosis in children under ketogenic diet.

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Spilioti, Martha; Pavlou, Evangelos; Gogou, Maria; Katsanika, Irene; Papadopoulou-Alataki, Efimia; Grafakou, Olga; Gkampeta, Anastasia; Dinopoulos, Argyrios; Evangeliou, Athanasios

2016-07-01

Although ketogenic diet has been proven useful in the management of intractable seizures, interactions with other medicines have been reported. This study reports two patients on co-administration with ketogenic diet and valproate appearing undesirable side effects after increase or decrease of valproate pharmaceutical levels. Totally 75 patients suffering from drug-resistant epilepsy were treated with ketogenic diet in our departments. Their age varied from 6 months to 9 years. All patients were followed for at least 12 months and up to five years. Clinical and laboratory variables have been regularly assessed. In 75 patients treated with ketogenic diet and valproate at the same time treatment was well tolerated. Two patients presented mild to moderate undesirable effects. In these patients the removal of valproate treatment resulted in an increase of ketosis with respective clinical signs. The conversion of the diet from 4:1 to 1:1 and 2,5:1 respectively resulted in reduction of ketosis and clinical improvement. In the majority of cases co-administration of valproate and ketogenic diet seems to be safe. In two cases, valproate appeared to have a negative effect on ketosis (and weaning it led to over-ketosis). This interaction is worthy of future study. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Clinical ketosis and standing behavior in transition cows.

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Itle, A J; Huzzey, J M; Weary, D M; von Keyserlingk, M A G

2015-01-01

Ketosis is a common disease in dairy cattle, especially in the days after calving, and it is often undiagnosed. The objective of this study was to compare the standing behavior of dairy cows with and without ketosis during the days around calving to determine if changes in this behavior could be useful in the early identification of sick cows. Serum β-hydroxybutyrate (BHBA) was measured in 184 cows on a commercial dairy farm twice weekly from 2 to 21d after calving. Standing behavior was measured from 7d before calving to 21d after calving using data loggers. Retrospectively, 15 cows with clinical ketosis (3 consecutive BHBA samples >1.2mmol/L and at least one sample of BHBA >2.9mmol/L) were matched with 15 nonketotic cows (BHBA ketosis occurred 4.5±2.1d after calving. Total daily standing time was longer for clinically ketotic cows compared with nonketotic cows during wk -1 (14.3±0.6 vs. 12.0±0.7h/d) and on d 0 (17.2±0.9 vs. 12.7±0.9h/d) but did not differ during the other periods. Clinically ketotic cows exhibited fewer standing bouts compared with nonketotic cows on d 0 only (14.6±1.9 vs. 20.9±1.8bouts/d). Average standing bout duration was also longer for clinically ketotic cows on d 0 compared with nonketotic cows [71.3min/bout (CI: 59.3 to 85.5) vs. 35.8min/bout (CI: 29.8 to 42.9)] but was not different during the other periods. Differences in standing behavior in the week before and on the day of calving may be useful for the early detection of clinical ketosis in dairy cows. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The concentration of free amino acids in blood serum of dairy cows with primary ketosis.

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Marczuk, J; Brodzki, P; Brodzki, A; Kurek, Ł

2018-03-01

Ketosis is a common condition found in the initial stages of lactation in high-yielding dairy cows. The major cause of ketosis is a negative energy balance. During the energy deficiency, proteolysis processes develop parallel to lipolysis. During proteolysis, muscle tissue can be used as a source of amino acid. To date, the participation of amino acids in gluconeogenesis (glucogenic amino acids) and ketogenesis (ketogenic amino acids) has not been determined in detail. This paper presents the study on determination of the parameters of protein and free amino acid metabolism in blood serum of dairy cows with primary ketosis compared to healthy cows. This study contributes to better understanding of the role of amino acids in pathogenesis of ketosis. A total of 30 cows, divided into two groups: experimental (15 cows with ketosis) and control (15 healthy cows), were included in the study. The concentrations of glucose, β-hydroxybutyrate, total protein, albumin, urea, and free amino acids were determined in peripheral blood. Statistically significantly higher concentrations of glutamine, glutamic acid, isoleucine (p≤0.001), and tyrosine (p≤0.05) were found in cows with primary ketosis compared to healthy cows. Significant decrease in the concentrations of asparagine, histidine, methionine, and serine (p≤0.001), alanine, leucine, lysine and proline (p≤0.05) was observed. Significant increase of total ketogenic and glucogenic amino acids (p≤0.05), and an increased ratio of total ketogenic and glucogenic amino acids to total amino acids (p≤0.001) were noted in cows with ketosis. In our study, the changes, in particular observed in amino acid concentration in cows with primary ketosis, indicate its intensive use in both ketogenesis and gluconeogenesis processes. Therefore, a detailed understanding of the role that amino acids play in gluconeogenesis and ketogenesis will improve ketosis diagnostics and monitoring the course of a ketosis episode. Perhaps, the

Effects of a combination butaphosphan and cyanocobalamin product and insulin on ketosis resolution and milk production.

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Gordon, J L; Duffield, T F; Herdt, T H; Kelton, D F; Neuder, L; LeBlanc, S J

2017-04-01

The objective of this study was to determine the effects of butaphosphan-cyanocobalamin (B+C), glargine insulin, and propylene glycol on resolution of ketosis and average daily milk yield after treatment. Cows from 16 herds in Ontario, Canada, and 1 herd in Michigan were tested at weekly intervals between 3 and 16 DIM. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. All ketotic cows were given a baseline treatment of 3 d of 300 g of propylene glycol orally. Animals were then randomly assigned to treatment with 3 doses of either 25 mL of B+C or 25 mL of saline placebo and 1 dose of either 2 mL (200 IU) of glargine insulin or 2 mL of saline placebo in a 2 × 2 factorial arrangement. Outcomes of interest on all farms were ketosis cure (blood BHB ketosis cure (blood BHB ketosis diagnosis were 2.1 times more likely (95% CI = 1.2 to 3.7) to be cured if treated with B+C. Animals in lactation 3 or higher that had blood glucose concentrations ketosis treatment in animals with blood glucose ketosis diagnosis. It also suggests that blood glucose concentration may be an important predictor of success of ketosis treatment. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

FGF-21: promising biomarker for detecting ketosis in dairy cows.

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Xu, Chuang; Xu, Qiushi; Chen, Yuanyuan; Yang, Wei; Xia, Cheng; Yu, Hongjiang; Zhu, Kuilin; Shen, Taiyu; Zhang, Ziyang

2016-03-01

The objective of this study was to investigate the measurement of serum fibroblast growth factor-21 (FGF-21), a protein mainly synthesized by the liver, as a sensitive biomarker for diagnosis of ketosis in dairy cows. Ninety Holstein-Friesian dairy cows (60 healthy and 30 ketosis cases) were selected and divided into a Ketosis group (K), and a Control group (C). We measured serum FGF-21 and other biochemical parameters by commercial ELISA kits. In a combined population of all 90 cows, we found that serum FGF-21 level was lower (P ketosis. When the β-hydroxybutyric acid (BHBA) level increased over 1.2 mmol/L, the FGF-21 level tended to decline below 300.85 pg/ml. The area under the receiver operating characteristic curve (AUC-ROC) for serum FGF-21 for diagnosis of fatty liver was 0.952-0.025 [95% confidence interval (CI) 0.904, 1.000] which was higher than the AUC-ROC for glucose (Glc) and other tested parameters. We concluded that FGF-21 could be a diagnostic parameter in the evaluation and auxiliary diagnosis of changes in the energy metabolism state, and serum FGF-21 measurement would have a considerable clinical impact and lead to greater profitability in the dairy industry.

Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography/mass spectrometry.

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Zhang, Hongyou; Wu, Ling; Xu, Chuang; Xia, Cheng; Sun, Lingwei; Shu, Shi

2013-09-26

Ketosis is an important problem for dairy cows` production performance. However, it is still little known about plasma metabolomics details of dairy ketosis. A gas chromatography/mass spectrometry (GC/MS) technique was used to investigate plasma metabolic differences in cows that had clinical ketosis (CK, n=22), subclinical ketosis (SK, n=32), or were clinically normal controls (NC, n=22). The endogenous plasma metabolome was measured by chemical derivatization followed by GC/MS, which led to the detection of 267 variables. A two-sample t-test of 30, 32, and 13 metabolites showed statistically significant differences between SK and NC, CK and NC, and CK and SK, respectively. Orthogonal signal correction-partial least-square discriminant analysis (OPLS-DA) revealed that the metabolic patterns of both CK and SK were mostly similar, with the exception of a few differences. The development of CK and SK involved disturbances in many metabolic pathways, mainly including fatty acid metabolism, amino acid metabolism, glycolysis, gluconeogenesis, and the pentose phosphate pathway. A diagnostic model arbitrary two groups was constructed using OPLS-DA and receiver-operator characteristic curves (ROC). Multivariate statistical diagnostics yielded the 19 potential biomarkers for SK and NC, 31 for CK and NC, and 8 for CK and SK with area under the curve (AUC) values. Our results showed the potential biomarkers from CK, SK, and NC, including carbohydrates, fatty acids, amino acids, even sitosterol and vitamin E isomers, etc. 2-piperidinecarboxylic acid and cis-9-hexadecenoic acid were closely associated with metabolic perturbations in ketosis as Glc, BHBA and NEFA for dealing with metabolic disturbances of ketosis in clinical practice. However, further research is needed to explain changes of 2,3,4-trihydroxybutyric acid, 3,4-dihydroxybutyric acid, α-aminobutyric acid, methylmalonic acid, sitosterol and α-tocopherol in CK and SK, and to reveal differences between CK and SK. Our

Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

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Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A

2017-01-01

Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm 3 , mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.

Peripartum back fat thickness of multiparous Holstein-Friesian cows with displacement of the abomasum or ketosis.

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Yamakawa, Kazuhiro; Aoki, Takahiro; Matsui, Motozumi; Yamada, Kazutaka; Ishii, Mitsuo

2012-05-01

To establish a method to predict postpartum diseases using prepartum back fat thickness (BFT), the peripartum BFTs of 54 healthy multiparous cows before calving, which were diagnosed with postpartum displacement of the abomasum (DA), clinical ketosis or subclinical ketosis were compared with those of healthy cows from 8 weeks before the expected calving date to 8 weeks after calving. The peripartum BFTs of the cows with DA or clinical ketosis were significantly higher than those of healthy cows. The peripartum BFTs of the cows with subclinical ketosis were not significantly higher than those of the healthy cows.

Ketosis in buffalo (Bubalus bubalis): clinical findings and the associated oxidative stress level.

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Youssef, Mohamed A; El-Khodery, Sabry Ahmed; El-deeb, Wael M; Abou El-Amaiem, Waleed E E

2010-12-01

As little is known about the oxidant/antioxidant status in buffalo with ketosis, the present study was delineated to assess the oxidative stress level associated with clinical ketosis in water buffalo. A total of 91 parturient buffalo at smallholder farms were studied (61 suspected to be ketotic and 30 healthy). Clinical and biochemical investigations were carried out for each buffalo. Based on clinical findings and the level of beta-hydroxybutyrate (BHB), buffalo were allocated into ketotic (42), subclinical cases (19). Clinically, there was an association between clinical ketosis and anorexia (pketosis compared with subclinical and control cases, there was a significant increase (pketosis.

Brain Cell Swelling During Hypocapnia Increases with Hyperglycemia or Ketosis

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Glaser, Nicole; Bundros, Angeliki; Anderson, Steve; Tancredi, Daniel; Lo, Weei; Orgain, Myra; O'Donnell, Martha

2014-01-01

Severe hypocapnia increases the risk of DKA-related cerebral injury in children, but the reason for this association is unclear. To determine whether the effects of hypocapnia on the brain are altered during hyperglycemia or ketosis, we induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451± 78 mg/dL) and 15 ketotic rats (beta-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40±3 mmHg). In a subset (n=35), after 2 hrs of hypocapnia, pCO2 levels were normalized (40±3 mmHg) and ADC and CBF measurements repeated. Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in striatal hyperemia. These effects were not substantially altered by hyperglycemia or ketosis, however, declines in ADC during hypocapnia were greater during both hyperglycemia and ketosis. We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia. PMID:24443981

Ketosis Onset Type 2 Diabetes Had Better Islet β-Cell Function and More Serious Insulin Resistance

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Lu, Hongyun; Hu, Fang; Zeng, Yingjuan; Zou, Lingling; Luo, Shunkui; Sun, Ying; Liu, Hong; Sun, Liao

2014-01-01

Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P = 0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC0–0.5, AUC0–1, AUC0–3 (P ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM. PMID:24829925

Hyperglycaemia and ketosis in a non-diabetic patient--an unusual cause of delayed recovery.

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Pawar, Sundeep T; Nath, Soumya S; Ansari, Farrukh

2014-01-01

We report a case of hyperglycaemia and ketosis developing in a non-diabetic patient who underwent a neurosurgical procedure under general anaesthesia. A 52-year-old non-diabetic female patient underwent excision of acoustic neuroma under general anaesthesia. Pancreatic function was not disturbed and she received a single dose of dexamethasone (8 mg) and paracetamol (1 g). Delayed recovery from anaesthesia occurred. On investigation, she was found to have hyperglycaemia and ketosis. She was further managed on the line of diabetic ketoacidosis. After 24 hours, when blood glucose had normalised and ketosis abated, she could be weaned from mechanical ventilation and extubated. The patient did not receive any drugs known to cause such a condition. To the best of our knowledge, hyperglycaemia and ketosis developing in a non-diabetic patient causing delayed recovery and extubation is here reported for the first time.

HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus

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Zhu, Bing; Bu, Le; Zhang, Manna; Gusdon, Aaron M.; Zheng, Liang; Rampersad, Sharvan; Li, Jue; Qu, Shen

2016-01-01

Ketosis in patients with type 2 diabetes mellitus (T2DM) is overlooked due to atypical symptoms. The objective of this study is to evaluate the value of hemoglobin A1c (HbA1c) as a screening tool for ketosis in T2DM patients. This retrospective study consisted of 253 T2DM patients with ketosis at Shanghai 10th People’s Hospital during a period from January 1, 2011 to June 30, 2015. A control group consisted of 221 T2DM patients without ketosis randomly selected from inpatients during the same period. Receiver operating characteristic curve (ROC) analysis was used to examine the sensitivity and specificity of HbA1c as an indicator for ketosis. Higher HbA1c levels were correlated with ketosis. In patients with newly diagnosed T2DM, the area under the curve (AUC) was 0.832, with 95% confidence interval (CI) 0.754–0.911. The optimal threshold was 10.1% (87 mmol/mol). In patients with previously diagnosed T2DM, the AUC was 0.811 (95% CI: 0.767–0.856), with an optimal threshold of 8.6% (70 mmol/mol). HbA1c is a potential screening tool for ketosis in patients with T2DM. Ketosis is much more likely with HbA1c values at ≥10.1% in patients with newly diagnosed T2DM and HbA1c values at ≥8.6% in patients with previously diagnosed T2DM. PMID:28009017

Pathogenesis of A-beta+ ketosis-prone diabetes

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A-beta+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible beta-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnit...

Prevalence of ketosis in dairy cows in milk shed areas of Odisha state, India

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Sangram Biswal

2016-11-01

Full Text Available Aim: The present study was conducted to ascertain the prevalence of ketosis in dairy cows in dairy herds, milksheds, and mixed population of milk cows selected randomly in milkshed areas of Odisha state, India. Materials and Methods: The investigation was conducted in 280 private dairy herds with variable herd size of 10-15 cows comprising crossbred Jersey cows (CBJ, crossbred Holstein Friesian (CHF cows, and indigenous local breeds. The analysis of urine (Rothera’s test, milk (Ross test, and blood samples of 2760 test cows were conducted through qualitative assessment by Rothera’s test and Ross test, respectively, for the presence of ketone bodies to screen the ketotic animals. Cut-points have been decided based on β-hydroxybutyric acid level (≥1.2-1.4 mmol/L in milk. Results: We noted positive cases of ketosis with a prevalence rate of 36.7% (1014/2760 entailing 27.2% in clinical ketosis and 9.6% in subclinical ketosis. The breed wise incident rate was recorded to be the highest (38.0% in CBJs. The age-wise prevalence rate was found to be the highest (40.8% in the age group of 5.5-6.5 years. The season wise prevalence rate in 5th calver was recorded to be the highest (38.6% in summer season as compared to other seasons. The prevalence of ketosis was observed to be the highest at 56.7% on the first stage of lactation at the 1st month after 2 weeks. The incidence rates for clinical and subclinical ketosis were found to be 25.2%; 12.2%, 26.6%; 11.2% and 30.3%; 2.9% in CBJ, CHF and indigenous cows, respectively. The breed wise overall prevalence rate was recorded to be 38.0% in CBJ, 37.8% in CHF, and 33.2% in indigenous cows. Conclusion: Ketosis and subclinical ketosis is highly prevalent metabolic disorder and has severe effect on the production status of affected animal and needs to be prevented, rather than treated, by maintaining cows in good and healthy conditions. We have attempted to give great attention for diagnosis, management

Prevalence of ketosis in dairy cows in milk shed areas of Odisha state, India

Science.gov (United States)

Biswal, Sangram; Nayak, Dhruba Charan; Sardar, Kautuk Kumar

2016-01-01

Aim: The present study was conducted to ascertain the prevalence of ketosis in dairy cows in dairy herds, milksheds, and mixed population of milk cows selected randomly in milkshed areas of Odisha state, India. Materials and Methods: The investigation was conducted in 280 private dairy herds with variable herd size of 10-15 cows comprising crossbred Jersey cows (CBJ), crossbred Holstein Friesian (CHF) cows, and indigenous local breeds. The analysis of urine (Rothera’s test), milk (Ross test), and blood samples of 2760 test cows were conducted through qualitative assessment by Rothera’s test and Ross test, respectively, for the presence of ketone bodies to screen the ketotic animals. Cut-points have been decided based on β-hydroxybutyric acid level (≥1.2-1.4 mmol/L) in milk. Results: We noted positive cases of ketosis with a prevalence rate of 36.7% (1014/2760) entailing 27.2% in clinical ketosis and 9.6% in subclinical ketosis. The breed wise incident rate was recorded to be the highest (38.0%) in CBJs. The age-wise prevalence rate was found to be the highest (40.8%) in the age group of 5.5-6.5 years. The season wise prevalence rate in 5th calver was recorded to be the highest (38.6%) in summer season as compared to other seasons. The prevalence of ketosis was observed to be the highest at 56.7% on the first stage of lactation at the 1st month after 2 weeks. The incidence rates for clinical and subclinical ketosis were found to be 25.2%; 12.2%, 26.6%; 11.2% and 30.3%; 2.9% in CBJ, CHF and indigenous cows, respectively. The breed wise overall prevalence rate was recorded to be 38.0% in CBJ, 37.8% in CHF, and 33.2% in indigenous cows. Conclusion: Ketosis and subclinical ketosis is highly prevalent metabolic disorder and has severe effect on the production status of affected animal and needs to be prevented, rather than treated, by maintaining cows in good and healthy conditions. We have attempted to give great attention for diagnosis, management, and control

Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

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Villamena, Frederick A.

2018-01-01

Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations. PMID:29607218

Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2.

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Kang, Dong Young; S P, Nipin; Darvin, Pramod; Joung, Youn Hee; Byun, Hyo Joo; Do, Chang Hee; Park, Kyung Do; Park, Mi Na; Cho, Kwang Hyun; Yang, Young Mok

2017-07-03

Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis. We constructed an in vitro ketosis model by glucose starvation. We used this model to test the anti-ketosis effects of momilactone B. A primary target for treating ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down stored fat to produce triglycerides. We showed that momilactone B could regulate the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B suppressed the expression of HMGCS2 through the increased expression of STAT5b. We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression.

Ketosis Onset Type 2 Diabetes Had Better Islet β-Cell Function and More Serious Insulin Resistance

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Hongyun Lu

2014-01-01

Full Text Available Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM, but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases and nonketotic onset group (78 cases. After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β and insulin resistance (HOMA-IR. Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD than nonketotic group (P=0.04. Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC0–0.5, AUC0–1, AUC0–3 (P<0.05. Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P<0.05. From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM.

Assessment of thyroid hormones, insulin and magnesium in dairy cattle with subclinical ketosis

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A Sadeghi-nasab

2011-08-01

Full Text Available Ketosis, with ethologically energy deficiency, is one of the commonest metabolic diseases of dairy cattle. Assessment of some serum hormonal and metabolic status can be beneficent in prediction and diagnosis of subclinical ketosis. This study is performed for evaluation and comparison of thyroid hormones, insulin and magnesium of subclinical ketosis and healthy cows. During 60 days in milk (DIM serum Beta hydroxy butyric acid (BHBA and glucose levels of 200 dairy cattle have been measured. Based on 1.4 mmol/l of BHBA as a cut of point experimented animals separated to subclinical and healthy groups. Mean values of serum T3 and T4 of affected cows were significantly higher than non-affected (p

Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis

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van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd

2015-01-01

This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene

A field study to determine the prevalence, dairy herd management systems, and fresh cow clinical conditions associated with ketosis in western European dairy herds.

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Berge, Anna C; Vertenten, Geert

2014-01-01

The aim of this study was to determine the prevalence, major management systems, and fresh cow clinical conditions associated with ketosis in western European dairy herds. A total of 131 dairies were enrolled in Germany, France, Italy, the Netherlands, and the United Kingdom during 2011 to 2012. A milk-based test for ketones (Keto-Test; Sanwa Kagaku Kenkyusho Co. Ltd., Nagoya, Japan; distributed by Elanco Animal Health, Antwerp, Belgium) was used for screening cows between d 7 and 21 after calving and ketosis was defined as a Keto-Test ≥100µmol/L. Study cows were observed for clinical disease up to 35d postcalving. Multivariate analysis (generalized estimating equation logistic regression) was performed to determine country, farm, management, feed, and cow factors associated with ketosis and to determine associations between ketosis and fresh cow diseases. Thirty-nine percent of the cows were classified as having ketosis. The herd average of ketosis was 43% in Germany, 53% in France, 31% in Italy, 46% in the Netherlands, and 31% in the United Kingdom. Of the 131 farms, 112 (85%) had 25% or more of their fresh cows resulting as positive for ketosis. Clinical ketosis was not reported in most farms and the highest level of clinical ketosis reported was 23%. The risks of ketosis were significantly lower in Italy and the United Kingdom compared with France, the Netherlands, and Germany. Larger herd size was associated with a decreased risk of ketosis. The farms that fed partially mixed rations had 1.5 times higher odds of ketosis than those that fed total mixed rations. Cows that calved in April to June had the highest odds of ketosis, with about twice as high odds compared with cows that calved in July to September. The cows that calved in January to March tended to have 1.5 times higher risk of ketosis compared with cows that calved in July to September. The odds of ketosis in parity 2 and parity 3 to 7 was significantly higher (1.5 and 2.8 times higher

1,3,5,8-tetrahydroxyxanthone regulates ANGPTL3-LPL pathway to lessen the ketosis in mice.

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Xiao, Hong-Bo; Sun, Zhi-Liang; Zhou, Nan

2012-05-12

Ketosis is a metabolic disorder closely associated with both lipid and carbohydrate metabolism. Recent studies show that angiopoietin-like protein 3 (ANGPTL3) contributes to the development of metabolic disorder. The objective of this study was to explore the inhibitory effect of 1,3,5,8-tetrahydroxyxanthone (Xan), a naturally occurring flavonoid compound, on ketosis and the mechanisms involved in this regulation. After 4weeks, Xan (10 or 30mg/kg, intragastrically) treatment decreased plasma total ketone bodies, malondialdehyde, 8-isoprostane, triglyceride, total cholesterol levels, and hepatic ANGPTL3 expression concomitantly with increased plasma glucose concentration and adipose lipoprotein lipase (LPL) expression in ketosis murine. The present results suggest that Xan regulates ANGPTL3-LPL pathway to lessen the ketosis in mice. Copyright © 2012 Elsevier B.V. All rights reserved.

The effect of storage temperature on the accuracy of a cow-side test for ketosis

OpenAIRE

Hubbard, Jennifer; LeBlanc, Stephen; Duffield, Todd; Bagg, Randal; Dubuc, Jocelyn

2010-01-01

The objective of this study was to assess the effect of storage conditions on the accuracy of a milk test strip for ketosis. Storage at 21°C for up to 18 wk had little effect on accuracy for diagnosis and classification of subclinical ketosis.

Identification of novel pathways in pathogenesis of ketosis in dairy cows via iTRAQ/MS

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Shu Shi

2016-09-01

Full Text Available Introduction: To identify novel pathways involved in the pathogenesis of ketosis, an isobaric tag for relative and absolute quantitation/mass spectrometry was used to define differences in protein expression profiles between healthy dairy cows and those with clinical or subclinical ketosis.

Comparative clinical and haematological investigations in lactating cows with subclinical and clinical ketosis

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Vania Marutsova

2015-10-01

Full Text Available Ketosis of lactating cows is among the most common metabolic diseases in modern dairy farms. The economic importance of the disease is caused by the reduced milk yield and body weight loss, poor feed conversion, lower conception rates, culling and increased mortality of affected animals. In the present study, a total of 47 high-yielding dairy cows up to 45 days in milk (DIM are included. All animals were submitted to physical examination wich included checking the rectal body temperature, heart rate, respiratory and rumen contraction rates, and inspection of visible mucous coats. The body condition was scored, and blood β-hydroxybutyrate (BHBA concentrations were assayed. The cows were divided into 3 groups: first group (control (n=24 with blood β-hydroxybutyrate level 2.6 mmol/l (clinical ketosis. Whole blood samples were obtained and analyzed for Red Blood Cell (RBC, 1012/l, Hemoglobin (HGB, g/l, Hematocrit (HCT, %, Mean Corpuscular Volume (MCV, fl, Mean Corpuscular Hemoglobin (MCH, pg, Mean Corpuscular Hemoglobin Concentration (MCHC, g/l, White Blood Cell (WBC, 109/l, Lymphocytes (LYM, 109/l, Monocytes (MON, 109/l, Granulocytes (GRA, 109/l, Red Blood Distribution Width (RDW, %, Red Blood Cell Distribution Width Absolute (RDWa, fl, Platelets (PLT, 109/l and Mean Platelet Volume (MPV, fl. In this study, deviations in the clinical parameters in the control group and in those with subclinical ketosis were not identified. The cows from the third group (clinical ketosis exhibited hypotonia, anorexia and body weight loss vs. control group. Hematological analysis showed leukocytosis and lymphocytosis in cows with subclinical ketosis vs. control group. In cows with clinical ketosis WBC counts decreased (leukopenia, while hemoglobin content and hematocrit values are higher vs. control group. Blood BHBA values are higher in both groups of ketotic cows vs. the control group. The other analyzed parameters (RBC, MCH, MCHC, MCV, RDW, RDWa, MON, GRA, PLT

The effect of storage temperature on the accuracy of a cow-side test for ketosis

Science.gov (United States)

Hubbard, Jennifer; LeBlanc, Stephen; Duffield, Todd; Bagg, Randal; Dubuc, Jocelyn

2010-01-01

The objective of this study was to assess the effect of storage conditions on the accuracy of a milk test strip for ketosis. Storage at 21°C for up to 18 wk had little effect on accuracy for diagnosis and classification of subclinical ketosis. PMID:20676298

Prevalence of subclinical ketosis and relationships with postpartum diseases in European dairy cows.

Science.gov (United States)

Suthar, V S; Canelas-Raposo, J; Deniz, A; Heuwieser, W

2013-05-01

Subclinical ketosis (SCK) is defined as concentrations of β-hydroxybutyrate (BHBA) ≥ 1.2 to 1.4 mmol/L and it is considered a gateway condition for other metabolic and infectious disorders such as metritis, mastitis, clinical ketosis, and displaced abomasum. Reported prevalence rates range from 6.9 to 43% in the first 2 mo of lactation. However, there is a dearth of information on prevalence rates considering the diversity of European dairy farms. The objectives of this study were to (1) determine prevalence of SCK, (2) identify thresholds of BHBA, and (3) study their relationships with postpartum metritis, clinical ketosis, displaced abomasum, lameness, and mastitis in European dairy farms. From May to October 2011, a convenience sample of 528 dairy herds from Croatia, Germany, Hungary, Italy, Poland, Portugal, Serbia, Slovenia, Spain, and Turkey was studied. β-Hydroxybutyrate levels were measured in 5,884 cows with a handheld meter within 2 to 15 d in milk (DIM). On average, 11 cows were enrolled per farm and relevant information (e.g., DIM, postpartum diseases, herd size) was recorded. Using receiver operator characteristic curve analyses, blood BHBA thresholds were determined for the occurrence of metritis, mastitis, clinical ketosis, displaced abomasum, and lameness. Multivariate binary logistic regression models were built for each disease, considering cow as the experimental unit and herd as a random effect. Overall prevalence of SCK (i.e., blood BHBA ≥ 1.2 mmol/L) within 10 countries was 21.8%, ranging from 11.2 to 36.6%. Cows with SCK had 1.5, 9.5, and 5.0 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively. Multivariate binary logistic regression models demonstrated that cows with blood BHBA levels of ≥ 1.4, ≥ 1.1 and ≥ 1.7 mmol/L during 2 to 15 DIM had 1.7, 10.5, and 6.9 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively, compared with cows with lower

Ketosis in dairy cows: etiologic factors, monitoring, treatment

NARCIS (Netherlands)

van der Drift, S.G.A.

2013-01-01

Ketosis is a metabolic disorder that mainly occurs during the negative energy balance in early-lactation dairy cows. It is characterized by elevated concentrations of ketone bodies in blood (hyperketonemia), urine, and milk. The thesis of Saskia van der Drift covers investigations on etiologic

Critical thresholds of liver function parameters for ketosis prediction in dairy cows using receiver operating characteristic (ROC) analysis.

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Sun, Yuhang; Wang, Bo; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Wu, Ling; Xia, Cheng

2015-01-01

Fatty liver syndrome and ketosis are important metabolic disorders in high-producing cows during early lactation with fatty liver usually preceding ketosis. To date, parameters for early prediction of the risk of ketosis have not been investigated in China. To determine the predictive value of some parameters on the risk of ketosis in China. In a descriptive study, 48 control and 32 ketotic Holstein Friesian cows were randomly selected from one farm with a serum β-hydroxybutyrate (BHBA) concentration of 1.20 mmol/L as cutoff point. The risk prediction thresholds for ketosis were determined by receiver operating characteristic (ROC) analysis. In line with a high BHBA concentration, blood glucose concentration was significantly lower in ketotic cows compared to control animals (2.77 ± 0.24 versus 3.34 ± 0.03 mmol/L; P = 0.02). Thresholds were more than 0.76 mmol/L for nonesterified fatty acids (NEFA, with 65% sensitivity and 92% specificity), more than 104 U/L for aspartate aminotransferase (AST, 74% and 85%, respectively), less than 140 U/L for cholinesterase (CHE, 75% and 59%, respectively), and more than 3.3 µmol/L for total bilirubin (TBIL, 58% and 83%, respectively). There were significant correlations between BHBA and glucose (R = -4.74), or CHE (R = -0.262), BHBA and NEFA (R = 0.520), or AST (R = 0.525), or TBIL (R = 0.278), or direct bilirubin (DBIL, R = 0.348). AST, CHE, TBIL and NEFA may be useful parameters for risk prediction of ketosis. This study might be of value in addressing novel directions for future research on the connection between ketosis and liver dysfunction.

Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum.

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Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

2016-08-01

The objective of this investigation was to search for alterations in blood variables related to innate immunity and carbohydrate and lipid metabolism during the transition period in cows affected by ketosis. One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected at -8, -4, week of disease diagnosis (+1 to +3weeks), and +4weeks relative to parturition from 6 healthy cows (CON) and 6 cows with ketosis and were analyzed for serum variables. Results showed that cows with ketosis had greater concentrations of serum β-hydroxybutyric acid (BHBA), interleukin (IL)-6, tumor necrosis factor (TNF), serum amyloid A (SAA), and lactate in comparison with the CON animals. Serum concentrations of BHBA, IL-6, TNF, and lactate were greater starting at -8 and -4weeks prior to parturition in cows with ketosis vs those of CON group. Cows with ketosis also had lower DMI and milk production vs CON cows. Milk fat also was lower in ketotic cows at diagnosis of disease. Cows affected by ketosis showed an activated innate immunity and altered carbohydrate and lipid metabolism several weeks prior to diagnosis of disease. Serum IL-6 and lactate were the strongest discriminators between ketosis cows and CON ones before the occurrence of ketosis, which might be useful as predictive biomarkers of the disease state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison between New-Onset and Old-Diagnosed Type 2 Diabetes with Ketosis in Rural Regions of China

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Du, Shichun; Yang, Xia; Shi, Degang; Su, Qing

2016-01-01

Objectives. Type 2 diabetes (T2D) with ketosis was common because of late diagnosis and lacking adequate treatment in rural regions of China. This study aimed to provide the data of T2D with ketosis among inpatients in a south-west border city of China. Methods. Data of 371 patients of T2D with ketosis who were hospitalized between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan, China, were analyzed. New-onset and old-diagnosed T2D patients presenting with ketosis were compared according to clinical characteristics, laboratory results, and chronic diabetic complications. Results. Overall, the blood glucose control was poor in our study subjects. Male predominated in both groups (male prevalence was 68% in new-onset and 64% in old-diagnosed groups). Overweight and obesity accounted for 50% in new-onset and 46% in old-diagnosed cases. Inducements of ketosis were 13.8% in new-onset and 38.7% in old-diagnosed patients. Infections were the first inducements in both groups. The prevalence of chronic complications of diabetes was common in both groups. Conclusions. More medical supports were needed for the early detection and adequate treatment of diabetes in rural areas of China. PMID:26966435

Changes in the blood indicators and body condition of high yielding Holstein cows with retained placenta and ketosis

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Zenon Nogalski

2012-01-01

Full Text Available The aim of this study was to determine the effect of changes in body condition in the dry period and the early lactation period on the incidence of retained placenta and ketosis in 94 high-yielding Holstein-Friesian cows. Body condition scoring was performed every two weeks from the beginning of the dry period until week 18 of lactation. Blood for the measuring of indicators of metabolism was sampled in weeks 1 and 2 ante partum and in weeks 1, 2, 3, 7 and 15 post partum. Retained placenta was reported in 11 cows, and ketosis was diagnosed in 18 animals. One week ante partum, the serum profile of cows diagnosed with ketosis during lactation revealed 0.52 mmol/l β-hydroxybutyric acid and 0.29 mmol/l non-esterified fatty acids on average. One week post partum, the serum profile of cows with ketosis revealed 1.59 mmol/l β-hydroxybutyric acid and 1.09 mmol/l non-esterified fatty acids and cows with retained placenta 1.65 and 1.41, respectively. From the week 5 ante partum to the point of lowest body condition the average body condition loss reached 1.4 points in cows with retained placenta, 1.1 points in cows with ketosis, and 0.8 points in healthy cows. Retained placenta and ketosis increased significantly conception rates by 0.47 and 0.50, respectively. Our results show that monitoring changes in the body condition and non-esterified fatty acids and β-hydroxybutyric acid blood levels in high-yielding cows in the transition period, followed by taking relevant disease-control measures, may be effective in reducing the incidence of retained placenta and ketosis in dairy cattle herds.

Prevalence and clinical characteristics of non-alcoholic fatty liver disease in newly diagnosed patients with ketosis-onset diabetes.

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Li, T-T; Wang, A-P; Lu, J-X; Chen, M-Y; Zhao, C-C; Tang, Z-H; Li, L-X; Jia, W-P

2018-03-21

As the prevalence and clinical characteristics of non-alcoholic fatty liver disease (NAFLD) are still unknown in ketosis-onset diabetes, the present study compared the characteristics of NAFLD in type 1 diabetes (T1D), ketosis-onset and non-ketotic type 2 diabetes (T2D) patients. This cross-sectional study was performed with newly diagnosed Chinese patients with diabetes, including 39 T1D, 165 ketosis-onset and 173 non-ketotic T2D, with 30 non-diabetics included as controls. NAFLD was determined by hepatic ultrasonography, then its clinical features were analyzed and its associated risk factors evaluated. NAFLD prevalence in patients with ketosis-onset diabetes (61.8%) was significantly higher than in controls (23.3%; P=0.003) and in T1D patients (15.4%; Pketosis-onset and non-ketotic T2D patients (52.6%; P=0.229), although BMI and alanine aminotransferase (ALT) proved to be independent risk factors for the presence of NAFLD in both these groups whereas, in T1D patients, serum uric acid levels were independent risk factors. NAFLD prevalence and risk factors in ketosis-onset diabetes were similar to those in non-ketotic T2D, but different from those in T1D. These data provide further evidence that ketosis-onset diabetes should be classified as a subtype of T2D rather than idiopathic T1D. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Healthcare Resource Utilization and Costs Associated with Ketosis Events in Pediatric and Adult Patients with Type 1 Diabetes Mellitus in the UK.

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Thalange, Nandu; Aldhouse, Natalie Valerie Jane; Kitchen, Helen; Howard, Daniel; Tutkunkardas, Deniz; Håkan-Bloch, Jonas

2017-10-01

Ketosis is a metabolic state associated with insulin deficiency. Untreated, it develops into diabetic ketoacidosis, a significant contributor to mortality and morbidity in people with type 1 diabetes mellitus (T1DM). Little is understood about how patients utilize healthcare resources during ketosis events. This study aimed to identify and quantify healthcare resource utilization and provide estimates of associated costs of ketosis events in T1DM, treated unaided or with healthcare professional (HCP) assistance in the UK. Qualitative interviews with adult patients, pediatric carers, and HCPs identified resources used by patients/carers during ketosis events. An online quantitative survey was then used to quantify patients/carers resource use during their/their child's most recent ketosis event, and HCPs estimated patient resource uptake to corroborate the findings. Associated costs estimated from UK data sources were applied to the survey results to calculate the cost of ketosis events in adults and children. Quantitative survey responses from 93 adults, 76 carers, and 52 HCPs were analyzed. Patients and carers monitored ketosis during and following the event with ketone strips and additional glucose strips, and administered treatment comprising insulin and pump set changes where appropriate. Additionally, patients/carers accessed phone services and many received follow-up medical appointments. In total, 70% (n = 65) of adult and 66% (n = 50) of pediatric ketosis events were managed at home, for which resource use costs per event were £23.87 and £38.00 respectively. Remaining events were treated in NHS facilities costing £217.57 per adult and £352.92 per child. Weighted averages identified that ketosis events cost £81.98 per adult and £142.97 per child. Indirect costs from work productivity loss increase these figures to £225.11 per adult and £256.88 per child. Healthcare resource use for ketosis events is high in adults and children with T1DM and

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

Science.gov (United States)

2013-01-01

Background The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. Methods In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. Results The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, pketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both pketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. Conclusions The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2

Serum and urine trace metals in ketosis

Energy Technology Data Exchange (ETDEWEB)

Burch, R.E.; Hiner, C.; Sullivan, J.F.

1974-01-01

Three groups of male rats were housed in metabolic cages. The control group was fed ad libitum, a second group was fasted and diabetes was induced in the third group by the subcutaneous injection of alloxan. After 48 hours all animals were bled and livers, which were quick-frozen in situ, were obtained. Fasted and diabetic animals were ketotic as manifested by lowering urinary pH and elevated urinary and blood acetoacetate and ..beta..-hydroxybutyrate. Blood and hepatic content of acetate was elevated in diabetic versus control rats. Blood and hepatic content of acetate was not increased in fasted animals. In fasted rats total urinary Zn and Cu were decreased and Mg and Ca did not differ significantly from control values. In diabetic rats total urinary excretion of Mg was increased whereas urinary Zn, Cu and Ca levels did not differ significantly from control values. In fasted animals only serum Zn was diminished. In diabetic rats serum Cu and Ca were decreased and serum Mg was increased while serum Zn was unchanged. Thus, the ketosis of fasting differs from the ketosis of diabetes in several of its metabolic manifestations. 11 references, 9 figures.

(1)H-Nuclear magnetic resonance-based plasma metabolic profiling of dairy cows with clinical and subclinical ketosis.

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Sun, L W; Zhang, H Y; Wu, L; Shu, S; Xia, C; Xu, C; Zheng, J S

2014-03-01

The purpose of this study was to assess the metabolic profile of plasma samples from cows with clinical and subclinical ketosis. According to clinical signs and 3-hydroxybutyrate plasma levels, 81 multiparous Holstein cows were selected from a dairy farm 7 to 21 d after calving. The cows were divided into 3 groups: cows with clinical ketosis, cows with subclinical ketosis, and healthy control cows. (1)H-Nuclear magnetic resonance-based metabolomics was used to assess the plasma metabolic profiles of the 3 groups. The data were analyzed by principal component analysis, partial least squares discriminant analysis, and orthogonal partial least-squares discriminant analysis. The differences in metabolites among the 3 groups were assessed. The orthogonal partial least-squares discriminant analysis model differentiated the 3 groups of plasma samples. The model predicted clinical ketosis with a sensitivity of 100% and a specificity of 100%. In the case of subclinical ketosis, the model had a sensitivity of 97.0% and specificity of 95.7%. Twenty-five metabolites, including acetoacetate, acetone, lactate, glucose, choline, glutamic acid, and glutamine, were different among the 3 groups. Among the 25 metabolites, 4 were upregulated, 7 were downregulated, and 14 were both upregulated and downregulated. The results indicated that plasma (1)H-nuclear magnetic resonance-based metabolomics, coupled with pattern recognition analytical methods, not only has the sensitivity and specificity to distinguish cows with clinical and subclinical ketosis from healthy controls, but also has the potential to be developed into a clinically useful diagnostic tool that could contribute to a further understanding of the disease mechanisms. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Low cortisol levels in blood from dairy cows with ketosis: a field study.

Science.gov (United States)

Forslund, Kristina B; Ljungvall, Orjan A; Jones, Bernt V

2010-05-20

An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Cortisol, insulin, beta-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research.

Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus.

Science.gov (United States)

Kruljac, Ivan; Ćaćić, Miroslav; Ćaćić, Petra; Ostojić, Vedran; Štefanović, Mario; Šikić, Aljoša; Vrkljan, Milan

2017-01-01

Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department. Cox proportional hazard models were used to analyze the link between patient characteristics and mortality. During an observation time of 33.4 months, death of any cause occurred in 40.9 % of the non-ketotic hyperglycemia group and 30.2 % of the DK group (hazard ratio in the diabetic ketosis group, 0.63; 95 % confidence interval 0.48-0.82; P = 0.0005). Patients with diabetic ketosis had a lower incidence of symptomatic heart failure and had improved renal function. They used less furosemide and antihypertensive drugs, more metformin and lower insulin doses, all of which was independently associated with decreased mortality. Plasma glucose and glycated hemoglobin levels were similar in both groups. Patients with hyperglycemic crisis and diabetic ketosis have decreased all-cause mortality when compared to those with non-ketotic hyperglycemia. diabetic ketosis might be a compensatory mechanism rather than a complication in patients with hyperglycemic crises, but further prospective studies are warranted.

Use of test day milk fat and milk protein to detect subclinical ketosis in dairy cattle in Ontario.

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Duffield, T F; Kelton, D F; Leslie, K E; Lissemore, K D; Lumsden, J H

1997-01-01

Serum beta-hydroxybutyrate (BHB) levels were determined for 1333 dairy cows in various stages of lactation and parity on 93 dairy farms in Ontario. The data were collected in a cross-sectional manner, as part of the 1992 Ontario Dairy Monitoring and Analysis Program. The median serum BHB was 536 mumol/L for all cows, with a range of 0 to 5801 mumol/L. When subclinical ketosis was defined as a serum BHB level of 1200 mumol/L or higher, the prevalence of ketosis for cows in early lactation ( 149 DIM), and dry cows were 5.3%, 3.2%, and 1.6%, respectively. The mean serum BHB was significantly higher in the early group compared with each of the other 3 groups (P ketosis. However, test-day fat percent and test-day protein percent, used alone or in combination, were not useful screening tests for identifying cows with subclinical ketosis. PMID:9360791

Diet-Induced Ketosis Improves Cognitive Performance in Aged Rats

Science.gov (United States)

Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O.; Tsipis, Constantinos P.; Puchowicz, Michelle A.; LaManna, Joseph C.

2010-01-01

Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1α levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions. PMID:20204773

Low cortisol levels in blood from dairy cows with ketosis: a field study

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Jones Bernt V

2010-05-01

Full Text Available Abstract Background An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA. Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Methods Cortisol, insulin, β-hydroxybutyric acid (BHBA, non esterified fatty acids (NEFA, and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. Results No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method ( Conclusions The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research.

Ketone bodies in blood of dairy cows: Prevalence and monitoring of subclinical ketosis

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Marek Krempaský

2014-01-01

Full Text Available The aim of this study was to investigate the relationship between concentration of non-esterified fatty acid and ketone bodies in blood of dairy cows, and to evaluate these concentrations for the detection of prevalence of subclinical ketosis. The second aim was to compare the concentration of β-hydroxybutyric acid determined by an electronic handheld meter Precision Xtra® with serum concentration of β-hydroxybutyric acid analysed in laboratory with izotachometric and photometric method, respectively. Blood samples were collected from jugular vein 4–6 h after morning feeding in three groups of Holstein cows (n = 909 according to the lactation phase from 51 different herds with similar husbandry characteristics. High lipomobilization (non-esterified fatty acid ≥ 0.35 mmol·l-1, mean concentration 0.34 ± 0.15 mmol·l-1 was detected in 30.3% of antepartum cows, while increased concentrations of β-hydroxybutyric acid (≥ 1.0 mmol·l-1, prevalence of subclinical ketosis were detected in 18.5% and 14.1% of the early lactation and mid lactation cows, respectively. The correlation coefficient (r = 0.84, P P ® test and plasma or serum β-hydroxybutyric acid concentration determined by isotachophoresis and photometrical method, respectively. Our results show that the monitoring of changes in the blood concentration of β-hydroxybutyric acid in high-yielding cows in the early postpartum period by the electronic handheld meter Precision Xtra® may be effective in reducing the incidence of ketosis and health problems associated with ketosis in dairy cattle herds.

Neuroglycopenia in normoglycaemic patients, and the potential benefit of ketosis

NARCIS (Netherlands)

Willemsen, MAAP; Soorani-Lunsing, RJ; Pouwels, E; Klepper, J

We report a patient with recurrent symptoms of neuroglycopenia due to a defective glucose transport into brain. The potential benefit of ketosis in neuroglycopenia is discussed from the therapeutic concept of a ketogenic diet in GLUT1-deficiency syndrome.

RELATIONSHIP BETWEEN SOME BIOCHEMICAL PARAMETERS IN HEALTHY AND DAIRY COWS WITH SUBCLINICAL KETOSIS

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Gülşah Akgül

2017-07-01

Full Text Available The aim of the presented study is to compare beta-hydroxy butyric acid (BHBA, glucose (GLU gamma-glutamyl transferase (GGT, phosphorus (P, calcium (Ca, and albumin (Alb values of healthy animals and animals suffering from subclinical ketosis. The material in this study consisted of 15 healthy cows and 15 cows with subclinical ketosis on a commercial dairy farm located in Bursa (Turkey. Significant differences (p<0.001 were observed in BHBA, GLU, and Ca between the two groups. Results of this study might indicate the importance of calcium metabolism in the pathogenesis of the disease.

Effects of elevated parameters of subclinical ketosis on the immune system of dairy cows: in vivo and in vitro results.

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Schulz, Kirsten; Frahm, Jana; Kersten, Susanne; Meyer, Ulrich; Reiche, Dania; Sauerwein, Helga; Dänicke, Sven

2015-01-01

Using an established model in which subclinical ketosis is induced, the response of differential blood counts and levels of various haematological variables, including the inflammatory marker haptoglobin (Hp), were tested over the last six weeks of parturition until the 56th day post-partum in cows with lower or higher body condition scores (LBC and HBC, respectively; n = 9/group). Animals in the HBC group evidenced subclinical ketosis whereas LBC animals were metabolically healthy. For in vitro examination with ß-hydroxybutyrate (BHB) as a further stimulus, peripheral blood mononuclear cell (PBMC) counts of cows with and without subclinical ketosis (n = 5/group) were observed. Counts of leucocytes, granulocytes and lymphocytes (LY) peaked at day 1 post-partum in HBC cows, with a more marked increase in heifers. In subclinical ketosis LY count increased again, with significantly higher values in the HBC group. The red blood cell (RBC) profile was affected by parity (counts were higher in heifers). Hp showed a positive linear correlation with BHB and non-esterified fatty acids (NEFA; R(2) = 0.41). PBMC from cows that were not pre-stressed with subclinical ketosis were more sensitive to increasing levels of BHB in vitro, as evidenced by both their higher proliferative capability and increased release of nitric oxide (NO). In summary, cows with subclinical ketosis showed a heightened immune response compared with metabolically healthy individuals, based on increased LY counts, increasing stimulative properties of PBMC and a relationship between Hp and typically increased values of BHB and NEFA. Concentrations of BHB in vivo during subclinical ketosis did not alter the proliferative capability of bovine PBMC in vitro, which was first significantly decreased at a dosage of 5 mM BHB.

Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

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2014-01-01

Background The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. Methods A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. Results After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. Conclusions The prevalence and risk of lower limb

Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

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Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

2010-01-01

Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

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Milene L. Brownlow

2017-05-01

Full Text Available Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a augment cognitive outcomes in healthy subjects; and (b prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD, ketone supplemented (KS, or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the

Displaced abomasum and ketosis in dairy cows

OpenAIRE

Stengärde, Lena

2010-01-01

High producing dairy cows struggle to meet energy demands and handle various transitional changes in late gestation and early lactation. Negative energy balance in early lactation is inevitable and metabolic disorders may follow as a consequence of a deep negative energy balance. This thesis studies associations between blood profiles and body condition score (BCS) in dairy cows, and displaced abomasum (DA) or clinical ketosis, and investigates risk factors for the two diseases at the herd le...

Randomized clinical field trial on the effects of butaphosphan-cyanocobalamin and propylene glycol on ketosis resolution and milk production.

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Gordon, J L; LeBlanc, S J; Kelton, D F; Herdt, T H; Neuder, L; Duffield, T F

2017-05-01

The purpose of this study was to determine the effects of a butaphosphan-cyanocobalamin combination product (B+C) and 2 durations of propylene glycol treatment (PG; 3 versus 5 d) on ketosis resolution and early lactation milk yield. Cows from 9 freestall herds (8 in Ontario and 1 in Michigan) were tested at weekly intervals between 3 and 16 d in milk. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. Ketotic cows were randomly assigned to treatment with 25 mL of B+C or 25 mL of saline placebo for 3 d and 3 or 5 d of 300 g of PG orally in a 2 × 2 factorial arrangement. Outcomes evaluated for all farms included ketosis cure (blood BHB ketosis cure (blood BHB 2.4 mmol/L at the time of enrollment were 1.7 times more likely [95% confidence interval (CI): 1.4 to 2.2] to cure and had a decrease of 0.25 ± 0.11 mmol/L blood BHB at 1 wk after enrollment if treated with 5 d of PG compared with 3 d, though this response was not seen in animals with BHB of 1.2 to 2.4 mmol/L at enrollment. Cows with blood glucose concentrations ketosis diagnosis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ketosis After Cardiopulmonary Bypass in Children Is Associated With an Inadequate Balance Between Oxygen Transport and Consumption.

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Klee, Philippe; Arni, Delphine; Saudan, Sonja; Schwitzgebel, Valérie M; Sharma, Ruchika; Karam, Oliver; Rimensberger, Peter C

2016-09-01

Hyperglycemia after cardiac surgery and cardiopulmonary bypass in children has been associated with worse outcome; however, causality has never been proven. Furthermore, the benefit of tight glycemic control is inconsistent. The purpose of this study was to describe the metabolic constellation of children before, during, and after cardiopulmonary bypass, in order to identify a subset of patients that might benefit from insulin treatment. Prospective observational study, in which insulin treatment was initiated when postoperative blood glucose levels were more than 12 mmol/L (216 mg/dL). Tertiary PICU. Ninety-six patients 6 months to 16 years old undergoing cardiac surgery with cardiopulmonary bypass. None. Metabolic tests were performed before anesthesia, at the end of cardiopulmonary bypass, at PICU admission, and 4 and 12 hours after PICU admission, as well as 4 hours after initiation of insulin treatment. Ketosis was present in 17.9% patients at the end of cardiopulmonary bypass and in 31.2% at PICU admission. Young age was an independent risk factor for this condition. Ketosis at PICU admission was an independent risk factor for an increased difference between arterial and venous oxygen saturation. Four hours after admission (p = 0.05). Insulin corrected ketosis within 4 hours. In this study, we found a high prevalence of ketosis at PICU admission, especially in young children. This was independently associated with an imbalance between oxygen transport and consumption and was corrected by insulin. These results set the basis for future randomized controlled trials, to test whether this subgroup of patients might benefit from increased glucose intake and insulin during surgery to avoid ketosis, as improving oxygen transport and consumption might improve patient outcome.

Ketosis in type 2 diabetes mellitus: complication or compensatory mechanism?

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Ivan Kruljac

2016-06-01

Full Text Available The exact clinical role of diabetic ketosis in patients presenting to emergency departments with hyperglycemic crises is largely unknown. The aim of this brief review is to provide insights into possible mechanisms and clinical impact of diabetic ketosis in patients with hyperglycemic crises and clinical features of type 2 diabetes mellitus (T2DM. Patients with T2DM have impaired ketogenesis and lower blood ketone levels. High insulin, low glucagon, IGF-I, ghrelin and adiponectin levels are associated with suppressed ketogenesis. Adenosine 5’-monophosphate-activated protein kinase is an enzyme expressed in skeletal muscle and seems to have pivotal role in impaired ketogenesis. An increase in ketogenesis is associated with weight loss, increase in insulin sensitivity and serum IGF-I levels, which have beneficial effects on glycemia but also on cardiovascular morbidity and mortality. Ketone bodies are far more efficient fuel sources than glucose, especially in diabetics with heart failure and kidney disease. In theory, ketogenesis in patients with T2DM can be improved by low- carbohydrate and low-calorie diet, physical activity, moderate alcohol use, metformin, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 agonists and sodium/glucose cotransporter 2 (SGLT-2 inhibitors. SGLT-2 inhibitors are the most potent inducers of ketogenesis. They induce profound glycosuria with a consequent shift to fatty acid metabolism and increased ketogenesis. This could potentially explain how SGLT-2 inhibitor empagliflozin lowers cardiovascular mortality and slowers progression of kidney disease. Therefore, we believe that diabetic ketosis in patients with hyperglycemic crisis may be a compensatory mechanism, rather than a complication itself. Further prospective studies are needed to test this hypothesis.

Microfluidic biosensor for β-Hydroxybutyrate (βHBA) determination of subclinical ketosis diagnosis.

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Weng, Xuan; Zhao, Wenting; Neethirajan, Suresh; Duffield, Todd

2015-02-12

Determination of β-hydroxybutyrate (βHBA) is a gold standard for diagnosis of Subclinical Ketosis (SCK), a common disease in dairy cows that causes significant economic loss. Early detection of SCK can help reduce the risk of the disease progressing into clinical stage, thus minimizing economic losses on dairy cattle. Conventional laboratory methods are time consuming and labor-intensive, requiring expensive and bulky equipment. Development of portable and robust devices for rapid on-site SCK diagnosis is an effective way to prevent and control ketosis and can significantly aid in the management of dairy animal health. Microfluidic technology provides a rapid, cost-effective way to develop handheld devices for on-farm detection of sub-clinical ketosis. In this study, a highly sensitive microfluidics-based biosensor for on-site SCK diagnosis has been developed. A rapid, low-cost microfluidic biosensor with high sensitivity and specificity was developed for SCK diagnosis. Determination of βHBA was employed as the indicator in the diagnosis of SCK. On-chip detection using miniaturized and cost-effective optical sensor can be finished in 1 minute with a detection limit of 0.05 mM concentration. Developed microfluidic biosensor was successfully tested with the serum samples from dairy cows affected by SCK. The results of the developed biosensor agreed well with two other laboratory methods. The biosensor was characterized by high sensitivity and specificity towards βHBA with a detection limit of 0.05 mM. The developed microfluidic biosensor provides a promising prototype for a cost-effective handheld meter for on-site SCK diagnosis. By using microfluidic method, the detection time is significantly decreased compared to other laboratory methods. Here, we demonstrate a field-deployable device to precisely identify and measure subclinical ketosis by specific labeling and quantification of β-hydroxybutyate in cow blood samples. A real-time on-site detection system will

Antepartal insulin-like growth factor 1 and insulin-like growth factor binding protein 2 concentrations are indicative of ketosis in dairy cows.

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Piechotta, M; Mysegades, W; Ligges, U; Lilienthal, J; Hoeflich, A; Miyamoto, A; Bollwein, H

2015-05-01

A study involving a small number of cows found that the concentrations of insulin-like growth hormone 1 (IGF1) may be a useful predictor of metabolic disease. Further, IGF1 may provide also a pathophysiological link to metabolic diseases such as ketosis. The objective of the current study was to test whether the low antepartal total IGF1 or IGF1 binding protein (IGFBP) concentrations might predict ketosis under field conditions. Clinical examinations and blood sampling were performed antepartum (262-270 d after artificial insemination) on 377 pluriparous pregnant Holstein Friesian cows. The presence of postpartum diseases were recorded (ketosis, fatty liver, displacement of the abomasum, hypocalcemia, mastitis, retention of fetal membranes, and clinical metritis or endometritis), and the concentrations of IGF1, IGFBP2, IGFBP3, and nonesterified fatty acids were measured. Cows with postpartum clinical ketosis had lower IGF1 concentrations antepartum than healthy cows. The sensitivity of antepartal IGF1 as a marker for postpartum ketosis was 0.87, and the specificity was 0.43; a positive predictive value of 0.91 and a negative predictive value of 0.35 were calculated. The cows with ketosis and retained fetal membranes had lower IGFBP2 concentrations compared with the healthy cows. It can be speculated that lower IGF1 production in the liver during late pregnancy may increase growth hormone secretions and lipolysis, thereby increasing the risk of ketosis. Lower IGFBP2 concentrations may reflect the suppression of IGFBP2 levels through higher growth hormone secretion. In conclusion, compared with nonesterified fatty acids as a predictive parameter, IGF1 and IGFBP2 may represent earlier biomarkers of inadequate metabolic adaptation to the high energy demand required postpartum. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Breath Ketone Testing: A New Biomarker for Diagnosis and Therapeutic Monitoring of Diabetic Ketosis

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Yue Qiao

2014-01-01

Full Text Available Background. Acetone, β-hydroxybutyric acid, and acetoacetic acid are three types of ketone body that may be found in the breath, blood, and urine. Detecting altered concentrations of ketones in the breath, blood, and urine is crucial for the diagnosis and treatment of diabetic ketosis. The aim of this study was to evaluate the advantages of different detection methods for ketones, and to establish whether detection of the concentration of ketones in the breath is an effective and practical technique. Methods. We measured the concentrations of acetone in the breath using gas chromatography-mass spectrometry and β-hydroxybutyrate in fingertip blood collected from 99 patients with diabetes assigned to groups 1 (−, 2 (±, 3 (+, 4 (++, or 5 (+++ according to urinary ketone concentrations. Results. There were strong relationships between fasting blood glucose, age, and diabetic ketosis. Exhaled acetone concentration significantly correlated with concentrations of fasting blood glucose, ketones in the blood and urine, LDL-C, creatinine, and blood urea nitrogen. Conclusions. Breath testing for ketones has a high sensitivity and specificity and appears to be a noninvasive, convenient, and repeatable method for the diagnosis and therapeutic monitoring of diabetic ketosis.

Prevalence and Clinico-Pathology of Ketosis in Dairy Cows in Tigray ...

African Journals Online (AJOL)

Tadesse

An investigation to study the prevalence and clinico-pathology of ketosis in dairy cows ... The clinical observations in ketotic cows were anorexia, refusal to .... The decrease in milk yield was 36-100% in 5 cases followed by 30-36% in 5 cases.

Incidence and clinical vital parameters in primary ketosis of Murrah buffaloes

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Kumar, Ankit; Sindhu, Neelesh; Kumar, Parmod; Kumar, Tarun; Charaya, Gaurav; Surbhi; Jain, V. K.; Sridhar

2015-01-01

Aim: The present study was undertaken to ascertain the incidence and clinical vital parameters in cases of primary ketosis in Murrah buffaloes brought to teaching veterinary clinical complex, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar and from adjoining villages of the district Hisar, Haryana, India. Materials and Methods: The investigation was conducted on 24 clinical cases (out of total 145 screened) of primary ketosis. The diagnosis was confirmed on the basis of clinical signs and significantly positive two tests for ketone bodies in urine (Rothera’s and Keto-Diastix strip test). Data collected were statistically analyzed using independent Student’s t-test. Results: Overall incidence of disease in these areas was found to be 16.55% and all the animals were recently parturited (mean: 1.42±0.14 month), on an average in their third lactation (mean: 2.38±0.30) and exhibited clinical signs such as selective anorexia (refusal to feed on concentrate diet), drastic reduction in milk yield (mean: 64.4±5.35%), ketotic odor from urine, breath, and milk and rapid loss of body condition. All the clinical vital parameters in ketotic buffaloes (body temperature, heart rate, respiration rate, and rumen movements) were within normal range. Conclusion: Primary ketosis in Murrah buffaloes was the most common seen in the third lactation, within the first 2 months after parturition with characteristics clinical signs and no variability in vital parameters. The disease has severe effect on the production status of affected animal. PMID:27047203

Incidence and clinical vital parameters in primary ketosis of Murrah buffaloes

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Ankit Kumar

2015-09-01

Full Text Available Aim: The present study was undertaken to ascertain the incidence and clinical vital parameters in cases of primary ketosis in Murrah buffaloes brought to teaching veterinary clinical complex, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar and from adjoining villages of the district Hisar, Haryana, India. Materials and Methods: The investigation was conducted on 24 clinical cases (out of total 145 screened of primary ketosis. The diagnosis was confirmed on the basis of clinical signs and significantly positive two tests for ketone bodies in urine (Rothera’s and Keto-Diastix strip test. Data collected were statistically analyzed using independent Student’s t-test. Results: Overall incidence of disease in these areas was found to be 16.55% and all the animals were recently parturited (mean: 1.42±0.14 month, on an average in their third lactation (mean: 2.38±0.30 and exhibited clinical signs such as selective anorexia (refusal to feed on concentrate diet, drastic reduction in milk yield (mean: 64.4±5.35%, ketotic odor from urine, breath, and milk and rapid loss of body condition. All the clinical vital parameters in ketotic buffaloes (body temperature, heart rate, respiration rate, and rumen movements were within normal range. Conclusion: Primary ketosis in Murrah buffaloes was the most common seen in the third lactation, within the first 2 months after parturition with characteristics clinical signs and no variability in vital parameters. The disease has severe effect on the production status of affected animal.

Risk factors for displaced abomasum or ketosis in Swedish dairy herds.

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Stengärde, L; Hultgren, J; Tråvén, M; Holtenius, K; Emanuelson, U

2012-03-01

Risk factors associated with high or low long-term incidence of displaced abomasum (DA) or clinical ketosis were studied in 60 Swedish dairy herds, using multivariable logistic regression modelling. Forty high-incidence herds were included as cases and 20 low-incidence herds as controls. Incidence rates were calculated based on veterinary records of clinical diagnoses. During the 3-year period preceding the herd classification, herds with a high incidence had a disease incidence of DA or clinical ketosis above the 3rd quartile in a national database for disease recordings. Control herds had no cows with DA or clinical ketosis. All herds were visited during the housing period and herdsmen were interviewed about management routines, housing, feeding, milk yield, and herd health. Target groups were heifers in late gestation, dry cows, and cows in early lactation. Univariable logistic regression was used to screen for factors associated with being a high-incidence herd. A multivariable logistic regression model was built using stepwise regression. A higher maximum daily milk yield in multiparous cows and a large herd size (p=0.054 and p=0.066, respectively) tended to be associated with being a high-incidence herd. Not cleaning the heifer feeding platform daily increased the odds of having a high-incidence herd twelvefold (pketosis in Swedish dairy herds. These results confirm the importance of housing, management and feeding in the prevention of metabolic disorders in dairy cows around parturition and in early lactation. Copyright © 2011 Elsevier B.V. All rights reserved.

Attenuation of Brain Hyperbaric Oxygen Toxicity of Fasting is Not Related to Ketosis

National Research Council Canada - National Science Library

Chavko, M

1999-01-01

The objective of this study was to determine if protection from HBO2 seizures by acute, short fasting is related to the ketosis or to the mild hypoglycemia resulting from this treatment, or to both...

NMR metabolomic analysis of dairy cows reveals milk glycerophosphocholine to phosphocholine ratio as prognostic biomarker for risk of ketosis.

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Klein, Matthias S; Buttchereit, Nina; Miemczyk, Sebastian P; Immervoll, Ann-Kathrin; Louis, Caridad; Wiedemann, Steffi; Junge, Wolfgang; Thaller, Georg; Oefner, Peter J; Gronwald, Wolfram

2012-02-03

Ketosis is a common metabolic disease in dairy cows. Diagnostic markers for ketosis such as acetone and beta-hydroxybutyric acid (BHBA) are known, but disease prediction remains an unsolved challenge. Milk is a steadily available biofluid and routinely collected on a daily basis. This high availability makes milk superior to blood or urine samples for diagnostic purposes. In this contribution, we show that high milk glycerophosphocholine (GPC) levels and high ratios of GPC to phosphocholine (PC) allow for the reliable selection of healthy and metabolically stable cows for breeding purposes. Throughout lactation, high GPC values are connected with a low ketosis incidence. During the first month of lactation, molar GPC/PC ratios equal or greater than 2.5 indicate a very low risk for developing ketosis. This threshold was validated for different breeds (Holstein-Friesian, Brown Swiss, and Simmental Fleckvieh) and for animals in different lactations, with observed odds ratios between 1.5 and 2.38. In contrast to acetone and BHBA, these measures are independent of the acute disease status. A possible explanation for the predictive effect is that GPC and PC are measures for the ability to break down phospholipids as a fatty acid source to meet the enhanced energy requirements of early lactation.

[Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own clinical experience].

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Ostrowska-Nawarycz, L; Rapacka, E; Baszczyński, J; Górski, P; Czajka, J; Makowski, M; Kudzin, A

2000-04-01

The aim of the study was to evaluate renal activity during cyclic vomiting with ketosis. The clinical material was obtained from 50 cases of children hospitalized in Department of Pediatrics Military Medical University within 1993-1999 what makes about 1% of all patients. The examined group consisted of 26 boys (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3 to 8 times) because of acetonemic vomiting. The special attention during the laboratory studies was paid to evaluation of renal activity. Vomiting with ketosis were associated with temporary kidneys acute dysfunction in 46% of cases. In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with kidneys dysfunction was observed mainly with the children in pre-school age.

Determination of single nucleotide polymorphisms associated with subclinical ketosis in Jersey cattle

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Subclinical ketosis is a fresh cow disorder that is costly in terms of lost milk production and treatment cost. Although treatment and prevention strategies are available, prevention requires targeting animals that are likely to develop the disease. Whole-herd genotyping is becoming more common with...

Arginine metabolism is altered in adults with A-B + ketosis-prone diabetes

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A-B + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible B cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved. The objective of this study was to determine the relation be...

The role of exogenous insulin in the complex of hepatic lipidosis and ketosis associated with insulin resistance phenomenon in postpartum dairy cattle.

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Hayirli, A

2006-10-01

As a result of a marked decline in dry matter intake (DMI) prior to parturition and a slow rate of increase in DMI relative to milk production after parturition, dairy cattle experience a negative energy balance. Changes in nutritional and metabolic status during the periparturient period predispose dairy cattle to develop hepatic lipidosis and ketosis. The metabolic profile during early lactation includes low concentrations of serum insulin, plasma glucose, and liver glycogen and high concentrations of serum glucagon, adrenaline, growth hormone, plasma beta-hydroxybutyrate and non-esterified fatty acids, and liver triglyceride. Moreover, during late gestation and early lactation, flow of nutrients to fetus and mammary tissues are accorded a high degree of metabolic priority. This priority coincides with lowered responsiveness and sensitivity of extrahepatic tissues to insulin, which presumably plays a key role in development of hepatic lipidosis and ketosis. Hepatic lipidosis and ketosis compromise production, immune function, and fertility. Cows with hepatic lipidosis and ketosis have low tissue responsiveness to insulin owing to ketoacidosis. Insulin has numerous roles in metabolism of carbohydrates, lipids and proteins. Insulin is an anabolic hormone and acts to preserve nutrients as well as being a potent feed intake regulator. In addition to the major replacement therapy to alleviate severity of negative energy balance, administration of insulin with concomitant delivery of dextrose increases efficiency of treatment for hepatic lipidosis and ketosis. However, data on use of insulin to prevent these lipid-related metabolic disorders are limited and it should be investigated.

Screening for ketosis using multiple logistic regression based on milk yield and composition.

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Kayano, Mitsunori; Kataoka, Tomoko

2015-11-01

Multiple logistic regression was applied to milk yield and composition data for 632 records of healthy cows and 61 records of ketotic cows in Hokkaido, Japan. The purpose was to diagnose ketosis based on milk yield and composition, simultaneously. The cows were divided into two groups: (1) multiparous, including 314 healthy cows and 45 ketotic cows and (2) primiparous, including 318 healthy cows and 16 ketotic cows, since nutritional status, milk yield and composition are affected by parity. Multiple logistic regression was applied to these groups separately. For multiparous cows, milk yield (kg/day/cow) and protein-to-fat (P/F) ratio in milk were significant factors (Pketosis. For primiparous cows, lactose content (%), solid not fat (SNF) content (%) and milk urea nitrogen (MUN) content (mg/dl) were significantly associated with ketosis (Pketosis, provided the sensitivity, specificity and AUC values of (1) 0.711, 0.726 and 0.781; and (2) 0.678, 0.767 and 0.738, respectively.

Risk factors for subclinical and clinical ketosis and association with production parameters in dairy cows in the Netherlands.

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Vanholder, T; Papen, J; Bemers, R; Vertenten, G; Berge, A C B

2015-02-01

Ketosis is associated with many transition cow diseases and the subclinical form has been found to be a common condition in high-producing dairy cows. The objectives of this field study in the Netherlands were (1) to determine risk factors for subclinical ketosis [SCK; 1.2-2.9mmol of β-hydroxybutyrate (BHBA)/L of serum] and clinical ketosis (CK: ≥3.0mmol of BHBA/L of serum) at 7 to 14 d in milk and (2) to assess the association of SCK and CK with production parameters at the first dairy herd improvement (DHI) testing. Twenty-three dairies were enrolled by a local veterinary practice from 2009 to 2010, and 1,715 cows were screened for ketosis by measuring serum BHBA concentrations at 7 to 14 d in milk. Overall, 47.2% of cows had SCK and 11.6% had CK. Mixed generalized logit models with a random effect of herd were used to evaluate cow level factors associated with SCK and CK. The associations of SCK and CK with milk production parameters were tested using mixed linear models with a random effect of herd. Cows at a moderate (3.25-3.75) or fat (≥4) body condition score before calving were more likely to develop SCK and CK than thin (body condition score≤3.0) cows. The risk for developing SCK was higher in parity 2 and older cows compared with heifers, whereas for CK only, parity ≥3 cows had a higher risk. The quarter of the year in which a cow calved was associated with the risk for SCK and CK. For SCK quarter 1 (January-March) and quarter 2 (April-June), and for CK quarter 1, quarter 2, and quarter 3 (July-September) all increased the risk of development of the condition compared with quarter 4 (October-December). An increased yield of colostrum at first milking was associated with increasing risk for SCK and CK. Prolonged previous lactation length and dry period length were both associated with increased odds for SCK and CK. Subclinical ketosis and CK were associated with a higher milk yield, a higher milk fat percentage, and a lower milk protein percentage

Correlation between composition of the bacterial community and concentration of volatile fatty acids in the rumen during the transition period and ketosis in dairy cows.

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Wang, Xiaoxu; Li, Xiaobing; Zhao, Chenxu; Hu, Pan; Chen, Hui; Liu, Zhaoxi; Liu, Guowen; Wang, Zhe

2012-04-01

The transition period is a severe challenge to dairy cows. Glucose supply cannot meet demand and body fat is mobilized, potentially leading to negative energy balance (NEB), ketosis, or fatty liver. Propionate produces glucose by gluconeogenesis, which depends heavily on the number and species of microbes. In the present study, we analyzed the rumen microbiome composition of cows in the transition period, cows with ketosis, and nonperinatal cows by terminal restriction fragment length polymorphism (TRFLP) analysis of 16S rRNA genes and quantitative PCR. TRFLP analysis indicated that the quantity of Veillonellaceae organisms was reduced and that of Streptococcaceae organisms was increased in rumen samples from the transition period and ketosis groups, with the number of Lactobacillaceae organisms increased after calving. Quantitative PCR data suggested that the numbers of the main propionate-producing microbes, Megasphaera elsdenii and Selenomonas ruminantium, were decreased, while numbers of the main lactate-producing bacterium, Streptococcus bovis, were increased in the rumen of cows from the transition period and ketosis groups, with the number of Lactobacillus sp. organisms increased after calving. Volatile fatty acid (VFA) and glucose concentrations were decreased, but the lactic acid concentration was increased, in rumen samples from the transition period and ketosis groups. Our results indicate that the VFA concentration is significantly related to the numbers of Selenomonas ruminantium and Megasphaera elsdenii organisms in the rumen.

Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes.

Science.gov (United States)

Cartwright, Martina M; Hajja, Waddah; Al-Khatib, Sofian; Hazeghazam, Maryam; Sreedhar, Dharmashree; Li, Rebecca Na; Wong-McKinstry, Edna; Carlson, Richard W

2012-10-01

Ketoacidotic syndromes are frequently encountered in acute care medicine. This article focuses on ketosis and ketoacidotic syndromes associated with intoxications, alcohol abuse, starvation, and certain dietary supplements as well as inborn errors of metabolism. Although all of these various processes are characterized by the accumulation of ketone bodies and metabolic acidosis, there are differences in the mechanisms, clinical presentations, and principles of therapy for these heterogeneous disorders. Pathophysiologic mechanisms that account for these disorders are presented, as well as guidance regarding identification and management. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute nutritional ketosis: implications for exercise performance and metabolism

Science.gov (United States)

2014-01-01

Ketone bodies acetoacetate (AcAc) and D-β-hydroxybutyrate (βHB) may provide an alternative carbon source to fuel exercise when delivered acutely in nutritional form. The metabolic actions of ketone bodies are based on sound evolutionary principles to prolong survival during caloric deprivation. By harnessing the potential of these metabolic actions during exercise, athletic performance could be influenced, providing a useful model for the application of ketosis in therapeutic conditions. This article examines the energetic implications of ketone body utilisation with particular reference to exercise metabolism and substrate energetics. PMID:25379174

Association between Serum Albumin Concentration and Ketosis Risk in Hospitalized Individuals with Type 2 Diabetes Mellitus.

Science.gov (United States)

Cheng, Po-Chung; Hsu, Shang-Ren; Cheng, Yun-Chung

2016-01-01

Objective. This study examined the association between serum albumin concentration and ketosis risk in hospitalized individuals with type 2 diabetes mellitus (T2DM). Methods. A retrospective cross-sectional study was conducted at a medical center in Taiwan. Inclusion criteria were endocrinology ward inpatients exceeding 21 years of age, with preexisting diagnosis of T2DM, and blood glucose above 13.9 millimoles per liter (mmol/L) at admission. Individuals without measurement of serum albumin, urine ketone, or hemoglobin A1C, or harboring active infection, myocardial infarction, cerebrovascular event, cirrhosis, malignancy, or overt proteinuria were excluded. Using serum albumin concentration below 3.0 grams per deciliter to define hypoalbuminemia, 151 hypoalbuminemic cases and 104 normoalbuminemic controls were enrolled. The presence of ketones in urine established ketosis. Results. The prevalence of ketonuria was 48% in hypoalbuminemic subjects compared to 30% in normoalbuminemic controls (odds ratio (OR): 2.15; 95% confidence interval (CI): 1.26-3.57; P = 0.004). Moreover, among the 156 subjects with serum beta-hydroxybutyrate measurement in addition to urine ketone, 33% of the hypoalbuminemic individuals had ketonemia exceeding 3 mmol/L compared to 19% of those with normoalbuminemia (OR: 2.12, 95% CI: 0.99-4.48, P = 0.051). Conclusions. Serum albumin concentration is inversely associated with ketosis risk in hospitalized individuals with T2DM.

Genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins.

Science.gov (United States)

Koeck, A; Miglior, F; Jamrozik, J; Kelton, D F; Schenkel, F S

2013-07-01

The aim of this study was to investigate the genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins. Health data recorded by producers were available from the national dairy cattle health system in Canada. Test-day records of milk, fat, and protein yields were obtained from the routine milk recoding scheme. Ketosis and displaced abomasum were defined as binary traits (0 = healthy; 1 = sick) based on whether or not the cow had at least 1 case of the respective disease in the period from calving to 100 d after calving. Mean frequencies of ketosis and displaced abomasum were 4.1 and 2.7%, respectively. The following milk production traits were considered: milk yield, fat percentage (Fat%), protein percentage (Prot%), fat-to-protein (F:P) ratio, and F:P ratio >1.5. The trait F:P ratio >1.5 was scored as 1 or 0, based on whether or not the cow had an F:P ratio >1.5. For milk production traits, the first (5-30 d in milk) and the second (31-60 d in milk) test days were considered. Data were analyzed using bivariate linear animal models. Average heritabilities of 0.02 and 0.04 were obtained for ketosis and displaced abomasum, respectively. For milk production traits, the lowest heritabilities were obtained for F:P >1.5 (0.04 to 0.08), whereas the highest estimates were found for Prot% (0.27 to 0.38). Ketosis and displaced abomasum were genetically uncorrelated with milk yield in early lactation. Moderate favorable correlations were found between metabolic diseases and milk composition traits. Ketosis was significantly correlated with Fat% (0.33), F:P ratio (0.30), and F:P ratio >1.5 (0.35) at the first test day, whereas all genetic correlations with milk composition traits at the second test day were not significant and close to zero. Significant favorable genetic correlations were also found between displaced abomasum and F:P ratio (0.26), F:P ratio >1.5 (0.25) and Prot% (-0.19) at the first test

Relationships among ketosis, serum metabolites, body condition, and reproductive outcomes in dairy cows.

Science.gov (United States)

Shin, Eun-Kyung; Jeong, Jae-Kwan; Choi, In-Soo; Kang, Hyun-Gu; Hur, Tai-Young; Jung, Young-Hun; Kim, Ill-Hwa

2015-07-15

We determined the relationships among ketosis, serum metabolites, body condition, and reproductive disorders and performance in dairy cows. Blood samples from 213 dairy cows were collected at 4 and 2 weeks prepartum, just after calving, and at 1, 2, 4, 6, and 8 weeks postpartum to measure serum β-hydroxybutyrate, nonesterified fatty acids (NEFAs), glucose, total cholesterol, urea nitrogen, aspartate aminotransferase, γ-glutamyltransferase, and progesterone concentrations. Cows were grouped on the basis of the β-hydroxybutyrate concentration at 1 and/or 2 weeks postpartum into two groups: the ketotic group (≥1200 μmol/L, n = 59) and the nonketotic group (50% pus), and subclinical endometritis was diagnosed by evaluation of uterine cytology (>18% neutrophils) at 4 weeks postpartum. Ovarian cysts were diagnosed by ultrasonography, and resumption of postpartum cyclicity was evaluated by progesterone concentrations (≥1 ng/mL) at 4, 6, and 8 weeks postpartum. In the ketotic group, NEFA levels were higher (P ≤ 0.0005), whereas glucose (P ketosis, increased reproductive disorders, and decreased reproductive performance in dairy cows. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of β-hydroxybutyrate and isoproterenol on lipolysis in isolated adipocytes from periparturient dairy cows and cows with clinical ketosis.

Science.gov (United States)

van der Drift, S G A; Everts, R R; Houweling, M; van Leengoed, L A M G; Stegeman, J A; Tielens, A G M; Jorritsma, R

2013-06-01

An in vitro model was used to investigate effects of β-hydroxybutyrate and isoproterenol (β-adrenergic receptor agonist) on lipolysis in isolated adipocytes from late pregnant and recently calved dairy cows (n=5) and cows with clinical ketosis (n=3). Incubation with 3.0 mmol/L β-hydroxybutyrate reduced lipolysis in isolated adipocytes. This inhibitory effect was lower in the first lactation week (47%±16%) compared with late pregnancy (71%±6.5%). Incubation with 0.3 μmol/L isoproterenol stimulated lipolysis in isolated adipocytes from periparturient dairy cows. Basal lipolysis resulted in non-esterified fatty acid to glycerol ratios in the incubation media of 2.0±0.23 in prepartum samples, 2.1±0.23 in the first lactation week and 2.2±0.09 in cows with clinical ketosis. β-Hydroxybutyrate reduced lipolysis by 45%±9.6% in isolated adipocytes from cows with clinical ketosis, indicating that impaired feedback of β-hydroxybutyrate may not play a role in the disease etiology. Copyright © 2012 Elsevier Ltd. All rights reserved.

The impact of subclinical ketosis in dairy cows on greenhouse gas emissions of milk production

NARCIS (Netherlands)

Mostert, P.F.; Bokkers, E.A.M.; Middelaar, van C.E.; Boer, de I.J.M.

2016-01-01

This study aimed to estimate the impact of subclinical ketosis (SCK) and related diseases in dairy cows on greenhouse gas (GHG) emissions of milk production. A dynamic stochastic Monte Carlo simulation model was developed and combined with life cycle assessment (LCA) to quantify the impact of SCK

Ketone Body Acetoacetate Buffers Methylglyoxal via a Non-enzymatic Conversion during Diabetic and Dietary Ketosis

DEFF Research Database (Denmark)

Salomon, Trine; Sibbersen, Christian; Hansen, Jakob

2017-01-01

now demonstrate that during ketosis, another meta- bolic route is operative via direct non-enzymatic aldol reaction between methylglyoxal and the ke- tone body acetoacetate, leading to 3-hydroxyhex- ane-2,5-dione. This novel metabolite is present at a concentration of 10%–20% of the methylglyoxal...

Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4 in Cows with Subclinical Ketosis.

Directory of Open Access Journals (Sweden)

Kirsten Schulz

Full Text Available The inhibition of dipeptidyl peptidase-4 (DPP4 via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332 for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight was well tolerated in healthy lactating pluriparous cows (n = 6 with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12. The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic

Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis

Science.gov (United States)

Schulz, Kirsten; Frahm, Jana; Kersten, Susanne; Meyer, Ulrich; Rehage, Jürgen; Piechotta, Marion; Meyerholz, Maria; Breves, Gerhard; Reiche, Dania; Sauerwein, Helga; Dänicke, Sven

2015-01-01

The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like

Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis.

Science.gov (United States)

Schulz, Kirsten; Frahm, Jana; Kersten, Susanne; Meyer, Ulrich; Rehage, Jürgen; Piechotta, Marion; Meyerholz, Maria; Breves, Gerhard; Reiche, Dania; Sauerwein, Helga; Dänicke, Sven

2015-01-01

The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like

Estimating the economic impact of subclinical ketosis in dairy cattle using a dynamic stochastic simulation model

NARCIS (Netherlands)

Mostert, P.F.; Bokkers, E.A.M.; Middelaar, van C.E.; Hogeveen, H.; Boer, de I.J.M.

2018-01-01

The objective of this study was to estimate the economic impact of subclinical ketosis (SCK) in dairy cows. This metabolic disorder occurs in the period around calving and is associated with an increased risk of other diseases. Therefore, SCK affects farm productivity and profitability.

Economic value of ionophores and propylene glycol to prevent disease and treat ketosis in Canada.

Science.gov (United States)

Gohary, Khaled; Overton, Michael W; Von Massow, Michael; LeBlanc, Stephen J; Lissemore, Kerry D; Duffield, Todd F

2016-07-01

A partial budget model was developed to evaluate the economic value of Rumensin Controlled Release Capsule (CRC) boluses when administered before calving to reduce disease and increase milk production. After accounting for disease incidences in a herd and the percentage by which Rumensin CRC can reduce them, and the increase in milk production attributable to administration of Rumensin CRC, the return on investment (ROI) per lactation was 4:1. Another partial budget model was developed to estimate the economic value of propylene glycol (PG) to treat ketosis when diagnosed by 3 different cow-side tests or when administered to all cows without using any cow-side testing. After accounting for the sensitivity and specificity of each test, ROI per lactation ranged from 2:1 to 4:1. The ROI was 2:1 when no cow-side testing was used. In conclusion, prevention of diseases that occur in the postpartum period and treatment of ketosis after calving yielded a positive ROI that varies based on disease incidence and method of diagnosis.

Ketosis, ketogenic diet and food intake control: a complex relationship

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Antonio ePaoli

2015-02-01

Full Text Available Though the hunger-reduction phenomenon reported during ketogenic diets is well known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK release while reducing orexigenic signals e.g. via ghrelin. However ketone bodies (KB seem to be able to increase food intake through AMP-activated protein kinase (AMPK phosphorylation, gamma-aminobutyric acid (GABA and the release and production of adiponectin. The aim of this review is to provide an overview of our current knowledge of the effects of ketogenic diet (KD on food control in an effort to unify the apparently contradictory data into a coherent picture.

Ketosis, ketogenic diet and food intake control: a complex relationship.

Science.gov (United States)

Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M; Mangar, Devanand

2015-01-01

Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.

Ketosis, ketogenic diet and food intake control: a complex relationship

Science.gov (United States)

Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M.; Mangar, Devanand

2015-01-01

Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture. PMID:25698989

Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First Clinical Sign

Directory of Open Access Journals (Sweden)

A. Herrero-Ruiz

2017-01-01

Full Text Available We present the clinical case of a patient who was admitted with an onset of diabetes mellitus (DM with associated ketosis and whose clinical, hormonal, and radiological evolution revealed the presence of primary hyperparathyroidism, pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the context of multiple endocrine neoplasia type 1 (MEN1. DM is relatively common in cases of acromegaly, but it is not generally associated with ketosis. Simultaneously, the patient presented a meningioma, which is associated with pituitary macroadenoma only in extremely rare cases.

Update on diagnosis, pathogenesis and management of ketosis-prone Type 2 diabetes mellitus

OpenAIRE

Smiley, Dawn; Chandra, Prakash; Umpierrez, Guillermo E

2011-01-01

Diabetic ketoacidosis (DKA) has been considered a key clinical feature of Type 1 diabetes mellitus; however, increasing evidence indicates that DKA is also a common feature of Type 2 diabetes (T2DM). Many cases of DKA develop under stressful conditions such as trauma or infection but an increasing number of cases without precipitating cause have been reported in children and adults with T2DM. Such patients present with severe hyperglycemia and ketosis as in Type 1 diabetes mellitus but can di...

Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis

Science.gov (United States)

Stadler, Krisztian; Bonini, Marcelo G.; Dallas, Shannon; Duma, Danielle; Mason, Ronald P.; Kadiiska, Maria B.

2008-01-01

Diabetic patients frequently encounter ketosis that is characterized by the breakdown of lipids with the consequent accumulation of ketone bodies. Several studies have demonstrated that reactive species are likely to induce tissue damage in diabetes, but the role of the ketone bodies in the process has not been fully investigated. In this study, electron paramagnetic resonance (EPR) spectroscopy combined with novel spin-trapping and immunological techniques has been used to investigate in vivo free radical formation in a murine model of acetone-induced ketosis. A six-line EPR spectrum consistent with the α-(4-pyridyl-1-oxide)-N-t-butylnitrone radical adduct of a carbon-centered lipid-derived radical was detected in the liver extracts. To investigate the possible enzymatic source of these radicals, inducible nitric oxide synthase (iNOS) and NADPH oxidase knockout mice were used. Free radical production was unchanged in the NADPH oxidase knockout but much decreased in the iNOS knockout mice, suggesting a role for iNOS in free radical production. Longer-term exposure to acetone revealed iNOS overexpression in the liver together with protein radical formation, which was detected by confocal microscopy and a novel immunospin-trapping method. Immunohistochemical analysis revealed enhanced lipid peroxidation and protein oxidation as a consequence of persistent free radical generation after 21 days of acetone treatment in control and NADPH oxidase knockout but not in iNOS knockout mice. Taken together, our data demonstrate that acetone administration, a model of ketosis, can lead to protein oxidation and lipid peroxidation through a free radical-dependent mechanism driven mainly by iNOS overexpression. PMID:18559982

Blood parameters in Swedish dairy herds with high or low incidence of displaced abomasum or ketosis.

Science.gov (United States)

Stengärde, Lena; Holtenius, Kjell; Emanuelson, Ulf; Hultgren, Jan; Niskanen, Rauni; Tråvén, Madeleine

2011-10-01

Sixty dairy herds were studied to investigate the association between long-term incidence of displaced abomasum and clinical ketosis and body condition score and blood profiles, including parameters estimating energy metabolism and hepatic lipidosis in the periparturient period and early lactation. Blood samples were taken around parturition and in early lactation from cows without apparent clinical symptoms of metabolic disorders. A difference in metabolism between high and low incidence herds was shown post-partum by a lower metabolic index (the revised Quantitative Insulin Sensitivity Check Index, RQUICKI), and tendencies for higher concentrations of glucose, insulin and non-esterified fatty acids in the high incidence herds. High incidence herds had more cows and produced on average 1400kg energy-corrected milk per cow per year more than the low incidence herds. No differences were found in parameters reflecting liver cell damage. In the first 3weeks post-partum the RQUICKI was a more sensitive marker of herds with a high incidence of displaced abomasum and clinical ketosis than any of the individual parameters, but further research is needed before practical applications of the RQUICKI can be foreseen. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis.

Science.gov (United States)

van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd

2015-05-01

This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. β-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study of the levels of beta hydroxy butyrate, glucose, protein and albumin in Holstein cows with subclinical ketosis

Directory of Open Access Journals (Sweden)

B Amouoghli Tabrizi

2007-08-01

Full Text Available The objective of this study was to comparatively evaluate the levels of beta hydroxy butyrate (BHB, glucose, protein and albumin in serum of healthy Holstein cows and those with subclinical ketosis. In this survey, blood samples were collected at two stages from cows selected at 7 dairy farms in Shahriar province of Tehran. Five to 7 ml of blood were taken from the coccygeal vein of 100 cows during the last week of pregnancy when the animals were dry and once again 2 months after parturition from the same cows, their sera separated and the amounts of BHB, glucose, protein and albumin determined by enzymatic techniques and commercially available kits. With the cut point of BHB at 1.2, 1.4 and 1.7 mmol/lit, the percentage of cows affected with subclinical ketosis were 18, 14 and 4 percent, respectively. Mean levels of BHB in ketotic cows was significantly higher than healthy cows before and after parturition while mean levels of glucose, protein and albumin was significantly lower during the same periods (P

Effects of beta-hydroxybutyrate and isoproterenol on lipolysis in isolated adipocytes from periparturient dairy cows and cows with clinical ketosis

NARCIS (Netherlands)

van der Drift, S. G. A.; Everts, R. R.; Houweling, M.; van Leengoed, L. A. M. G.; Stegeman, J. A.; Tielens, A. G. M.; Jorritsma, R.

An in vitro model was used to investigate effects of beta-hydroxybutyrate and isoproterenol (beta-adrenergic receptor agonist) on lipolysis in isolated adipocytes from late pregnant and recently calved dairy cows (n = 5) and cows with clinical ketosis (n =3). Incubation with 3.0 mmol/L

A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents.

Science.gov (United States)

Roberts, Michael D; Holland, A Maleah; Kephart, Wesley C; Mobley, C Brooks; Mumford, Petey W; Lowery, Ryan P; Fox, Carlton D; McCloskey, Anna E; Shake, Joshua J; Mesquita, Paulo; Patel, Romil K; Martin, Jeffrey S; Young, Kaelin C; Kavazis, Andreas N; Wilson, Jacob M

2016-05-15

We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise. Copyright © 2016 the American Physiological Society.

Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein.

Science.gov (United States)

Bielohuby, Maximilian; Menhofer, Dominik; Kirchner, Henriette; Stoehr, Barbara J M; Müller, Timo D; Stock, Peggy; Hempel, Madlen; Stemmer, Kerstin; Pfluger, Paul T; Kienzle, Ellen; Christ, Bruno; Tschöp, Matthias H; Bidlingmaier, Martin

2011-01-01

Low-carbohydrate/high-fat diets (LC-HFDs) in rodent models have been implicated with both weight loss and as a therapeutic approach to treat neurological diseases. LC-HFDs are known to induce ketosis; however, systematic studies analyzing the impact of the macronutrient composition on ketosis induction and weight loss success are lacking. Male Wistar rats were pair-fed for 4 wk either a standard chow diet or one of three different LC-HFDs, which only differed in the relative abundance of fat and protein (percentages of fat/protein in dry matter: LC-75/10; LC-65/20; LC-55/30). We subsequently measured body composition by nuclear magnetic resonance (NMR), analyzed blood chemistry and urine acetone content, evaluated gene expression changes of key ketogenic and gluconeogenic genes, and measured energy expenditure (EE) and locomotor activity (LA) during the first 4 days and after 3 wk on the respective diets. Compared with chow, rats fed with LC-75/10, LC-65/20, and LC-55/30 gained significantly less body weight. Reductions in body weight were mainly due to lower lean body mass and paralleled by significantly increased fat mass. Levels of β-hydroxybutyate were significantly elevated feeding LC-75/10 and LC-65/20 but decreased in parallel to reductions in dietary fat. Acetone was about 16-fold higher with LC-75/10 only (P ketosis. LC-HFDs must be high in fat, but also low in protein contents to be clearly ketogenic. Independent of the macronutrient composition, LC-HFD-induced weight loss is not due to increased EE and LA.

Effects of prepartal body condition score and peripartal energy supply of dairy cows on postpartal lipolysis, energy balance and ketogenesis: an animal model to investigate subclinical ketosis.

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Schulz, Kirsten; Frahm, Jana; Meyer, Ulrich; Kersten, Susanne; Reiche, Dania; Rehage, Jürgen; Dänicke, Sven

2014-08-01

Subclinical ketosis is a metabolic disorder which often goes undiagnosed and leads to constricted performance and an impairment of general condition. In the current study subclinical ketosis was characterised by a β-hydroxybutyrate (BHB) concentration of >1·2 mmol/l in blood serum. To generate this metabolic situation, an animal model was created. The model, based on group-specific interaction of dietary energy supply and body condition, is appropriate for testing the medical effectiveness of treating this kind of ketosis and its concomitants. During the trial, 18 dairy cows (primiparous and pluriparous) were assigned, according to their body condition score (BCS) 6 weeks before expected parturition, to a normal [6.78 MJ net energy for lactation (NEL)/kg dry matter; 20% concentrate] or to a high-energy feeding group (7·71 MJ NEL/kg dry matter; 60% concentrate). Therefore cows with the highest BCS were allocated to the high-energy group to enhance the contrast with the control group. Statistical analysis was done using the MIXED procedure of SAS. Effects were declared significant when P-values were ⩽0.05. Owing to the higher energy concentration and dry matter intake, the energy intake and balance was significantly higher in the high-energy feeding group, with strong effects on lipid metabolism and health in blood and liver post partum. Within the first 2 weeks after calving, 8 out of 9 cows (89%) of the high-energy group had BHB values indicative of subclinical ketosis. These cows also had significantly higher values of non-esterified fatty acids (NEFA), aspartate transaminase (AST) and glutamate dehydrogenase (GLDH) post partum, as well as a raised total lipid content of the liver. RQUICKI, a calculated parameter which is based on serum concentrations of glucose, insulin and NEFA to assess the insulin sensitivity, was not affected by treatment. Therefore, RQUICKI does not seem to be the right parameter for diagnosing decreased insulin sensitivity in cows

Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.

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Ryan, Karen K; Packard, Amy E B; Larson, Karlton R; Stout, Jayna; Fourman, Sarah M; Thompson, Abigail M K; Ludwick, Kristen; Habegger, Kirk M; Stemmer, Kerstin; Itoh, Nobuyuki; Perez-Tilve, Diego; Tschöp, Matthias H; Seeley, Randy J; Ulrich-Lai, Yvonne M

2018-01-01

In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual's nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect. Copyright © 2018 Endocrine Society.

Subclinical Ketosis on Dairy Cows in Transition Period in Farms with Contrasting Butyric Acid Contents in Silages

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Fernando Vicente

2014-01-01

Full Text Available This study examines the relationship between subclinical ketosis (SCK in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05. As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake.

Subclinical ketosis on dairy cows in transition period in farms with contrasting butyric acid contents in silages.

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Vicente, Fernando; Rodríguez, María Luisa; Martínez-Fernández, Adela; Soldado, Ana; Argamentería, Alejandro; Peláez, Mario; de la Roza-Delgado, Begoña

2014-01-01

This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake).

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review.

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Harvey, Cliff J D C; Schofield, Grant M; Williden, Micalla

2018-01-01

Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms "ketogenic diet", "ketogenic", "ketosis" and ketonaemia (/ ketonemia). Additionally, author names and reference lists were used for further search of the selected papers for related references. Evidence, from one mouse study, suggests that leucine doesn't significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn't reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse effects of a ketogenic diet during the induction phase. Those that

Economic and Managerial Analysis of Effective Managerial Strategies on Prevention from Ketosis in Transition Period in Shahroud Commercial Dairy Farms

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Kashfi, H.; Yazdani, A. R.; Latifi, M.; Shirani Bidabadi, F.

2011-01-01

The purpose of this research is to study any effects of managerial strategies on prevention of ketosis metabolic disorder in transition period in Shahroud commercial dairy farms. For this purpose, a questionnaire was prepared in order to obtain required information about the performance of these managerial strategies, performance costs, involvement situation with disorders relying upon clinical signs and treatment and health records, producing and economic situation, and fertility rate and its costs. The considered managerial guidelines include body condition score management or type evaluation in transition period, increase in dry matter intake close to parturition, using propylene glycol, using niacin, and high-quality feeding (the importance of feed quality) in transition period. Finally and upon arrangement of data, it was possible to study any effects of mentioned managerial strategies on related variants through multiple linear regressions. Furthermore, in order to study any relation among variables, we considered Pearson correlation coefficients as well. Finally, it was revealed that any application of managerial strategies for prevention from Ketosis in transition period has a significant effect in betterment of managerial and economic parameters. PMID:23738102

The cost of a case of subclinical ketosis in Canadian dairy herds.

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Gohary, Khaled; Overton, Michael W; Von Massow, Michael; LeBlanc, Stephen J; Lissemore, Kerry D; Duffield, Todd F

2016-07-01

The objective of this study was to develop a model to estimate the cost of a case of subclinical ketosis (SCK) in Canadian dairy herds. Costs were derived from the default inputs, and included increased clinical disease incidence attributable to SCK, $76; longer time to pregnancy, $57; culling and death in early lactation attributable to SCK, $26; milk production loss, $44. Given these figures, the cost of 1 case of SCK was estimated to be $203. Sensitivity analysis showed that the estimated cost of a case of SCK was most sensitive to the herd-level incidence of SCK and the cost of 1 day open. In conclusion, SCK negatively impacts dairy herds and losses are dependent on the herd-level incidence and factors included in the calculation.

Risk factors for clinical mastitis, ketosis, and pneumonia in dairy cattle on organic and small conventional farms in the United States.

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Richert, R M; Cicconi, K M; Gamroth, M J; Schukken, Y H; Stiglbauer, K E; Ruegg, P L

2013-07-01

The US regulations for production of organic milk include a strict prohibition against the use of antimicrobials and other synthetic substances. The effect of these regulations on dairy animal health has not been previously reported. The objective of this study was to characterize disease detection and identify risk factors for selected diseases on organic (ORG) and similarly sized conventional (CON) farms. Dairy herds (n=292) were enrolled across 3 states (New York, Oregon, Wisconsin) with CON herds matched to ORG herds based on location and herd size. During a single herd visit, information was collected about herd management practices and animal disease occurring in the previous 60 d, and paperwork was left for recording disease occurrences during 60 d after the visit. For analysis, CON herds were further divided into grazing and nongrazing. Poisson regression models were used to assess risk factors for rate of farmer-identified and recorded cases of clinical mastitis, ketosis, and pneumonia. An increased rate of farmer-identified and recorded cases of clinical mastitis was associated with use of CON management, use of forestripping, presence of contagious pathogens in the bulk tank culture, proactive detection of mastitis in postpartum cows, and stall barn housing. An increased rate of farmer-identified and recorded cases of ketosis was associated with having a more sensitive definition of ketosis, using stall barn housing, and feeding a greater amount of concentrates. An increased rate of farmer-identified and recorded cases of pneumonia was associated with a lack of grazing, small or medium herd size, and Jersey as the predominant breed. Overall, disease definitions and perceptions were similar among grazing systems and were associated with the rate of farmer-identified and recorded cases of disease. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets.

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Prabhakar, Amlendu; Quach, Ashley; Zhang, Haojiong; Terrera, Mirna; Jackemeyer, David; Xian, Xiaojun; Tsow, Francis; Tao, Nongjian; Forzani, Erica S

2015-04-22

Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy. A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual's energy expenditure. On Day 7, ketone buildup from FK was measured. A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content. In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R(2) = 0.92), and lower body mass index (R(2) = 0.71) was observed during FK.

Inflammatory biomarkers are associated with ketosis in periparturient Holstein cows.

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Abuajamieh, Mohannad; Kvidera, Sara K; Fernandez, Maria V Sanz; Nayeri, Amir; Upah, Nathan C; Nolan, Erin A; Lei, Sam M; DeFrain, Jeffery M; Green, Howard B; Schoenberg, Katie M; Trout, William E; Baumgard, Lance H

2016-12-01

Ketosis is a prevalent periparturient metabolic disorder and we hypothesize that lipopolysaccharide (LPS) infiltration may play a key role in its etiology. Study objectives were to characterize biomarkers of inflammation during the transition period in healthy and clinically diagnosed ketotic cows. Cows were retrospectively categorized into one of two groups: healthy and clinically diagnosed ketotic. Two data sets were utilized; the first dataset (Study A) was obtained as a subset of cows (n=16) enrolled in a larger experiment conducted at the Iowa State University Dairy utilizing Holstein cows (8 healthy; 8 ketotic), and the second dataset (Study B; 22 healthy; 22 ketotic) was obtained from a commercial farm. For both experiments, blood samples were collected prior to and following calving. Ketotic cows in both studies had reduced milk production compared to healthy cows (P6 fold and ~4 fold; P=0.04 and P=0.03), and lipopolysaccharide binding protein (66 and 45%; Pketosis in transition dairy cows. Copyright © 2016 Elsevier Ltd. All rights reserved.

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review

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Cliff J. d C. Harvey; Grant M. Schofield; Micalla Williden

2018-01-01

Background Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. Methods PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science So...

Elevated Apoptosis in the Liver of Dairy Cows with Ketosis.

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Du, Xiliang; Chen, Liang; Huang, Dan; Peng, Zhicheng; Zhao, Chenxu; Zhang, Yuming; Zhu, Yiwei; Wang, Zhe; Li, Xinwei; Liu, Guowen

2017-01-01

Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively. Liver histology, TUNEL and Oil red O staining were performed in liver tissue samples. TG contents were measured using an enzymatic kit; Caspase 3 assays were carried out using the Caspase 3 activity assay kit; oxidation and antioxidant markers were measured using biochemical kits; apoptosis pathway were determined by qRT-PCR and western blot. Ketotic cows displayed hepatic fat accumulation. The hepatic malondialdehyde (MDA) content was significantly increased, but the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were markedly decreased in ketotic cows compared with control cows, indicating that ketotic cows displayed severe oxidative stress. Significantly higher serum levels of the hepatic damage markers AST, ALT, GGT and GLDH were observed in ketotic cows than in control cows. The blood concentration of the apoptotic marker CK18 M30 and the number of TUNEL-positive cells in the liver of ketotic cows were 1.19- and 2.61-fold, respectively, higher than the values observed in control cows. Besides, Caspase 3 activity was significantly increased in the liver of ketosis cows. Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) was markedly decreased, which

Elevated Apoptosis in the Liver of Dairy Cows with Ketosis

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Xiliang Du

2017-09-01

Full Text Available Background/Aims: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. Methods: The blood aspartate aminotransferase (AST, alanine aminotransferase (ALT, glutamate dehydrogenase (GLDH and gamma-glutamyl transferase (GGT activities and the haptoglobin (HP, serum amyloid A (SAA and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30 concentrations were determined by commercially available kits and ELISA kits, respectively. Liver histology, TUNEL and Oil red O staining were performed in liver tissue samples. TG contents were measured using an enzymatic kit; Caspase 3 assays were carried out using the Caspase 3 activity assay kit; oxidation and antioxidant markers were measured using biochemical kits; apoptosis pathway were determined by qRT-PCR and western blot. Results: Ketotic cows displayed hepatic fat accumulation. The hepatic malondialdehyde (MDA content was significantly increased, but the activities of catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GSH-Px were markedly decreased in ketotic cows compared with control cows, indicating that ketotic cows displayed severe oxidative stress. Significantly higher serum levels of the hepatic damage markers AST, ALT, GGT and GLDH were observed in ketotic cows than in control cows. The blood concentration of the apoptotic marker CK18 M30 and the number of TUNEL-positive cells in the liver of ketotic cows were 1.19- and 2.61-fold, respectively, higher than the values observed in control cows. Besides, Caspase 3 activity was significantly increased in the liver of ketosis cows. Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK and p38 mitogen-activated protein kinase (p38MAPK were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1

Utility of inline milk fat and protein ratio to diagnose subclinical ketosis and to assign propylene glycol treatment in lactating dairy cows.

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Jenkins, Nicholas T; Peña, Gustavo; Risco, Carlos; Barbosa, Carolina C; Vieira-Neto, Achilles; Galvão, Klibs N

2015-08-01

The objective was to identify a fat-to-protein ratio (FPR) cut-off to diagnose subclinical ketosis (SCK) and to evaluate the effect of propylene glycol (PPG) treatment of cows with high FPR. The optimized cut-off was > 1.42; sensitivity (Se) = 92%; specificity (Sp) = 65%. A cut-off > 1.5 was selected for the PPG trial for balanced Se-Sp. Fat-to-protein ratio cut-offs > 1.25, 1.35, 1.50, 1.60, and 1.70 resulted in Se-Sp of 100% to 49%, 96% to 59%, 75% to 78%, 33% to 90%, and 8% to 96%, respectively. The proportions of cows with FPR > 1.25, 1.35, 1.42, 1.50, 1.60, and 1.70 were 60%, 50%, 44%, 30%, 14%, and 6%, respectively. Incidences of clinical ketosis and milk yield were similar between cows that received 400 mL of PPG (n = 34) and control cows (n = 38). Prevalence of SCK at enrollment was 29.2%; therefore, FPR > 1.5 is not indicated for treatment. Lower cut-offs should be used for screening.

Polymorphisms within the APOBR gene are highly associated with milk levels of prognostic ketosis biomarkers in dairy cows.

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Tetens, Jens; Heuer, Claas; Heyer, Iris; Klein, Matthias S; Gronwald, Wolfram; Junge, Wolfgang; Oefner, Peter J; Thaller, Georg; Krattenmacher, Nina

2015-04-01

Essentially all high-yielding dairy cows experience a negative energy balance during early lactation leading to increased lipomobilization, which is a normal physiological response. However, a severe energy deficit may lead to high levels of ketone bodies and, subsequently, to subclinical or clinical ketosis. It has previously been reported that the ratio of glycerophosphocholine to phosphocholine in milk is a prognostic biomarker for the risk of ketosis in dairy cattle. It was hypothesized that this ratio reflects the ability to break down blood phosphatidylcholine as a fatty acid resource. In the current study, 248 animals from a previous study were genotyped with Illumina BovineSNP50 BeadChip, and genome-wide association studies were carried out for the milk levels of phosphocholine, glycerophosphocholine, and the ratio of both metabolites. It was demonstrated that the latter two traits are heritable with h2 = 0.43 and h2 = 0.34, respectively. A major quantitative trait locus was identified on cattle chromosome 25. The APOBR gene, coding for the apolipoprotein B receptor, is located within this region and was analyzed as a candidate gene. The analysis revealed highly significant associations of polymorphisms within the gene with glycerophosphocholine as well as the metabolite ratio. These findings support the hypothesis that differences in the ability to take up blood phosphatidylcholine from low-density lipoproteins play an important role in early lactation metabolic stability of dairy cows and indicate APOBR to contain a causative variant. Copyright © 2015 the American Physiological Society.

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

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Stengärde Lena

2008-08-01

Full Text Available Abstract Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations. Cows were examined and blood sampled every three weeks from four weeks ante partum (ap to nine weeks postpartum (pp. Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA, insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds.

Management of diabetic ketosis and ketoacidosis with intramuscular regular insulin in a low-resource family medicine setting

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Sudhakar Basetty

2017-01-01

Full Text Available Background: India is facing an epidemic of diabetes mellitus (DM. Effective management of complications of DM is a challenge in resource-poor areas of India. This study addresses the need to explore low-cost methods to manage diabetic ketosis (DK and diabetic ketoacidosis (DKA. Objectives: To demonstrate the use of intramuscular (IM regular insulin as a safe alternative method to control DK and DKA in a family practice setting. Materials and Methods: A retrospective chart review was done for 34 patients admitted with DK and DKA in a family medicine unit for the urban poor over 5 years. Data on age, sex, precipitating factors, blood pressure, number of days of hospitalization, amount of insulin, and time required to control blood glucose (BG and to correct acidosis were entered into EpiData version 3.1 and analyzed using SPSS software version 17. Results: Administration of IM regular insulin was effective in reducing the BG to < 250 mg/dL in patients with DK and DKA. The mean time required for this in the ketosis group was 3.8 h and in the ketoacidosis group was 3.9 h. The mean amount of insulin required for correction of acidosis in the ketoacidosis group was 72.3 units and the mean time to achieve this was 33 h. Of the 34 patients, only one in the ketoacidosis group had hypoglycemia. There was no fatality or referral of any patient. Conclusion: This study demonstrates that IM regular insulin is a safe alternative method in managing DK and DKA in a family medicine setting.

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

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Stengärde, Lena; Tråvén, Madeleine; Emanuelson, Ulf; Holtenius, Kjell; Hultgren, Jan; Niskanen, Rauni

2008-01-01

Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds. PMID:18687108

Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and decreases ketosis during fasting and induced hepatic lipidosis.

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Blanchard, Géraldine; Paragon, Bernard M; Milliat, Fabien; Lutton, Claude

2002-02-01

This study was designed to determine whether dietary carnitine supplement could protect cats from ketosis and improve carnitine and lipid metabolism in experimental feline hepatic lipidosis (FHL). Lean spayed queens received a diet containing 40 (CL group, n = 7) or 1000 (CH group, n = 4) mg/kg of L-carnitine during obesity development. Plasma fatty acid, beta-hydroxybutyrate and carnitine, and liver and muscle carnitine concentrations were measured during experimental induction of FHL and after treatment. In control cats (CL group), fasting and FHL increased the plasma concentrations of fatty acids two- to threefold (P 10-fold (from a basal 0.22 +/- 0.03 to 1.70 +/- 0.73 after 3 wk fasting and 3.13 +/- 0.49 mmol/L during FHL). In carnitine-supplemented cats, these variables increased significantly (P < 0.0001) only during FHL (beta-hydroxybutyrate, 1.42 +/- 0.17 mmol/L). L-Carnitine supplementation significantly increased plasma, muscle and liver carnitine concentrations. Liver carnitine concentration increased dramatically from the obese state to FHL in nonsupplemented cats, but not in supplemented cats, which suggests de novo synthesis of carnitine from endogenous amino acids in control cats and reversible storage in supplemented cats. These results demonstrate the protective effect of a dietary L-carnitine supplement against fasting ketosis during obesity induction. Increasing the L-carnitine level of diets in cats with low energy requirements, such as after neutering, and a high risk of obesity could therefore be recommended.

Towards practical application of sensors for monitoring animal health; design and validation of a model to detect ketosis.

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Steensels, Machteld; Maltz, Ephraim; Bahr, Claudia; Berckmans, Daniel; Antler, Aharon; Halachmi, Ilan

2017-05-01

The objective of this study was to design and validate a mathematical model to detect post-calving ketosis. The validation was conducted in four commercial dairy farms in Israel, on a total of 706 multiparous Holstein dairy cows: 203 cows clinically diagnosed with ketosis and 503 healthy cows. A logistic binary regression model was developed, where the dependent variable is categorical (healthy/diseased) and a set of explanatory variables were measured with existing commercial sensors: rumination duration, activity and milk yield of each individual cow. In a first validation step (within-farm), the model was calibrated on the database of each farm separately. Two thirds of the sick cows and an equal number of healthy cows were randomly selected for model validation. The remaining one third of the cows, which did not participate in the model validation, were used for model calibration. In order to overcome the random selection effect, this procedure was repeated 100 times. In a second (between-farms) validation step, the model was calibrated on one farm and validated on another farm. Within-farm accuracy, ranging from 74 to 79%, was higher than between-farm accuracy, ranging from 49 to 72%, in all farms. The within-farm sensitivities ranged from 78 to 90%, and specificities ranged from 71 to 74%. The between-farms sensitivities ranged from 65 to 95%. The developed model can be improved in future research, by employing other variables that can be added; or by exploring other models to achieve greater sensitivity and specificity.

Prevalence of subclinical ketosis in mainly pasture-grazed dairy cows in New Zealand in early lactation.

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Compton, C W R; McDougall, S; Young, L; Bryan, M A

2014-01-01

The main aim of this study was to describe the prevalence of primary subclinical ketosis (SCK) in mainly pasture-grazed dairy cows in three dairy-farming regions of New Zealand 7-12, and 35-40 days post-calving. A second aim was to investigate herd- and cow-level factors associated with the prevalence of SCK. A cross-sectional longitudinal prevalence survey was undertaken in 1,620 dairy cows from 57 herds. A random sample of cows without disease in the prior 30 days were enrolled at one farm visit within 5 days of calving, and blood samples were collected 7 and 28 days later (7-12 and 35-40 days post-calving) for measurement of beta-hydroxy butyrate (BHBA) concentrations using an electronic cow-side meter. SCK was defined as blood BHBA concentration ≥1.4 mmol/L. Mean cow-level prevalence of SCK varied with interval post-calving (16.8 and 3.2% at 7-12 days and 35-40 days post-calving, respectively) and age (13.0 and 13.1% of 2-year olds and ≥8-year olds, respectively, compared to 7.2% of 3-4-year-old cows). Mean herd-level prevalence of SCK was 14.3 (min 0, max 60.0)% and 2.6 (min 0, max 24.4)% at 7-12 days and 35-40 days post-calving, respectively, and was greater in Southland (13.3%) than Waikato and Canterbury herds (6.9 and 4.7%, respectively). This is the first population-based report of the prevalence of SCK in New Zealand dairy herds and demonstrates that age and interval post-calving are important risk factors determining prevalence; and that there is wide variation in prevalence between herds. Subclinical ketosis may be unrecognised but common in many New Zealand dairy cows in the first 2 weeks of lactation.

Usefulness of postmortem biochemistry in identification of ketosis: Diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition.

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Tani, Naoto; Michiue, Tomomi; Chen, Jian-Hua; Oritani, Shigeki; Ishikawa, Takaki

2016-09-01

A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis.

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Buckingham, Bruce A; Raghinaru, Dan; Cameron, Fraser; Bequette, B Wayne; Chase, H Peter; Maahs, David M; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Ly, Trang; Aye, Tandy; Hramiak, Irene; Clarson, Cheril; Stein, Robert; Gallego, Patricia H; Lum, John; Sibayan, Judy; Kollman, Craig; Beck, Roy W

2015-07-01

Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system. In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight. Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis. In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Body condition score, nonesterified fatty acids and beta-hydroxybutyrate concentrations in goats with subclinical ketosis

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V. Marutsova

2017-12-01

Full Text Available Abstract. Studies were conducted to establish the influence of the values of β-hydroxybutyric acid (ВНВА and non-esterified fatty acids (NEFA in the blood on the assessment of body condition score (BCS of goats with subclinical ketosis (SCK. A total of 113 dairy goats with yearly milk yield of 680 L, in their 2nd to 3rd lactation and average body weight 50-60 кg were included in the study. The goats were divided in three groups: І group (n=27 – pregnant (from pre-partum days 15 to 0; ІІ group (n=28 – recently kidded (from postpartum days 0 to 15 and ІІІ group (n=58 – lactating (from postpartum days 30 to 45. It was established that the quantity of BHBA in goats from control groups I, II and III were between 0.17±0.11 mmol/l and 0.56±0.11 mmol/l. In goats from the three groups with SCK signs, blood BHBA was statistically significantly elevated vs control goats – from 0.88±0.11 mmol/l to 1.2±0.42 mmol/l (р<0.001. Blood ВНВА <0.8 mmol/l in goats are indicative a good transition from pregnancy to lactation, whereas an amount between 0.8 mmol/l and 1.6 mmol /l are indicative of the SCK. Blood BHBA concentrations indicative for clinical ketosis were not established in goats from the three groups (ВНВА <1.6 mmol/l. The body condition scores (BCS of goats from the control groups was within the reference range – 2.45±0.3 – 2.85±0.2, whereas in goats with SCK – declines of varying degrees of reliability. In goats from the three groups with SCK signs, blood NEFA was statistically significantly elevated vs control groups.

Evidence That in Uncontrolled Diabetes, Hyperglucagonemia Is Required for Ketosis but Not for Increased Hepatic Glucose Production or Hyperglycemia.

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Meek, Thomas H; Dorfman, Mauricio D; Matsen, Miles E; Fischer, Jonathan D; Cubelo, Alexis; Kumar, Monica R; Taborsky, Gerald J; Morton, Gregory J

2015-07-01

Several lines of evidence implicate excess glucagon secretion in the elevated rates of hepatic glucose production (HGP), hyperglycemia, and ketosis characteristic of uncontrolled insulin-deficient diabetes (uDM), but whether hyperglucagonemia is required for hyperglycemia in this setting is unknown. To address this question, adult male Wistar rats received either streptozotocin (STZ) to induce uDM (STZ-DM) or vehicle and remained nondiabetic. Four days later, animals received daily subcutaneous injections of either the synthetic GLP-1 receptor agonist liraglutide in a dose-escalating regimen to reverse hyperglucagonemia or its vehicle for 10 days. As expected, plasma glucagon levels were elevated in STZ-DM rats, and although liraglutide treatment lowered glucagon levels to those of nondiabetic controls, it failed to attenuate diabetic hyperglycemia, elevated rates of glucose appearance (Ra), or increased hepatic gluconeogenic gene expression. In contrast, it markedly reduced levels of both plasma ketone bodies and hepatic expression of the rate-limiting enzyme involved in ketone body production. To independently confirm this finding, in a separate study, treatment of STZ-DM rats with a glucagon-neutralizing antibody was sufficient to potently lower plasma ketone bodies but failed to normalize elevated levels of either blood glucose or Ra. These data suggest that in rats with uDM, hyperglucagonemia is required for ketosis but not for increased HGP or hyperglycemia. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice.

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Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J F; Müller, Timo D; Pfluger, Paul T; Seeley, Randy J

2015-10-01

Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.

Evaluation of a point-of-care electrochemical meter to detect subclinical ketosis and hypoglycaemia in lactating dairy cows.

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Zakian, A; Tehrani-Sharif, M; Mokhber-Dezfouli, M R; Nouri, M; Constable, P D

2017-04-01

To evaluate and validate a hand-held electrochemical meter (Precision Xtra®) as a screening test for subclinical ketosis and hypoglycaemia in lactating dairy cattle. Method comparison study using a convenience sample. Blood samples were collected into plain tubes from the coccygeal vessels of 181 Holstein cows at 2-4 weeks of lactation during summer in Iran. Blood β-hydroxybutyrate concentration (BHB) and glucose concentration were immediately measured by the electrochemical meter after applying 20 μL of blood to the reagent strip. Passing-Bablok regression and Bland-Altman plots were used to determine the accuracy of the meter against laboratory reference methods (BHB dehydrogenase and glucose oxidase). Serum BHB ranged from 0.1 to 7.3 mmol/L and serum glucose ranged from 0.9 to 5.1 mmol/L. Passing-Bablok regression analysis indicated that the electrochemical meter and reference methods were linearly related for BHB and glucose, with a slope estimate that was not significantly different from 1.00. Clinically minor, but statistically significant, differences were present for the intercept value for Passing-Bablok regression analysis for BHB and glucose, and bias estimates in the Bland-Altman plots for BHB and glucose. The electrochemical meter provided a clinically useful method to detect subclinical ketosis and hypoglycaemia in lactating dairy cows. Compared with other method validation studies using the meter, we attributed the improved performance of the electrochemical meter to application of a fixed volume of blood (20 μL) to the reagent strip, use of the meter in hot ambient conditions and use of glucose oxidase as the reference method for glucose analysis. © 2017 Australian Veterinary Association.

HLA Class II Alleles Susceptibility Markers of Type 1 Diabetes Fail to Specify Phenotypes of Ketosis-Prone Diabetes in Adult Tunisian Patients

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Lilia Laadhar

2011-01-01

Full Text Available We aimed to characterize the different subgroups of ketosis-prone diabetes (KPD in a sample of Tunisian patients using the Aβ scheme based on the presence or absence of β-cell autoantibodies (A+ or A− and β-cell functional reserve (β+ or β− and we investigated whether HLA class II alleles could contribute to distinct KPD phenotypes. We enrolled 43 adult patients with a first episode of ketosis. For all patients we evaluated clinical parameters, β-cell autoimmunity, β-cell function and HLA class II alleles. Frequency distribution of the 4 subgroups was 23.3% A+β−, 23.3% A−β−, 11.6% A+β+ and 41.9% A−β+. Patients from the group A+β− were significantly younger than those from the group A−β− (P=.002. HLA susceptibility markers were significantly more frequent in patients with autoantibodies (P=.003. These patients also had resistance alleles but they were more frequent in A+β+ than A+β− patients (P=.04. Insulin requirement was not associated to the presence or the absence of HLA susceptibility markers. HLA class II alleles associated with susceptibility to autoimmune diabetes have not allowed us to further define Tunisian KPD groups. However, high prevalence of HLA resistance alleles in our patients may reflect a particular genetic background of Tunisian KPD population.

Estimating the economic impact of subclinical ketosis in dairy cattle using a dynamic stochastic simulation model.

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Mostert, P F; Bokkers, E A M; van Middelaar, C E; Hogeveen, H; de Boer, I J M

2018-01-01

The objective of this study was to estimate the economic impact of subclinical ketosis (SCK) in dairy cows. This metabolic disorder occurs in the period around calving and is associated with an increased risk of other diseases. Therefore, SCK affects farm productivity and profitability. Estimating the economic impact of SCK may make farmers more aware of this problem, and can improve their decision-making regarding interventions to reduce SCK. We developed a dynamic stochastic simulation model that enables estimating the economic impact of SCK and related diseases (i.e. mastitis, metritis, displaced abomasum, lameness and clinical ketosis) occurring during the first 30 days after calving. This model, which was applied to a typical Dutch dairy herd, groups cows according to their parity (1 to 5+), and simulates the dynamics of SCK and related diseases, and milk production per cow during one lactation. The economic impact of SCK and related diseases resulted from a reduced milk production, discarded milk, treatment costs, costs from a prolonged calving interval and removal (culling or dying) of cows. The total costs of SCK were €130 per case per year, with a range between €39 and €348 (5 to 95 percentiles). The total costs of SCK per case per year, moreover, increased from €83 per year in parity 1 to €175 in parity 3. Most cows with SCK, however, had SCK only (61%), and costs were €58 per case per year. Total costs of SCK per case per year resulted for 36% from a prolonged calving interval, 24% from reduced milk production, 19% from treatment, 14% from discarded milk and 6% from removal. Results of the sensitivity analysis showed that the disease incidence, removal risk, relations of SCK with other diseases and prices of milk resulted in a high variation of costs of SCK. The costs of SCK, therefore, might differ per farm because of farm-specific circumstances. Improving data collection on the incidence of SCK and related diseases, and on consequences of

Association of HLA class II markers with autoantibody-negative ketosis-prone atypical diabetes compared to type 2 diabetes in a population of sub-Saharan African patients.

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Balti, Eric V; Ngo-Nemb, Marinette C; Lontchi-Yimagou, Eric; Atogho-Tiedeu, Barbara; Effoe, Valery S; Akwo, Elvis A; Dehayem, Mesmin Y; Mbanya, Jean-Claude; Gautier, Jean-François; Sobngwi, Eugene

2015-01-01

We investigated the association of HLA DRB1 and DQB1 alleles, haplotypes and genotypes with unprovoked antibody-negative ketosis-prone atypical diabetes (A(-) KPD) in comparison to type 2 diabetes (T2D). A(-) KPD and T2D sub-Saharan African patients aged 19-63 years were consecutively recruited. Patients positive for cytoplasmic islet cell, insulin, glutamic acid decarboxylase or islet antigen-2 autoantibodies were excluded. Odds ratios were obtained via logistic regression after considering alleles with a minimum frequency of 5% in the study population. Bonferroni correction was used in the case of multiple comparisons. Among the 130 participants, 35 (27%) were women and 57 (44%) were A(-) KPD. DRB1 and DQB1 allele frequencies were similar for both A(-) KPD and T2D patients; they did not confer any substantial risk even after considering type 1 diabetes susceptibility and resistance alleles. We found no association between A(-) KPD and the derived DRB1*07-DQB1*02:02 (OR: 0.55 [95%CI: 0.17-1.85], P=0.336); DRB1*11-DQB1*03:01 (OR: 2.42 [95%CI: 0.79-7.42], P=0.123); DRB1*15-DQB1*06:02 (OR: 0.87 [95%CI: 0.39-1.95], P=0.731) and DRB1*03:01-DQB1*02:01 (OR: 1.48 [95%CI: 0.55-3.96], P=0.437) haplotypes. Overall, we did not find any evidence of susceptibility to ketosis associated with DRB1 and DQB1 genotypes (all P>0.05) in A(-) KPD compared to T2D. Similar results were obtained after adjusting the analysis for age and sex. Factors other than DRB1 and DQB1 genotype could explain the propensity to ketosis in A(-) KPD. These results need to be confirmed in a larger population with the perspective of improving the classification and understanding of the pathophysiology of A(-) KPD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Suitability of capillary blood obtained by a minimally invasive lancet technique to detect subclinical ketosis in dairy cows by using 3 different electronic hand-held devices.

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Kanz, P; Drillich, M; Klein-Jöbstl, D; Mair, B; Borchardt, S; Meyer, L; Schwendenwein, I; Iwersen, M

2015-09-01

The objective of this study was to evaluate the suitability of capillary blood obtained by a minimally invasive lancet technique to detect subclinical ketosis in 49 prepartum and 191 postpartum Holstein-Friesian cows using 3 different electronic hand-held devices [FreeStyle Precision (FSP, Abbott), GlucoMen LX Plus (GLX, A. Menarini), NovaVet (NOV, Nova Biomedical)]. The β-hydroxybutyrate (BHBA) concentration in serum harvested from coccygeal blood samples was analyzed in a laboratory and used as a reference value. Capillary samples were obtained from the skin of the exterior vulva by using 1 of 3 different lancets. In all samples, the concentration of BHBA was immediately analyzed with all 3 hand-held devices used in random order. All lancets used in the study were eligible for capillary blood collection but differed in the total number of incisions needed. Spearman correlation coefficients between the BHBA concentrations in capillary blood and the reference test were highly significant with 83% for the FSP, 73% for the NOV, and 63% for the GLX. Using capillary blood, the FSP overestimated the mean BHBA concentration compared with the reference test (+0.08 mmol/L), whereas the GLX and NOV underestimated the mean concentration (-0.07 and -0.01 mmol/L). When a BHBA concentration of 1.2 mmol/L in serum was used to define subclinical ketosis, the corresponding analyses of receiver operating characteristics resulted in optimized thresholds for capillary blood of 1.1 mmol/L for the NOV and GLX devices, and of 1.0 mmol/L for the FSP. Based on these thresholds, sensitivities (Se) and specificities (Sp) were 89 and 84% for the NOV, 80 and 89% for the GLX, and 100 and 76% for the FSP. Based on a serum BHBA concentration of 1.4 mmol/L, analyses of receiver operating characteristics resulted in optimized cut-offs of 1.4 mmol/L for the FSP (Se 100%, Sp 92%), 1.3 mmol/L for the NOV (Se 80%, Sp 95%), and 1.1 mmol/L (Se 90%, Sp 85%) for the GLX. Using these optimized thresholds

Fibroblast growth factor 21 is not required for glucose homeostasis, ketosis and tumour suppression associated to ketogenic diets in mice

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Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M.; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J.F.; Müller, Timo D.; Pfluger, Paul T.; Seeley, Randy J.

2016-01-01

AIMS/HYPOTHESIS Ketogenic diets (KDs) increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. Metabolic benefits of KDs are regularly ascribed towards enhanced hepatic secretion of fibroblast growth factor (FGF) 21, and its systemic effects on fatty acid oxidation, energy expenditure and body weight. Ambiguous data from Fgf21 knockout strains and low FGF21 concentrations reported for humans in ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating therapeutic benefits of KDs on metabolism and cancer. METHODS We established a dietary model of increased vs. decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted or enriched with protein, respectively. We furthermore used wild type and Fgf21 knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumor growth after transplantation of Lewis-Lung-Carcinoma cells. RESULTS Hepatic and circulating but not adipose tissue FGF21 levels were profoundly increased by protein starvation and independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycemia upon protein and carbohydrate starvation and is dispensable for the effects of KDs on energy expenditure. Furthermore, the tumor-suppressing effects of KDs were independent from FGF21, and rather driven by concomitant protein and carbohydrate starvation. CONCLUSION/INTERPRETATION Our data indicate that multiple systemic effects of KDs exposure in mice that were previously ascribed towards increased FGF21 secretion are rather a consequence of protein malnutrition. PMID:26099854

Diseases, reproductive performance, and changes in milk production associated with subclinical ketosis in dairy cows: a meta-analysis and review.

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Raboisson, D; Mounié, M; Maigné, E

2014-12-01

Many studies have shown that subclinical ketosis (SCK) is associated with an increased risk of developing various diseases, reproductive disorders, and changes in milk production. The present work aims at producing an overview between this disorder and theses outcomes. A meta-analysis of the literature, including 131 different models from 23 papers, or a review when the literature was scarce was conducted. For each outcome, the odds ratio (OR), relative risk, or hazard ratio was presented for various moderators to reduce heterogeneity among the studies. The raw change in milk production associated with SCK was estimated and adjusted, taking into consideration the outcomes known to interact with milk production during the peripartum period. The results showed that 2 main categories of moderators had a significant effect on the adjusted risk. First, the adjustment made by defining SCK as (1) β-hydroxybutyrate concentration >1.4 mM, (2) nonesterified fatty acid (NEFA) concentration >0.4 mM prepartum, or (3) NEFA concentration >1.0 mM postpartum corrected the underestimated risk (despite low significance). This is because several trials reported the relevant risks using lower thresholds for the β-hydroxybutyrate or NEFA values. Using a low threshold leads to lower risk of disease compared with using a high threshold. Second, the correction produced using the polyfactorial terms corrected the overestimation of risk because many trials reported only univariable models. The relative risk or OR (95% confidence interval) related to abomasal displacement, clinical ketosis, early culling and death, metritis, placental retention, clinical mastitis, lameness, and a doubling of the SCC in cases with SCK were 3.33 (2.60-4.25), 5.38 (3.27-8.83), 1.92 (1.60-2.30), 1.75 (1.54-2.01), 1.52 (1.20-1.93), 1.61 (1.24-2.09), 2.01(1.64-2.44), and 1.42 (1.26-1.60), respectively. The precision level of the estimate depended on the outcome. The direct mean ± standard deviation of the 305-d

The Effect of Medium Chain Triglycerides on Time to Nutritional Ketosis and Symptoms of Keto-Induction in Healthy Adults: A Randomised Controlled Clinical Trial

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Cliff J. d C. Harvey

2018-01-01

Full Text Available Medium chain triglycerides (MCTs are ketogenic and might reduce adverse effects of keto-induction and improve time to ketosis and the tolerability of very low carbohydrate diets. This study investigates whether MCT supplementation improves time to nutritional ketosis (NK, mood, and symptoms of keto-induction. We compared changes in beta-hydroxybutyrate (BOHB, blood glucose, symptoms of keto-induction, and mood disturbance, in 28 healthy adults prescribed a ketogenic diet, randomised to receive either 30 ml of MCT, or sunflower oil as a control, three times per day, for 20 days. The primary outcome measured was the achievement of NK (≥0.5 mmol·L−1 BOHB. Participants also completed a daily Profile of Mood States and keto-induction symptom questionnaire. MCT resulted in higher BOHB at all time points and faster time to NK, a result that failed to reach significance. Symptoms of keto-induction resulted from both diets, with a greater magnitude in the control group, except for abdominal pain, which occurred with greater frequency and severity in the MCT-supplemented diet. There was a possibly beneficial effect on symptoms by MCT, but the effect on mood was unclear. Based on these results, MCTs increase BOHB compared with LCT and reduce symptoms of keto-induction. It is unclear whether MCTs significantly improve mood or time to NK. The trial was registered by the Australia New Zealand Clinical Trial Registry ACTRN12616001099415.

Short communication: Use of genomic and metabolic information as well as milk performance records for prediction of subclinical ketosis risk via artificial neural networks.

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Ehret, A; Hochstuhl, D; Krattenmacher, N; Tetens, J; Klein, M S; Gronwald, W; Thaller, G

2015-01-01

Subclinical ketosis is one of the most prevalent metabolic disorders in high-producing dairy cows during early lactation. This renders its early detection and prevention important for both economical and animal-welfare reasons. Construction of reliable predictive models is challenging, because traits like ketosis are commonly affected by multiple factors. In this context, machine learning methods offer great advantages because of their universal learning ability and flexibility in integrating various sorts of data. Here, an artificial-neural-network approach was applied to investigate the utility of metabolic, genetic, and milk performance data for the prediction of milk levels of β-hydroxybutyrate within and across consecutive weeks postpartum. Data were collected from 218 dairy cows during their first 5wk in milk. All animals were genotyped with a 50,000 SNP panel, and weekly information on the concentrations of the milk metabolites glycerophosphocholine and phosphocholine as well as milk composition data (milk yield, fat and protein percentage) was available. The concentration of β-hydroxybutyric acid in milk was used as target variable in all prediction models. Average correlations between observed and predicted target values up to 0.643 could be obtained, if milk metabolite and routine milk recording data were combined for prediction at the same day within weeks. Predictive performance of metabolic as well as milk performance-based models was higher than that of models based on genetic information. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of quantum dots-based biosensor towards on-farm detection of subclinical ketosis.

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Weng, Xuan; Chen, Longyan; Neethirajan, Suresh; Duffield, Todd

2015-10-15

Early detection of dairy animal health issues allows the producer or veterinarian to intervene before the animals' production levels, or even survival, is threatened. An increased concentration of β-hydroxybutyrate (βHBA) is a key biomarker for diagnosis of subclinical ketosis (SCK), and provides information on the health stress in cows well before any external symptoms are observable. In this study, quantum dots (QDs) modified with cofactor nicotinamide adenine dinucleotide (NAD(+)) were prepared for the sensing event, by which the βHBA concentration in the cow's blood and milk samples was determined via fluorescence analysis of the functionalized QDs. The detection was performed on a custom designed microfluidic platform combining with a low cost and miniaturized optical sensor. The sensing mechanism was first validated by a microplate reader method and then applied to the microfluidic platform. Standard βHBA solution, βHBA in blood and milk samples from cows were successfully measured by this novel technology with a detection limit at a level of 35 µM. Side by side comparison of the developed microfluidic biosensor with a commercial kit presented its good performance. Copyright © 2015 Elsevier B.V. All rights reserved.

Feeding a higher forage diet prepartum decreases incidences of subclinical ketosis in transition dairy cows.

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Vickers, L A; Weary, D M; Veira, D M; von Keyserlingk, M A G

2013-02-01

A common feeding practice during the dry period is to switch dairy cows to an energy-dense diet 3 wk prepartum, but this practice may lead to the overconsumption of energy and increase the risk of metabolic disease postpartum. The aim of this trial was to compare the metabolic status of transition Holstein dairy cows fed a 77% forage diet (77F; NEl = 1.46 Mcal/kg; NDF = 41%) vs. those fed an 87% forage diet (87F; NEl = 1.41 Mcal/kg; 48% NDF). Approximately 60 d before calving, cows were dried off, housed in a free stall barn, and fed the 87F diet. Three weeks before expected calving, cows were randomly assigned to either the 77F treatment and switched to this diet (n = 45) or assigned to the 87F treatment and stayed on the dry cow ration until parturition (n = 42). After parturition, all cows were fed a common lactation diet (NEl = 1.59 Mcal/kg; 36% NDF). Dry matter intake was measured daily from 2 wk before to 2 wk after calving. Blood was sampled daily for 10 d postpartum. Subclinical ketosis was diagnosed using a threshold of β-hydroxybutyrate (BHBA) ≥ 1.0 mmol/L after calving. The percentage of cows pregnant and odds of being pregnant for each treatment group were determined at 60, 90, and 120 d in milk through ultrasound by the herd veterinarian. Cows on the 87F diet consumed less DM prepartum than those on the 77F diet (12.7 ± 0.3 kg/d vs. 15.4 ± 0.3 kg/d, P ketosis (SCK; 49% vs. 17%; P = 0.001). Milk production tended to be less for cows fed the 87F diet prepartum (47.3 ± 0.4 kg/d vs. 48.8 ± 0.4 kg/d; P = 0.10) for the first 22 wk of lactation, which was significant for d 7 to 28 of lactation (44.6 ± 1.1 kg/d vs. 47.6 ± 1.0 kg/d; P = 0.05). Although sample size was small to draw strong conclusions on reproductive performance, at 120 d in milk, cows on the 87F diet were 0.3 times more likely to be pregnant (P = 0.03). These results indicate that feeding an 87F diet before calving can reduce rates of SCK in transition dairy cows.

Genetic analysis of milk β-hydroxybutyrate and its association with fat-to-protein ratio, body condition score, clinical ketosis, and displaced abomasum in early first lactation of Canadian Holsteins.

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Koeck, A; Jamrozik, J; Schenkel, F S; Moore, R K; Lefebvre, D M; Kelton, D F; Miglior, F

2014-11-01

The aim of this study was to estimate genetic parameters for milk β-hydroxybutyrate (BHBA) in early first lactation of Canadian Holstein cows and to examine its genetic association with indicators of energy balance (fat-to-protein ratio and body condition score) and metabolic diseases (clinical ketosis and displaced abomasum). Data for milk BHBA recorded between 5 and 100 d in milk was obtained from Valacta (Sainte-Anne-de-Bellevue, Québec, Canada), the Canadian Dairy Herd Improvement organization responsible for Québec and Atlantic provinces. Test-day milk samples were analyzed by mid-infrared spectrometry using previously developed calibration equations for milk BHBA. Test-day records of fat-to-protein ratio were obtained from the routine milk recording scheme. Body condition score records were available from the routine type classification system. Data on clinical ketosis and displaced abomasum recorded by producers were available from the national dairy cattle health system in Canada. Data were analyzed using linear animal models. Heritability estimates for milk BHBA at different stages of early lactation were between 0.14 and 0.29. Genetic correlations between milk BHBA were higher between adjacent lactation intervals and decreased as intervals were further apart. Correlations between breeding values for milk BHBA and routinely evaluated traits revealed that selection for lower milk BHBA in early lactation would lead to an improvement of several health and fertility traits, including SCS, calving to first service, number of services, first service to conception, and days open. Also, lower milk BHBA was associated with a longer herd life, better conformation, and better feet and legs. A higher genetic merit for milk yield was associated with higher milk BHBA, and, therefore, a greater susceptibility to hyperketonemia. Milk BHBA at the first test-day was moderately genetically correlated with fat-to-protein ratio (0.49), body condition score (-0.35), and

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review

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Cliff J. d C. Harvey

2018-03-01

Full Text Available Background Adaptation to a ketogenic diet (keto-induction can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. Methods PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms “ketogenic diet”, “ketogenic”, “ketosis” and ketonaemia (/ ketonemia. Additionally, author names and reference lists were used for further search of the selected papers for related references. Results Evidence, from one mouse study, suggests that leucine doesn’t significantly increase beta-hydroxybutyrate (BOHB but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn’t reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. Conclusions There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse

Recreational drug abuse in patients hospitalized for diabetic ketosis or diabetic ketoacidosis.

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Isidro, María L; Jorge, Segundo

2013-04-01

To evaluate the association between recreational drug use and diabetic ketosis (DK) and diabetic ketoacidosis (DKA) in our area. Retrospective examination of records from a 1,450 bed urban teaching hospital in Spain. All adult admissions for DK or DKA from January 1, 2005, to December 31, 2009 in our hospital were included. Demographic, exploratory (blood pressure, heart rate, respiratory rate), and analytical data (glucose, urea, creatinine, corrected Na(+), K(+), pH, HCO3(-) and HbA1c) at admittance were recorded. In 152 patients, 253 episodes of DK or DKA occurred. Screening for drug use was performed in 40.3% of the events; 20.6% of the episodes (n = 52) were shown to be substance abuse. Cocaine, followed by cannabis and alcohol, was the most frequently involved drug. Poly-substance abuse occurred in 67.3% of them. Comorbidities were present in 11.5 and 39.8% of the cases shown and not shown to be related to drug use (P = 0.00). Seventy percent of the patients who were at least once shown to have consumed drugs, and 15.9% of those who were never shown to have done so, were admitted more than once (P = 0.00). The frequency of recent drug misuse in patients presenting with DK or DKA was high. Substance abuse screening was frequently neglected. Adverse profile, most significantly in readmission to hospital, was found in the patients with positive drug findings. History taking in this context should routinely include questions on substance abuse, and toxicology screening may be worthwhile, particularly in those with the history of frequent readmissions.

Acylation stimulating protein, complement C3 and lipid metabolism in ketosis-prone diabetic subjects.

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Yan Liu

Full Text Available Ketosis-prone diabetes (KPDM is new-onset diabetic ketoacidosis without precipitating factors in non-type 1 diabetic patients; after management, some are withdrawn from exogenous insulin, although determining factors remain unclear.Twenty KPDM patients and twelve type 1 diabetic patients (T1DM, evaluated at baseline, 12 and 24 months with/without insulin maintenance underwent a standardized mixed-meal tolerance test (MMTT for 2 h.At baseline, triglyceride and C3 were higher during MMTT in KPDM vs. T1DM (p<0.0001 with no differences in non-esterified fatty acids (NEFA while Acylation Stimulating Protein (ASP tended to be higher. Within 12 months, 11 KPDM were withdrawn from insulin treatment (KPDM-ins, while 9 were maintained (KPDM+ins. NEFA was lower in KPDM-ins vs. KPDM+ins at baseline (p = 0.0006, 12 months (p<0.0001 and 24 months (p<0.0001 during MMTT. NEFA in KPDM-ins decreased over 30-120 minutes (p<0.05, but not in KPDM+ins. Overall, C3 was higher in KPDM-ins vs KPDM+ins at 12 months (p = 0.0081 and 24 months (p = 0.0019, while ASP was lower at baseline (p = 0.0024 and 12 months (p = 0.0281, with a decrease in ASP/C3 ratio.Notwithstanding greater adiposity in KPDM-ins, greater NEFA decreases and lower ASP levels during MMTT suggest better insulin and ASP sensitivity in these patients.

Significance of insulin resistance and oxidative stress in dairy cattle with subclinical ketosis during the transition period.

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Youssef, Mohamed; El-Ashker, Maged

2017-02-01

Health problems occurring during the transition period in dairy cattle are of utmost importance as they can decrease the animal's reproductive performance and favor the development of various metabolic diseases with resultant significant reproductive disorders. Among the commonly reported metabolic diseases occurring during that time, hyperketonemia is the most prevalent and could provoke a significant economic impact. The failing of a dairy cow to transit optimally between pregnancy and lactation is economically very relevant and should be considered. Until now, the role of insulin resistance (IR) in the etiology of subclinical ketosis (SCK) in dairy cattle is not clearly understood. This review aims to shed some light on the role of IR and oxidative stress in dairy cows with SCK during the transition period. The data presented in this review demonstrates that dairy cows could be vulnerable to the development of negative energy balance during transition. Moreover, the transitional cows could succumb to both IR and oxidative stress; however, the exact role of IR in cows with SCK needs further investigations. It is imperative to elaborate a suitable nutritional strategy to facilitate an easy transit of cows through this critical period and to minimize health problems and improve productivity during lactation.

Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives.

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Qiu, Hongyu; Novikov, Aleksandra; Vallon, Volker

2017-07-01

Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of antihyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk. However, a potential side effect that has been reported with SGLT2 inhibitors in patients with T2DM and particularly during off-label use in patients with type 1 diabetes is diabetic ketoacidosis. The US Food and Drug Administration recently warned that SGLT2 inhibitors may result in euglycemic ketoacidosis. Here, we review the basic metabolism of ketone bodies, the triggers of diabetic ketoacidosis, and potential mechanisms by which SGLT2 inhibitors may facilitate the development of ketosis or ketoacidosis. This provides the rationale for measures to lower the risk. We discuss the role of the kidney and potential links to renal gluconeogenesis and uric acid handling. Moreover, we outline potential beneficial effects of modestly elevated ketone body levels on organ function that may have therapeutic relevance for the observed beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system. Copyright © 2017 John Wiley & Sons, Ltd.

Subclinical ketosis in dairy cows: prevalence and risk factors in grazing production system.

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Garro, C J; Mian, L; Cobos Roldán, M

2014-10-01

The purpose of this study was to estimate the prevalence of Subclinical ketosis (SCK) between 4 and 19 days in milk (DIM) in a grazing production system and investigate the importance of potential risk factors for SCK. This cross-sectional study was conducted in dairy cows (n = 107), which had more of two parities. The concentration of β-hydroxybutyric (BHB) in blood was quantified through a hand-held meter. Potential risk factors evaluated were calving interval (CI), milk yield in previous lactation, metritis, dystocia, calf sex (male), parity (≤3 vs. ≥4) and pre-partum body condition score (BCS ≤ 3.5 vs. ≥3.75). Prevalence of SCK was 10.3% (95% CI 4.7-15) between 4 and 19 DIM. Risk factors identified were the occurrence of both metritis and pre-partum BCS ≥ 3.75. Cows with metritis had 4.9 (95% CI 1.17-20.98) times more risk of developing SCK than cows without metritis. And the cows with pre-partum BCS ≥ 3.75 had 5.25 (95% CI 1.32-21.11) times more risk of developing SCK than cows with pre-partum BCS ≤ 3.5. Metritis could induce a lower feed intake and promote the development of SCK. High pre-partum BCS could induce a greater mobilization of body reserves altering liver function and aggravating post-partum NEB. The results are indicative of the expected prevalence of SCK in grazing production system. Factors associated could help to identify cattle at risk of SCK and improve the management of strategies to limit the effects. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

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Haji Akbar

Full Text Available In rodents, fibroblast growth factor 21 (FGF21 has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON or receiving 50 g/d of L-carnitine (C50 from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100 resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM or lower-energy (CON; 1.34 Mcal/kg DM diet and received 0 (OVE:N, CON:N or 200 μg of LPS (OVE:Y, CON:Y into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

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Akbar, Haji; Batistel, Fernanda; Drackley, James K; Loor, Juan J

2015-01-01

In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study

Efficacy of controlled-release capsules containing monensin for the prevention of subclinical ketosis in pasture-fed dairy cows.

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Compton, C W R; Young, L; McDougall, S

2015-09-01

To determine the effectiveness of intra-rumenal controlled release capsules (CRC) containing 32 g of monensin administered pre-calving to reduce the cumulative incidence of subclinical ketosis (SCK) in mainly pasture-fed dairy cows. Cows (n=837) due to calve in the first 6 weeks of the spring calving period were enrolled from four commercial herds in the Waikato region of New Zealand in a blinded, randomised, negative-controlled field trial. Three weeks before the start of the calving period cows were randomly allocated to receive either no treatment (control) or a single CRC containing monensin and then blood sampled on two occasions, 7 days apart within 12 days following calving for measurement of concentrations of beta hydroxybutyrate (BHBA) in blood. Cows were diagnosed with SCK if the concentration of BHBA in blood in either of these samples was ≥1.2 mmol/L. Fewer treated cows were diagnosed with SCK within 12 days post-calving than control cows (144/340 (42.4%) vs. 192/336 (57.1%); p10 days prior to calving reduced the cumulative incidence of SCK of pasture-based dairy cows in commercial dairy herds within 12 days post-calving. Administration pre-calving of an intra-rumenal bolus containing monensin can be considered as one of a range of management options for the control of SCK in early lactation.

The effect of subclinical ketosis on activity at estrus and reproductive performance in dairy cattle.

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Rutherford, Andrew J; Oikonomou, Georgios; Smith, Robert F

2016-06-01

Our aims were to investigate the influence of subclinical ketosis (SCK) on physical activity at estrus using a neck accelerometer device and on future reproductive performance. Two hundred three Holstein-Friesian cows were studied on 3dairy farms in Northwest England between September 2013 and March 2014. Seventeen percent (35 of 203) of the enrolled cows were affected with SCK between 7 and 21d in milk, defined as a blood β-hydroxybutyrate concentration of 1.2 to 2.9mmol/L. Time to event analyses and multivariable regression analyses were used to assess the effect of SCK on reproductive performance and activity at estrus. The SCK cows exhibited a lower peak activity (measured as the number of standard deviations above mean activity) and shorter duration in activity clusters associated with first estrus and first insemination postpartum, compared with non-SCK cows. Peak activity and cluster duration associated with the insemination that led to a pregnancy were not different between SCK and non-SCK cows. Calving to first estrus, calving to first insemination, and calving to pregnancy intervals were prolonged in SCK cows. First insemination was 4.3 times (95% confidence interval=1.6 to 15.0) less likely to be successful in SCK cows compared with non-SCK cows. Adjusted mean number of inseminations per pregnancy was 2.8 for SCK cows and 2.0 for non-SCK cows. The current study confirms the long-lasting effects of SCK on reproductive efficiency. Furthermore, it is indicated that physical activity around estrus is reduced by SCK in early lactation, but this negative effect appears to diminish as cows progress through lactation. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes and Alcoholic Ketosis Are Associated with the Serum Uric Acid Level in Japanese Alcoholic Men.

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Yokoyama, Akira; Yokoyama, Tetsuji; Mizukami, Takeshi; Matsui, Toshifumi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

2016-05-01

To identify determinants of hyperuricemia in alcoholics. The serum uric acid (UA) levels of 1759 Japanese alcoholic men (≥40 years) were measured on their first visit or within 3 days after admission; ADH1B and ALDH2 genotyping on blood DNA samples were performed. Dipstick urinalyses for ketonuria and serum UA measurements were simultaneously performed for 621 men on their first visit. Serum UA levels of >416 μmol/l (7.0 mg/dl) and ≥535 μmol/l (9.0 mg/dl) were observed in 30.4 and 7.8% of the subjects, respectively. Ketonuria was positive in 35.9% of the subjects, and a multivariate analysis revealed that the ketosis level was positively associated with the UA level. The presence of the ADH1B*2 allele and the ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) among subjects with a high UA level of >416 μmol/l (vs. ≤416 μmol/l; 2.04 [1.58-2.65] and 1.48 [1.09-2.01], respectively) and those with a high UA level of ≥535 μmol/l (vs. ≤416 μmol/l; 2.29 [1.42-3.71] and 3.03 [1.51-6.08], respectively). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs (2.86 [1.61-5.10] and 6.21 [1.49-25.88] for a UA level of >416 μmol/l and ≥535 μmol/l, respectively), compared with the ADH1B*1/*1 plus ALDH2*1/*2 combination. The presence of diabetes and the consumption of Japanese sake rather than beer were negatively associated with the UA levels. The faster metabolism of ethanol and acetaldehyde by the ADH1B*2 allele and ALDH2*1/*1 genotype and higher ketosis levels were associated with higher UA levels in alcoholics, while diabetes and the consumption of sake were negative determinants. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Subclinical ketosis in post-partum dairy cows fed a predominantly pasture-based diet: defining cut-points for diagnosis using concentrations of beta-hydroxybutyrate in blood and determining prevalence.

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Compton, C W R; Young, L; McDougall, S

2015-09-01

Firstly, to define, in dairy cows in the first 5 weeks post-calving fed a predominantly pasture-based diet, cut-points of concentrations of beta-hydroxybutyrate (BHBA) in blood, above which there were associations with purulent vaginal discharge (PVD), reduced pregnancy rates (PR) and decreased milk production, in order to better define subclinical ketosis (SCK) in such cattle; and secondly, to determine the prevalence, incidence and risk factors for SCK. An observational field study was conducted in 565 cows from 15 spring-calving and predominantly pasture-fed dairy herds in two regions of New Zealand during the 2010- 2011 dairy season. Within each herd, a cohort of randomly selected cows (approximately 40 per herd) was blood sampled to determine concentrations of BHBA on six occasions at weekly intervals starting within 5 days of calving. The key outcome variables were the presence/absence of PVD at 5 weeks post-calving, PR after 6 weeks (6-week PR) and after the completion of the breeding season (final PR), and mean daily milk solids production. Two cut-points for defining SCK were identified: firstly concentration of BHBA in blood≥1.2 mmol/L within 5 days post-calving, which was associated with an increased diagnosis of PVD (24 vs. 8%); and secondly concentration of BHBA in blood≥1.2 mmol/L at any stage within 5 weeks post-calving, which was associated with decreased 6-week PR (78 vs. 85%). The mean herd-level incidence of SCK within 5 weeks post-calving was 68 (min 12; max 100)% and large variations existed between herds in peak prevalence of SCK and the interval post-calving at which such peaks occurred. Cows>8 years of age and cows losing body condition were at increased risk of SCK within 5 weeks of calving. Cows with concentration of BHBA in blood≥1.2 mmol/L in early lactation had a higher risk of PVD and lower 6-week PR. Cow and herd-level prevalence of SCK varied widely in early lactation. Subclinical ketosis is common and is significantly

Association of rumination time with subclinical ketosis in transition dairy cows.

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Kaufman, E I; LeBlanc, S J; McBride, B W; Duffield, T F; DeVries, T J

2016-07-01

The objective of this study was to characterize the relationship between rumination and subclinical ketosis (SCK) in transition dairy cows. A study was conducted on 4 commercial dairy farms in eastern Ontario, Canada. A total of 339 Holstein dairy cows (107 primiparous and 232 multiparous) were monitored for rumination activity and SCK from 14 d before calving until 28 d after calving. Rumination was recorded daily using an automated monitoring system. A blood sample was taken from the coccygeal vein of each cow for measurement of β-hydroxybutyrate (BHB) once weekly throughout the 6-wk observation period. Cows with BHB ≥1.2mmol/L in any of the 4 postpartum samples were considered to have SCK. Cases of retained placenta, metritis, milk fever, or mastitis during the study period were also recorded. Cows were categorized into 1 of 4 groups: healthy cows (HLT) that had no SCK or any other recorded health problem (n=139); cows treated for at least one health issue other than SCK (HLT+; n=50); cows with SCK (hyperketonemia; HYK) with no other health problems during transition (n=97); or cows (HYK+) that had SCK and one or more other health problems (n=53). Daily rumination time was summarized by week and comparisons were made between HLT and HYK and HYK+. From 2 wk before calving (wk -2) to 4 wk after calving (wk +4), there was no difference in rumination time (409±9.8min/d) among HLT, HYK, and HYK+ cows in their first lactation. Multiparous cows in HLT spent an average of 459±11.3min/d ruminating from wk -2 to wk +4. Multiparous HYK cows ruminated 25±12.8min/d less than HLT cows, whereas HYK+ cows ruminated 44±15.6min/d less than HLT cows. The largest differences in rumination time between HLT and HYK+ cows were seen during wk -1, +1, and +2, when HYK+ cows ruminated 48±17.2, 73±16.0, and 65±19.4min/d less than HLT cows, respectively. In multiparous cows, increased odds of HYK were associated with greater milk yield in the previous lactation, greater loss of

Short communication: Association of lying behavior and subclinical ketosis in transition dairy cows.

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Kaufman, E I; LeBlanc, S J; McBride, B W; Duffield, T F; DeVries, T J

2016-09-01

The objective of this study was to characterize the association of lying behavior and subclinical ketosis (SCK) in transition dairy cows. A total of 339 dairy cows (107 primiparous and 232 multiparous) on 4 commercial dairy farms were monitored for lying behavior and SCK from 14d before calving until 28 d after calving. Lying time, frequency of lying bouts, and average lying bout length were measured using automated data loggers 24h/d. Cows were tested for SCK 1×/wk by taking a blood sample and analyzing for β-hydroxybutyrate; cows with β-hydroxybutyrate ≥1.2mmol/L postpartum were considered to have SCK. Cases of retained placenta, metritis, milk fever, or mastitis during the study period were recorded and cows were categorized into 1 of 4 groups: healthy (HLT) cows had no SCK or any other health problem (n=139); cows treated for at least 1 health issue other than SCK (n=50); SCK (HYK) cows with no other health problems during transition (n=97); or subclinically ketotic plus (HYK+) cows that had SCK and 1 or more other health problems (n=53). Daily lying time was summarized by week and comparisons were made between HLT, HYK, and HYK+, respectively. We found no difference among health categories in lying time, bout frequency, or bout length fromwk -2 towk +4 relative to calving for first-lactation cows. Differences in lying time for multiparous cows were seen inwk +1, when HYK+ cows spent 92±24.0 min/d more time lying down than HLT cows, and duringwk +3 and +4 when HYK cows spent 44±16.7 and 41±18.9 min/d, respectively, more time lying down than HLT cows. Increased odds of HYK+ were found to be associated with higher parity, longer dry period, and greater stall stocking density inwk -1 and longer lying time duringwk +1. When comparing HYK to HLT cows, the same variables were associated with odds of SCK; however, lying time was not retained in the final model. These results suggest that monitoring lying time may contribute to identifying multiparous cows

Investigating the within-herd prevalence and risk factors for ketosis in dairy cattle in Ontario as diagnosed by the test-day concentration of β-hydroxybutyrate in milk.

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Tatone, Elise H; Duffield, Todd F; LeBlanc, Stephen J; DeVries, Trevor J; Gordon, Jessica L

2017-02-01

An observational study of 790 to over 3,000 herds was conducted to estimate the within-herd prevalence and cow-level risk factors for ketosis in dairy cattle in herds that participate in a Dairy Herd Improvement Association (DHIA) program. Ketosis or hyperketolactia (KET) was diagnosed as milk β-hydroxybutyrate ≥0.15 mmol/L at first DHIA test when tested within the first 30 d in milk. Seven hundred ninety-five herds providing at least 61 first milk tests from June 2014 to December 2015 were used to estimate the provincial within-herd prevalence of KET. All herds on DHIA in Ontario (n = 3,042) were used to construct cow-level multilevel logistic regression models to investigate the association of DHIA collected variables with the odds of KET at first DHIA milk test. Primiparous and multiparous animals were modeled independently. The cow-level KET prevalence in Ontario was 21%, with an average within-herd prevalence of 21% (standard deviation = 10.6) for dairy herds enrolled in a DHIA program. The prevalence of KET had a distinct seasonality with the lowest prevalence occurring from July to November. Automatic milking systems (AMS) were associated with increased within-herd prevalence, as well as increased odds of KET in multiparous animals at first test (odds ratio: 1.45; 95% confidence interval: 1.30 to 1.63). Jersey cattle had over 1.46 times higher odds of KET than Holstein cattle. Milk fat yield ≥1.12 kg/d at the last test of the previous lactation was associated with decreased odds of KET in the current lactation (odds ratio: 0.56; 95% confidence interval: 0.53 to 0.59). Increased days dry and longer calving intervals, for multiparous animals, and older age at first calving for primiparous animals increased the odds of KET at first test. This study confirms previous findings that increased days dry, longer calving intervals, and increased age at first calving are associated with increased odds of KET and is the first report of increased KET in herds with

Genetic parameters of blood β-hydroxybutyrate predicted from milk infrared spectra and clinical ketosis, and their associations with milk production traits in Norwegian Red cows.

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Belay, T K; Svendsen, M; Kowalski, Z M; Ådnøy, T

2017-08-01

The aim of this study was to estimate genetic parameters for blood β-hydroxybutyrate (BHB) predicted from milk spectra and for clinical ketosis (KET), and to examine genetic association of blood BHB with KET and milk production traits (milk, fat, protein, and lactose yields, and milk fat, protein, and lactose contents). Data on milk traits, KET, and milk spectra were obtained from the Norwegian Dairy Herd Recording System with legal permission from TINE SA (Ås, Norway), the Norwegian Dairy Association that manages the central database. Data recorded up to 120 d after calving were considered. Blood BHB was predicted from milk spectra using a calibration model developed based on milk spectra and blood BHB measured in Polish dairy cows. The predicted blood BHB was grouped based on days in milk into 4 groups and each group was considered as a trait. The milk components for test-day milk samples were obtained by Fourier transform mid-infrared spectrometer with previously developed calibration equations from Foss (Hillerød, Denmark). Veterinarian-recorded KET data within 15 d before calving to 120 d after calving were used. Data were analyzed using univariate or bivariate linear animal models. Heritability estimates for predicted blood BHB at different stages of lactation were moderate, ranging from 0.250 to 0.365. Heritability estimate for KET from univariate analysis was 0.078, and the corresponding average estimate from bivariate analysis with BHB or milk production traits was 0.002. Genetic correlations between BHB traits were higher for adjacent lactation intervals and decreased as intervals were further apart. Predicted blood BHB at first test day was moderately genetically correlated with KET (0.469) and milk traits (ranged from -0.367 with protein content to 0.277 with milk yield), except for milk fat content from across lactation stages that had near zero genetic correlation with BHB (0.033). These genetic correlations indicate that a lower BHB is genetically

How sensitive and specific is urinalysis 'dipstick' testing for detection of hyperglycaemia and ketosis? An audit of findings from coronial autopsies.

Science.gov (United States)

Mitchell, Rebecca; Thomas, Sunethra Devika; Langlois, Neil E I

2013-10-01

Biochemical analysis of glucose and ketones in the vitreous humour obtained at post-mortem examination is representative of the levels in the blood prior to death. Elevated levels can be indicative of conditions including diabetic ketoacidosis, which can be a cause for unexpected death. A rapid screening test for such conditions can be performed during the autopsy through urinalysis using test strips (urine 'dipstick' testing). The aim of this study was to assess the utility of urinalysis testing for post-mortem detection of derangements of glucose and ketone levels. The results of vitreous biochemical analysis and urinalysis were collated from 188 forensic autopsy cases. A vitreous glucose result of above 10 mmol/L was regarded as high. When this was compared to urinalysis results it was found that any urinalysis result above negative had a sensitivity of 0.83 and a specificity of 0.93. A vitreous ketone level of above 5 mmol/L was regarded as significantly elevated; a urinalysis result above negative had a sensitivity of 1, but a specificity of 0.12. Urinalysis ('dipstick' testing) for glucose has a good sensitivity and specificity for high vitreous glucose levels, which are regarded as indicative of pathological hyperglycaemia during life. It was found that urine testing for ketones either has an excellent sensitivity with low specificity or a poor sensitivity with a good specificity; however, this finding has to be viewed in the context of uncertainty of the biochemical level of significant ketosis.

A Program for Clinical Care in Physical Trauma.

Science.gov (United States)

1981-08-01

of the leg. This model increases the release of skeletal muscle amino acids, fails to develop ketosis during starvation and injury/infection, and...develop ketosis following starvation during this stress. This model has great benefit to evaluate therapies that would reverse the marked catabolic...appears to be the lack of ketosis that occurs in the starved animals that are also infected (Table I). This response is also associated with a marked fall

Genetics Home Reference: glycogen storage disease type VI

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... or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of ... and may use fats for energy, resulting in ketosis. Glycogen accumulates within liver cells, causing these cells ...

Genetics Home Reference: succinyl-CoA:3-ketoacid CoA transferase deficiency

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... elevated level of ketones in their blood (persistent ketosis). If the level of ketones gets too high, ... attacks, but are less likely to have persistent ketosis. Learn more about the gene associated with succinyl- ...

Genetics Home Reference: glycogen storage disease type IX

Science.gov (United States)

... or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of ... down glycogen for glucose contributes to hypoglycemia and ketosis. Reduced energy production in muscle cells leads to ...

Effects of butafosfan with or without cyanocobalamin on the metabolism of early lactating cows with subclinical ketosis.

Science.gov (United States)

Nuber, U; van Dorland, H A; Bruckmaier, R M

2016-02-01

Fifty-one dairy cows with subclinical ketosis were used to investigate the effects of butafosfan alone or in combination with cyanocobalamin on metabolism. Treatments included i.v. injection of 10 ml/100 kg of body weight with butafosfan (BUT) or combined cyanocobalamin with butafosfan (BUTCO) at a similar concentration as in Catosal(®) . Control cows (CON) received a 0.9% saline solution. Cows were injected on days 1-3 at 22.3 ± 0.7 days post-partum. Milk production and composition were not affected by the treatments. In plasma, CON cows had a significantly higher plasma NEFA concentration (0.59 ± 0.03 mm) across the study period than BUTCO cows (p < 0.05; 0.42 ± 0.03 mm), whereas the plasma NEFA concentration of BUT was intermediate (0.52 ± 0.03 mm) but not significantly different from CON. Both BUTCO and BUT cows had lower (p < 0.05) plasma BHBA concentrations (1.02 ± 0.06 mm and 1.21 ± 0.06 mm, respectively) across the study period than CON (1.34 ± 0.06 mm). Plasma glucose was not different between treatments, but plasma glucagon concentrations were consistently high in BUT compared to BUTCO and CON. Lowest post-treatment glucagon levels were observed in BUTCO. Hepatic mRNA abundance of liver X receptor α, a nuclear receptor protein involved in lipid metabolism, was higher in BUTCO compared to BUT and CON (p < 0.05) on day 7. Furthermore, on day 7, the mRNA abundance of beta-hydroxybutyrate dehydrogenase 2 was higher in BUTCO compared to BUT and CON (p < 0.01). In conclusion, injections of combined cyanocobalamin with butafosfan post-partum in early lactation ketotic dairy cows act on lipid metabolism with effects on plasma metabolites, most likely mediated via modified activity of key factors in the liver. Results indicate that the application of butafosfan only in combination with cyanocobalamin exhibits the expected positive effects on metabolism. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Comparison of 2 electronic cowside tests to detect subclinical ketosis in dairy cows and the influence of the temperature and type of blood sample on the test results.

Science.gov (United States)

Iwersen, M; Klein-Jöbstl, D; Pichler, M; Roland, L; Fidlschuster, B; Schwendenwein, I; Drillich, M

2013-01-01

The objective of this study was to determine the suitability of 2 electronic hand-held devices [FreeStyle Precision (FSP), Abbott GmbH & Co. KG, Wiesbaden, Germany and GlucoMen LX Plus (GLX), A. Menarini GmbH, Vienna, Austria] for measuring β-hydroxybutyrate (BHBA) in dairy cows. Three experiments were conducted to evaluate (1) the diagnostic performance of the devices, (2) the effect of the type of blood sample, and (3) the influence of the ambient temperature on the determined results. A total of 415 blood samples from lactating Holstein and Simmental cows were collected and analyzed with both devices (whole blood) and in a laboratory (serum). Correlation coefficients between whole-blood and serum BHBA concentrations were highly significant, with 94% for the FSP and 80% for the GLX device. Based on thresholds for subclinical ketosis of 1.2 and 1.4 mmol of BHBA/L, results obtained with the hand-held devices were evaluated by receiver operating characteristics analyses. This resulted in adjusted thresholds of 1.2 and 1.4 mmol/L for the FSP and 1.1 and 1.3 mmol/L for the GLX device. Applying these thresholds, sensitivities were 98 and 100% for the FSP and 80 and 86% for the GLX device, respectively. Corresponding specificities were 90 and 97% for the FSP and 87 and 96% for the GLX device, respectively. Additionally, concentrations of BHBA were tested with both devices in whole blood, EDTA-added whole blood, and in their resulting serum and plasma, collected from 65 animals. Determined BHBA concentrations were similar within each device for whole and EDTA-added blood, and in serum and plasma, but differed between whole blood and serum and between EDTA-added blood and plasma. Blood samples with low (0.4 mmol/L), medium (1.1 mmol/L), and high (1.6 mmol/L) BHBA concentrations were stored between +5 to +32°C and analyzed repeatedly at temperature levels differing by 4°C. Additionally, devices and test strips were stored at equal conditions and used for measurement

Incidence of diabetic ketosis and ketoacidosis in Caucasian adults with type 2 diabetes mellitus: a population-based study

Directory of Open Access Journals (Sweden)

Ivan Kruljac

2017-03-01

Full Text Available Aims: We aimed to analyze incidence and characteristics of patients with diabetic ketosis (DK and diabetic ketoacidosis (DKA in Caucasian adults with type 2 diabetes mellitus (T2DM. Methods: Studied population included 261,749 adults. DK criteria included plasma glucose >13.9 mmol/L and ketonuria >2, while in DKA bicarbonate <18 mEq/L or pH<7.30 was also required. Hyperglycemic crises without these criteria were defined as non-ketotic hyperglycemia (NKH. Results: During a 5-year period, we observed 630 episodes of DK and 215 episodes of DKA. Only 8.6% of DK episodes and 34.4% of DKA were attributed to type 1 diabetes mellitus (T1DM. Patients with T1DM were younger, leaner, majority had newly diagnosed disease, and hyperglycemia was the main cause of admission. Standardized incidence ratio for DK was 48.1 (95% confidence interval [CI] 44.5-52.1 and 17.0 (95% CI 14.9-19.4 for DKA. Incidence for both DK and DKA was increasing with age. In patients younger than 50, the incidence of DK and DKA was similar. However, dramatic rise in the incidence of DK was observed in both sexes after the age of 50. When compared with patients with NKH, the patients with DK had higher serum pH and bicarbonates. Patients with T2DM had a risk of 0.8% for developing DKA and 2.9% for DK over 5-year period. Conclusions: Our study showed that DK and DKA are not uncommon in Caucasian adults and the majority of episodes were contributed to T2DM. Incidence of DK is far more higher than the incidence of DKA in patients older than 50, who predominantly have T2DM. Moreover, patients with DK have higher serum pH and bicarbonates, both of which imply that DK and DKA are distinct clinical entities in patients with T2DM. Further studies are needed to assess the impact of these clinical entities.

Field Study of Dairy Cows with Reduced Appetite in Early Lactation: Clinical Examinations, Blood and Rumen Fluid Analyses

Directory of Open Access Journals (Sweden)

Steen A

2001-06-01

Full Text Available The study included 125 cows with reduced appetite and with clinical signs interpreted by the owner as indicating bovine ketosis 6 to 75 days postpartum. Almost all of the cows were given concentrates 2 to 3 times daily. With a practitioners view to treatment and prophylaxis the cows were divided into 5 diagnostic groups on the basis of thorough clinical examination, milk ketotest, decreased protozoal activity and concentrations, increased methylene blue reduction time, and increased liver parameters: ketosis (n = 32, indigestion (n = 26, combined ketosis and indigestion (n = 29, liver disease combined with ketosis, indigestion, or both (n = 15, and no specific diagnosis (n = 17. Three cows with traumatic reticuloperitonitis and 3 with abomasal displacement were not grouped. Nonparametric methods were used when groups were compared. Aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transferase and total bilirubin were elevated in the group with liver disease. Free fatty acids were significantly elevated in cows with ketosis, compared with cows with indigestion. Activity and concentrations of large and small protozoas were reduced, and methylene blue reduction time was increased in cows with indigestion. The rumen fluid pH was the same for groups of cows with and without indigestion. Prolonged reduced appetite before examination could have led to misclassification. Without careful interpretation of the milk ketotest, many cases with additional diagnoses would have been reported as primary ketosis. Thorough clinical examination together with feasible rumen fluid examination and economically reasonable blood biochemistry did not uncover the reason(s for reduced appetite in 14% of the cows. More powerful diagnostic methods are needed.

Metabolic predictors of post-partum disease and culling risk in dairy cattle.

Science.gov (United States)

Seifi, Hesam A; Leblanc, Stephen J; Leslie, Ken E; Duffield, Todd F

2011-05-01

A retrospective study was conducted to determine the relationship between serum non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), glucose and calcium (Ca) with the occurrence of displaced abomasum (DA), clinical ketosis and culling in Holstein cows. Eight hundred and forty-nine cows from 16 farms were sampled weekly for the first 3 weeks post-partum. The cows were under clinical observation from calving until 60 days in milk (DIM) and during this time there were 22 cases of DA, 31 cases of clinical ketosis and 39 cows were culled. Elevated concentrations of BHBA were associated with DA, clinical ketosis and culling. In the first week after calving, cows with serum BHBA ≥1000μmol/L had 13.6 times greater odds of developing DA than cows with lower values. Serum NEFA and BHBA concentrations during week 1 were associated with the subsequent occurrence of clinical ketosis. The odds of clinical ketosis were 6.3 times greater in cows with serum NEFA ≥ 1.0mmol/L in the first week after calving. In addition, cows with BHB ≥1200μmol/L in the first week after calving, were at 4.7 times greater risk of developing clinical ketosis. In the first and second weeks after calving the serum Ca concentration was associated with subsequent culling. In addition, cows with NEFA concentration ≥ 1.0mmol/L were 3.6 times more likely to be culled within the following 2 months. The study indicated that early post-partum serum BHBA, NEFA and Ca concentrations have potential as indicators of disease and culling risk in dairy cows. Copyright © 2010 Elsevier Ltd. All rights reserved.

Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study.

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Courchesne-Loyer, Alexandre; Croteau, Etienne; Castellano, Christian-Alexandre; St-Pierre, Valérie; Hennebelle, Marie; Cunnane, Stephen C

2017-07-01

Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11 C-AcAc and 18 F-fluorodeoxyglucose ( 18 F-FDG), respectively. During the KD, plasma ketones increased 8-fold ( p = 0.005) while plasma glucose decreased by 24% ( p = 0.005). CMRa increased 6-fold ( p = 0.005), whereas CMRglc decreased by 20% ( p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p < 0.0001). After four days on the KD, CMRa represented 17% of whole brain energy requirements in healthy adults with a 2-fold difference across brain regions (12-24%). The CMR of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements or approximately double the CMRa. Whether increased ketone availability raises CMR of ketones to the same extent in older people as observed here or in conditions in which chronic brain glucose hypometabolism is present remains to be determined.

Catecholamine, Corticosteroid and Ketone Excretion in Exercise and Hypoxia,

Science.gov (United States)

OHCS excretion tended to be higher during the experimental period and subsequently lower overnight during the hypoxia week. Ketosis occurred in two...subjects. In one of these it could be readily related to previous extraneous stress. Excretion of unidentified ketones in overnight urines was sometimes suspected and occurred beyond doubt following gross ketosis . (Author)

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

Science.gov (United States)

fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

The economic impact of subclinical ketosis at the farm level: Tackling the challenge of over-estimation due to multiple interactions.

Science.gov (United States)

Raboisson, D; Mounié, M; Khenifar, E; Maigné, E

2015-12-01

Subclinical ketosis (SCK) is a major metabolic disorder that affects dairy cows, and its lactational prevalence in Europe is estimated to be at 25%. Nonetheless, few data are available on the economics of SCK, although its management clearly must be improved. With this in mind, this study develops a double-step stochastic approach to evaluate the total cost of SCK to dairy farming. First, all the production and reproduction changes and all the health disorders associated with SCK were quantified using the meta-analysis from a previous study. Second, the total cost of SCK was determined with a stochastic model using distribution laws as input parameters. The mean total cost of SCK was estimated to be Є257 per calving cow with SCK (95% prediction interval (PI): Є72-442). The margin over feeding costs slightly influenced the results. When the parameters of the model are not modified to account for the conclusions from the meta-analysis and for the prevalence of health disorders in the population without SCK, the mean cost of SCK was overestimated by 68%, reaching Є434 per calving cow (95%PI: Є192-676). This result indicates that the total cost of complex health disorders is likely to be substantially overestimated when calculations use raw results from the literature or-even worse-punctual data. Excluding labour costs in the estimation reduced the SCK total cost by 12%, whereas excluding contributors with scarce data and imprecise calibrations (for lameness and udder health) reduced costs by another 18-20% (Є210, 95%PI=30-390). The proposed method accounted for uncertainty and variability in inputs by using distributions instead of point estimates. The mean value and associated prediction intervals (PIs) yielded good insight into the economic consequences of this complex disease and can be easily and practically used by decision makers in the field while simultaneously accounting for biological variability. Moreover, PIs can help prevent the blind use of economic

Separate housing for one month after calving improves production and health in primiparous cows but not in multiparous cows

DEFF Research Database (Denmark)

Østergaard, Søren; Thomsen, Peter; Burow, Elke

2010-01-01

no effect on mortality or reproductive efficiency. In primiparous cows, the number of medical treatments for ketosis was reduced by separate housing [hazard ratio 0.33, 95% confidence interval (CI): 0.13-0.83]. Clinical evaluations showed that separate housing decreased the scores for hock lesions in cows....... The hypothesis about fewer health problems could only be confirmed with regard to fewer primiparous cows being treated for ketosis....

Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

Science.gov (United States)

Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

2015-04-01

A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

Glucose concentration in capillary blood of dairy cows obtained by a minimally invasive lancet technique and determined with three different hand-held devices

OpenAIRE

Mair, B.; Drillich, M.; Klein-J?bstl, D.; Kanz, P.; Borchardt, S.; Meyer, L.; Schwendenwein, I.; Iwersen, M.

2016-01-01

Background Dairy cows have a massive demand for glucose at the onset of lactation. A poor adaption to this period leads to an excessive negative energy balance with an increased risk for ketosis and impaired animal health and production. Besides the measurement of ketones, analysing the glucose concentration in blood is reported as helpful instrument for diagnosis and differentiation of ketosis. Monitoring metabolic parameters requires multiple blood sampling. In other species, new blood samp...

Evaluation of propylene glycol and glycerol infusions as treatments for ketosis in dairy cows.

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Piantoni, P; Allen, M S

2015-08-01

To evaluate propylene glycol (PG) and glycerol (G) as potential treatments for ketosis, we conducted 2 experiments lasting 4 d each in which cows received one bolus infusion per day. Blood was collected before infusion, over 240min postinfusion, as well as 24 h postinfusion. Experiment 1 used 6 ruminally cannulated cows (26±7 d in milk) randomly assigned to 300-mL infusions of PG or G (both ≥99.5% pure) in a crossover design experiment with 2 periods. Within each period, cows were assigned randomly to infusion site sequence: abomasum (A)-cranial reticulorumen (R) or the reverse, R-A. Glucose precursors were infused into the R to simulate drenching and the A to prevent metabolism by ruminal microbes. Glycerol infused in the A increased plasma glucose concentration the most (15.8mg/dL), followed by PG infused in the R (12.6mg/dL), PG infused in the A (9.11mg/dL), and G infused in the R (7.3mg/dL). Infusion of PG into the R increased plasma insulin and insulin area under the curve (AUC) the most compared with all other treatments (7.88 vs. 2.13μIU/mL and 321 vs. 31.9min×μIU/mL, respectively). Overall, PG decreased plasma BHBA concentration after infusion (-6.46 vs. -4.55mg/dL) and increased BHBA AUC (-1,055 vs. -558min ×mg/dL) compared with G. Plasma NEFA responses were not different among treatments. Experiment 2 used 8 ruminally cannulated cows (22±5 d in milk) randomly assigned to treatment sequence in a Latin square design experiment balanced for carryover effects. Treatments were 300mL of PG, 300mL of G, 600mL of G (2G), and 300mL of PG + 300mL of G (GPG), all infused into the R. Treatment contrasts compared PG with each treatment containing glycerol (G, 2G, and GPG). Propylene glycol increased plasma glucose (14.0 vs. 5.35mg/dL) and insulin (7.59 vs. 1.11μIU/mL) concentrations compared with G, but only tended to increase glucose and insulin concentrations compared with 2G. Propylene glycol increased AUC for glucose (1,444 vs. 94.3mg/dL) and insulin (326

Accuracy of a cow-side test for the diagnosis of hyperketonemia and hypoglycemia in lactating dairy cows.

Science.gov (United States)

Macmillan, K; López Helguera, I; Behrouzi, A; Gobikrushanth, M; Hoff, B; Colazo, M G

2017-12-01

The objective of this study was to evaluate the use of a cow-side device (FreeStyle Precision Neo™) to diagnose ketosis and hypoglycemia based on measures of blood β-hydroxybutyrate (BHBA) and glucose. Eleven commercial dairy farms were visited and blood samples were taken from Holstein cows between 2 and 14days in milk, yielding 441 samples for BHBA analysis and 308 samples for glucose analysis. Concentrations of BHBA and glucose were measured in two ways, 1) using the cow-side device with whole blood immediately after sampling and 2) serum samples analyzed with a standard laboratory assay (Animal Health Laboratory, University of Guelph, Canada). The accuracy of the device was determined by comparing the results to the laboratory method as well as the ability to diagnose ketosis (BHBA ≥1.2mmol/L) and hypoglycemia (glucose cow-side device is accurate for rapid measurement of blood BHBA and diagnosis of ketosis on farms but is not accurate for measurement of blood glucose concentrations and diagnosis of hypoglycemia. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

Directory of Open Access Journals (Sweden)

Poirier Judes

2011-10-01

Full Text Available Abstract Background To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog in subjects with mild to moderate Alzheimer's disease (AD. Methods Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4 were examined. Results Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group. Conclusions Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD. Trial registration This trial was registered with ClinicalTrials.gov, registry number NCT00142805.

Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

Science.gov (United States)

2011-01-01

Background To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in subjects with mild to moderate Alzheimer's disease (AD). Methods Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4) were examined. Results Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group. Conclusions Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD. Trial registration This trial was registered with ClinicalTrials.gov, registry number NCT00142805. PMID:21992747

Nutritional and metabolic diseases involving the nervous system.

Science.gov (United States)

Kopcha, M

1987-03-01

This article will discuss eight diseases that alter normal nervous system function: hypovitaminosis A, water deprivation/salt toxicity, ammonia toxicosis, hypomagnesemia, hypocalcemia, nervous ketosis, hepatoencephalopathy, and rumen metabolic acidosis.

the capacity of megasphaera elsdenii strain ncimb 41125 to control ...

African Journals Online (AJOL)

David

SARA include grain treatment to reduce starch degradation, feed additives such as ... Keywords: Megasphaera elsdenii, ruminal acidosis, dairy cattle, beef cattle, sheep, ...... Mastitis. Retained foetal membranes. Metritis/endometritis. Ketosis.

Study of ketone body kinetics in children by a combined perfusion of /sup 13/C and /sup 2/H3 tracers

Energy Technology Data Exchange (ETDEWEB)

Bougneres, P.F.; Ferre, P.

1987-11-01

Ketone body kinetics were quantified in six children (3-5 yr old), who were fasted for 13-22 h, by a combined perfusion of (3-/sup 13/C)acetoacetate ((/sup 13/C)AcAc) and D-(-)-beta-(4,4,4-/sup 2/H3)hydroxybutyrate (beta-(/sup 2/H3)OHB) and gas chromatography-mass spectrometry analysis. Results were analyzed according to the single-pool (combined enrichments) or the two-accessible pools models. After 20-22 h of fasting, ketone body turnover rate was 30-50 mumol.kg-1.min-1, a rate achieved after several days of fasting in adults. At low ketosis, acetoacetate was the ketone body preferentially synthesized de novo and utilized irreversibly. When ketosis increased, acetoacetate irreversible disposal was not enhanced, since it was largely converted into beta-OHB, whereas beta-OHB irreversible disposal was very much increased. The single-pool and two-pool models gave similar ketone body turnover rates when (/sup 13/C)AcAc was the tracer, whereas the use of beta-(/sup 2/H3)OHB gave some more divergent results, especially at low ketosis. These studies demonstrate that ketogenesis is very active in short-term fasted children and that the use of a combined infusion of (/sup 13/C)AcAc and beta-(/sup 2/H3)OHB is a convenient way to give insight into individual ketone body kinetics.

Study of ketone body kinetics in children by a combined perfusion of 13C and 2H3 tracers

International Nuclear Information System (INIS)

Bougneres, P.F.; Ferre, P.

1987-01-01

Ketone body kinetics were quantified in six children (3-5 yr old), who were fasted for 13-22 h, by a combined perfusion of [3- 13 C]acetoacetate ([ 13 C]AcAc) and D-(-)-beta-[4,4,4- 2 H3]hydroxybutyrate (beta-[ 2 H3]OHB) and gas chromatography-mass spectrometry analysis. Results were analyzed according to the single-pool (combined enrichments) or the two-accessible pools models. After 20-22 h of fasting, ketone body turnover rate was 30-50 mumol.kg-1.min-1, a rate achieved after several days of fasting in adults. At low ketosis, acetoacetate was the ketone body preferentially synthesized de novo and utilized irreversibly. When ketosis increased, acetoacetate irreversible disposal was not enhanced, since it was largely converted into beta-OHB, whereas beta-OHB irreversible disposal was very much increased. The single-pool and two-pool models gave similar ketone body turnover rates when [ 13 C]AcAc was the tracer, whereas the use of beta-[ 2 H3]OHB gave some more divergent results, especially at low ketosis. These studies demonstrate that ketogenesis is very active in short-term fasted children and that the use of a combined infusion of [ 13 C]AcAc and beta-[ 2 H3]OHB is a convenient way to give insight into individual ketone body kinetics

Metabolic evaluation of dairy cows submitted to three different strategies to decrease the effects of negative energy balance in early postpartum

Directory of Open Access Journals (Sweden)

Alejandra M.B García

2011-12-01

Full Text Available In early lactation dairy cattle suffer metabolic alterations caused by negative energy balance, which predisposes to fatty liver and ketosis. The aim of this study was to evaluate the metabolic condition of high yielding dairy cows subjected to three treatments for preventing severe lipomobilization and ketosis in early lactation. Fifty four multiparous Holstein cows yielding >30 L/day were divided into four groups: control (CN= no treatment, glucose precursor (PG= propylene-glycol, hepatic protector (Mp= Mercepton®, and energy supplement with salts of linolenic and linoleic faty acids (Mg-E= Megalac-E®. Treatments were administrated randomly at moment of calving until 8 weeks postpartum. Blood samples were collected on days 1, 7, 14, 21, 28, 35, 42 and 49 postpartum. Body condition score (BCS was evaluated at the same periods and milk yield was recorded at 2nd, 4th, 5th, 6th, 7th, and 8th weeks of lactation. Concentrations of non-esterified fatty acids (NEFA, albumin, AST, ß-hydroxybutyrate (BHBA, cholesterol, glucose, total protein, urea and triglycerides were analyzed in blood samples. Cut-off points for subclinical ketosis were defined when BHBA >1.4 mmol/L and NEFA >0.7 mmol/L. General occurrence of subclinical ketosis was 24% during the period. An ascendant curve of cholesterol and glucose was observed from the 1st to the 8th week of lactation, while any tendency was observed with BHBA and NEFA, although differences among treatments were detected (p<0.05. BCS decreased from a mean of 3.85 at 1st week to 2.53 at 8th week of lactation (p=0.001. Milk yield was higher in the Mg-E group compared with the other treatment groups (p<0.05 Compared with the CN group, the treatments with Mp and PG did not show significant differences in blood biochemistry and milk yield. Cows receiving PG and Mg-E showed higher values of BHBA and NEFA (P<0.05, indicating accentuated lipomobilization. Supplementation with Mg-E also resulted in significant higher

Nutrition and udder health in dairy cows: a review

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O'Rourke D

2009-04-01

Full Text Available Abstract Mastitis is still one of the three main diseases that affects the profitability of dairy farmers. Despite the implementation of the five-point mastitis control programme in the early 1970 s, the incidence in the UK has not reduced dramatically over the past 10 years. A review of the scientific literature indicates that there is a link between nutrition and mastitis in the dairy cow. The major impact of nutrition on udder health is via suppression of the immune system. Cows in negative energy balance are at a higher risk of ketosis and clinical ketosis is associated with a two-fold increase in the risk of clinical mastitis. Trace minerals and vitamins that can affect udder health are selenium and vitamin E, copper, zinc, and vitamin A and β-carotene.

Antiseizure Effects of Ketogenic Diet on Seizures Induced with ...

African Journals Online (AJOL)

olayemitoyin

experimental data in Nigeria on the usefulness of KD in epilepsy models. This is ... Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. ..... in animal occurs through the inhibition of GABA.

Effect of Metformin on Potassium-adapted and Non- adapted ...

African Journals Online (AJOL)

increased hunger) [2]. Metformin is used in non-insulin dependent diabetics without a tendency to ketosis in whom dietary carbohydrate restriction has not controlled hyperglycemia and who remain symptomatic. Its main use is in obese patients ...

Ketogenic Diet in Refractory Childhood Epilepsy

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Amerins Weijenberg MD

2018-05-01

Full Text Available Background: Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. Methods: The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction. Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Results: Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days. The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Conclusions: Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis.

Ketogenic Diet in Refractory Childhood Epilepsy

Science.gov (United States)

Weijenberg, Amerins; van Rijn, Margreet; de Koning, Tom J.; Brouwer, Oebele F.

2018-01-01

Background: Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. Methods: The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Results: Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Conclusions: Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis. PMID:29872664

Ketogenic Diet in Refractory Childhood Epilepsy: Starting With a Liquid Formulation in an Outpatient Setting.

Science.gov (United States)

Weijenberg, Amerins; van Rijn, Margreet; Callenbach, Petra M C; de Koning, Tom J; Brouwer, Oebele F

2018-01-01

Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis.

Diabetic ketoacidosis: a challenging diabetes phenotype

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Cliona Small

2017-02-01

Full Text Available We describe three patients presenting with diabetic ketoacidosis secondary to ketosis prone type 2, rather than type 1 diabetes. All patients were treated according to a standard DKA protocol, but were subsequently able to come off insulin therapy while maintaining good glycaemic control. Ketosis-prone type 2 diabetes (KPD presenting with DKA has not been described previously in Irish patients. The absence of islet autoimmunity and evidence of endogenous beta cell function after resolution of DKA are well-established markers of KPD, but are not readily available in the acute setting. Although not emphasised in any current guidelines, we have found that a strong family history of type 2 diabetes and the presence of cutaneous markers of insulin resistance are strongly suggestive of KPD. These could be emphasised in future clinical practice guidelines.

Clinical approach to inherited metabolic diseases in the neonatal period: a 20-year survey

NARCIS (Netherlands)

Saudubray, J. M.; Ogier, H.; Bonnefont, J. P.; Munnich, A.; Lombes, A.; Hervé, F.; Mitchel, G.; Poll The, B.; Specola, N.; Parvy, P.

1989-01-01

Every newborn with unexplained neurological deterioration, ketosis, metabolic acidosis or hypoglycaemia should be suspected of having an inherited error of intermediary metabolism. Many of these conditions can be diagnosed clinically with the aid of simple laboratory investigations. Since a

Plasma testosterone and androstenedione in insulin dependent patients at time of diagnosis and during the first year of insulin treatment

DEFF Research Database (Denmark)

Gluud, C; Madsbad, S; Krarup, T

1982-01-01

Ten male patients and 6 female patients with newly diagnosed insulin dependent diabetes mellitus and significant ketosis were studied before and during the first year of insulin treatment. At onset plasma concentrations of testosterone and androstenedione were significantly (P less than 0...

Post-partum reproductive performance of the Icelandic dairy cow

International Nuclear Information System (INIS)

Eldon, J.; Olafsson, T.; Thorsteinsson, T.

1990-01-01

The aim of the studies was to monitor the reproductive performance of Icelandic dairy cow herds with and without histories of fertility problems under normal farming conditions. Artificial inseminations and calvings were recorded, pregnancy was diagnosed by rectal palpation, and progesterone concentration was measured by radioimmunoassay in sequential samples of milk. Blood samples were collected at regular intervals and the concentrations of glucose, urea, calcium and magnesium were determined. Clinical ketosis and low glucose were found in one third of the cows on problem farms. The mean time of first post-partum ovulation was 49 days for cows with ketosis, compared with 34 days for cows free of ketosis. Cows in the normal herds ovulated considerably later than is reported for many other breeds of dairy cows; however, the time of first post-partum AI, the time of conception and the conception rate were similar to those reported for other breeds. The effects of season and herd were statistically significant for the time of first post-partum ovulation, AI and conception; the effect of area was highly significant for the time of ovulation. Progesterone profiles showed that over 50% of the first post-partum ovarian cycles were short and had low progesterone concentrations. Season had significant effects on the length of the interval from calving to first post-partum ovulation, AI and conception, on the conception rate to first AI and consequently on the number of AIs per conception, and on the blood levels of glucose, urea and calcium. (author). 28 refs, 3 figs, 3 tabs

Metabolism and Whole-Body Fat Oxidation Following Post-Exercise Carbohydrate or Protein Intake

DEFF Research Database (Denmark)

Hall, Ulrika Andersson; Pettersson, Stefan; Edin, Fredrik

2018-01-01

: Protein supplementation immediately post-exercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 hours later. Neither did it affect resting fat oxidation during the post-exercise period despite increased insulin levels and attenuated ketosis. Carbohydrate...

Heritability estimates for methane emission in Holstein cows using breath measurements

DEFF Research Database (Denmark)

Lassen, Jan; Madsen, Jørgen; Løvendahl, Peter

2012-01-01

Enteric methane emission from ruminants contributes substantially to the greenhouse effect. Few studies have focused on the genetic variation in enteric methane emission from dairy cattle. The objective of this study was to estimate the heritability for enteric methane emission from Danish Holste...... to ketosis....

Hyperglycaemic emergencies are a common problem

African Journals Online (AJOL)

to presence of ketosis, standard bicarbonate level and serum osmolality: (I) mild diabetic keto-acidosis (OKA);. (h) severe DKA; (UI) hyperosmolar state; and. (iv) hyperglycaemia. Results. There were 131 admissions in 122 patients. Sixty-five occurred in non-insulin-dependent diabetics,. 45 in insulin-dependent diabetics ...

Case 22:Type II diabetes

Science.gov (United States)

Diabetes mellitus is characterized by elevated blood glucose levels. It is composed of two types depending on the pathogenesis. Type I diabetes is characterized by insulin deficiency and usually has its onset during childhood or teenage years. This is also called ketosis-prone diabetes. Type II diab...

Is the Modern High Potential Dairy Cow Suitable for Organic Farming Conditions?

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Harðarson Grétar H

2002-03-01

Full Text Available It is not acceptable to compromise animal welfare in any system of farming. Feeding should be aimed at meeting the nutritional requirements at the various stages of production. This paper deals with the detrimental effects that organic, extensive or low input farming systems may have on the energy status in early lactation of the high potential dairy cow. Bovine ketosis is the most important disease resulting from insufficient energy intake in early lactation. It is also important to realize that ketosis is a part of the so-called periparturient disease complex, which includes milk fever, mastitis, retained placenta, endometritis and poor fertility also. All these diseases are interrelated and reflect to a large extent the nutritional status of the animal. If organic dairy farming is to be successful the breeding programmes have to divert from selection for high yields as a main goal, to more emphasis on a flatter lactation curve, less production diseases and longevity.

Fulminant type 1 diabetes mellitus: a case report

Science.gov (United States)

Yunir, E.; Nenfiati

2018-03-01

Type 1 diabetes mellitus is a metabolic disease caused by insulin deficiency that results from destruction of β-cells in the pancreas. Based on American Diabetes Association, there are two types of type 1 diabetes mellitus: type 1A (autoimmune) and 1B (idiopathic). In this case, we are presenting a new archetype of type 1 diabetes named fulminant type 1 diabetes mellitus. This disease results from quick destruction of β-cells byanautoimmune mechanism. The manifestation of this disease consists of unspecific flu-like symptoms, abdominal symptoms, to specific hyperglycemia symptoms such as fatigue, malaise, change in mental status that are attributable to high blood glucose and ketosis. Laboratory examination reveals high blood glucose, normal glycosylated hemoglobin, ketosis or ketoacidosis, potassium depletion and elevation of liver function tests. Treatment consists of intravenous infusion followed by insulin injection for blood glucose control, followed by treatment of metabolic derangements such as acid-base and electrolyte disorder.

Animal Research International - Vol 6, No 1 (2009)

African Journals Online (AJOL)

Survey Of Ketosis And Hypoproteinaemia In Slaughtered Cattle In The Sahel Region Of Nigeria · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. IC Igbokwe, SN Okonkwo, HG Hamza, NA Igbokwe. http://dx.doi.org/10.4314/ari.v6i1.48099 ...

Short Communication: Elevated Concentrations of Oleic Acid and Long-Chain Fatty Acids in Milk Fat of Multiparous Subclinical Ketotic Cows

NARCIS (Netherlands)

Haelst, van Y.N.T.; Beeckman, A.; Knegsel, van A.T.M.; Fievez, V.

2008-01-01

The objective of this study was to determine whether concentrations of specific fatty acids in milk fat are a candidate for the early detection of subclinical ketosis. The case study included multiparous cows fed a lipogenic diet or a mixed glucogenic:lipogenic diet during the first 9 wk of

De invloed van bedrijfsfaktoren op het ontstaan van acetonemie (acetonurie) en slepende melkziekte bij melkkoeien

NARCIS (Netherlands)

Rijpkema, Y.S.

1968-01-01

About 140 farms, where dairy cows had clinical signs of ketosis or acetonuria, were studied to find out whether farm management had any influence on the occurrence of these phenomena and whether outbreaks could be prevented by practical measures in this field.

The results did not indicate that

Monitoring metabolic health of dairy cattle in the transition period.

Science.gov (United States)

LeBlanc, Stephen

2010-01-01

This paper reviews the importance of energy metabolism in transition dairy cows, its associations with disease and reproduction, and strategies for monitoring cows under field conditions during this critical time. Essentially all dairy cattle experience a period of insulin resistance, reduced feed intake, negative energy balance, hypocalcemia, reduced immune function, and bacterial contamination of the uterus soon before, or in the weeks after calving. One-third of dairy cows may be affected by some form of metabolic or infectious disease in early lactation. Routine, proactive actions, observations, or analysis are intended to accurately and efficiently provide early detection of problems, to provide an opportunity for investigation and intervention in order to limit the consequences and costs of health problems and reduced animal performance or welfare. Methods of early detection include monitoring of disease and culling records, feed intake, milk production, body condition, and simple metabolic tests. Methods, strategies, and interpretation of measurement of peripartum concentrations of non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB) as indicators of aspects of energy status and disease risk are reviewed. High NEFA (> 0.4 mmol/l) in the last 7 to 10 days before expected calving is associated with increased risk of displaced abomasum (DA), retained placenta, culling before 60 days in milk, and less milk production in the first 4 months of lactation. Subclinical ketosis (serum BHB >1200 to 1400 micromol/l) in the first or second week after calving is associated with increased risk of DA, metritis, clinical ketosis, endometritis, prolonged postpartum anovulation, increased severity of mastitis, and lower milk production in early lactation. There are several validated and practical tools for cow-side measurement of ketosis.

Deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase: a cause of lethal myopathy and cardiomyopathy in early childhood

NARCIS (Netherlands)

Rocchiccioli, F.; Wanders, R. J.; Aubourg, P.; Vianey-Liaud, C.; IJlst, L.; Fabre, M.; Cartier, N.; Bougneres, P. F.

1990-01-01

A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood beta-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's

Ketogenic diets and physical performance

Directory of Open Access Journals (Sweden)

Phinney SD

2004-08-01

Full Text Available Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15-25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

The inhibitory effect of acetoacetate on myocardial contraction

NARCIS (Netherlands)

Zimmerman, A.N.E.; Meijler, F.L.; Hülsmann, W.C.

1962-01-01

Williamson and Krebs 1 and Hall 2 have recently reported that acetoacetate, when added to the perfusion medium of an isolated heart in concentrations as high as or higher than in cases of mild ketosis, is oxidised in preference to glucose. These workers, and also Ottaway and Sarkar,3 have shown

Ketogenic diets and physical performance

Directory of Open Access Journals (Sweden)

Phinney Stephen D

2004-08-01

Full Text Available Abstract Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

Ketotic hyperglycemia with movement disorder

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Disha Awasthi

2012-01-01

Full Text Available Chorea, hemichorea-hemiballismus and severe partial seizures may be the presenting features of nonketotic hyperglycemia in older adults with type 2 diabetes, but cases in young adults with type 1 diabetes are rare. We hereby report a very rare case of diabetic ketosis with movement disorder in a young patient.

Suplementação de propilenoglicol para vacas no período peri-parto: efeitos sobre incidência de cetose, produção leiteira, escore corporal e primeiro estro pós-parto - DOI: 10.4025/actascianimsci.v25i1.2143 Supplementation of propyleneglycol to dairy cows in the periparturient period: effects on incidence of ketosis, milk yield, body condition score, and first estrus postpartum - DOI: 10.4025/actascianimsci.v25i1.2143

Directory of Open Access Journals (Sweden)

Carlos de Sousa Lucci

2003-04-01

Full Text Available Foi objetivo deste estudo analisar os efeitos da suplementação de propilenoglicol para vacas em lactação sob a ocorrência de cetose e as suas conseqüências na: a produção de leite; e b variação do escore de condição de corporal e primeiro estro pós-parto. Vinte e três vacas da raça Holandesa foram alocadas em dois tratamentos: 1 300mL de propilenoglicol (grupo tratamento, 11 vacas, 2 300 ml de água (grupo controle, 12 vacas, administrados através de beberagem no período peri-parto. Foram colhidas amostras de plasma para análise de ß-hidroxibutirato e realizada a avaliação do escore de condição (ECC corporal. A incidência de cetose subclínica foi de 9,1% e 33,5%; o primeiro estro pós-parto foi em média 40,18 e 45,17 dias no grupo tratamento e controle, respectivamente. Não houve efeito do tratamento ou tempo sobre produção de leite, embora a interação tempo tratamento foi significativa. O ECC do grupo tratamento foi maior que o do grupo controle, mas não sofreu variação nos primeiros 60 dias de lactação.The aim of this study was to analyse the effects of propyleneglycol supplementation to the periparturient cows on the occurrence of ketosis and its consequences on: a milk yield; b variation of body condition score and first estrus postpartum. Twenty-three Holstein cows were distributed into two treatments: a 300mL of propyleneglycol (group treatment, 11 cows, b 300mL of water (group control, 12 cows, administered through drench in the periparturient period. Plasma samples were collected to the analysis of ß-hydroxybutyrate and the body condition score (BCS was carried out. The incidence of subclinical ketosis was 9.1 and 33.5%, and the first postpartum estrus was in an average of 40.18 and 45.17 days, in the treatment groups and control, respectively. There was no effect of treatment or time on milk yield, although the interaction of time&lowest;treatment was significant. The BCS of the treatment group was

A Rare Case of β-Ketothiolase Deficiency

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B. Modh

2015-06-01

Full Text Available We are reporting a case of β-ketothiolase deficiency, a rare disorder of amino acid metabolism. A 10 month old child presented with complaints of vomiting, convulsions, fever and altered sensorium that on investigations showed metabolic acidosis, hyperammonemia and ketosis. Gas chromatography/ mass spectroscopic examination was suggestive of β-ketothiolase deficiency.

Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood "Villains" of Human Metabolism

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Manninen Anssi H

2004-12-01

Full Text Available Abstract During very low carbohydrate intake, the regulated and controlled production of ketone bodies causes a harmless physiological state known as dietary ketosis. Ketone bodies flow from the liver to extra-hepatic tissues (e.g., brain for use as a fuel; this spares glucose metabolism via a mechanism similar to the sparing of glucose by oxidation of fatty acids as an alternative fuel. In comparison with glucose, the ketone bodies are actually a very good respiratory fuel. Indeed, there is no clear requirement for dietary carbohydrates for human adults. Interestingly, the effects of ketone body metabolism suggest that mild ketosis may offer therapeutic potential in a variety of different common and rare disease states. Also, the recent landmark study showed that a very-low-carbohydrate diet resulted in a significant reduction in fat mass and a concomitant increase in lean body mass in normal-weight men. Contrary to popular belief, insulin is not needed for glucose uptake and utilization in man. Finally, both muscle fat and carbohydrate burn in an amino acid flame.

Survey of ketolactia, determining the main predisposing management factors and consequences in Hungarian dairy herds by using a cow-side milk test

Science.gov (United States)

Zechner, Gerhard; Csorba, Csaba; Könyves, László

2018-01-01

The aims of the survey were to determine the prevalence of ketosis in dairy herds by measuring the concentration of beta-hydroxybutyrate (BHBA) in milk by Keto-Test (Sanwa Kagaku Kenkyusho, Nagoya, Japan); risk factors and the relationship with postpartum diseases were investigated. 1667 early lactating (days in milk 0–75) cows were tested in 52 dairy herds in 2013 and 2014 years. In total, 29.3 per cent of samples were positive (BHBAMILK ≥100 µmol/l), including 3.7 per cent high positives (BHBAMILK ≥500 µmol/l). The prevalence was similar in herds with less than or more than 9000 kg milk yield (0.34 and 0.38, respectively, P=0.4); however, it was higher in the herds with more than 1000 cows than in smaller herds (ketosis (P<0.001). The results confirm the high prevalence of ketolactia in Hungarian dairy herds and its links to herd-related and cow-related risk factors and diseases occurring commonly in fresh cows. PMID:29868171

S .4lr. T;,rls|." \\/eek. 6 , ll 16 ( 19 i6 ) DIE trn-VLOEI) VAN VERSKILLEI ...

African Journals Online (AJOL)

MAYNARD, L.A. & LOOSLI, J.K., 1956. Animal Nutrition. New York: McGraw-Hill. MOIR, R.I. & HARRIS, L.E., 1962. Ruminal flora studies in sheep. I. Influence of N intake upon ruminal function. J. Nutr. 77, 282. NABARRO, J.D.N., SPENCER, A.G. & STOWERS, J.M., 1952. Metabolic studies in severe diabetic ketosis. Quart. J.

Author Details

African Journals Online (AJOL)

Umar, L A. Vol 24, No 3 (2006) - Articles Survey Of Ketosis In Lactating Wadara Cows Abstract. ISSN: 0794-4845. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER ...

Effect of group size and health status on behavior and feed intake of multiparous dairy cows in early lactation

DEFF Research Database (Denmark)

Jensen, Margit Bak; Proudfoot, Kathryn L.

2017-01-01

an existing group pen for 6 (N6) or 24 cows (N24) on d 4 after calving. Cows were considered sick if they were diagnosed with and treated for milk fever, mastitis, or retained placenta, diagnosed with subclinical ketosis or metritis within 3 d of calving, or were diagnosed and treated for any other infection...

Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

Science.gov (United States)

Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

2016-03-01

Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. © 2016 New York Academy of Sciences.

Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

Science.gov (United States)

Thompson, Lindsey; Fecske, Erin; Salim, Mohammad; Hall, Ara

2017-02-01

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Cardiopulmonary bypass considerations for pediatric patients on the ketogenic diet.

Science.gov (United States)

Melchior, R W; Dreher, M; Ramsey, E; Savoca, M; Rosenthal, T

2015-07-01

There is a population of children with epilepsy that is refractory to anti-epileptic drugs. The ketogenic diet, a high-fat, low-carbohydrate regimen, is one alternative treatment to decrease seizure activity. Special considerations are required for patients on the ketogenic diet undergoing cardiopulmonary bypass (CPB) to prevent exposure to glucose substrates that could alter ketosis, increasing the risk of recurrent seizures. A 2-year-old, 9 kilogram male with a history of infantile spasms with intractable epilepsy, trisomy 21 status post tetralogy of Fallot repair, presented to the cardiac operating room for closure of a residual atrial septal defect. All disciplines of the surgical case minimized the use of carbohydrate-containing and contraindicated medications. Changes to the standard protocol and metabolic monitoring ensured the patient maintained ketosis. All disciplines within cardiac surgery need to be cognizant of patients on the ketogenic diet and prepare a modified protocol. Future monitoring considerations include thromboelastography, electroencephalography and continuous glucose measurement. Key areas of focus with this patient population in the cardiac surgical theater are to maintain a multidisciplinary approach, alter the required CPB prime components, address cardiac pharmacological concerns and limit any abnormal hematological occurrences. © The Author(s) 2014.

Study of the exhaled acetone in type 1 diabetes using quantum cascade laser spectroscopy.

Science.gov (United States)

Reyes-Reyes, Adonis; Horsten, Roland C; Urbach, H Paul; Bhattacharya, Nandini

2015-01-06

The acetone concentration exhaled in the breath of three type 1 diabetes patients (two minors and one adult) and one healthy volunteer is studied using a quantum cascade laser-based spectroscopic system. Using the acetone signature between 1150 and 1250 cm(-1) and a multiline fitting method, the concentration variations on the order of parts per billion by volume were measured. Blood glucose and ketone concentrations in blood measurements were performed simultaneously to study their relation with acetone in exhaled breath. We focus on personalized studies to better understand the role of acetone in diabetes. For each volunteer, we performed a series of measurements over a period of time, including overnight fastings of 11 ± 1 h and during ketosis-hyperglycemia events for the minors. Our results highlight the importance of performing personalized studies because the response of the minors to the presence of ketosis was consistent but unique for each individual. Also, our results emphasize the need for performing more studies with T1D minors, because the acetone concentration in the breath of the minors differs, with respect to those reported in the literature, which are based on adults.

Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows.

Science.gov (United States)

González, Felix Diaz; Muiño, Rodrigo; Pereira, Víctor; Campos, Rómulo; Benedito, José Luis

2011-09-01

Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 µmol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea.

Effects of a combination of plant bioactive lipid compounds and biotin compared with monensin on body condition, energy metabolism and milk performance in transition dairy cows

Science.gov (United States)

Hausmann, Janis; Deiner, Carolin; Patra, Amlan K.; Immig, Irmgard; Starke, Alexander

2018-01-01

The aim of this study was to test whether a combination of plant bioactive lipid compounds (also termed ‘essential oils’) and biotin (PBLC+B) could decrease the mobilization of body reserves and ketosis incidence in postpartum dairy cows. We compared non-supplemented control (CON) cows with cows receiving monensin (MON) as a controlled-release capsule at d -21, and with cows receiving PBLC+B from day (d) -21 before calving until calving (Phase 1) and further until d 37 after calving (Phase 2), followed by PBLC+B discontinuation from d 38 to d 58 (Phase 3). The PBLC+B cows had higher body weight and higher back fat thickness than CON cows and lesser body weight change than MON and CON cows in Phase 3. Body condition score was not different among groups. Milk protein concentration tended to be higher on the first herd test day in PBLC+B vs. CON cows. Milk fat concentration tended to be highest in PBLC+B cows throughout Phases 2 and 3, with significantly higher values in PBLC+B vs. MON cows on the second herd test day. Yields of energy-corrected milk were higher in PBLC+B vs. CON and MON cows in Phase 2 and higher in PBLC+B and MON cows vs. CON cows in Phase 3. The incidence of subclinical ketosis was 83%, 61% and 50% in CON, PBLC+B and MON cows, respectively, with lower mean β-hydroxybutyrate values in MON than in PBLC+B cows in Phase 1 prepartum. The serum triglyceride concentration was higher in PBLC+B vs. CON cows on d 37. No differences were observed in serum glucose, urea, non-esterified fatty acids, cholesterol and bilirubin concentrations. Aspartate transaminase and γ-glutamyltranspeptidase but not glutamate dehydrogenase activities tended to be highest in MON and lowest in PBLC+B in Phase 2. We conclude that PBLC+B prevent body weight loss after parturition and are associated with similar ketosis incidence and partly higher yields of energy-corrected milk compared to MON supplementation of dairy cows. PMID:29584764

Effect of Calcium Borogluconate Injection pre and Immediately Postpartum on Production Performance, Incidence of Metabolic Disorders and Situation of the Uterus After Calving in Cows Fed Anionic Diets

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H. Amanlou

2012-10-01

Full Text Available The objective of this study was to determine the effect of calcium borogluconate injection 48 and 24 hours prepartum and immediately after parturition on dry matter intake at day of calving, milk yield, incidence of metabolic disorders and uterine conditions during the first 21 days postpartum in cows fed anionic diets. Thirty six lactating dairy cows were balanced by parity (1, 2, 3+ and allocated to 4 subcutaneous injection treatments of 15.2 gr calcium as borogluconate at different times pre and postpartum than expected calving date . Group 1 consisted of 9 cows receiving no treatment before or after parturition. Group 2 consisted of 9 cows receiving calcium borogluconate 48 h prepartum.Group 3 consisted of 9 cows receiving calcium borogluconate 24 h prepartum. Group 4 consisted of 9 cows receiving 15.2 gr of ca as borogluconate immediately postpartum. Dry matter intake was in treatments 1, 2, 3 and 4 was 10.87, 12.32, 12.63 and 15.03 kg in the first 24 h after calving, respectively And indicated significantly difference among treatments. milk yield in 2, 3 and 4 treatments was significantly greater than group 1 in the first 21 days of lactation (38.7, 38.9, 40.3 vs 36.07 kg/d. Treatment had a significant effect on the subclinical hypocalcemia incidence so incidence risk of subclinical hypocalcemia in 1 treatment was 10 times more likely than 4 treatment. Data regression analysis indicated that 4 treatment had a significant effect on the ketosis incidence. So that the cows no calcium injection 2.43 times more likely to experience ketosis than 4 treatment. But experimental treatments were not significantly effect on the incidence of milk fever, displacement abomasum, retained placenta, metritis and endometritis. In general, calcium injection, especially immediately after parturation increased the dry matter intake in day of calving and reduced metabolic disorders such as hypocalcaemia and ketosis.

Metabolic disorders in dairy Simmentals - prevalence risk and effect on subsequent daily milk traits

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Vesna Gantner

2018-01-01

Full Text Available In order to analyse metabolic disorders in Simmental cows, 2.641.223 test-day records have been used. The metabolic disorders prevalence risk was indicated by the fat to protein (F/P ratio, while the subclinical disorder was demonstrated using the F/P ratio and daily production. In terms of the ketosis prevalence risk (KPR, the highest prevalence risks occurred at the 20th lactation day in all tested cows with exception of cows in parity P4+ which experienced peak prevalence risk at 25th lactation day. A steady decrease of KPR after peak prevalence was observed in all animals except the 3rd lactation cows which experienced the second peak prevalence at the 30th lactation day, after which the prevalence risk continued to decline. The highest acidosis prevalence risk (APR was detected among 4+ parity cows. Considering the lactation stage, the highest APR occurred within the first 10 days, with the indication from 16 to 23 %, depending on parity. The peak prevalence risk was followed by a considerable decline during the ensuing 20 days. The prevalence risk began to increase among all cows after the 25th lactation day. Furthermore, there was a considerable decrease in a daily milk yield and variation of daily milk contents due to subclinical disorders. The most noticeable drop in daily milk yield, for both ketosis/acidosis, was detected in cows in 4+ parity in the amounts of 7.45 kg/day and 2.73 kg/day respectively. There was also a production decline in the subsequent milk controls. Subclinical disorders can also substantially change daily milk contents. The daily fat content was considerably reduced by the subclinical ketosis and the same parameter was considerably increased by the subclinical acidosis. The opposite trends were detected for daily protein content. Since indication criteria was set on Holstein population and considering the fact that Simmental cows produce noticeably less, some adjustment is needed before a routine use of test

Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells.

Science.gov (United States)

Hillreiner, Maria; Flinspach, Claudia; Pfaffl, Michael W; Kliem, Heike

2016-01-01

Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC) challenged with the mastitis pathogen Escherichia coli (E. coli). Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from milk and challenged in culture with 3 mM BHBA and E. coli. pbMEC stimulated with E. coli for 6 h or 30 h showed an up-regulation of several innate immune genes, whereas co-stimulation of pbMEC with 3 mM BHBA and E. coli resulted in the down-regulation of CCL2, SAA3, LF and C3 gene expression compared to the challenge with solely the bacterial stimulus. These results indicated that increased BHBA concentrations may be partially responsible for the higher mastitis susceptibility of dairy cows in early lactation. Elevated levels of BHBA in blood and milk during negative energy balance and ketosis are likely to impair innate immune function in the bovine mammary gland by attenuating the expression of a broad range of innate immune genes.

Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells.

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Maria Hillreiner

Full Text Available Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC challenged with the mastitis pathogen Escherichia coli (E. coli. Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from milk and challenged in culture with 3 mM BHBA and E. coli. pbMEC stimulated with E. coli for 6 h or 30 h showed an up-regulation of several innate immune genes, whereas co-stimulation of pbMEC with 3 mM BHBA and E. coli resulted in the down-regulation of CCL2, SAA3, LF and C3 gene expression compared to the challenge with solely the bacterial stimulus. These results indicated that increased BHBA concentrations may be partially responsible for the higher mastitis susceptibility of dairy cows in early lactation. Elevated levels of BHBA in blood and milk during negative energy balance and ketosis are likely to impair innate immune function in the bovine mammary gland by attenuating the expression of a broad range of innate immune genes.

High somatic cell counts and changes in milk fat and protein contents around insemination are negatively associated with conception in dairy cows

OpenAIRE

Albaaj, Ahmad; Foucras, Gilles; Raboisson, Didier

2017-01-01

The fertility of dairy cows has decreased dramatically worldwide over the last few decades, and several causes of this trend have been reported. Several studies have associated compromised udder health with deteriorating reproduction performance. Subclinical ketosis (SCK) has also been reported to be a risk factor for decreased conception. The objective of the present study was to describe how SCK might interact with the reported association between udder health and conception in dairy cows. ...

Peripartal rumination dynamics and health status in cows calving in hot and cool seasons.

Science.gov (United States)

Paudyal, S; Maunsell, F; Richeson, J; Risco, C; Donovan, A; Pinedo, P

2016-11-01

Our objective was to evaluate the effect of season of calving, associated with variable levels of heat stress, on the dynamics of rumination during the prepartum period and early lactation of cows that were healthy or affected by peripartal health disorders. Three weeks before the estimated due date, 210 multiparous Holstein cows at the University of Florida Dairy Unit were affixed with a neck collar containing rumination loggers, providing rumination time (RT) in 2-h periods. One blood sample was collected in a subpopulation of cows (n=76) at 12 to 48h postcalving to assess metabolic status by determining serum calcium, nonesterified fatty acid, and β-hydroxybutyrate concentrations. The occurrence of peripartal health disorders (dystocia, clinical ketosis, clinical hypocalcemia, metritis, and mastitis) was assessed by University of Florida veterinarians and trained farm personnel. We analyzed the dynamics of daily RT over ± 14d relative to parturition in cows that were healthy or affected by specific health disorders by season of calving [hot season, June to September (n=77); cool season, November to April (n=118)] using repeated measures analysis and comparison of least squares means at different time points relative to calving. Rumination was consistently reduced on the day of calving in both healthy and sick cows in both the hot and cool seasons. Only hot-season calvings had shorter average daily RT prepartum and postpartum in cows affected by severe negative energy balance and subclinical ketosis. Dystocia during the hot season was associated with shorter daily RT prepartum; for cool-season calvings, cows with dystocia had reduced RT postpartum. We also observed reduced RT in cows with ketosis prepartum and postpartum in both the hot and cool seasons. Daily RT was reduced postpartum in cows with hypocalcemia and mastitis that calved during the cool season, and it was shorter in cows with metritis in both the hot and cool seasons. Our results indicated that

The effect of nutritional management of the dairy cow on reproductive efficiency.

Science.gov (United States)

Roche, James F

2006-12-01

The cause of low fertility in dairy cows is multifactorial. Poor nutrition during the dry and early postpartum periods results in reduced glucose, insulin, insulin-like growth factor (IGF-I) and low LH pulse frequency with concomitant increases in beta-hydroxy butyrate, non-esterified fatty acids (NEFA) and triacylglycerol. Cows must mobilize large lipid, but also some protein reserves, with a consequent increased incidence of such metabolic disorders as hypocalcaemia, acidosis, ketosis, fatty liver and displaced abomasums. The occurrence of milk fever and ketosis affects uterine contractions, delays calving and increases the risk of retained foetal membranes (RFM) and endometritis. The nutritional risk factors that cause RFM are hypocalcaemia, high body condition score (BCS) at calving and deficiencies in Vitamin E and selenium. The risk factors for endometritis are hypocalcaemia, RFM, high triacylglycerol and NEFA. Thus, metabolic disorders predispose cows to gynaecological disorders, thereby reducing reproductive efficiency. Cows that are overconditioned at calving or those that lose excess body weight are more likely to have a prolonged interval to first oestrus, thereby prolonging days open. Nutritionally induced postpartum anoestrus is characterized by turnover of dominant follicles incapable of producing sufficient oestradiol to induce ovulation due to reduced LH pulse frequency. High nutrition can also increase metabolic clearance rate of steroid hormones such as progesterone or oestradiol. Lower concentrations of oestradiol on the day of oestrus are highly correlated with the occurrence of suboestrus, thereby making the detection of oestrus in high yielding cows even more difficult. Nutrition also affects conception rate (CR) to AI. Cows that develop hypocalcaemia, ketosis, acidosis or displaced abomasums have lower CRs and take longer to become pregnant. Excessive loss of BCS and excess protein content of the ration can reduce CR while supplemental fats

Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells

OpenAIRE

Hillreiner, Maria;Flinspach, Claudia;Pfaffl, Michael W.;Kliem, Heike

2017-01-01

Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC) challenged with the mastitis pathogen Escherichia coli (E. coli). Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from m...

Ketogenic diet for high partial pressure oxygen diving.

Science.gov (United States)

Valadao, Jason M; Vigilante, John A; DiGeorge, Nicholas W; O'Connor, Sunila E; Bear, Alexandria; Kenyon, Jeffrey; Annis, Heather; Dituri, Joseph; Dituri, Amy E; Whelan, Harry T

2014-01-01

A ketogenic diet (KD) may decrease central nervous system oxygen toxicity symptoms in divers, and in view of this implication a feasibility/ toxicity pilot study was performed to demonstrate tolerance of KD while performing normal diving profiles. The exact mechanism of neuroprotection from the KD remains unknown; however, evidence to support the efficacy of the KD in reducing seizures is present in epilepsy and oxygen toxicity studies, and may provide valuable insight in diving activities. Three divers (two males and one female ages 32-45 with a history of deep diving and high pO2 exposure) on the KD made dives to varying depths in Hawaii using fully closed-circuit MK-15 and Inspiration rebreathers. These rebreathers have an electronically controlled set point, allowing the divers to monitor and control the oxygen level in the breathing loop, which can be varied manually by the divers. Oxygen level was varied during descent, bottom depth and ascent (decompression). Divers fasted for 12-18 hours before diet initiation. The ketosis level was verified by urinating on a Ketostix (reagent strips for urinalysis). Ketosis was achieved and was easily monitored with Ketostix in the simulated operational environment. The KD did not interfere with the diving mission; no seizure activity or signs or symptoms of CNS toxicity were observed, and there were no adverse effects noted by the divers while on the KD.

A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes

OpenAIRE

Saslow, LR; Kim, S; Daubenmier, JJ; Moskowitz, JT; Phinney, SD; Goldman, V; Murphy, EJ; Cox, RM; Moran, P; Hecht, FM

2014-01-01

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n ...

Survey Of Ketosis In Lactating Wadara Cows | Igbokwe | Tropical ...

African Journals Online (AJOL)

http://dx.doi.org/10.4314/tv.v24i3.4588 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER RESOURCES... for Researchers · for Journals · for Authors · for Policy Makers ...

Survey Of Ketosis And Hypoproteinaemia In Slaughtered Cattle In ...

African Journals Online (AJOL)

Serum ketone and total protein concentrations of 966 cattle slaughtered at the metropolitan abattoir, Maiduguri, Nigera, were estimated durng the dry and rainy months of the year. None of the sera had a titrable ketone concentration. Serum total protein (STP) concentration of <60.0 g/L,considered as hypoproteinaemia, was ...

Survey Of Ketosis In Lactating Wadara Cows | Igbokwe | Tropical ...

African Journals Online (AJOL)

Milk samples collected from 203 lactating Wadara cows at various periods of lactation from April to August, 1999, in Borno State, Nigeria, were negative for ketones by Rothera\\'s test. The protein, lactose, fat and total solids contents of 30 milk samples were 12.5 6.7mg/ml, 12.3 2.0mg/ml, 3.2 1.2% and 12.9 2.8%, ...

Clinical features of diabetes mellitus in Japan as observed in a hospital outpatient clinic

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Wada, Sunao; Toda, Shintaro; Omori, Yoshiaki; Yamakido, Michio; Blackard, W G

1963-04-18

A university diabetes clinic in Japan was characterized by age at examination, age at onset, sex ratio, microangiopathies, atherosclerotic complications, weight, heredity, and diet. The findings in this clinic, along with those from other diabetes clinics in Japan, were compared with studies on Western diabetics. The similarities between the 2 diabetic populations far outnumbered the dissimilarities. However, diabetes mellitus in Japan is distinguished by infrequent occurrence of juvenile diabetes and ketosis, relative lack of atherosclerotic complications, and reversal of the sex ratio. 39 references, 7 tables.

On the Metabolism of Exogenous Ketones in Humans

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Brianna J. Stubbs

2017-10-01

Full Text Available Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE; (R-3-hydroxybutyl (R-3-hydroxybutyrate, or ketone salts (KS; sodium plus potassium βHB.Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001, which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001, but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12 or a continuous nasogastric infusion (n = 4 to maintain blood D-βHB concentrations greater than 1 mM. Both drinks

Insulin suppresses the AMPK signaling pathway to regulate lipid metabolism in primary cultured hepatocytes of dairy cows.

Science.gov (United States)

Li, Xinwei; Li, Yu; Ding, Hongyan; Dong, Jihong; Zhang, Renhe; Huang, Dan; Lei, Lin; Wang, Zhe; Liu, Guowen; Li, Xiaobing

2018-05-01

Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKα inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-α (PPARα), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKα induced by AICAR could reverse the effect of insulin on PPARα, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKα signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis.

Imact of feeding and post prandial time on plasma ketone bodies in sows during transition and lactation

DEFF Research Database (Denmark)

Theil, Peter Kappel; Olesen, A K; Flummer, Christine

2013-01-01

Two experiments were conducted with the aim of studying how dietary fat source, reproductive stage (Exp. 1), and diurnal variation (Exp. 2) affect plasma ketone bodies in sows. In Exp. 1, 40 second-parity sows were fed 1 of 5 lactation diets from 7 d prepartum until 28 d postpartum, with low or h......, therefore, primary ketosis does not appear to be a major problem in sows. In addition, this study indicates that the intermediary metabolism of sows was challenged when sows were exposed to high fat diets in late gestation....

Forced eye closure-induced reflex seizure and non-ketotic hyperglycemia

International Nuclear Information System (INIS)

Tiras, Raziye; Mutlu, Aytul; Ozben, Serkan; Aydemir Tuba; Ozerab, Feriha

2009-01-01

We report an uncommon case of 53-year-old female patient with partial seizure induced by forced voluntary eye closure due to non-ketotic hyperglycemia. The initial laboratory tests showed an elevated blood glucose level of 550 mg/dL but no evidence of ketosis. Brain magnetic resonance imaging was normal. When the blood glucose levels decreased slowly to about 150 mg/dL in five days, the seizures ended completely. No anticonvulsants were used. Since seizures are generally refractory to antiepileptic medication, control of blood glucose is essential. (author)

A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes.

Science.gov (United States)

Maahs, David M; Calhoun, Peter; Buckingham, Bruce A; Chase, H Peter; Hramiak, Irene; Lum, John; Cameron, Fraser; Bequette, B Wayne; Aye, Tandy; Paul, Terri; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Kollman, Craig; Beck, Roy W

2014-07-01

Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels. Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred. Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P 2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P 250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm. Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis. © 2014 by the American Diabetes Association.

Biliary clearance of bromosulfophthalein in healthy and ketotic Holstein cows

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Danijela Kirovski

2013-09-01

Full Text Available Ketosis is a metabolic disorder closely associated with liver lipidosis. Numerous tests have been developed to detect hepatic dysfunction in dairy cows. Bromosulfophthalein (BSP clearance is established as a sensitive index of hepatic function. The objective of this study was to examine the difference of biliary excretion of BSP between ketotic and healthy Holstein cows and to correlate this excretion with other indicators of liver dysfunction. Twenty puerperal Holstein cows divided in two groups (10 cows each were involved in the study. The first group included healthy and the second group ketotic cows. Blood samples were taken 10 days after parturition. Concentrations of total protein, albumin, total bilirubin, Ca, P, total lipids, urea and glucose were determined. Immediately after blood sampling, BSP test was performed. Blood samples were taken 5 and 45 minutes after injection, and the percentage of retained pigment in the sample obtained at minute 45 was calculated. Blood albumin and glucose concentrations were significantly higher in healthy then ketotic cows. Total bilirubin concentration was significantly higher in ketotic than healthy cows. BSP excretion was significantly higher in ketotic compared to healthy cows. There was a significant positive correlation between BSP values and total bilirubin concentrartions in both healthy and ketotic cows and a significant negative correlation between BSP values and glucose concentrartions in both healthy and ketotic cows. In conclusion, biliary clearance of BSP may be used as a reliable method for the detection of hepatic dysfunction associated with clinical symptoms of ketosis in dairy cows.

Benefits of the nonfasting ketogenic diet compared with the initial fasting ketogenic diet.

Science.gov (United States)

Kim, Dong Wook; Kang, Hoon Chul; Park, Jung Chae; Kim, Heung Dong

2004-12-01

The ketogenic diet (KD) is traditionally introduced with an initial period of fasting and fluid restriction that is difficult and sometimes complicated by moderate dehydration. This investigation compares the efficacy and tolerability of the nonfasting ketogenic diet (NFKD) and the conventional initial-fasting ketogenic diet (IFKD). Forty-one children with intractable epilepsy were treated with the NFKD, beginning with a gradual increase in calories with no initial fasting or fluid restriction. This NFKD population was compared retrospectively with 83 recent historical control subjects who were treated with the IFKD. Efficacy, tolerability, time until strong ketosis, and occurrence of complications were compared. Fourteen (34.1%) patients became seizure-free for at least 3 months after the NFKD, compared with 29 (34.9%) after the IFKD. There was no significant difference in days until strong urinary ketosis between the 2 groups. The incidence of hypoglycemia was also not significantly different between the groups as most other laboratory findings, although the blood urea nitrogen was elevated in 24.1% of the IFKD group and in only 12.2% of the NFKD patients without statistical significance. Conversely, moderate dehydration was significantly less frequent in the NFKD group (12.2%) than in the IFKD group (62.7%). Finally, these results were reflected to the shortening of the hospitalization period in the NFKD group. These observations suggest that initial fasting and fluid restriction are not essential for the KD and that the tolerability of this treatment may be improved. These data support our intention to conduct a formal, prospective, randomized trial comparing 2 forms of the KD.

Rumen-protected choline: A significance effect on dairy cattle nutrition.

Science.gov (United States)

Jayaprakash, G; Sathiyabarathi, M; Robert, M Arokia; Tamilmani, T

2016-08-01

Choline is a vitamin-like substance it has multi-function in animal production, reproduction, and health. The transition period is most crucial stage in lactation cycle of dairy cows due to its association with negative hormonal and energy balances. Unfortunately, unprotected choline easily degrades in the rumen; therefore, choline added to the diet in a rumen-protected form. The use of rumen-protected choline (RPC) is a preventive measurement for the fatty liver syndrome and ketosis; may improve milk production as well as milk composition and reproduction parameters. This review summarizes the effectiveness of RPC on animal production, health, and reproduction.

Effects of a ketogenic diet on brain metabolism in epilepsy

DEFF Research Database (Denmark)

Korsholm, Kirsten; Law, Ian

2013-01-01

For a subpopulation of drug-resistant epilepsies, a ketogenic diet constitutes the treatment of choice. A ketogenic diet is a high-fat, low-protein, and low-carbohydrate diet, which induces ketosis. Despite the use in treatment of epilepsy since 1924, the clinical efficacy was not demonstrated...... in a controlled, randomized trial until 2008, showing its capability of reducing seizure frequency with more than 50%. However, the exact mechanism of this form of treatment is still unknown. We report here a patient with drug-resistant epilepsy on a ketogenic diet, where a brain 18F-FDG PET examination...

Validation of genomic predictions for wellness traits in US Holstein cows.

Science.gov (United States)

McNeel, Anthony K; Reiter, Brenda C; Weigel, Dan; Osterstock, Jason; Di Croce, Fernando A

2017-11-01

The objective of this study was to evaluate the efficacy of wellness trait genetic predictions in commercial herds of US Holstein cows from herds that do not contribute phenotypic information to the evaluation. Tissue samples for DNA extraction were collected from more than 3,400 randomly selected pregnant Holstein females in 11 herds and 2 age groups (69% nulliparous, 31% primiparous) approximately 30 to 60 d before their expected calving date. Lactation records from cows that calved between September 1, 2015, and December 31, 2015, were included in the analysis. Genomically enhanced predicted transmitting abilities for the wellness traits of retained placenta, metritis, ketosis, displaced abomasum, mastitis, and lameness were estimated by the Zoetis genetic evaluation and converted into standardized transmitting abilities. Mean reliabilities of the animals in the study ranged between 45 and 47% for each of the 6 traits. Animals were ranked by their standardized transmitting abilities within herd and age group then assigned to 1 of 4 groups of percentile-based genetic groups of equal size. Adverse health events, including retained placenta, metritis, ketosis, displaced abomasum, mastitis, and lameness, were collected from on-farm herd management software, and animal phenotype was coded as either healthy (0), diseased (1), or excluded for each of the 6 outcomes of interest. Statistical analysis was performed using a generalized linear mixed model with genetic group, age group, and lactation as fixed effects, whereas herd and animal nested within herd were set as random effects. Results of the analysis indicated that the wellness trait predictions were associated with differences in phenotypic disease incidence between the worst and best genetic groups. The difference between the worst and best genetic groups in recorded disease incidence was 2.9% for retained placenta, 10.8% for metritis, 1.1% for displaced abomasum, 1.7% for ketosis, 7.4% for mastitis, and 3

Development of Fourier transform mid-infrared calibrations to predict acetone, β-hydroxybutyrate, and citrate contents in bovine milk through a European dairy network.

Science.gov (United States)

Grelet, C; Bastin, C; Gelé, M; Davière, J-B; Johan, M; Werner, A; Reding, R; Fernandez Pierna, J A; Colinet, F G; Dardenne, P; Gengler, N; Soyeurt, H; Dehareng, F

2016-06-01

To manage negative energy balance and ketosis in dairy farms, rapid and cost-effective detection is needed. Among the milk biomarkers that could be useful for this purpose, acetone and β-hydroxybutyrate (BHB) have been proved as molecules of interest regarding ketosis and citrate was recently identified as an early indicator of negative energy balance. Because Fourier transform mid-infrared spectrometry can provide rapid and cost-effective predictions of milk composition, the objective of this study was to evaluate the ability of this technology to predict these biomarkers in milk. Milk samples were collected in commercial and experimental farms in Luxembourg, France, and Germany. Acetone, BHB, and citrate contents were determined by flow injection analysis. Milk mid-infrared spectra were recorded and standardized for all samples. After edits, a total of 548 samples were used in the calibration and validation data sets for acetone, 558 for BHB, and 506 for citrate. Acetone content ranged from 0.020 to 3.355mmol/L with an average of 0.103mmol/L; BHB content ranged from 0.045 to 1.596mmol/L with an average of 0.215mmol/L; and citrate content ranged from 3.88 to 16.12mmol/L with an average of 9.04mmol/L. Acetone and BHB contents were log-transformed and a part of the samples with low values was randomly excluded to approach a normal distribution. The 3 edited data sets were then randomly divided into a calibration data set (3/4 of the samples) and a validation data set (1/4 of the samples). Prediction equations were developed using partial least square regression. The coefficient of determination (R(2)) of cross-validation was 0.73 for acetone, 0.71 for BHB, and 0.90 for citrate with root mean square error of 0.248, 0.109, and 0.70mmol/L, respectively. Finally, the external validation was performed and R(2) obtained were 0.67 for acetone, 0.63 for BHB, and 0.86 for citrate, with respective root mean square error of validation of 0.196, 0.083, and 0.76mmol/L. Although

Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

Science.gov (United States)

Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

2013-01-01

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

Science.gov (United States)

RIEGER, JOHANNES; BÄHR, OLIVER; MAURER, GABRIELE D.; HATTINGEN, ELKE; FRANZ, KEA; BRUCKER, DANIEL; WALENTA, STEFAN; KÄMMERER, ULRIKE; COY, JOHANNES F.; WELLER, MICHAEL; STEINBACH, JOACHIM P.

2014-01-01

Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3–13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12–124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (pketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet. PMID:24728273

An attempt to prevent production diseases in dairy cows by intense monitoring and ad hoc treatment

Directory of Open Access Journals (Sweden)

Matteo G. Coiatelli

2015-11-01

Full Text Available A trial has been performed on 201 dairy cows from two Italian commercial herds in order to verify whether the mitigation of a recognized negative energy balance (NEB by a therapeutic mean may influence the incidence of peri-partum diseases. All animals were tested for beta-hydroxybutyrate (β-HOB and non-esterified fatty acids (NEFA three times a week from 2 weeks before the expected due time to 2 weeks after calving. Animals whose blood levels were above β-HOB>1.2 or NEFA>0.5 mmol/L were declared POSITIVE and then split in two groups. Group T animals (n=57 were treated with a glycogenic treatment (ENERGAN KETOSIS, Virbac. The treatment was repeated daily as long as biochemical values remained abnormal. Group C animals (n=48 served as untreated controls. Animals with values within the physiological range over the study period were said NEGATIVE (n=96. This study confirmed that animals presenting excessive β-HOB or NEFA concentrations show a higher risk to get sick during the study period (P<0.05, the major risk being clinical ketosis (P<0.01 and in a lesser extend retention of the placenta (P=0.09. The application of a glycogenic treatment did not show an impact on blood metabolite levels due to huge individual differences. However, application of the treatment for an average duration of 5 days tends to reduce the incidence of all the diseases related to a NEB. Moreover, untreated control animals were more likely to get dislocation of the abomasum (P<0.05 than NEGATIVE animals whereas treated animals were not.

Diagnostic and Prognostic Significance of Lipid Profiles in Holstein Dairy Cattle with Displaced Abomasum: Before and After Surgical Operation

Directory of Open Access Journals (Sweden)

Arafat Khalphallah

2016-01-01

Full Text Available The study aimed to describe the pattern of changes in clinical findings and lipid metabolism profiles in dairy cattle with displacement of the abomasum (DA from day 0 until day 30 after operation. The study was conducted on DA cattle (n= 25 belonged to dairy farms in Hokkaido area, Japan. Cows were examined and sampled at days 0 (operation, 7 and 30. They were clinically and biochemically examined to estimate BCS and many serum biochemical constituents such as lecithin:cholesterol acyltransferase (LCAT and apolipoprotein B-100 (apoB-100, β-hydroxybutyric acid (BHBA, non-esterified fatty acids (NEFAs and aspartate amino transferase (AST. Based on blood BHBA at day 0, DA cows were classified into three categories; DA only (<1.2 mmol/l, DA with subclinical ketosis (DA SCK (1.2-2.4 mmol/l and DA with clinical ketosis (DA CK (≥2.5 mmol/l. The changes in the pattern of serum biochemical constituents throughout this study indicated recovery of diseased cows and significant effect of surgical operation. Serum biochemical constituents returned to their physiological values indicating that these cows were restoring their normal physiological status. This was reflected through a significant (P＜0.05 elevation of LCAT, apoB-100, and cholesterol and a significant (P＜0.05 reduction in AST, NEFAs and BHBA (Not in DA group, in all DA groups particularly at day 30 when their values compared with those at day 0. The current study also recorded no remarkable changes (P＞0.05 between the diseased groups except for NEFA and BHBA (at day 0 between DA group and the other two groups at any of the three sampling days.

Prevalence and Clinico-Pathology of Ketosis in Dairy Cows in Tigray ...

African Journals Online (AJOL)

The clinical observations in ketotic cows were anorexia, refusal to take concentrate and decrease in milk yield. There was 30-100% decrease in milk yield in most of the cases. The body temperature, pulse and respiration rates were within normal range with decreased rumen motility. Feces were scanty, mucoid and dry; and ...

Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite

NARCIS (Netherlands)

Soeters, Maarten R.; Serlie, Mireille J.; Sauerwein, Hans P.; Duran, Marinus; Ruiter, Jos P.; Kulik, Willem; Ackermans, Mariëtte T.; Minkler, Paul E.; Hoppel, Charles L.; Wanders, Ronald J. A.; Houten, Sander M.

2012-01-01

Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid

Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows.

Science.gov (United States)

Ceciliani, Fabrizio; Lecchi, Cristina; Urh, Christiane; Sauerwein, Helga

2018-04-30

The transition from late pregnancy to early lactation is a critical period in a dairy cow's life due to the rapidly increasing drain of nutrients from the maternal organism towards the foetus and into colostrum and milk. In order to cope with the challenges of parturition and lactation, comprehensive adaptive reactions comprising the endocrine and the immune system need to be accomplished. There is high variation in this coping ability and both metabolic and infectious diseases, summarized as "production diseases", such as hypocalcaemia (milk fever), fatty liver syndrome, laminitis and ketosis, may occur and impact welfare, productive lifespan and economic outcomes. Proteomics and metabolomics have emerged as valuable techniques to characterize proteins and metabolite assets from tissue and biological fluids, such as milk, blood and urine. In this review we provide an overview on metabolic status and physiological changes during the transition period and the related production diseases in dairy cows, and summarize the state of art on proteomics and metabolomics of biological fluids and tissues involved in metabolic stress during the peripartum period. We also provide a current and prospective view of the application of the recent achievements generated by omics for biomarker discovery and their potential in diagnosis. For high-yielding dairy cows there are several "occupational diseases" that occur mainly during the metabolic challenges related to the transition from pregnancy to lactation. Such diseases and their sequelae form a major concern for dairy production, and often lead to early culling of animals. Beside the economical perspective, metabolic stress may severely influence animal welfare. There is a multitude of studies about the metabolic backgrounds of such so called production diseases like ketosis, fatty liver, or hypocalcaemia, although the investigations aiming to assess the complexity of the pathophysiological reactions are largely focused on gene

Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

Directory of Open Access Journals (Sweden)

Rebecca C Schugar

Full Text Available Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666 that is very high in fat (~94% kcal, very low in carbohydrate (~1% kcal, low in protein (~5% kcal, and choline restricted (~300 mg/kg provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal and choline contents (300 mg/kg vs. 5 g/kg. C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.

Science.gov (United States)

Rieger, Johannes; Bähr, Oliver; Maurer, Gabriele D; Hattingen, Elke; Franz, Kea; Brucker, Daniel; Walenta, Stefan; Kämmerer, Ulrike; Coy, Johannes F; Weller, Michael; Steinbach, Joachim P

2014-06-01

Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (pketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

Role of β-hydroxybutyrate, its polymer poly-β-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease

Directory of Open Access Journals (Sweden)

Elena N. Dedkova

2014-07-01

Full Text Available We provide a comprehensive review of the role of β-hydroxybutyrate (β-OHB, its linear polymer poly-β-hydroxybutyrate (PHB and inorganic polyphosphate (polyP in mammalian health and disease. β-OHB is a metabolic intermediate that constitutes 70% of ketone bodies produced during ketosis. Although ketosis has been generally considered as an unfavorable pathological state (e.g. diabetic ketoacidosis in type-1 diabetes mellitus, it has been suggested that induction of mild hyperketonemia may have certain therapeutic benefits. β-OHB is synthesized in the liver from acetyl-CoA by β-hydroxybutyrate dehydrogenase and can be used as alternative energy source. Elevated levels of PHB are associated with pathological states. In humans, short-chain, complexed PHB (cPHB is found in a wide variety of tissues and in atherosclerotic plaques. Plasma cPHB concentrations correlate strongly with atherogenic lipid profiles, and PHB tissue levels are elevated in type-1 diabetic animals. However, little is known about mechanisms of PHB action especially in the heart. In contrast to β-OHB, PHB is a water-insoluble, amphiphilic polymer that has high intrinsic viscosity and salt-solvating properties. cPHB can form non-specific ion channels in planar lipid bilayers and liposomes. PHB can form complexes with polyP and Ca2+ which increases membrane permeability. The biological roles played by polyP, a ubiquitous phosphate polymer with ATP-like bonds, have been most extensively studied in prokaryotes, however polyP has recently been linked to a variety of functions in mammalian cells, including blood coagulation, regulation of enzyme activity in cancer cells, cell proliferation, apoptosis and mitochondrial ion transport and energy metabolism. Recent evidence suggests that polyP is a potent activator of the mitochondrial permeability transition pore in cardiomyocytes and may represent a hitherto unrecognized key structural and functional component of the mitochondrial

ß-Hydroxybutyrate Activates the NF-κB Signaling Pathway to Promote the Expression of Pro-Inflammatory Factors in Calf Hepatocytes

Directory of Open Access Journals (Sweden)

Xiaoxia Shi

2014-01-01

Full Text Available Background/Aims: ß-hydroxybutyrate (BHBA is the major component of ketone bodies in ketosis. Dairy cows with ketosis often undergo oxidative stress. BHBA is related to the inflammation involved in other diseases of dairy cattle. However, whether BHBA can induce inflammatory injury in dairy cow hepatocytes and the potential mechanism of this induction are not clear. The NF-κB pathway plays a vital role in the inflammatory response. Methods: Therefore, this study evaluated the oxidative stress, pro-inflammatory factors and NF-κB pathway in cultured calf hepatocytes treated with different concentrations of BHBA, pyrrolidine dithiocarbamate (PDTC, an NF-κB pathway inhibitor and N-acetylcysteine (NAC, antioxidant. Results: The results showed that BHBA could significantly increase the levels of oxidation indicators (MDA, NO and iNOS, whereas the levels of antioxidation indicators (GSH-Px, CAT and SOD were markedly decreased in hepatocytes. The IKKß activity and phospho-IκBa (p-IκBa contents were increased in BHBA-treated hepatocytes. This increase was accompanied by the increased expression level and transcription activity of p65. The expression levels of NF-κB-regulated inflammatory cytokines, namely TNF-a, IL-6 and IL-1ß, were markedly increased after BHBA treatment, while significantly decreased after NAC treatment. However, the p-IκBa level and the expression and activity of p65 and its target genes were markedly decreased in the PDTC + BHBA group compared with the BHBA (1.8 mM group. Moreover, immunocytofluorescence of p65 showed a similar trend. Conclusion: The present data indicate that higher concentrations of BHBA can induce cattle hepatocyte inflammatory injury through the NF-κB signaling pathway, which may be activated by oxidative stress.

[Enterobiasis in pediatric subjects in north-western Italy: a study of home remedies].

Science.gov (United States)

Dutto, M; Montù, D; Raineri, G

2012-01-01

The present study examines the most common home remedies in the Piedmont region of northwest Italy currently used in the treatment of pediatric enterobiasis, commonly known as pinworm infection. The remedies in question, typically based on popular beliefs and as such are nearly useless, were noted through interviews with subjects who had come to the local Hygiene and Public Health Services offices for information about pinworm prevention and treatment. Analysis of replies by the subjects clearly indicates that local families are ill-prepared to recognize the symptoms this parasitic infection; often it is confused with pediatric ketosis, therefore leading to inappropriate treatment which at times may be potentially harmful to the patient.

PERAWATAN GIGI PADA ANAK DENGAN MAPLE SYRUP URINE DISEASE (LAPORAN KASUS

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Tri Fajari

2015-07-01

Full Text Available Maple Syrup Urine Disease is a disparity of leusin decarboxilation, and isoleusin of valin defect that is synthesized with complex enzyme systems. It is a rare disease and represents disparity. In some cases can generate ketosis that grows according to health change and can cause comma. Dental treatment of a child with Maple Syrup Urine Disease was not clearly mentioned, there is only a factor such as infection, which is very dangerous at any age, and can generate irregular metabolism. Dental treatment of a child with Maple Syrup Urine Disease accompanied by mental retardation must be done continuously to avoid infection that can result in the death of the patients.

Euglycemic diabetic ketoacidosis in pregnancy

International Nuclear Information System (INIS)

Tarif, N.; Al-Badr, W.

2007-01-01

Diabetic ketoacidosis (DKA) can be a catastrophic event during pregnancy, complicating almost nine percent of diabetics in pregnancy. It includes both maternal and fetal mortality. Ketosis has been implicated in fetal distress and causes adverse neurological outcome. DKA with relatively low blood sugar levels is called euglycemic DKA, which is a rare entity and reported usually in type I diabetic patients. A 37-years-old Saudi female patient known to have type II diabetes developed euglycemic [blood glucose level 4.3 mmol/L (78 mg/dl) DKA while in her fifth pregnancy. She responded to intravenous dextrose and insulin with gradual improvement. Euglycemic DKA should be considered in type II diabetics during pregnancy and treated promptly. (author)

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes.

Science.gov (United States)

Kanikarla-Marie, Preeti; Jain, Sushil K

2016-06-01

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute starvation ketoacidosis in pregnancy with severe hypertriglyceridemia: A case report.

Science.gov (United States)

Hui, Li; Shuying, Li

2018-05-01

Pregnant women are more prone to ketosis due to the relative insulin resistance, accelerated lipolysis and increased free fatty acids. We report a pregnant woman with hyperlipidemia, who experienced severe metabolic acidosis after a short period of starvation. Based on her clinical symptoms, exclusion diagnosis and therapeutic diagnosis, her condition was diagnosed as starvation ketoacidosis. An emergency caesarean section under general anesthesia was implemented 2 hours after her admission. The metabolic acidosis was treated with fluid resuscitation using compound sodium lactate, bicarbonate, and 5% dextrose together with insulin 6U. Both mother and baby were discharged clinically well. Starvation ketoacidosis may happen in special patient who was in pregnancy and with severe hypertriglyceridemia, after just one day fasting and vomiting.

Bilateral dystonia in type 1 diabetes: a case report

Directory of Open Access Journals (Sweden)

Yasuhara Akihiro

2008-11-01

Full Text Available Abstract Introduction Diabetic hemichorea-hemiballismus is a rare complication of type 2 diabetes. Here, we report a case with type 1 diabetes, with hemichorea and bilateral dystonia manifested as hyperglycemia-induced involuntary movement. Case presentation A 62-year-old Japanese women with body weight loss of 30 kg during the past year developed symptoms of thirst, polydipsia and polyuria. She also presented with hemichorea and bilateral dystonia for 5 days and extremely high plasma glucose (774 mg/dl, hemoglobin A1c (21.2% and glycated albumin (100% with ketosis. Based on the presence of glutamic acid decarboxylase antibodies (18,000 U/ml; normal Conclusion Hyperglycemia-induced involuntary movement is one of the manifestations of dystonia and hemichorea-hemiballism.

The inverse problem of brain energetics: ketone bodies as alternative substrates

Energy Technology Data Exchange (ETDEWEB)

Calvetti, D; Occhipinti, R [Case Western Reserve University, Department of Mathematics, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Somersalo, E [Helsinki University of Technology, Institute of Mathematics, P. O. Box 1100, FIN-02015 HUT (Finland)], E-mail: daniela.calvetti@case.edu, E-mail: rossana.occhipinti@case.edu, E-mail: erkki.somersalo@tkk.fi

2008-07-15

Little is known about brain energy metabolism under ketosis, although there is evidence that ketone bodies have a neuroprotective role in several neurological disorders. We investigate the inverse problem of estimating reaction fluxes and transport rates in the different cellular compartments of the brain, when the data amounts to a few measured arterial venous concentration differences. By using a recently developed methodology to perform Bayesian Flux Balance Analysis and a new five compartment model of the astrocyte-glutamatergic neuron cellular complex, we are able to identify the preferred biochemical pathways during shortage of glucose and in the presence of ketone bodies in the arterial blood. The analysis is performed in a minimally biased way, therefore revealing the potential of this methodology for hypothesis testing.

The inverse problem of brain energetics: ketone bodies as alternative substrates

International Nuclear Information System (INIS)

Calvetti, D; Occhipinti, R; Somersalo, E

2008-01-01

Little is known about brain energy metabolism under ketosis, although there is evidence that ketone bodies have a neuroprotective role in several neurological disorders. We investigate the inverse problem of estimating reaction fluxes and transport rates in the different cellular compartments of the brain, when the data amounts to a few measured arterial venous concentration differences. By using a recently developed methodology to perform Bayesian Flux Balance Analysis and a new five compartment model of the astrocyte-glutamatergic neuron cellular complex, we are able to identify the preferred biochemical pathways during shortage of glucose and in the presence of ketone bodies in the arterial blood. The analysis is performed in a minimally biased way, therefore revealing the potential of this methodology for hypothesis testing

The inverse problem of brain energetics: ketone bodies as alternative substrates

Science.gov (United States)

Calvetti, D.; Occhipinti, R.; Somersalo, E.

2008-07-01

Little is known about brain energy metabolism under ketosis, although there is evidence that ketone bodies have a neuroprotective role in several neurological disorders. We investigate the inverse problem of estimating reaction fluxes and transport rates in the different cellular compartments of the brain, when the data amounts to a few measured arterial venous concentration differences. By using a recently developed methodology to perform Bayesian Flux Balance Analysis and a new five compartment model of the astrocyte-glutamatergic neuron cellular complex, we are able to identify the preferred biochemical pathways during shortage of glucose and in the presence of ketone bodies in the arterial blood. The analysis is performed in a minimally biased way, therefore revealing the potential of this methodology for hypothesis testing.

Molecular insights into the mechanisms of liver-associated diseases in early-lactating dairy cows: hypothetical role of endoplasmic reticulum stress.

Science.gov (United States)

Ringseis, R; Gessner, D K; Eder, K

2015-08-01

The transition period represents the most critical period in the productive life of high-yielding dairy cows due to both metabolic and inflammatory stimuli, which challenge the liver and predispose dairy cows to develop liver-associated diseases such as fatty liver and ketosis. Despite the fact that all high-yielding dairy cows are affected by marked metabolic stress due to a severe negative energy balance (NEB) during early lactation, not all cows develop liver-associated diseases. Although the reason for this is largely unknown, this indicates that the capacity of the liver to cope with metabolic and inflammatory challenges varies between individual high-yielding dairy cows. Convincing evidence exists that endoplasmic reticulum (ER) stress plays a key role in the development of fatty liver, and it has been recently shown that ER stress occurs in the liver of high-yielding dairy cows. This indicates that ER stress may be involved in the development of liver-associated diseases in dairy cows. The present review shows that the liver of dairy cows during early lactation is exposed to several metabolic and inflammatory challenges, such as non-esterified fatty acids, tumour necrosis factor α, interleukin-1β, reactive oxygen species and lipopolysaccharides, which are known inducers of ER stress. Thus, ER stress may represent a molecular basis for fatty liver development and account for the frequent occurrence of fatty liver and ketosis in high-yielding dairy cows. Interindividual differences between dairy cows in the activation of hepatic stress response pathways, such as nuclear factor E2-related factor 2, which is activated during ER stress and reduces the sensitivity of tissues to oxidative and inflammatory damage, might provide an explanation at the molecular level for differences in the capacity to cope with pathological inflammatory challenges during early lactation and the susceptibility to develop liver-associated diseases between early-lactating dairy cows

Transition diseases in grazing dairy cows are related to serum cholesterol and other analytes.

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Pilar Sepúlveda-Varas

Full Text Available The objectives of this study were to describe the incidence of postpartum disease and to evaluate the association with serum cholesterol concentrations during the first 3 weeks after calving in grazing dairy cows. The association between non-esterified fatty acids (NEFA, β-hydroxybutyrate (BHBA, calcium and postpartum diseases was also evaluated. A total of 307 Holstein dairy cows from 6 commercial grazing herds in Osorno, Chile, were monitored from calving until 21 days in milk. Cases of retained placenta, clinical hypocalcemia and clinical mastitis were recorded by the farmer using established definitions. Twice weekly, cows were evaluated for metritis by the same veterinarian based on vaginal discharge and body temperature. Postpartum blood samples were collected weekly and analyzed for serum concentrations of cholesterol, NEFA, BHBA and calcium. Cows were considered as having subclinical ketosis if BHBA >1.2 mmol/L, and subclinical hypocalcemia if calcium <2.0 mmol/L in any of the 3 weekly samples. Overall, 56% of the cows studied developed at least one clinical or subclinical disease after calving. Incidence of individual diseases was 8.8% for retained placenta, 4.2% for clinical hypocalcemia, 11.7% for clinical mastitis, 41.1% for metritis, 19.9% for subclinical hypocalcemia and 16.6% for subclinical ketosis. Lower postpartum cholesterol in cows was associated with developing severe metritis or having more than one clinical disease after calving. For every 0.4 mmol/L decrease in serum cholesterol cows were nearly twice as likely to be diagnosed with multiple clinical diseases after calving. Higher BHBA concentrations and lower calcium concentrations during week 1 were associated with severe cases of metritis. Low serum calcium concentration during week 1 was also associated with developing more than one clinical disorder after calving. In conclusion, the incidence of postpartum diseases can be high even in grazing herds and lower serum

Diabetes classification: grey zones, sound and smoke: Action LADA 1

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Leslie, R D G; Kolb, H; Schloot, N C

2008-01-01

-insulin-requiring diabetes, an islet autoantibody such as glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA), and no need for insulin treatment for several months post-diagnosis. But while some would split diabetes into distinct subtypes, there is a strong case......Diseases gain identity from clinical phenotype as well as genetic and environmental aetiology. The definition of type 1 diabetes is clinically exclusive, comprising patients who are considered insulin dependent at diagnosis, whilst the definition of type 2 diabetes is inclusive, only excluding...... those who are initially insulin dependent. Ketosis-prone diabetes (KPD) and latent autoimmune diabetes in adults (LADA) are each exclusive forms of diabetes which are, at least initially, clinically distinct from type 2 diabetes and type 1 diabetes, and each have a different natural history from...

Ketogenic diet in endocrine disorders: Current perspectives

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Gupta, L; Khandelwal, D; Kalra, S; Gupta, P; Dutta, D; Aggarwal, S

2017-01-01

Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.” PMID:29022562

Ketogenic diet in endocrine disorders: Current perspectives

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L Gupta

2017-01-01

Full Text Available Ketogenic diet (KD is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.”

Effect of diet on maintenance of acid-basal balance in blood of dairy cows

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Gaál T.

2003-01-01

Full Text Available High-performance breeds of ruminants often exhibit production disorders which can be accompanied by a disturbed acid-basal balance. Most of the disorders in the acid-basal balance are closely related to digressions in the diet norms of these animals. A deficiency or surplus of energy equally cause disorders in the acid-basal status of the organism. Metabolic acidosis is the most frequent of the four types of basic disorders in the acid-basal balance in ruminants. It appears as a consequence of rumen acidosis, ketosis, or diarrhea. Acute disorders in the acid-basal balance are far more dangerous than chronic ones. Therapy of the basic diseases is generally sufficient compensation for the effects of the acid-basal disorders, but in certain cases it is necessary to perform alkalization, that is, acidification of the rumen content using the necessary preparations.

Biochemical adaptation of camelids during periods where feed is withheld

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J. Wensvoort

2001-03-01

Full Text Available Biochemical changes during fasting or the withholding of feed for 5 day were studied in serum of camelids (dromedary camel, llama and ruminants (sheep, steers. Camels maintained low levels of 13-hydroxybutyrate (BHB and high levels of glucose but showed some increased levels of non-esterified fatty acid (NEFA and urea when fasting. Sheep and steers showed a rise in serum BHB and much higher increases of NEFA than camels and llamas. Sheep showed decreased serum glucose. The llama showed some increase in BHB but NEFA was lower than the other three species. The results indicate that camelids have a unique ability to control lipolytic and gluconeogenic activity to prevent or postpone the state of ketosis. Understanding and manipulation of these metabolic mechanisms in cattle and sheep could have great benefit to the livestock industry.

Diabetes, insulin and exercise

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Richter, Erik; Galbo, H

1986-01-01

The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so......-called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

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Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

2013-02-15

During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

Neuronal-glial interactions in rats fed a ketogenic diet.

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Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

2006-01-01

Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

Glucose concentration in capillary blood of dairy cows obtained by a minimally invasive lancet technique and determined with three different hand-held devices.

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Mair, B; Drillich, M; Klein-Jöbstl, D; Kanz, P; Borchardt, S; Meyer, L; Schwendenwein, I; Iwersen, M

2016-02-24

Dairy cows have a massive demand for glucose at the onset of lactation. A poor adaption to this period leads to an excessive negative energy balance with an increased risk for ketosis and impaired animal health and production. Besides the measurement of ketones, analysing the glucose concentration in blood is reported as helpful instrument for diagnosis and differentiation of ketosis. Monitoring metabolic parameters requires multiple blood sampling. In other species, new blood sampling techniques have been introduced in which small amounts of blood are rapidly analysed using electronic hand-held devices. The objective of this study was to evaluate the suitability of capillary blood for blood glucose measurement in dairy cows using the hand-held devices FreeStyle Precision (FSP, Abbott), GlucoMen LX Plus (GLX, A. Menarini) and the WellionVet GLUCO CALEA, (WGC, MED TRUST). In total, 240 capillary blood samples were obtained from dry and fresh lactating Holstein-Friesian cows. Blood was collected from the skin of the exterior vulva by using a lancet. For method comparison, additional blood samples were taken from a coccygeal vessel and analyzed in a laboratory. Glucose concentrations measured by a standard laboratory method were defined as the criterion standard. The Pearson correlation coefficients between the glucose concentrations analyzed in capillary blood with the devices and the reference were 73% for the FSP, 81% for the GLX and 41% for the WGC. Bland-Altman plots showed biases of -18.8 mg/dL for the FSP, -11.2 mg/dL for the GLX and +20.82 mg/dL for the WGC. The optimized threshold determined by a Receiver Operating Characteristics analysis to detect hyperglycemia using the FSP was 43 mg/dL with a sensitivity (Se) and specificity (Sp) of 76 and 80%. Using the GLX and WGC optimized thresholds were 49 mg/dL (Se = 92%, Sp = 85%) and 95 mg/dL (Se = 39%, Sp = 92%). The results of this study demonstrate good performance characteristics for the GLX

Intermittent metabolic switching, neuroplasticity and brain health

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Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

2018-01-01

During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

Bedside ketone determination in diabetic children with hyperglycemia and ketosis in the acute care setting.

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Ham, Melissa R; Okada, Pamela; White, Perrin C

2004-03-01

Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus marked by characteristic biochemical derangements. Diagnosis and management involve frequent evaluation of these biochemical parameters. Reliable bedside equivalents for these laboratory studies may help reduce the time to treatment and reduce costs. We evaluated the precision and bias of a bedside serum ketone meter in the acute care setting. Serum ketone results using the Precision Xtra glucometer/ketone meter (Abbott Laboratories, MediSense Products Inc., Bedford, MA, USA) correlated strongly with the Children's Medical Center of Dallas' laboratory values within the meter's value range. Meter ketone values steadily decreased during the treatment of DKA as pH and CO(2) levels increased and acidosis resolved. Therefore, the meter may be useful in monitoring therapy for DKA. This meter may also prove useful in identifying patients at risk for DKA in physicians' offices or at home.

Epidemiology of diabetes mellitus in Hiroshima and Nagasaki

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Freedman, L R; Blackard, W G; Sagan, L A; Ishida, Morihiro; Hamilton, H B

1965-06-10

Data have been presented on the finding of glycosuria and the diagnosis of diabetes mellitus during four years of a long-term study of the health of population samples of Hiroshima and Nagasaki. Diabetes and glycosuria are much more common in Hiroshima than in Nagasaki and in both cities these findings are more frequent in males than in females. The prevalence of diabetes appears to be increasing in Hiroshima males. Findings in diabetics were compared with nondiabetics. In general, Japanese diabetics are similar to diabetics in other countries concerning their increased risk of obesity, hypertension, proteinuria, hypercholesterolemia, and cardiovascular and cerebrovascular diagnoses. This is of particular interest in the light of evidence that ketosis and severe abnormalities of carbohydrate metabolism are rare in Japan as compared to Western countries. Despite a lower prevalance of diabetes in Japanese females than in males, the abnormalities associated with diabetes appear to occur more commonly in female diabetics than in male diabetics.

Early Stage Prurigo Pigmentosa : A Case Report

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Emel ONAYGİL

2018-05-01

Full Text Available Prurigo pigmentosa is a rare inflammatory dermatosis that primarily affects adolescents and young adults. Even though it is most commonly seen in Japanese women, other countries have reported cases with increasing frequency. It is characterized by erythematous papules and macules on the trunk, neck and chest that resolve leaving a reticulate hyperpigmentation. Some endogenous factors related with ketosis like fasting, diet, diabetes, pregnancy and exogenous agents like chrome, nickel, para-amino compounds have been accused of playing a role in etiology. Here we would like to present a case of a 16-year-old female patient who was referred to our clinic with pruritic lesions on the trunk and neck, consistent with the initial phase of prurigo pigmentosa, after a period of strict diet. Prurigo pigmentosa is a disease with distinctive histologic and clinical features. Due to its rare occurrence, an accurate diagnosis may be particularly challenging. Clinicopathological correlation is therefore crucial in the diagnosis of the disease in its early phase.

Energetic status of crossbreed dairy cows during transition period in two different seasons

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T. F. Moreira

2015-10-01

Full Text Available ABSTRACTWe used 31 crossbreed dairy cows to compare the energetic profile in summer and winter. Blood samples were taken weekly prepartum, at calving and on days 2, 5, 10, 15, 21 and 30 postpartum. All metabolic indicators analyzed were influenced by the physiological status. The glucose concentrations were higher during winter while the triglyceride concentrations and lactate dehydrogenase (LDH were higher in the summer. The season influenced the concentrations of cholesterol, AST and GGT, showing a different pattern between summer and winter. Non-esterified fatty acids (NEFA and beta-hidroxibutirate (BHB were not influenced by the season. Cows that calved during winter had a greater body condition score (BCS and lost more BCS until calving. During summer, 32.26% of the animals and 29.03% during winter had NEFA concentrations above the optimum level and 22.58% of the animals in summer and 19.35% in the winter had subclinical ketosis at some point during the transition period, making then more susceptible to diseases.

A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

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Sahin Erdol MD

2016-05-01

Full Text Available Succinyl-CoA:3-oxoacid CoA transferase (SCOT deficiency is an autosomal recessive disorder of ketone body utilization that is clinically characterized with intermittent ketoacidosis crises. We report here the second Turkish case with SCOT deficiency. She experienced 3 ketoacidotic episodes: The first ketoacidotic crisis mimicked diabetic ketoacidosis because of the associated hyperglycemia. Among patients with SCOT deficiency, the blood glucose levels at the first crises were variable, and this case had the highest ever reported blood glucose level. She is a compound heterozygote with 2 novel mutations, c.517A>G (K173E and c.1543A>G (M515V, in exons 5 and 17 of the OXCT1 gene, respectively. In patient’s fibroblasts, SCOT activity was deficient and, by immunoblot analysis, SCOT protein was much reduced. The patient attained normal development and had no permanent ketosis. The accurate diagnosis of SCOT deficiency in this case had a vital impact on the management strategy and outcome.

Role of carbohydrate metabolism in grass tetany

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Miller, J.K.; Madsen, F.C.; Lentz, D.E.; Hansard, S.L.

1977-01-01

Clinical hypomagnesemia is confined primarily to beef cattle in the United States but also occurs in dairy cattle in other countries, probably due to different management practices. During periods when grass tetany is likely, early vegetative temperate zone grasses are usually low in total readily available carbohydrates and magnesium but high in potassium and nitrogen. The tetany syndrome may include hypoglycemia and ketosis, suggesting an imbalance in intermediary energy metabolism. Many enzyme systems critical to cellular metabolism, including those which hydrolyze and transfer phosphate groups, are activated by Mg. Thus, by inference, Mg is required for normal glucose utilization, fat, protein, nucleic acid and coenzyme synthesis, muscle contraction, methyl group transfer, and sulfate, acetate, and formate activation. Numerous clinical and experimental studies suggest an intimate relationship between metabolism of Mg and that of carbohydrate, glucagon, and insulin. The objective is to review this literature and suggest ways in which these relationships might contribute to a chain of events leading to grass tetany.

The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

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Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

2015-02-01

Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients. © The Author(s) 2014.

Ketogenic dietary therapy for epilepsy and other disorders: current perspectives

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Neal EG

2014-04-01

Full Text Available Elizabeth G Neal 1Matthew's Friends Clinics, Lingfield, UK, 2UCL Institute of Child Health, London, UK Abstract: The ketogenic diet (KD is a high-fat, restricted-carbohydrate regime, originally designed to mimic metabolic responses to fasting and has been used since the 1920s as a treatment for epilepsy. Modified variants of the KD include the addition of medium-chain triglyceride and less-restrictive modified Atkins and low glycemic index protocols. Scientifically proven as treatment for intractable seizures in children, these ketone-generating diets are increasingly also being used in adults. They are the treatment of choice in glucose transporter type 1 deficiency syndrome and pyruvate dehydrogenase deficiency. Evidence for the potential of KD therapy to be included within the treatment options for cancer and neurodegenerative disorders is more limited, albeit an exciting area of research with future clinical potential. This review discusses the key aspects of KD therapy, including the efficacy of treatments and clinical implementation. The importance of appropriate initiation, adequate clinical supervision, regular monitoring, and assessment of nutritional needs is highlighted. Keywords: diet, seizures, ketosis

Clinical survey to detect diabetes mellitus, Hiroshima

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Rudnick, P A; Anderson, Jr, P S

1961-07-19

Data from this study are in agreement with the general observations that diabetes is not uncommon in Japan. In an adult study population in Hiroshima 108 patients with diabetes were detected, yielding the prevalence rate of 3.02 percent. Nearly one-half of the patients were diagnosed initially as a result of the routine detection program. Although in females a trend with exposure is suggested by the raw data no statistically significant differences could be demonstrated. However, the size of the sample involved does not permit confident negative conclusions. Additional clinical and laboratory observations were completed in order to characterize the manifestation of diabetes in these subjects. Late manifestations of diabetes frequently were found, but atherosclerotic complications were nonexistent. This is considered to be related to the low fat, high carbohydrate diet of the Japanese. The lack of ketosis, apparently low prevalence rate for juveniles, and male preponderance suggest that diabetes in Japan differs from the disease found in many Western countries. 69 references, 1 figure, 9 tables.

IMPROVEMENT OF THE BIOCHEMICAL AND METABOLIC BIOMARKERS IN RESPONSE TO THE THERAPEUTIC MANAGEMENT IN KETOTIC DAIRY COWS

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S. Biswal

2017-06-01

Full Text Available The aim of this study was to investigate the changes in biochemical and metabolic biomarkers in urine, milk and blood of ketotic dairy cows in and around Bhubaneswar, Odisha, India, before and after treatment. Thirty of 100 ketotic cows identified from a population of 1014 cows were equally divided into three groups of 10 animals each while group IV selected from the population under investigation was treated as control. Following treatment in group III, the ALT, AST, ALP and LDH levels observed in ketotic animals at pre-treatment were decreased maximum at post-treatment. It can be concluded that the treatment package comprising of Dextrose (25% intravenously, sodium propionate (orally, liver extract with vitamin B complex injection intramuscularly, dexamethasone injection intravenously and insulin injection subcutaneously practiced in group III was the most efficacious and superior to group I and II in the treatment of bovine ketosis for bringing the biochemical profiles to normal. The therapeutic regimen of group III exhibited better performance than other groups might be due to the synergistic therapeutic effect of insulin in glucose metabolism.

Free radical activity during development of insulin-dependent diabetes mellitus in the rat

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Pitkaenen, O.M.; Akerblom, H.K.; Sariola, H.; Andersson, S.M. (Univ. of Helsinki (Finland)); Martin, J.M. (Hospital for Sick Children, Toronto, Ontario (Canada)); Hallman, M. (Univ. of California, Irvine (United States))

1991-01-01

Free radical-induced lipid peroxidation was quantified by measuring expired pentane from diabetic prone BB Wistar rats of 45-90 d of age. Insulin-dependent diabetes mellitus was manifest at the age of 71 {plus minus} 8 d. Expired pentane increased from 2.1 {plus minus} 0.7 to 5.0 {plus minus}3.0 pmol/100g/min (p <0.01) at manifestation of the disease and remained high throughout the test period. In healthy age-matched control rats it persisted low. In rats made diabetic with streptozotocin, expired pentane remained low. The changes in expired pentane suggest that the development of endogenous insulin-dependent diabetes mellitus in BB rats is associated with increased free radical activity. This is not due to hyperglycemia or ketosis per se, and reflects a fundamental difference in the free radical activity between the spontaneously diabetic BB rats and the disease produced by streptozotocin. Development of spontaneous insulin-dependent diabetes in BB rats is associated with increased free radical activity that persists after the manifestation of the disease.

Serum calcium and magnesium level in dairy cows at calving

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A.M. Pulimeno

2011-03-01

Full Text Available Milk fever and hypocalcaemia are post-partum metabolic diseases affecting about 6% of dairy cows and are due to a fail of the homeostatic metabolism regulating the calcium blood level around 9 and 10mg/100mL. The calcium drainage to the mammary gland along with the reduced capacity of the animal to mobilize calcium from bone reserve lead to a drop of the calcium blood level under 5-6mg/100mL with paresis like clinical symptoms known as milk fever. The incidence of the clinical milk fever is low, however the occurrence of mild hypocalcaemia (subclinical could be as high as 15- 20% within few days after calving, particularly in multiparous cows. The hypocalcaemia status as for the reduced bone calcium mobilization and intestinal absorption leads to reduced feed intake and make it a good start for ketosis, retained placenta, displaced abomasums and mastitis problems (Beede, 1991. The acid-base balance of the cow in the late pregnancy is determinant for hypocalcaemia............

Ramadan and diabetes: As-Saum (The fasting

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Mohammed Abdul Jaleel

2011-01-01

Full Text Available Ramadan, the ninth month of Islamic lunar calendar, is marked by religious ritual of fasting from early dawn till sunset by Muslims. Islam has allowed many categories of people to be exempt totally or temporarily from fasting. Patients with uncontrolled diabetes face possible major metabolic risks including hypoglycemia, hyperglycemia with or without the risk of impending ketosis, dehydration, and thrombosis. Diabetics can be stratified into four categories based on their level of risk associated with fasting. The recommended ruling for persons in categories 1 and 2 is that they are prohibited from fasting to prevent harming themselves based on the certainty or the preponderance of probability that harm will occur, whereas the recommended ruling for those in categories 3 and 4 is that they should fast. The strategies to ensure safety of diabetics who are planning to fast include Ramadan-focused patient education, pre-Ramadan medical assessment, following a healthy diet and physical activity pattern, physician-recommended modifications in medication protocol and therapeutic recommendations and checking blood glucose as and when required.

Diabetes mellitus in the young: Gliptins or sulfonylurea after metformin?

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J Muthukrishnan

2012-01-01

Full Text Available Introduction: Diagnosis and initial management of diabetes mellitus (DM in the young are clinical dilemma. Gliptins may be a safer and more effective option than sulfonylureas. Few Indian studies have addressed this issue of clinical relevance. Aim: To compare the use of sitagliptin and glimepiride as early add-on drugs along with metformin in young patients with DM to achieve optimum glycemic targets. Methods: This was a prospective, open-label, cohort study set in a tertiary care hospital in North India. Newly diagnosed patients of DM ≤35 year of age were initially treated to pre-defined glycemic goals (Fasting plasma glucose (FPG 70-130, post prandial glucose (PPG 180, PPG > 250 mg/dl with/without catabolic symptoms/ketosis were withdrawn. Results: Sitagliptin with metfromin and metfromin alone group fared better than the glimepiride group for glycemic control, lesser treatment failures, and less weight gain. Conclusion : In this limited study, we found that sitagliptin is a safer and more effective option in young, newly diagnosed patients with DM. Findings of this study are relevant for clinical practice in Indian setting.

Sodium-glucose co-transporter-2 inhibitors and euglycemic ketoacidosis: Wisdom of hindsight

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Awadhesh Kumar Singh

2015-01-01

Full Text Available Sodium-glucose co-transporter-2 inhibitors (SGLT-2i are newly approved class of oral anti-diabetic drugs, in the treatment of type 2 diabetes, which reduces blood glucose through glucouresis via the kidney, independent, and irrespective of available pancreatic beta-cells. Studies conducted across their clinical development program found, a modest reduction in glycated hemoglobin ranging from −0.5 to −0.8%, without any significant hypoglycemia. Moreover, head-to-head studies versus active comparators yielded comparable efficacy. Interestingly, weight and blood pressure reduction were additionally observed, which was not only consistent but significantly superior to active comparators, including metformin, sulfonylureas, and dipeptydylpeptide-4 inhibitors. Indeed, these additional properties makes this class a promising oral anti-diabetic drug. Surprisingly, a potentially fatal unwanted side effect of diabetic ketoacidosis has been noted with its widespread use, albeit rarely. Nevertheless, this has created a passé among the clinicians. This review is an attempt to pool those ketosis data emerging with SGLT-2i, and put a perspective on its implicated mechanism.

On-farm evaluation of the effect of metabolic diseases on the shape of the lactation curve in dairy cows through the MilkBot lactation model.

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Hostens, M; Ehrlich, J; Van Ranst, B; Opsomer, G

2012-06-01

The effects of metabolic diseases (MD) occurring during the transition period on milk production of dairy cows have been evaluated in many different ways, often with conflicting conclusions. The present study used a fitted lactation model to analyze specific aspects of lactation curve shape and magnitude in cows that avoided culling or death in the first 120 d in milk (DIM). Production and health records of 1,946 lactations in a 1-yr follow-up study design were collected from a transition management facility in Germany to evaluate both short- and long-term effects of MD on milk production. Milk production data were fitted with the nonlinear MilkBot lactation model, and health records were used to classify cows as healthy (H), affected by one MD (MD), or by multiple MD (MD+). The final data set contained 1,071 H, 348 MD, and 136 MD+ cows, with distinct incidences of 3.7% twinning, 4.8% milk fever, 3.6% retained placenta, 15.4% metritis, 8.3% ketosis, 2.0% displaced abomasum, and 3.7% mastitis in the first 30 DIM. The model containing all healthy and diseased cows showed that lactations classified as H had milk production that increased faster (lower ramp) and also declined faster (lower persistence) compared with cows that encountered one or more metabolic problems. The level of production (scale) was only lowered in MD+ cows compared with H and MD cows. Although the shape of the lactation curve changed when cows encounter uncomplicated (single) MD or complicated MD (more than one MD), the slower increase to a lower peak seemed to be compensated for by greater persistency, resulting in the overall 305-d milk production only being lowered in MD+ cows. In the individual disease models, specific changes in the shape of the lactation curve were found for all MD except twinning. Milk fever, retained placenta, ketosis, and mastitis mainly affected the lactation curve when accompanied by another MD, whereas metritis and displaced abomasum affected the lactation curve

Completeness of metabolic disease recordings in Nordic national databases for dairy cows.

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Espetvedt, M N; Wolff, C; Rintakoski, S; Lind, A; Østerås, O

2012-06-01

The four Nordic countries Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) all have national databases where diagnostic events in dairy cows are recorded. Comparing and looking at differences in disease occurrence between countries may give information on factors that influence disease occurrence, optimal diseases control and treatment strategies. For such comparisons to be valid, the data in these databases should be standardised and of good quality. The objective of the study presented here was to assess the quality of metabolic disease recordings, primarily milk fever and ketosis, in four Nordic national databases. Completeness of recording figures of database registrations at two different levels was chosen as a measure of data quality. Firstly, completeness of recording of all disease events on a farm regardless of veterinary involvement, called 'Farmer observed completeness', was determined. Secondly, completeness of recording of veterinary treated disease events only, called 'Veterinary treated completeness', was determined. To collect data for calculating these completeness levels a simple random sample of herds was obtained in each country. Farmers who were willing to participate, recorded for 4 months in 2008, on a purpose made registration form, any observed illness in cows, regardless of veterinary involvement. The number of participating herds was 105, 167, 179 and 129 in DK, FI, NO and SE respectively. In total these herds registered 247, 248, 177 and 218 metabolic events for analysis in DK, FI, NO and SE, respectively. Data from national databases were subsequently extracted, and the two sources of data were matched to find the proportion, or completeness, of diagnostic events registered by farmers that also existed in national databases. Matching was done using a common diagnostic code system and allowed for a discrepancy of 7 days for registered date of the event. For milk fever, the Farmer observed completeness was 77%, 67%, 79% and 79

An audit of the contribution to post-mortem examination diagnosis of individual analyte results obtained from biochemical analysis of the vitreous.

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Mitchell, Rebecca; Charlwood, Cheryl; Thomas, Sunethra Devika; Bellis, Maria; Langlois, Neil E I

2013-12-01

Biochemical analysis of the vitreous humor from the eye is an accepted accessory test for post-mortem investigation of cause of death. Modern biochemical analyzers allow testing of a range of analytes from a sample. However, it is not clear which analytes should be requested in order to prevent unnecessary testing (and expense). The means and standard deviation of the values obtained from analysis of the vitreous humor for sodium, potassium, chloride, osmolality, glucose, ketones (β-hydroxybutyrate), creatinine, urea, calcium, lactate, and ammonia were calculated from which the contribution of each analyte was reviewed in the context of post-mortem findings and final cause of death. For sodium 32 cases were regarded as high (more than one standard deviation above the mean), from which 9 contributed to post-mortem diagnosis [drowning (4), heat related death (2), diabetic hyperglycemia (2), and dehydration (1)], but 25 low values (greater than one standard deviation below the mean) made no contribution. For chloride 29 high values contributed to 4 cases--3 drowning and 1 heat-related, but these were all previously identified by a high sodium level. There were 29 high and 35 low potassium values, none of which contributed to determining the final cause of death. Of 22 high values of creatinine, 12 contributed to a diagnosis of renal failure. From 32 high values of urea, 18 contributed to 16 cases of renal failure (2 associated with diabetic hyperglycemia), 1 heat-related death, and one case with dehydration. Osmolarity contributed to 12 cases (5 heat-related, 4 diabetes, 2 renal failure, and 1 dehydration) from 36 high values. There was no contribution from 32 high values and 19 low values of calcium and there was no contribution from 4 high and 2 low values of ammonia. There were 11 high values of glucose, which contributed to the diagnosis of 6 cases of diabetic hyperglycemia and 21 high ketone levels contributed to 8 cases: 4 diabetic ketosis, 3 hypothermia, 3

Thresholds of whole-blood β-hydroxybutyrate and glucose concentrations measured with an electronic hand-held device to identify ovine hyperketonemia.

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Pichler, M; Damberger, A; Schwendenwein, I; Gasteiner, J; Drillich, M; Iwersen, M

2014-03-01

Metabolic disorders, especially hyperketonemia, are very common in dairy sheep. The whole-blood concentrations of β-hydroxybutyrate (BHBA) and glucose can be determined by commercially available electronic hand-held devices, which are used in human medicine and for the detection of ketosis in dairy cows. The aim of this study was to evaluate the suitability of the hand-held device Precision Xceed (PX; Abbott Diabetes Care Inc., Abbott Park, IL) to detect hyperketonemia in ewes. An additional objective of this study was to evaluate the agreement between samples obtained by minimal invasive venipuncture of an ear vein and measurements of whole-blood samples from the jugular vein (vena jugularis, v. jug.). Blood samples taken from the v. jug. were collected from 358 ewes on 4 different farms. These samples and a blood drop obtained from an ear vein were analyzed simultaneously on farm with the PX. For method comparison, the samples obtained from the v. jug. were also analyzed by standard methods, which served as the gold standard at the Central Laboratory of the University of Veterinary Medicine Vienna, Austria. The correlation coefficients between the serum BHBA concentration and the concentrations measured with the hand-held meter in the whole blood from an ear vein and the v. jug. were 0.94 and 0.96, respectively. The correlation coefficients of plasma and whole-blood glucose concentration were 0.68 for the v. jug. and 0.47 for the ear vein. The mean glucose concentration was significantly lower in animals classified as hyperketonemic (BHBA ≥ 1.6 mmol/L) compared with healthy ewes. Whole-blood concentrations of BHBA and glucose measured with the PX from v. jug. showed a constant negative bias of 0.15 mmol/L and 8.4 mg/dL, respectively. Hence, a receiver operating characteristic analysis was performed to determine thresholds for the PX to detect hyperketonemia in ewes. This resulted in thresholds for moderate ketosis of BHBA concentrations of 0.7 mmol/L in blood

Internist, anesthesiologist and surgeon use of ketogenic diet.

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Cenci, Lorenzo; Paoli, Antonio; Omar, Hesham R; Dalvi, Prachiti; Camporesi, Enrico M; Mangar, Devanand; Quartesan, Silvia; Fiorito, Alberto; Bosco, Gerardo

2018-03-01

Ketogenic diet is being increasingly utilized in recent decades because of its success as an effective tool for short and intermediate-term weight loss. Promoting physiological ketosis from a drastically low carbohydrate diet is the fundamental basis for this diet regime. Though debated, these diets have been demonstrated to be effective, at least in the short- to medium terms, to manage excess weight, hyperlipidemia, and other cardiovascular risk factors. We reviewed the cardiovascular, metabolic, anesthetic, and postsurgical profiles in the literature and summarized technical issues of anesthesia and surgery along with long-term changes from published papers. Doubts with ketogenic diet were raised due to possible renal damage caused by significant excretion of nitrogen found in animal models, the effects of acidosis, and the concerns of increasing triglycerides and cholesterol levels. Though current literature supports the efficacy of very low carbohydrate keto-diets their potential negative effects on renal function and acidosis are debated. An increase in nitrogen excretion during protein metabolism in the postoperative period could lead to renal damage. Research on the value of ketogenic diets is emerging because of its value in weight loss and in managing other pathologies.

[3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome].

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Eirís, J; Ribes, A; Fernández-Prieto, R; Rodríguez-García, J; Rodríguez-Segade, S; Castro-Gago, M

1998-06-01

3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of ketogenesis and Leucine catabolism. HMG-CoA lyase catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy or coma and apnoea. Biochemically there is a characteristic absence of ketosis with hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The urinary organic acid profile includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric acids. Here, we report the case of a 17-year-old girl who presented in both ten months and five years of age a clinical picture characterized by lethargy leading to apnea and coma, hepatomegaly, hypoglycemia, metabolic acidosis, hyperammoniemia, elevated serum transaminases and absence of ketonuria. Diagnostic of Reye syndrome was suggested by hystopathologic finding of hepatic steatosis and clinical and biochemical data. As of 11 years old, laboratory investigations revealed carnitine deficiency and characteristic aciduria. Confirmatory enzyme diagnosis revealing deficiency of HMG-CoA lyase was made in cultured fibroblasts. Our report constitutes an example of the presentation of HMG-CoA lyase deficiency as recurrent Reye-like syndrome.

Short communication: survey of fresh cow management practices of dairy cattle on small and large commercial farms.

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Heuwieser, W; Iwersen, M; Gossellin, J; Drillich, M

2010-03-01

The objective was to conduct a survey of current fresh cow management practices that have an effect on health and diseases postpartum considering different herd sizes of commercial dairy farms. A mail survey regarding aspects of the fresh cow program including general management issues, calving, diseases, and veterinary service was conducted utilizing a convenience sample. A total of 429 survey forms were returned (12.0% response rate) and could be used for final analysis. Only 21.6% of the farms had a designated fresh cow pen. Almost every farm executed some type of fresh cow examination. Only 18.5% of farm managers documented the observations. Most of the dairy managers used more or less subjective criteria such as general appearance (97.0%) and appetite (69.7%). Only a minority of the responding dairy managers monitored their fresh cows using objective (fever 33.6%) or semiquantitative measures (subclinical ketosis 2.8%; body condition score 36.4%). On most farms, the veterinarian visited the herd only if needed (72.6%). Most cases of retained fetal membranes were treated by manual removal (72.3%) and antibiotic pills (89.5%). Several challenges and opportunities were identified to improve cow management practices.

Short communication: Association of disease incidence and adaptive immune response in Holstein dairy cows.

Science.gov (United States)

Thompson-Crispi, K A; Hine, B; Quinton, M; Miglior, F; Mallard, B A

2012-07-01

The objective of this study was to use previously calculated estimated breeding values for cell- (CMIR) and antibody-mediated immune responses (AMIR) to determine associations between immune response (IR) and economically important diseases of dairy cattle. In total, 699 Holsteins were classified as high, average, or low for CMIR, AMIR, and overall IR (combined CMIR and AMIR), and associations with mastitis, metritis, ketosis, displaced abomasums, and retained fetal membranes were determined. The incidence of mastitis was higher among average cows as compared with cows classified as high AMIR [odds ratio (OR)=2.5], high CMIR (OR=1.8), or high IR (OR=1.8). Low-CMIR cows had a higher incidence of metritis (OR=11.3) and low-IR cows had a higher incidence of displaced abomasum (OR=4.1) and retained fetal membrane (OR=2.8) than did average responders. Results of this study show that cows classified as high immune responders have lower occurrence of disease, suggesting that breeding cattle for enhanced IR may be a feasible approach to decrease the incidence of infectious and metabolic diseases in the dairy industry. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Autoradiographic studies of the protein metabolism and histochemical demonstration of the zinc content of the brain in diabetic rats. 1

International Nuclear Information System (INIS)

Gatzke, H.D.; Wildmeister, W.

1979-01-01

Diabetes mellitus was induced in rats by application of streptozotocin: 40 mg/kg body weight streptozotocin produced a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin caused a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals received 308 MBq/animal 3 H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of 3 H-leucine in different areas of the rat brain were measured. The values of the control animals were compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the 3 H-leucine values of the diabetic animals were considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the 3 H-leucine values as well as the zinc content of diabetic animals decreased according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions was discussed. (author)

Effect of potassium and hypomagnesemia on insulin in the bovine

Energy Technology Data Exchange (ETDEWEB)

Lentz, D.E.; Madsen, F.C.; Miller, J.K.; Hansard, S.L.

1976-01-01

Grass tetany in cattle has been associated with the consumption of early spring forages high in potassium (K) and low in magnesium (Mg). Alterations in serum Mg and K may affect intermediary carbohydrate metabolism, resulting in hypoglycemia and ketosis that often accompany grass tetany. We investigated these interrelationships by infusing potassium chloride (KCl) intravenously in normal (plasma Mg greater than 2.1 mg/100 ml) and Mg-deficient (plasma Mg less than .7 mg/100 ml) 9-month-old Holstein bull calves and intraruminally into nonpregnant, nonlactating Holstein cows. Plasma levels of both K and immunoreactive insulin (IRI) were elevated (P less than .01) by 1.14, 2, and 3 percent KCl (51, 64, and 135 mg K/kg) in calves and by 550 g KCl (440 mg K/kg body weight) in cows. Plasma K was lower (P less than .01) and IRI higher (P less than .01) in Mg-deficient calves than in normal calves during 2 percent KCl infusion. These results suggest that prolonged elevation of K and insulin in ruminants could lead to a series of metabolic disturbances that may play an important role in the etiology of grass tetany.

Restricting carbohydrates to fight head and neck cancer—is this realistic?

International Nuclear Information System (INIS)

Klement, Rainer J.

2014-01-01

Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are (1) targeting the origin and specific aspects of tumor glycolysis; (2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill; (3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself

Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

Science.gov (United States)

Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

2013-01-01

Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand. PMID:23801097

Evaluation of the effect of bolus administration of 50% dextrose solution on measures of electrolyte and energy balance in postpartum dairy cows.

Science.gov (United States)

Wagner, Sarah A; Schimek, Daniel E

2010-09-01

To determine the effect of IV administration of a bolus of 50% dextrose solution on electrolyte and energy balance and effect of blood collection site on serum electrolyte values in postparturient dairy cows. 24 clinically normal multiparous cows. A bolus of 50% dextrose solution (0.5 L [n=8 cows]), 50% dextrose solution (1.0 L [8]), or saline (0.9% NaCl) solution (1.0 L, control treatment [8]) was administered via jugular venipuncture 5 to 10 days after parturition. Pretreatment and posttreatment blood samples were analyzed for concentrations of calcium, magnesium, phosphorus, potassium, glucose, insulin, beta-hydroxybutyric acid (BHBA), and nonesterified fatty acids. Coccygeal vessel and jugular vein blood samples were obtained prior to treatment, and electrolyte concentrations were compared. Treatment with 50% dextrose decreased phosphorus concentration in serum, compared with the control treatment. Suppression of BHBA and nonesterified fatty acid concentrations following dextrose treatment lasted for dextrose solution may be at risk for hypophosphatemia, and 1 treatment with 0.5 or 1 L of 50% dextrose solution is unlikely to prevent or resolve acetonemia (ketosis). The risk of hypophosphatemia may be underestimated when coccygeal vessel blood samples are used for diagnosis.

Effects of β-hydroxybutyricacid on the synthesis and assembly of very low-density lipoprotein in bovine hepatocytes in vitro.

Science.gov (United States)

Deng, Q; Ma, D; Shi, Z; Huang, W; Du, X; Gao, W; Zhu, X; Lei, L; Zhang, M; Sun, G; Yuan, X; Li, X; Wang, Z; Liu, G; Li, X

2016-04-01

β-Hydroxybutyricacid (BHBA) is an important metabolite that involved in the development of ketosis and fatty liver in dairy cows. Dairy cows with fatty liver displayed high blood concentration of BHBA and very low-density lipoprotein (VLDL) assembly. The effects of BHBA on VLDL synthesis and assembly in hepatocytes of cows were unclear. In this study, bovine hepatocytes were cultured and treated with different concentrations of BHBA. We found that BHBA treatment upregulated the mRNA and protein levels of apolipoprotein B100 (ApoB 100), apolipoprotein E (ApoE) and microsomal triglyceride transfer protein (MTTP) and showed in a firstly increased and then decreased trend. Meanwhile, the mRNA and protein levels of LDLR showed in a reverse trend. Consequently, VLDL content was significantly increased in medium-dose BHBA treatment group, while decreased in high-dose group. These results indicate that the effects of BHBA on the VLDL synthesis showed in a dose-dependent manner that low levels of BHBA increase VLDL synthesis and high levels of BHBA decrease VLDL synthesis. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Hyperemesis gravidarum presenting as jaundice and transient hyperthyroidism complicated with acute pancreatitis.

Science.gov (United States)

Weng, Meng Tzu; Wei, Shu Chen; Wong, Jau Min; Chang, Tien Chun

2005-03-01

Hyperemesis gravidarum is an extreme form of nausea and vomiting during pregnancy. Its presenting symptoms include vomiting, disturbed nutrition, electrolyte imbalance, ketosis, extreme weight loss, renal and/or liver damage. It is rare for a hyperemesis gravidarum patient to present with jaundice, hyperthyroidism and idiopathic acute pancreatitis during the same hospitalization period. Here, we report such a case. A 25-year-old pregnant woman without underlying liver or thyroid disease was admitted due to jaundice noted for 2 days at 8 weeks of gestational age. Hyperthyroidism symptoms of tachycardia and finger tremor also bothered her. After treatment with parenteral fluid and antithyroid agents, her clinical condition improved. However, an episode of idiopathic pancreatitis occurred after nausea and vomiting subsided. Bowel rest with parenteral fluid and nutrition supplement was given and the increased pancreatic enzyme level gradually subsided. Follow-up liver and thyroid function were normal after gestational age of 26 weeks. She delivered a healthy female baby without low birth body weight at gestational age of 39 weeks. Rapid diagnosis and supportive care are important for the hyperemesis gravidarum patient with the complication of acute pancreatitis.

Study on some risk factors and effects of bovine ketosis on dairy cows from the Galicia region (Spain).

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Viña, C; Fouz, R; Camino, F; Sanjuán, M L; Yus, E; Diéguez, F J

2017-10-01

The study was designed to determine the relation between β-hydroxybutyrate (BHB) concentrations in milk from dairy cows after calving and the length of the previous lactation, the dry period and the 305-day normalized production, and to assess the influence of BHB concentrations on culling and test-day milk productions and somatic cell counts (SCC) throughout the lactation that followed the BHB measurement. The data used in the study were obtained from 59 187 cows in the Galicia region (Spain). BHB determination was performed using Fourier-transformed infrared spectrometry from the milk samples collected from each cow on the first post-partum test day. For statistical analysis, the following methods were applied: (i) ordinal regression to assess the effect of the length of the previous lactation, the dry period and the 305-day normalized milk production on milk BHB, (ii) a Cox model to estimate the influence of the BHB concentration on risk of culling (overall and for a variety of reasons) and (iii) linear regression to assess the link between BHB and the milk yield and SCC obtained from each of the tests day performed throughout lactation. The probability of having higher BHB concentrations increased when the length of the previous lactation (p = 0.006), the dry period (p = 0.003) and the 305-day normalized milk yield (p = 0.005) increased. However, the slight increase observed (especially for the case of the dry period and the 305-day milk yield) would not justify that measures be implemented to reduce these traits. Higher concentrations of BHB led to an increased risk of culling due to 'death' (p ≤ 0.001) and 'urgent slaughter' (p ≤ 0.002) (both causes of involuntary culling). It also led to a reduction in milk production (p < 0.001) and an increase in SCC (p < 0.001) in the post-partum; from that moment onward (including peak lactation), there were no differences in those two parameters depending on the BHB levels. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows.

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Esposito, Giulia; Irons, Pete C; Webb, Edward C; Chapwanya, Aspinas

2014-01-30

The biological cycles of milk production and reproduction determine dairying profitability thus making management decisions dynamic and time-dependent. Diseases also negatively impact on net earnings of a dairy enterprise. Transition cows in particular face the challenge of negative energy balance (NEB) and/or disproportional energy metabolism (fatty liver, ketosis, subacute, acute ruminal acidosis); disturbed mineral utilization (milk fever, sub-clinical hypocalcemia); and perturbed immune function (retained placenta, metritis, mastitis). Consequently NEB and reduced dry matter intake are aggravated. The combined effects of all these challenges are reduced fertility and milk production resulting in diminishing profits. Risk factors such as NEB, inflammation and impairment of the immune response are highly cause-and-effect related. Thus, managing cows during the transition period should be geared toward reducing NEB or feeding specially formulated diets to improve immunity. Given that all cows experience a reduced feed intake and body condition, infection and inflammation of the uterus after calving, there is a need for further research on the immunology of transition dairy cows. Integrative approaches at the molecular, cellular and animal level may unravel the complex interactions between disturbed metabolism and immune function that predispose cows to periparturient diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Energy balance in transition cows and its association with health, reproduction and milk production.

Science.gov (United States)

Furken, C; Nakao, T; Hoedemaker, M

2015-01-01

It was the purpose of this study to determine the effects of non-esterified fatty acids (NEFA) concentrations at different time periods of the transition period as well as lactation number on metabolism, health, reproduction and milk production in dairy cows. This trial was conducted in a single dairy herd located in Northern Germany. Of the herd, which comprised 330 lactating Holstein cows housed in a free stall barn and fed a total mixed ration (TMR), 83 primiparous and multiparous cows were randomly selected. Animals were checked for body condition score (BCS), locomotion score, calving data, quality of colostrum, reproductive measures, daily rectal temperature of the first 10 days post-partum (p. p.), health data and culling rates up to 200 days in milk (DIM) as well as milk production until 305 DIM. Three different time periods were considered: 3 and 1 week ante partum (a. p.); partus and 1 week p. p.; 3 weeks p. p. Animals with NEFA concentrations ≥ 0.4 mmol/l ante partum had a higher risk of no ovarian activity in week 5 p. p. and of subclinical ketosis post partum than cows with lower NEFA concentrations (p reproduction of dairy cows.

Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP): ROLE OF AMP AS AN ALLOSTERIC INHIBITOR.

Science.gov (United States)

Sato, Shogo; Jung, Hunmin; Nakagawa, Tsutomu; Pawlosky, Robert; Takeshima, Tomomi; Lee, Wan-Ru; Sakiyama, Haruhiko; Laxman, Sunil; Wynn, R Max; Tu, Benjamin P; MacMillan, John B; De Brabander, Jef K; Veech, Richard L; Uyeda, Kosaku

2016-05-13

The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential metabolite levels in response to spawning-induced inappetence in Atlantic salmon Salmo salar.

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Cipriano, Rocco C; Smith, McKenzie L; Vermeersch, Kathleen A; Dove, Alistair D M; Styczynski, Mark P

2015-03-01

Atlantic salmon Salmo salar undergo months-long inappetence during spawning, but it is not known whether this inappetence is a pathological state or one for which the fish are adapted. Recent work has shown that inappetent whale sharks can exhibit circulating metabolite profiles similar to ketosis known to occur in humans during starvation. In this work, metabolite profiling was used to explore differences in analyte profiles between a cohort of inappetent spawning run Atlantic salmon and captively reared animals that were fed up to and through the time of sampling. The two classes of animals were easily distinguished by their metabolite profiles. The sea-run fish had elevated ɷ-9 fatty acids relative to the domestic feeding animals, while other fatty acid concentrations were reduced. Sugar alcohols were generally elevated in inappetent animals, suggesting potentially novel metabolic responses or pathways in fish that feature these compounds. Compounds expected to indicate a pathological catabolic state were not more abundant in the sea-run fish, suggesting that the animals, while inappetent, were not stressed in an unnatural way. These findings demonstrate the power of discovery-based metabolomics for exploring biochemistry in poorly understood animal models. Copyright © 2015 Elsevier Inc. All rights reserved.

Growth rate, health and welfare in a dairy herd with natural suckling until 6–8 weeks of age: a case report

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Mejdell Cecilie

2007-06-01

Full Text Available Abstract Over a period of two years, growth rate and health were measured for dairy calves allowed to suckle their mothers up to 6–8 weeks of age. Thirty-one calves were weighted weekly, and the mean daily growth rate was 1.2 ± 0.03 kg from birth up to 13 weeks of age. Illness in calves and young stock was not observed. In the cows, the mean incidences of ketosis, displaced abomasum, puerperal paresis, mastitis, teat injury and retained placenta were 0, 0, 8, 22, 1 and 1%, respectively, during a 6-year period. The mean daily gain of 56 growing bulls was 1.4 kg when slaughtered at 15 months of age, which is higher than the mean daily gain of 0.95 kg in the population. Probiotics, hormones and vaccines were not used, and antibiotics were only used for treating illness. The present study indicates many advantages and few problems when dairy calves are penned together with the cows and allowed natural feeding up to 6–8 weeks of age. This production system was easy to manage, preferred by the farmer, and may satisfy the public concern regarding the practice of immediate separation of cow and calf in commercial milk production.

Ketogenic diets, mitochondria, and neurological diseases

Science.gov (United States)

Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

2014-01-01

The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

Diabetic subjects diagnosed through the Diabetes Prevention Trial-Type 1 (DPT-1) are often asymptomatic with normal A1C at diabetes onset.

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Triolo, Taylor M; Chase, H Peter; Barker, Jennifer M

2009-05-01

Upon diagnosis of type 1 diabetes, patients are usually symptomatic, and many have ketoacidosis. Screening for islet autoantibodies (IAs) has been shown to decrease A1C level and rate of hospitalization at diabetes onset. Metabolic tests and the presence of symptoms were described at diabetes onset during the Diabetes Prevention Trial-Type 1 (DPT-1). The DPT-1 screened relatives of patients with type 1 diabetes for islet cell autoantiobodies (ICAs). Those with positive ICAs had intravenous and oral glucose tolerance tests (IVGTTs and OGTTs) and were randomized into one of two prevention trials. Throughout the DPT-1 parenteral and oral insulin study, 246 people were diagnosed with type 1 diabetes. Of the 246 subjects diagnosed with diabetes, 218 had data regarding the presence of symptoms, and 138 (63.3%) reported no symptoms suggestive of diabetes. Eight subjects (3.67%) presented with ketosis. Subjects presented with a mean +/- SD A1C of 6.41 +/- 1.15%. At diagnosis, 90 subjects (50.8%) had A1C in the normal range (IA followed by OGTT) may allow diagnosis of diabetes before severe metabolic decompensation. Screening with A1C will miss identifying many of the subjects with newly diagnosed type 1 diabetes in this cohort.

Influence of diseases and metabolic disorders on cow weight changes

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Šárka Podlahová

2012-10-01

Full Text Available Requirements on increasing economic efficiency of cattle breeding force farmers to use the latest up-to-datetechnology for monitoring and management of farming quality. Regular weighing and data processing can forinstance discover mistakes that can indicate defects, e.g. nutrition deficiencies, incorrect embryonic development,health problems, demanding nursing intervention. The aim of the research was to monitor manifestations of diseasesand metabolic disorders in the course of weight curve based on data from an automated system for weighing the liveweight of dairy cows. There was used in the weighing unit for milking robots Astronaut A3 (Lely company to obtainweight data of individual cows. There were selected dairy cows with the longest period of lactation or already dryingoff, and especially dairy cows with various health problems for study. Limiting values of weight changes wereestablished after assembling a general equation of mass curve. In the sphere of the diseases there was manifestedonly ketosis in the weight curves with a loss of 10.2 kg / day (38% weight loss. The results of the study will beapplied for compiling algorithm that will be implemented in the complete management system of cattle breeding,monitoring the dairy cows every day and highlight possible deviations exceeding of physiological changes in weight.

Effect of live yeast culture Saccharomyces cerevisiae on milk production and some blood parameters

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Judit Peter Szucs

2013-05-01

Full Text Available The aim of this study was to investigate the effect of live yeast culture (Saccharomyces cerevisiae Sc 47 on milk yield, milk composition and some blood parameters of dairy cows during their early lactation on farm conditions. The live yeast culture was given in the diet of heifers and cows (5 g day-1 solid Actisaf for 14 days before calving and exclusively for the treated cows 12 g day-1 dissolved in 500 ml of water, during 14 days after calving. The experiment took until 100th day of lactation on farm conditions. Yeast culture supplementation was the most effective for the performance of primiparous cows: It was advantageous for blod plasma parameters: decreased the beta-hydroxy butyrate (BHB content and free fatty acids (FFA which indicated the protection of the animals against ketosis or other metabolic disorders. Increased the daily milk production and the lactose /glucose content of the milk. The live yeast culture increased the lactose content of the milk and decreased the somatic cell count of multiparous cows. The listed parameters were not significant (P<0.05 compare to the results of positive control groups. The applied live yeast culture supplementation did not significant affect for other performance of the cows.

The Impact of Hyperglycemic Emergencies on the Kidney and Liver

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Feng Bai

2013-01-01

Full Text Available Studies on the alterations of liver and kidney function parameters in patients with diabetic ketoacidosis (DKA and diabetic ketosis (DK were limited. Participants with DKA, DK, non-DK, and healthy controls were enrolled in the current study. Parameters of liver and kidney function were measured and evaluated. The patients with DKA had higher levels of plasma glucose, hemoglobin A1c (HbA1c, uric acid, and creatinine but lower levels of transferases and protein compared with the other three groups ( for all. The patients with DK had higher levels of plasma glucose and HbA1c but lower levels of glutamyl transpeptidase and protein compared with the non-DK and control groups (. Prealbumin levels were significantly reduced in the severe DKA patients compared with the mild/moderate DKA patients. Serum prealbumin levels were correlated with albumin levels (, , HCO3 (, , and arterial pH (, in the DKA patients. A diagnostic analysis showed that lower prealbumin levels significantly reflected the presence of hyperglycemic emergencies (. Liver and kidney function parameters deteriorated, especially in DKA. Prealbumin levels can be of value in detecting the presence of hyperglycemic crisis. This clinical trial is registered with ChiCTR-OCH-12003077.

Nonpharmacological treatment of epilepsy

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V S Saxena

2011-01-01

Full Text Available Nonpharmacological treatment of epilepsy includes surgery, vagal nerve stimulation, ketogenic diet, and other alternative/complementary therapies, e.g., yoga, Ayurveda, electroencephalography (EEG biofeedback technique, aerobic exercise, music therapy, transcranial magnetic stimulation, acupuncture, and herbal remedies (traditional Chinese medicine. Alternative therapies, despite the term, should not be considered as an alternative to antiepileptic medication; they complement accepted drug treatment. Alternative therapies like yoga, through techniques that relax the body and mind, reduce stress, improve seizure control, and also improve quality of life. Ketogenic diet is a safe and effective treatment for intractable epilepsies; it has been recommended since 1921. The diet induces ketosis, which may control seizures. The most successful treatment of epilepsy is with modern antiepileptic drugs, which can achieve control of seizures in 70-80% cases. Patients opt for alternative therapies because they may be dissatisfied with antiepileptic drugs due to their unpleasant side effects, the long duration of treatment, failure to achieve control of seizures, cultural beliefs and, in the case of women, because they wish to get pregnant Surgical treatment may lead to physical and psychological sequelae and is an option only for a minority of patients. This article presents supportive evidence from randomized controlled trials done to assess the benefit of non-pharmacological treatment.

Autoradiographic studies of the protein metabolism and histochemical demonstration of the zinc content of the brain in diabetic rats. 1. Streptozotocin-induced diabetes

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Gatzke, H D [Freie Univ. Berlin (Germany, F.R.); Wildmeister, W [Krankenhaus Kempen (Germany, F.R.). Innere Klinik

1979-11-01

Diabetes mellitus was induced in rats by application of streptozotocin: 40 mg/kg body weight streptozotocin produced a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin caused a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals received 308 MBq/animal /sup 3/H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of /sup 3/H-leucine in different areas of the rat brain were measured. The values of the control animals were compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the /sup 3/H-leucine values of the diabetic animals were considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the /sup 3/H-leucine values as well as the zinc content of diabetic animals decreased according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions was discussed.

Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats.

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Abdelhamid, Amir Mohamed; Abdelaziz, Rania Ramadan; Salem, Hatem Abdelrahman Ali

2018-03-06

Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA 1c . It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.

Characterization of peripartum rumination and activity of cows diagnosed with metabolic and uterine diseases.

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Liboreiro, Daniela N; Machado, Karine S; Silva, Paula R B; Maturana, Milton M; Nishimura, Thiago K; Brandão, Alice P; Endres, Márcia I; Chebel, Ricardo C

2015-10-01

The objectives of the current experiment were to characterize the correlation among total serum Ca, nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and haptoglobin concentrations and daily rumination time (DRT) and activity of periparturient cows and to determine the association between periparturient events and peripartum DRT and activity. Holstein animals (nulliparous = 77, parous = 219) were enrolled in the experiment approximately 21 d before expected calving date. Cows were fitted with individual Heat Rumination Long Distance collars (HRLD, SCR Engineers Ltd., Netanya, Israel) from enrollment until approximately 21 ± 3 d postpartum. Blood samples collected weekly from enrollment to 21 d postpartum were used to determine concentrations of NEFA, BHBA, and haptoglobin. Blood samples collected within 72 h after calving were used to determine total serum Ca concentration. Subclinical ketosis was characterized by BHBA > 1,000 µmol/L in any sample, and subclinical hypocalcemia was characterized by Ca Cows were examined 1, 7 ± 3, and 14 ± 3 d postpartum for diagnosis of retained fetal membrane and metritis. Total Ca (r = 0.15), NEFA (r = -0.27), and haptoglobin (r = -0.18) concentrations were weakly correlated with DRT. Concentration of BHBA (r = -0.14) was weakly correlated with activity. Postpartum DRT was reduced among cows that delivered twins compared with cows that delivered singletons (437.9 ± 4.8 vs. 385.9 ± 17.1 min/d). Prepartum (465.8 ± 4.1 vs 430.8 ± 14.9 arbitrary units) and postpartum (536.5 ± 5.5 vs. 480.3 ± 19.4 arbitrary units) activity were reduced among cows that delivered twins compared with cows that delivered singletons. Delivery of stillborn calves was associated with reduced DRT prepartum (478.0 ± 5.9 vs. 417.0 ± 23.4 min/d) and postpartum (437.2 ± 4.8 vs. 386.5 ± 19.3 min/d). On the other hand, cows delivering stillborn calves had increased activity prepartum compared with cows delivering live calves (499.3 ± 16

Seizure tests distinguish intermittent fasting from the ketogenic diet

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Hartman, Adam L.; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J. Marie

2010-01-01

Summary Purpose Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Methods Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ~ 12 days, starting at 3–4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. Results The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz–induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. Discussion In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. PMID:20477852

Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

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Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

2016-06-01

Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

Plasma Vitamin E and Blood Selenium Concentrations in Norwegian Dairy Cows: Regional Differences and Relations to Feeding and Health

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Østerås O

2005-12-01

Full Text Available Plasma α-tocopherol (vit E and blood selenium (Se concentrations in February were determined in samples from 314 dairy cows in Norway, selected to provide a representative subset of the Norwegian dairy cow population. Each sample was followed by a questionnaire with information about feeding of the cow at the time of sampling. The results were correlated to herd data and to calving and health data for each cow from the Norwegian Dairy Herd Recording System and the Norwegian Cattle Health Recording System. The mean concentrations were 6.9 μg vit E per ml plasma and 0.16 μg Se per g blood. Both levels were highest in mid lactation. Plasma vit E varied with the amount of silage fed to the cow, while blood Se varied with the amount of concentrates and mineral supplements, and with geographical region. No differences in vit E or Se levels were found between cows with recorded treatments for mastitis, parturient paresis or reproductive disorders in the lactation during or immediately prior to sampling, and those without such treatments. For ketosis, a small difference in blood Se was found between the groups with or without recorded treatments. It is concluded that winter-fed lactating cows in Norway had an adequate plasma level of vit E and a marginal-to-adequate level of Se.

Plasma Vitamin E and Blood Selenium Concentrations in Norwegian Dairy Cows: Regional Differences and Relations to Feeding and Health

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Sivertsen T

2006-12-01

Full Text Available Plasma α-tocopherol (vit E and blood selenium (Se concentrations in February were determined in samples from 314 dairy cows in Norway, selected to provide a representative subset of the Norwegian dairy cow population. Each sample was followed by a questionnaire with information about feeding of the cow at the time of sampling. The results were correlated to herd data and to calving and health data for each cow from the Norwegian Dairy Herd Recording System and the Norwegian Cattle Health Recording System. The mean concentrations were 6.9 μg vit E per ml plasma and 0.16 μg Se per g blood. Both levels were highest in mid lactation. Plasma vit E varied with the amount of silage fed to the cow, while blood Se varied with the amount of concentrates and mineral supplements, and with geographical region. No differences in vit E or Se levels were found between cows with recorded treatments for mastitis, parturient paresis or reproductive disorders in the lactation during or immediately prior to sampling, and those without such treatments. For ketosis, a small difference in blood Se was found between the groups with or without recorded treatments. It is concluded that winter-fed lactating cows in Norway had an adequate plasma level of vit E and a marginal-to-adequate level of Se.

Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models.

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Samala, Ramakrishna; Willis, Sarah; Borges, Karin

2008-10-01

Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. Feeding 4:1 and 6:1 KDs ad lib to 3-week-old (adolescent) mice resulted in 1.2-2.2mM d-BHB in plasma, but did not consistently change glucose levels. The 6:1 KD reproducibly elevated the CC50 (current that initiates seizures in 50% mice tested) in the 6-Hz model after 14 days of feeding to adolescent CD1 mice. Higher plasma d-BHB levels correlated with anticonvulsant effects. Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.

Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment.

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Chung, Hae-Yun; Park, Yoo Kyoung

2017-09-01

Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients. Article search was performed from 1985 through 2017 and finally 10 articles were analyzed. The review focused on the results of human trials for cancer patients and checked the feasibility of using ketogenic diet for cancer patients as adjuvant therapy. The main outcomes showed improvement of body weight changes, anthropometric changes, serum blood profiles, and reduction in novel marker for tumor progression, TKTL1, and increase of ketone body. Lactate concentration was reduced, and no significant changes were reported in the measurements of quality of life. Ketogenic diet may be efficacious in certain cancer subtypes whose outcomes appear to correlate with metabolic status, but the results are not yet supportive and inconsistent. Therefore, it warrants further studies.

Risperidone-induced type 2 diabetes presenting with diabetic ketoacidosis

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Clarissa Ern Hui Fang

2018-05-01

Full Text Available A 28-year-old male presented with 2 days of vomiting and abdominal pain, preceded by 2 weeks of thirst, polyuria and polydipsia. He had recently started risperidone for obsessive-compulsive disorder. He reported a high dietary sugar intake and had a strong family history of type 2 diabetes mellitus (T2DM. On admission, he was tachycardic, tachypnoeic and drowsy with a Glasgow Coma Scale (GCS of 10/15. We noted axillary acanthosis nigricans and obesity (BMI 33.2 kg/m2. Dipstick urinalysis showed ketonuria and glycosuria. Blood results were consistent with diabetic ketoacidosis (DKA, with hyperosmolar state. We initiated our DKA protocol, with intravenous insulin, fluids and potassium, and we discontinued risperidone. His obesity, family history of T2DM, acanthosis nigricans and hyperosmolar state prompted consideration of T2DM presenting with ‘ketosis-prone diabetes’ (KPD rather than T1DM. Antibody markers of beta-cell autoimmunity were subsequently negative. Four weeks later, he had modified his diet and lost weight, and his metabolic parameters had normalised. We reduced his total daily insulin dose from 35 to 18 units and introduced metformin. We stopped insulin completely by week 7. At 6 months, his glucometer readings and glycated haemoglobin (HbA1c level had normalised.

Measuring breath acetone for monitoring fat loss: Review.

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Anderson, Joseph C

2015-12-01

Endogenous acetone production is a by-product of the fat metabolism process. Because of its small size, acetone appears in exhaled breath. Historically, endogenous acetone has been measured in exhaled breath to monitor ketosis in healthy and diabetic subjects. Recently, breath acetone concentration (BrAce) has been shown to correlate with the rate of fat loss in healthy individuals. In this review, the measurement of breath acetone in healthy subjects is evaluated for its utility in predicting fat loss and its sensitivity to changes in physiologic parameters. BrAce can range from 1 ppm in healthy non-dieting subjects to 1,250 ppm in diabetic ketoacidosis. A strong correlation exists between increased BrAce and the rate of fat loss. Multiple metabolic and respiratory factors affect the measurement of BrAce. BrAce is most affected by changes in the following factors (in descending order): dietary macronutrient composition, caloric restriction, exercise, pulmonary factors, and other assorted factors that increase fat metabolism or inhibit acetone metabolism. Pulmonary factors affecting acetone exchange in the lung should be controlled to optimize the breath sample for measurement. When biologic factors are controlled, BrAce measurement provides a non-invasive tool for monitoring the rate of fat loss in healthy subjects. © 2015 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Eating and rumination activities two weeks prepartum to one month postpartum in 100 healthy cows and cows with peripartum diseases.

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Braun, U; Buchli, H; Hässig, M

2017-10-01

Eating and rumination activities were investigated in 100 cows from 14 days prepartum to 30 days postpartum. All cows were clinically healthy at the start of the study. A pressure sensor incorporated into the noseband of a halter was used to record jaw movements, which allowed the quantification of the daily duration of eating and rumination, number of regurgitated cuds and number of chewing cycles per cud. The cows were retrospectively divided into 2 main groups healthy (n = 24) and ill cows (n = 76), and the latter were further divided into the following subgroups: cows with periparturient paresis (n = 12), retained placenta (n = 13), metritis (n = 17), primary ketosis (n = 19) and lameness (n = 6). Healthy cows had the shortest eating and rumination times on the day of calving; duration of eating decreased continually before and increased steadily after calving. In contrast, duration of rumination varied little except for a significant drop on the days of calving. Compared with healthy cows, eating times of ill cows were significantly shorter before and after calving and rumination time was reduced on days 2 to 4 postpartum. The duration of eating differed between healthy and ill cows before calving, and therefore the usefulness of eating and rumination variables for early recognition of periparturient diseases in cows requires further investigation.

Seizure tests distinguish intermittent fasting from the ketogenic diet.

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Hartman, Adam L; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J Marie

2010-08-01

Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ∼12 days, starting at 3-4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz-induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

Rethinking fat as a fuel for endurance exercise.

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Volek, Jeff S; Noakes, Timothy; Phinney, Stephen D

2015-01-01

A key element contributing to deteriorating exercise capacity during physically demanding sport appears to be reduced carbohydrate availability coupled with an inability to effectively utilize alternative lipid fuel sources. Paradoxically, cognitive and physical decline associated with glycogen depletion occurs in the presence of an over-abundance of fuel stored as body fat that the athlete is apparently unable to access effectively. Current fuelling tactics that emphasize high-carbohydrate intakes before and during exercise inhibit fat utilization. The most efficient approach to accelerate the body's ability to oxidize fat is to lower dietary carbohydrate intake to a level that results in nutritional ketosis (i.e., circulating ketone levels >0.5 mmol/L) while increasing fat intake for a period of several weeks. The coordinated set of metabolic adaptations that ensures proper interorgan fuel supply in the face of low-carbohydrate availability is referred to as keto-adaptation. Beyond simply providing a stable source of fuel for the brain, the major circulating ketone body, beta-hydroxybutyrate, has recently been shown to act as a signalling molecule capable of altering gene expression, eliciting complementary effects of keto-adaptation that could extend human physical and mental performance beyond current expectation. In this paper, we review these new findings and propose that the shift to fatty acids and ketones as primary fuels when dietary carbohydrate is restricted could be of benefit for some athletes.

Recurrent nightly ketosis after prolonged exercise in type 1 diabetes - the need for glycogen replacement strategies. Case report and review of literature

NARCIS (Netherlands)

van Albada, M. E.; Bakker-van Waarde, W. M.

2016-01-01

Exercise in diabetes patients has many benefits but also several risks, of which hypoglycemia is most often discussed. We present a case with recurrent keto-acidosis post-exercise, in which we hypothesize that glycogen replacement strategies were insufficient. Our experience in this case and review

Recurrent nightly ketosis after prolonged exercise in type 1 diabetes - the need for glycogen replacement strategies. Case report and review of literature

NARCIS (Netherlands)

van Albada, M. E.; Bakker-van Waarde, W. M.

Exercise in diabetes patients has many benefits but also several risks, of which hypoglycemia is most often discussed. We present a case with recurrent keto-acidosis post-exercise, in which we hypothesize that glycogen replacement strategies were insufficient. Our experience in this case and review

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

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Kusenda, M; Kaske, M; Piechotta, M; Locher, L; Starke, A; Huber, K; Rehage, J

2013-01-01

Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. Dexamethasone treatment affects whole body insulin sensitivity. Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 μg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows. Copyright © 2012 by the American College of Veterinary Internal Medicine.

How Metabolic Diseases Impact the Use of Antimicrobials: A Formal Demonstration in the Field of Veterinary Medicine.

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Raboisson, Didier; Barbier, Maxime; Maigné, Elise

2016-01-01

Decreasing the use of antimicrobials has become a primary objective for both human and veterinary medicine in many countries. Medical prevention and good nutrition are seen as key parameters for reducing antimicrobial use. However, little consideration has been given to how metabolic diseases may influence the use of antimicrobials in humans and animals through limiting the prevalence and severity of infectious diseases. To quantify this relationship using the example of a common metabolic disease in dairy cows (subclinical ketosis, SCK), we constructed a stochastic model reporting the total quantity of curative antimicrobials for a given population with the prevalence of cows at risk for SCK. We considered the prevalence of SCK, the relative risk of the disease in cases of SCK compared to no SCK and the use of antimicrobials to treat SCK-induced infectious diseases. Reducing the percentage of cows at risk for SCK from 80% to 10% was associated with an average decrease in the use of antimicrobials of 11% (prevalence of SCK from 34% to 17%, respectively) or 25% (prevalence of SCK from 68% to 22%, respectively), depending on the relative risk to contract SCK if risk was present. For a large percentage of the cows at risk for SCK, using a preventive bolus of monensin reduced the use of curative antimicrobials to the same level that was observed when the percentage of cows at risk for SCK was low. The present work suggests similar approaches for obesity and diabetes.

Comparison of palmitic acid kinetics during glucose or ketone body infusions

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Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

1986-03-05

Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of (1-/sup 14/C) palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat.

Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

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Wood Richard J

2006-05-01

Full Text Available Abstract Background Diets that restrict carbohydrate (CHO have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. Methods We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy. A total of 27 single nucleotide polymorphisms (SNPs were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. Results Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF, hepatic glycogen synthase (GYS2, cholesteryl ester transfer protein (CETP and galanin (GAL genes were significantly associated with weight loss. Conclusion A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma.

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Mohammed G Abdelwahab

Full Text Available INTRODUCTION: The ketogenic diet (KD is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. METHODS: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. RESULTS: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173 and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001. Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. CONCLUSIONS: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

THE EFFECTS OF ORAL ADMINISTRATION OF PROPYLENE GLYCOL AND CALCIUM PROPIONATE IN DAIRY COWS

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C. GAVAN

2009-10-01

Full Text Available This study was designed to determine the effects of the oral administration of propylene glycol and calcium propionate on performance of dairy cows. Treatments were 10 l water (control, 10 l water+300 ml propylene glycol (GP and 10 l water+500 g calcium propionate (CP. Animals were mainly of Holstein breeds and were fed and managed in a commercial setting. The cows were divided randomly into an experimental group, n=24 (n=12 with PG and n=12 with CP and a control group, n=11. Cows received the assigned treatment within 10 hours of calving and 24 hours after calving. Health events were recorded during calving and for the first 21 days in milk (DIM. Health examinations were performed on cows that appeared not well. The cows were milked three times daily and milk production was recorded electronically. Milk solid content and somatic cell score were determinate from three consecutive milking weekly till 20 DIM and than monthly till 110 DIM. Retained placenta, hypocalcaemia, displaced abomasums, ketosis and metritis were low in treatment groups (with PG and CP. The cows receiving PG had 2.8 Kg/day grater milk production than control group. The cows receiving CP had 1.7 kg/day grater milk production than control group. Prophylactic administration of PG and CP drenches to Holstein cows may be justified by potentially higher milk yields and reduced health complications.

Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

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Natalia M. Branis

2015-01-01

Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

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Yuen, Alan W C; Walcutt, Isabel A; Sander, Josemir W

2017-09-01

Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes.

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Sofou, Kalliopi; Dahlin, Maria; Hallböök, Tove; Lindefeldt, Marie; Viggedal, Gerd; Darin, Niklas

2017-03-01

Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues. Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed. Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe-except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients. Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.

Diagnostic Challenge in a Patient with Severe Anion Gap Metabolic Acidosis

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Eugene M. Tan

2015-01-01

Full Text Available The approach to the patient with acute renal failure and elevated anion and osmolal gap is difficult. Differential diagnoses include toxic alcohol ingestion, diabetic or starvation ketoacidosis, or 5-oxoproline acidosis. We present a 76-year-old female with type 2 diabetes mellitus, who was found at home in a confused state. Laboratory analysis revealed serum pH 6.84, bicarbonate 5.8 mmol/L, pCO2 29 mmHg, anion gap 22.2 mmol/L, osmolal gap 17.4 mOsm/kg, elevated beta-hydroxybutyrate (4.2 mmol/L, random blood sugar 213 mg/dL, creatinine 2.1 mg/dL, and potassium 7.5 mmol/L with no electrocardiogram (EKG changes. Fomepizole and hemodialysis were initiated for presumed ethylene glycol or methanol ingestion. Drug screens returned negative for ethylene glycol, alcohols, and acetaminophen, but there were elevated urine levels of acetone (11 mg/dL. The acetaminophen level was negative, and 5-oxoproline was not analyzed. After 5 days in the intensive care unit (ICU, her mental status improved with supportive care. She was discharged to a nursing facility. Though a diagnosis was not established, our patient’s presentation was likely due to starvation ketosis combined with chronic acetaminophen ingestion. Acetone ingestion is less likely. Overall, our case illustrates the importance of systematically approaching an elevated osmolal and anion gap metabolic acidosis.

Comparison between Serum and Saliva Biochemical Constituents in Dairy Cows during Lactation and Dry Period

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Mahmoud R. Abd Ellah

2015-07-01

Full Text Available The present study was undertaken to compare serum and salivary biochemical constituents during lactation and dry period in dairy cows. Also, the present study evaluated for the first time the salivary biochemical constituents in dairy cows. The study was carried out using 45 healthy multiparous Holstein cows maintained in dairy farms located in Morioka city (Iwate prefecture, Japan. Cows were classified into groups based on the month of lactation. Serum, saliva and milk samples were collected and analyzed. Data were statistically analyzed and the variation in serum and salivary biochemical constituents during lactation and dry period were discussed. From the present study, it could be concluded that the 1st month of lactation has the highest levels for serum free fatty acids (FFA, β- Hydroxy butyric acid (BHBA and aceto Acetic acid (ACAC. The dry period has the highest serum glucose level and the lowest serum FFA, BHBA and aspartate aminotransferase levels. Both serum and salivary FFA showed the highest value during the 1st month of lactation. Saliva contains a high level of gamma glutamyl transferase. The level of ammonia in saliva is higher than its serum level during all months of lactation and dry period. Most of the biochemical constituents in saliva change in different way from serum during lactation and dry period. Milk protein/fat ratio of 0.7 may be not indicative for subclinical ketosis.

Comparison of palmitic acid kinetics during glucose or ketone body infusions

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Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

1986-01-01

Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of [1- 14 C] palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat

Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine consanguineous Pakistani families.

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Ijaz, Sadaqat; Zahoor, Muhammad Yasir; Imran, Muhammad; Ramzan, Khushnooda; Bhinder, Munir Ahmad; Shakeel, Hussain; Iqbal, Muhammad; Aslam, Asim; Shehzad, Wasim; Cheema, Huma Arshad; Rehman, Habib

2017-10-26

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani families affected with FBPase deficiency. Nine families having one or two individuals affected with FBPase deficiency were enrolled over a period of 3 years. All FBP1 exonic regions including splicing sites were PCR-amplified and sequenced bidirectionally. Familial cosegregation of mutations with disease was confirmed by direct sequencing and PCR-RFLP analysis. Three different FBP1 mutations were identified. Each of two previously reported mutations (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA), which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase function. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals. FBPase deficiency is often fatal in the infancy and early childhood. Early diagnosis and prompt treatment is therefore crucial to preventing early mortality. We recommend the use of c.472C>T and c.841G>A mutations as first choice genetic markers for molecular diagnosis of FBPase deficiency in Pakistan.

Type 2 diabetes in children: Clinical aspects and risk factors

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P V Rao

2015-01-01

Full Text Available A strong link between obesity, insulin resistance, and metabolic syndrome has been reported with development of a new paradigm to type 2 diabetes mellitus (T2DM, with some evidence suggesting that beta-cell dysfunction is present before the onset of impaired glucose tolerance. Differentiating type 1 diabetes mellitus (T1DM from T2DM is actually not very easy and there exists a number of overlapping characteristics. The autoantibody frequencies of seven antigens in T1DM patients may turn out to be actually having T2DM patients (pre-T2DM. T2DM patients generally have increased C-peptide levels (may be normal at time of diagnosis, usually no auto-antibodies, strong family history of diabetes, obese and show signs of insulin resistance (hypertension, acanthosis, PCOS. The American Academy of Paediatrics recommends lifestyle modifications ± metformin when blood glucose is 126-200 mg/dL and hemoglobin A1c (HbA1c 200 mg/dL and HbA1c >8.5, with or without ketosis. Metformin is not recommended if the patient is ketotic, because this increases the risk of lactic acidosis. Metformin is currently the only oral hypoglycemic that has been approved for use in children. Knowing these subtle differences in mechanism, and knowing how to test patients for which mechanism (s are causing their diabetes mellitus, may help us eventually tailor treatment programs on an individual basis.

Clinical Characteristics of Wolfram Syndrome in Chinese Population and a Novel Frameshift Mutation in WFS1.

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Duan, Lian; Li, Qian; Tong, An-Li; Mao, Jiang-Feng; Yu, Miao; Yuan, Tao; Chai, Xiao-Feng; Gu, Feng

2018-01-01

Wolfram syndrome (WS) is a rare, degenerative, and hereditary disorder characterized by ear diabetes mellitus (DM) and optic atrophy (OA). We aim to characterize clinical features in Chinese patients who had been poorly studied until now. We performed a retrospective review of patients with WS seen in the Peking Union Medical College Hospital from 2002 to 2017. Data including demographic data, clinical presentations, examination results, family history, and genetic analysis were described. Six patients with WS were identified, meeting the diagnostic criteria of the coincidence of DM and OA before 15 years old or the existence of two WFS1 mutations. All were male, with the median age of 14.5 years (range 10-19 years). Blood glucose impairment, OA, and diabetes insipidus were present in all (100%), hearing impairment in four (66.7%), urological abnormalities in four (66.7%), neurological abnormalities in one (16.7%), and endocrine disorder in one (16.7%). Rare presentation includes cataract, glaucoma, and spina bifida occulta. Diabetes was insulin-dependent and not ketosis onset, with antibody to glutamic acid decarboxylase and islet cell negative. Genetic analysis revealed mutations in WFS1 in three patients. A novel frameshift mutation (p.Asp151Glufs*93) was identified in exon 4 of WFS1 . Our series of WS patients indicated that WS is a degenerative disease with a wide and variable spectrum, characterized by ear non-autoimmune DM and bilateral OA. Genetic analysis is recommended when suspected of WS.

Relationships between certain metabolic diseases and selected serum biochemical parameters in seropositive dairy cows against Neospora caninum infection in different stages of lactation

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Alekish, Myassar O.; Talafha, Abdelsalam Q; Alshehabat, Musa A; Ismail, Zuhair A Bani

Neospora caninum is an important cause of abortion in dairy cattle. The general health of affected cows has not been investigated before. Therefore, the main objective of this study was to identify possible relationships between certain metabolic diseases and selected serum biochemical parameters in seropositive dairy cows against N. caninum antibodies in different stages of lactation. The study was carried out using 72 N. caninum seropositive cows and 61 seronegative dairy cows (control). Serum from all cows was tested to determine their N. caninum status (seropositive vs seronegative) using commercially available indirect enzyme-linked immunosorbent assay test kit (iELISA). In addition, serum biochemical parameters including beta-hydroxybutyrate (BHB), glucose, creatinine, blood urea nitrogen, total protein, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyltranspeptidase (GGT) were determined using routine laboratory methods. The stage of lactation was obtained at the time of sampling from farm records. Student independent t-test showed that there was a significant difference in the serum concentrations of BHB, AST, ALT, and LDH between seropositive and seronegative cows. There was no significant association between seropositivity and the stage of lactation. However, multivariable logistic regression analysis showed that there was a strong association between seropositivity and BHB concentrations. Results of this study indicate a possible relationship between N. caninum seropositivity and certain metabolic diseases such as ketosis and fatty liver syndrome in dairy cows.

Different ketogenesis strategies lead to disparate seizure outcomes.

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Dolce, Alison; Santos, Polan; Chen, Weiran; Hoke, Ahmet; Hartman, Adam L

2018-07-01

Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration. Male NIH Swiss mice (aged 3-4 weeks) were fed for 12-13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 Hz threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondrial respiration was tested in brain tissue isolated from similarly-fed seizure-naïve mice. KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondrial respiration between diet regimens. KD and CD-IF do not share identical antiseizure mechanisms. These differences were not explained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further. Published by Elsevier B.V.

Anorexia nervosa in children and adolescents: diagnosis, treatment and the role of the pediatrician.

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Silber, T J

2013-02-01

The diagnosis and treatment of anorexia nervosa (AN) in children and adolescents has some commonality but also differs from that of this condition in adults. A new understanding of AN is emerging: research data from the fields of epidemiology, genetics, and brain biology, suggest that there may be an underlying brain diathesis predisposing towards AN. It is now proposed that that what starts as a harmless diet, once it turns into a more prolonged food restriction may trigger an eating disorder in a genetically neurobiologically predisposed population. The condition may be then perpetuated by the biochemical changes induced by weight loss, ketosis, and the impact of the ensuing malnutrition on the brain (starvation illness). This change of paradigm from a psychological understanding to a neurobiological conceptualization calls for an early intervention to assure nutritional rehabilitation as soon as an eating disorder is suspected in children, without needing to wait for all the classical features of the diagnosis as seen in adults. This new model is agnostic about the origins of the disease and questions the classic assumption of "an underlying family pathology". It gives strong support to treatments such as Family Based Treatment, also referred to as the "Maudsley method". Essentially this consists of empowering parents to monitor and supervise the nutritional rehabilitation of their children. Hence pediatricians no longer need to be bystanders when treating these children and adolescents. They now have a clearly defined role: early diagnosticians, clinical monitors (of potential medical complications), nutrition advisors, and as members of a multidisciplinary team, patient and family advocates and educators.

New Nordic Diet versus Average Danish Diet: A Randomized Controlled Trial Revealed Healthy Long-Term Effects of the New Nordic Diet by GC-MS Blood Plasma Metabolomics.

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Khakimov, Bekzod; Poulsen, Sanne Kellebjerg; Savorani, Francesco; Acar, Evrim; Gürdeniz, Gözde; Larsen, Thomas M; Astrup, Arne; Dragsted, Lars O; Engelsen, Søren Balling

2016-06-03

A previous study has shown effects of the New Nordic Diet (NND) to stimulate weight loss and lower systolic and diastolic blood pressure in obese Danish women and men in a randomized, controlled dietary intervention study. This work demonstrates long-term metabolic effects of the NND as compared with an Average Danish Diet (ADD) in blood plasma and reveals associations between metabolic changes and health beneficial effects of the NND including weight loss. A total of 145 individuals completed the intervention and blood samples were taken along with clinical examinations before the intervention started (week 0) and after 12 and 26 weeks. The plasma metabolome was measured using GC-MS, and the final metabolite table contained 144 variables. Significant and novel metabolic effects of the diet, resulting weight loss, gender, and intervention study season were revealed using PLS-DA and ASCA. Several metabolites reflecting specific differences in the diets, especially intake of plant foods and seafood, and in energy metabolism related to ketone bodies and gluconeogenesis formed the predominant metabolite pattern discriminating the intervention groups. Among NND subjects, higher levels of vaccenic acid and 3-hydroxybutanoic acid were related to a higher weight loss, while higher concentrations of salicylic, lactic, and N-aspartic acids and 1,5-anhydro-d-sorbitol were related to a lower weight loss. Specific gender and seasonal differences were also observed. The study strongly indicates that healthy diets high in fish, vegetables, fruit, and whole grain facilitated weight loss and improved insulin sensitivity by increasing ketosis and gluconeogenesis in the fasting state.

Nutritional strategies to optimize dairy cattle immunity.

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Sordillo, L M

2016-06-01

Dairy cattle are susceptible to increased incidence and severity of both metabolic and infectious diseases during the periparturient period. A major contributing factor to increased health disorders is alterations in bovine immune mechanisms. Indeed, uncontrolled inflammation is a major contributing factor and a common link among several economically important infectious and metabolic diseases including mastitis, retained placenta, metritis, displaced abomasum, and ketosis. The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. There is now a greater appreciation that certain mediators of the immune system can have a reciprocal effect on the metabolism of nutrients. Thus, any disturbances in nutritional or immunological homeostasis can provide deleterious feedback loops that can further enhance health disorders, increase production losses, and decrease the availability of safe and nutritious dairy foods for a growing global population. This review will discuss the complex interactions between nutrient metabolism and immune functions in periparturient dairy cattle. Details of how either deficiencies or overexposure to macro- and micronutrients can contribute to immune dysfunction and the subsequent development of health disorders will be presented. Specifically, the ways in which altered nutrient metabolism and oxidative stress can interact to compromise the immune system in transition cows will be discussed. A better understanding of the linkages between nutrition and immunity may facilitate the design of nutritional regimens that will reduce disease susceptibility in early lactation cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reveal genes functionally associated with ACADS by a network study.

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Chen, Yulong; Su, Zhiguang

2015-09-15

Establishing a systematic network is aimed at finding essential human gene-gene/gene-disease pathway by means of network inter-connecting patterns and functional annotation analysis. In the present study, we have analyzed functional gene interactions of short-chain acyl-coenzyme A dehydrogenase gene (ACADS). ACADS plays a vital role in free fatty acid β-oxidation and regulates energy homeostasis. Modules of highly inter-connected genes in disease-specific ACADS network are derived by integrating gene function and protein interaction data. Among the 8 genes in ACADS web retrieved from both STRING and GeneMANIA, ACADS is effectively conjoined with 4 genes including HAHDA, HADHB, ECHS1 and ACAT1. The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with ACADS are HAHDA, HADHB, ECHS1 and ACAT1. Interestingly, the ontological aspect of genes in the ACADS network reveals that ACADS, HAHDA and HADHB play equally vital roles in fatty acid metabolism. The gene ACAT1 together with ACADS indulges in ketone metabolism. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of ACADS, HAHDA, HADHB, ECHS1 and ACAT1 not only with lipid metabolism but also with infant death syndrome, skeletal myopathy, acute hepatic encephalopathy, Reye-like syndrome, episodic ketosis, and metabolic acidosis. The current study presents a comprehensible layout of ACADS network, its functional strategies and candidate disease approach associated with ACADS network. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical Characteristics of Wolfram Syndrome in Chinese Population and a Novel Frameshift Mutation in WFS1

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Lian Duan

2018-02-01

Full Text Available ObjectiveWolfram syndrome (WS is a rare, degenerative, and hereditary disorder characterized by ear diabetes mellitus (DM and optic atrophy (OA. We aim to characterize clinical features in Chinese patients who had been poorly studied until now.MethodsWe performed a retrospective review of patients with WS seen in the Peking Union Medical College Hospital from 2002 to 2017. Data including demographic data, clinical presentations, examination results, family history, and genetic analysis were described.ResultsSix patients with WS were identified, meeting the diagnostic criteria of the coincidence of DM and OA before 15 years old or the existence of two WFS1 mutations. All were male, with the median age of 14.5 years (range 10–19 years. Blood glucose impairment, OA, and diabetes insipidus were present in all (100%, hearing impairment in four (66.7%, urological abnormalities in four (66.7%, neurological abnormalities in one (16.7%, and endocrine disorder in one (16.7%. Rare presentation includes cataract, glaucoma, and spina bifida occulta. Diabetes was insulin-dependent and not ketosis onset, with antibody to glutamic acid decarboxylase and islet cell negative. Genetic analysis revealed mutations in WFS1 in three patients. A novel frameshift mutation (p.Asp151Glufs*93 was identified in exon 4 of WFS1.ConclusionOur series of WS patients indicated that WS is a degenerative disease with a wide and variable spectrum, characterized by ear non-autoimmune DM and bilateral OA. Genetic analysis is recommended when suspected of WS.

Diabetes tipo 2 en niños y adolescentes: aspectos clínico-epidemiológicos, patogénicos y terapéuticos Type 2 diabetes mellitus in children and adolescents: clinicoepidemiological, pathogenic and therapeutic aspects

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Manuel Emiliano Licea Puig

2008-04-01

Full Text Available OBJETIVO: debido al incremento sostenido en la incidencia de la diabetes mellitus tipo 2 en personas OBJECTIVE: due to the sustained increase in the incidence of type 2 diabetes mellitus in persons under 20, the clinicoepidemiological, pathogenic and therapeutic aspects of type 2 diabetes mellitus in children and adolescents were reviewed. DEVELOPMENT: in children, it is estimated that type 2 diabetes mellitus accounts for 2-3 % of all cases. However, in the last years, there has been a ten-fold increase. Its prevalence is higher among Afro-Americans, Hispanics and native Americans, in puberty and in those with history of type 2 maternal diabetes mellitus. Type 2 diabetes mellitus is the result of the interaction of genetic and environmental factors (obesity, physical inactivity, poor nutritional habits, among others. There is a wide range of clinical manifestations: severe hyperglycaemia with ketonuria and ketosis to a mild hyperglycaemia. 50 % may be asymptomatic. Obesity, Acantosis nigricans, family history of type 2 diabetes mellitus, puberty, and type 2 maternal diabetes mellitus are risk factors. It prevails in females, autoimmunity is rare and the dependence on insulin may be episodic. Those with the highest hyperglycaemia have lower levels of insulinemia and peptide C. When hyperglycaemia is mild, diet, physical exercise and, in some cases, the administration of oral drugs, such as metformin, may be useful. CONCLUSIONS: type 2 diabetes mellitus in children and adolescents is a reality. Evolutively, most of them do not need insulin therapy. They may have retinopathy, microalbuminuria, dyslipidemia and arterial hypertension on diagnosis. Risk populations should be actively screened.

Long-term outcome of isobutyryl-CoA dehydrogenase deficiency diagnosed following an episode of ketotic hypoglycaemia

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S. Santra

2017-03-01

Full Text Available Isobutyryl-CoA Dehydrogenase Deficiency (IBDD is an inherited disorder of valine metabolism caused by mutations in ACAD8. Most reported patients have been diagnosed through newborn screening programmes due to elevated C4-carnitine levels and appear clinically asymptomatic. One reported non-screened patient had dilated cardiomyopathy and anaemia at the age of two years. We report a 13 month old girl diagnosed with IBDD after developing hypoglycaemic encephalopathy (blood glucose 1.9 mmol/l during an episode of rotavirus-induced gastroenteritis. Metabolic investigations demonstrated an appropriate ketotic response (free fatty acids 2594 μmol/l, 3-hydroxybutyrate 3415 μmol/l, mildly elevated plasma lactate (3.4 mmol/l, increased C4-carnitine on blood spot and plasma acylcarnitine analysis and other metabolic abnormalities secondary to ketosis. After recovery, C4-carnitine remained increased and isobutyrylglycine was detected on urine organic acid analysis. Free carnitine was normal in all acylcarnitine samples. IBDD was confirmed by finding a homozygous c.845C > T substitution in ACAD8. The patient was given, but has not used, a glucose polymer emergency regimen and after ten years' follow-up has had no further episodes of hypoglycaemia nor has she developed cardiomyopathy or anaemia. Psychomotor development has been normal to date. Though we suspect IBDD did not contribute to hypoglycaemia in this patient, patients should be followed-up carefully and glucose polymer emergency regimens may be indicated if recurrent episodes of hypoglycaemia occur.

Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation

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Evans, Mark; Cogan, Karl E.

2016-01-01

Abstract Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β‐hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post‐exercise recovery period, and the ability to utilise ketone bodies is higher in exercise‐trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti‐lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with βHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of βHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes. PMID:27861911

Deficiência da 3-OH-3-metil-glutaril-CoA-liase como causa de coma no período neonatal: relato de caso 3-hydroxy-3-methylglutaryl-CoA-lyase deficiency as coma etiology in the neonatal period: case report

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ERASMO BARBANTE CASELLA

1998-09-01

Full Text Available Estudamos um paciente que apresentou dois episódios de coma no primeiro mês de vida, com descompensação metabólica, nos quais se observou hipoglicemia e acidose metabólica acentuada, sem cetonúria. O estudo dos ácidos orgânicos urinários demonstrou elevação acentuada de 3-OH-3-metil-glutárico, 3-metil-glutacônico, 3-metil-glutárico e 3-OH-isovalérico. Os sinais e sintomas clínicos associados às alterações metabólicas citadas permitiram o diagnóstico da deficiência da 3-OH-3-metil-glutaril-CoA-liase, entidade de origem autossômica recessiva, passível de ser tratada, como no caso estudado, com dieta hipoproteica, restrita em leucina, hipogordurosa e rica em carboidratos, associada a L-carnitina e evitando-se períodos prolongados de jejum.We report a patient that presented two episodes of coma in the neonatal period, with severe metabolic acidosis and hypoglycemia, without ketosis. The urinary organic acid analysis showed increased amounts of 3-hydroxy-3-methyl-glutaric, 3-methylglutaconic, 3-methylglutaric and 3-hydroxyisovaleric acid. The deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase was diagnosed by the clinical and metabolic features. This disease shows autosomal recessive inheritance and the treatment is done by a diet with restriction of protein (mainly leucine and lipids, high in carbohydrate content, and the avoidance of fasting and carnitine supplementation.

Hepatic lipidosis in anorectic, lactating holstein cattle: a retrospective study of serum biochemical abnormalities.

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Cebra, C K; Garry, F B; Getzy, D M; Fettman, M J

1997-01-01

The association between hepatic lipidosis (HL) and disease in 59 anorectic, ketotic, lactating Holstein heifers and cows was investigated. Severe HL, as determined by histologic evaluation of liver tissue, was present in 46 animals; only half of these animals required intensive treatment for ketosis, and only half had serum biochemical evidence of liver disease, as determined by the presence of a last value of 2-fold or greater than the upper limit of the reference ranges for at least 2 of the 4 serum tests: gamma-glutamyl transferase, aspartate aminotransferase, and sorbitol dehydrogenase activities and bile acid concentrations. Most cattle with biochemical evidence of liver disease and severe HL had been lactating for 14 or more days. Cows that required intensive treatment inconsistently had serum biochemical evidence of liver disease. Although cattle with severe HL had significantly higher serum bilirubin concentrations and aspartate aminotransferase and sorbitol dehydrogenase activities than cattle with less severe lipidosis, the specificity of abnormally high serum sorbitol dehydrogenase activity or bilirubin concentration for severe lipidosis was only 8%. Abnormally high serum aspartate aminotransferase activity was 83% sensitive and 62% specific for severe lipidosis. Serum glucose and total carbon dioxide concentrations were significantly lower in cattle with severe lipidosis than in those with mild or moderate lipidosis, and low serum glucose or total carbon dioxide concentrations were rare in cattle without severe lipidosis. From these data, we conclude that the use of a single biochemical or histopathologic criterion to define severity of disease or degree of liver compromise in anorectic, ketotic cows results in the misidentification of many animals.

Postpartum body condition score and results from the first test day milk as predictors of disease, fertility, yield, and culling in commercial dairy herds.

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Heuer, C; Schukken, Y H; Dobbelaar, P

1999-02-01

The study used field data from a regular herd health service to investigate the relationships between body condition scores or first test day milk data and disease incidence, milk yield, fertility, and culling. Path model analysis with adjustment for time at risk was applied to delineate the time sequence of events. Milk fever occurred more often in fat cows, and endometritis occurred between calving and 20 d of lactation more often in thin cows. Fat cows were less likely to conceive at first service than were cows in normal condition. Fat body condition postpartum, higher first test day milk yield, and a fat to protein ratio of > 1.5 increased body condition loss. Fat or thin condition or condition loss was not related to other lactation diseases, fertility parameters, milk yield, or culling. First test day milk yield was 1.3 kg higher after milk fever and was 7.1 kg lower after displaced abomasum. Higher first test day milk yield directly increased the risk of ovarian cyst and lameness, increased 100-d milk yield, and reduced the risk of culling and indirectly decreased reproductive performance. Cows with a fat to protein ratio of > 1.5 had higher risks for ketosis, displaced abomasum, ovarian cyst, lameness, and mastitis. Those cows produced more milk but showed poor reproductive performance. Given this type of herd health data, we concluded that the first test day milk yield and the fat to protein ratio were more reliable indicators of disease, fertility, and milk yield than was body condition score or loss of body condition score.

Racial Disparities in the Pathogenesis of Type 2 Diabetes and its Subtypes in the African Diaspora: A New Paradigm.

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Gaillard, Trudy R; Osei, Kwame

2016-03-01

The global epidemic of diabetes has extended to the developing countries including Sub-Sahara Africa. In this context, blacks with type 2 diabetes in the African Diaspora continue to manifest 1.5-2 times higher prevalent rates than in their white counterparts. Previous studies have demonstrated that blacks with and without type 2 diabetes have alterations in hepatic and peripheral insulin sensitivity, beta-cell function, and hepatic insulin clearance as well as hepatic glucose dysregulation when compared to whites. In addition, non-diabetic blacks in the African Diaspora manifest multiple metabolic mediators that predict type 2 diabetes and its subtypes. These pathogenic modifiers include differences in subclinical inflammation, oxidative stress burden, and adipocytokines in blacks in the African Diaspora prior to clinical diagnosis. Consequently, blacks in the African Diaspora manifest subtypes of type 2 diabetes, including ketosis-prone diabetes and J type diabetes. Given the diversity of type 2 diabetes in blacks in the African Diaspora, we hypothesize that blacks manifest multiple early pathogenic defects prior to the diagnosis of type 2 diabetes and its subtypes. These metabolic alterations have strong genetic component, which appears to play pivotal and primary role in the pathogenesis of type 2 diabetes and its subtypes in blacks in the African Diaspora. However, environmental factors must also be considered as major contributors to the higher prevalence of type 2 diabetes and its subtypes in blacks in the African Diaspora. These multiple alterations should be targets for early prevention of type 2 diabetes in blacks in the African Diaspora.

A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes.

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Saslow, Laura R; Kim, Sarah; Daubenmier, Jennifer J; Moskowitz, Judith T; Phinney, Stephen D; Goldman, Veronica; Murphy, Elizabeth J; Cox, Rachel M; Moran, Patricia; Hecht, Fredrick M

2014-01-01

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.

Metabolic predictors of peri-partum diseases and their association with parity in dairy cows.

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Ruprechter, Gretel; Adrien, Maria de Lourdes; Larriestra, Alejandro; Meotti, Otavio; Batista, Chester; Meikle, Ana; Noro, Mirela

2018-02-19

The predictive values of plasma non-esterified fatty acid (NEFA), beta-hydroxybutyrate (BHB), cholesterol, albumin and calcium to predict risk of peripartum diseases in primiparous (PP) and multiparous (MP) Holstein cows was investigated. Besides it was assessed if the health status interacted with parity on body condition score and metabolic profiles during the transition period. Dairy cows (126 PP and 182 MP) from a commercial dairy free stall herd (loose-housing system) were weekly body condition scored and tail bled for metabolites determination from -3 to +4 weeks relative to calving. Peripartum diseases were diagnosed by a single trained veterinarian, while subclinical diseases (ketosis and hypocalcemia) were diagnosed at the laboratory. Cows were classified as healthy cows, cows with one event, or cows with two clinical events following a prospective observational cohort study, with only healthy cows enrolled at the beginning of the study. The largest incidence was for metritis (26.6%) followed by retained placenta (17.2%) and mastitis (15.2%) with no effect of parity, while subclinical hypocalcemia incidence was greater in MP than PP cows (43% vs 9.5%) respectively. In MP cows albumin concentrations were predictive for metritis at week -2 and for retained placenta at weeks -2 and -1, while cholesterol was predictive for mastitis at week -2, -1 and at calving. The interaction between health status and parity affected all metabolites during the transition period. This study showed a different evolution of metabolic profiles in healthy and sick cows during the transition according to parity, pointing out albumin and cholesterol as diseases predictors before calving. Copyright © 2018 Elsevier Ltd. All rights reserved.

Trans-arterial xenotransplantation (Tx) of newborn porcine islet (NPI). A clinic trial for type I diabetes

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Wang Wei; Mo Zhaohui; Huang Zufa; Luo Xianming; Liu Sheng; Ye Bin; Li Bing; Liu Yingxin

2002-01-01

Objective: Liver is an important site to host transplanted islets, and implanting of islets by hepatic artery is simpler than by portal vein. Authors' study evaluated efficiency of the method and possible complication in a clinical setting. Methods: From October 1998 to June 2000, 4 type I diabetic patients received 4 x 10 6 (2 cases) and 8 x 10 6 (2 cases) of NPI through hepatic artery. Before Tx, all cases had the history with ketosis and acidosis. Exogenous insulin doses used for these cases were 25-48 units and their GHb was 9%-11%. After Tx, the NPI recipients were treated with immunosuppressants including cyclosporin 8 mg/kg for 12 months, cellcept 2 g/d for 25 days, and methylprednisolone 500 mg at 1 st day, then reduced to 50 mg for 3 days until to 10 mg for 1 month. Liver function and CD4/CD8 of the recipients were measured before and after Tx. Results: After Tx, the dose of exogenous insulin was increased to 60 mg due to methylprednisolone treatment. When methylprednisolone dose was decreased, the requirement for insulin was reduced to 32%-58% of the dose used before Tx. The reduction of required insulin for NPI recipients was proportional to the number of implanted NPI. In addition, GHb was also reduced to normal level (4%-6%) 3 months after Tx. No significant alterations of liver function and CD4 and CD8 in blood were observed after Tx. Conclusion: Trans-arterial intro-hepatic xenotransplantation of NPI is an efficient and safe therapeutic method for type I diabetes. Combination of cyclosporin, cellcept, and methylprednisolone is an effective immunosuppressive strategy for NPI xenograft transplantation

Ketogenic Diet Therapy in Infants: Efficacy and Tolerability.

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Wirrell, Elaine; Eckert, Susan; Wong-Kisiel, Lily; Payne, Eric; Nickels, Katherine

2018-05-01

This study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. Infants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. Twenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital. Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1). Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. The ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake. Copyright © 2018 Elsevier Inc. All rights reserved.

Ketogenic diet and astrocyte/neuron metabolic interactions

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Vamecq Joseph

2007-05-01

Full Text Available The ketogenic diet is an anticonvulsant diet enriched in fat. It provides the body with a minimal protein requirement and a restricted carbohydrate supply, the vast majority of calories (more than 80-90% being given by fat. Though anticonvulsant activity of ketogenic diet has been well documented by a large number of experimental and clinical studies, underlying mechanisms still remain partially unclear. Astrocyte-neuron interactions, among which metabolic shuttles, may influence synaptic activity and hence anticonvulsant protection. The astrocyte-neuron metabolic shuttles may be themselves influenced by the availability in energetic substrates such as hydrates of carbon and fats. Historically, ketogenic diet had been designed to mimic changes such as ketosis occurring upon starvation, a physiological state already known to exhibit anticonvulsant protection and sometimes referred to as “water diet”. For this reason, a special attention should be paid to metabolic features shared in common by ketogenic diet and starvation and especially those features that might result in anticonvulsant protection. Compared to feeding by usual mixed diet, starvation and ketogenic diet are both characterised by increased fat, lowered glucose and aminoacid supplies to cells. The resulting impact of these changes in energetic substrates on astrocyte/neuron metabolic shuttles might have anticonvulsant and/or neuroprotective properties. This is the aim of this communication to review some important astrocyte/neuron metabolic interactions (astrocyte/neuron lactate shuttle, glutamateinduced astrocytic glycolysis activation, glutamate/glutamine cycle along with the neurovascular coupling and the extent to which the way of their alteration by starvation and/or ketogenic diet might result in seizure and/or brain protection.

A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth.

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De Feyter, Henk M; Behar, Kevin L; Rao, Jyotsna U; Madden-Hennessey, Kirby; Ip, Kevan L; Hyder, Fahmeed; Drewes, Lester R; Geschwind, Jean-François; de Graaf, Robin A; Rothman, Douglas L

2016-08-01

The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Ketone body oxidation was studied using (13)C MR spectroscopy in combination with infusion of a (13)C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. The level of (13)C-beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease.

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Moreno, Basilio; Crujeiras, Ana B; Bellido, Diego; Sajoux, Ignacio; Casanueva, Felipe F

2016-12-01

The long-term effect of therapeutic diets in obesity treatment is a challenge at present. The current study aimed to evaluate the long-term effect of a very low-calorie-ketogenic (VLCK) diet on excess adiposity. Especial focus was set on visceral fat mass, and the impact on the individual burden of disease. A group of obese patients (n = 45) were randomly allocated in two groups: either the very low-calorie-ketogenic diet group (n = 22), or a standard low-calorie diet group; (n = 23). Both groups received external support. Adiposity parameters and the cumulative number of months of successful weight loss (5 or 10 %) over a 24-month period were quantified. The very low-calorie-ketogenic diet induced less than 2 months of mild ketosis and significant effects on body weight at 6, 12, and 24 months. At 24 months, a trend to regress to baseline levels was observed; however, the very low-calorie-ketogenic diet induced a greater reduction in body weight (-12.5 kg), waist circumference (-11.6 cm), and body fat mass (-8.8 kg) than the low-calorie diet (-4.4 kg, -4.1 cm, and -3.8 kg, respectively; p ketogenic diet group experienced a reduction in the individual burden of obesity because reduction in disease duration. Very low-calorie-ketogenic diet patients were 500 months with 5 % weight lost vs. the low-calorie diet group (350 months; p ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease.

Effect of One Month Duration Ketogenic and non-Ketogenic High Fat Diets on Mouse Brain Bioenergetic Infrastructure

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Selfridge, J. Eva; Wilkins, Heather M.; Lezi, E; Carl, Steven M.; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H.

2014-01-01

Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain’s aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated. PMID:25104046

Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation.

Science.gov (United States)

Evans, Mark; Cogan, Karl E; Egan, Brendan

2017-05-01

Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β-hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post-exercise recovery period, and the ability to utilise ketone bodies is higher in exercise-trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti-lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with βHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of βHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Effect of Non-Esterified Fatty Acids on Fatty Acid Metabolism-Related Genes in Calf Hepatocytes Cultured in Vitro

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Peng Li

2013-11-01

Full Text Available Background: NEFA plays numerous roles in the metabolism of glucose, lipids, and proteins. A number of experimental studies have shown that NEFA may have an important role in fatty acid metabolism in the liver, especially in dairy cows that experience negative energy balance (NEB during early lactation. Methods: In this study, using fluorescent quantitative RT-PCR, ELISA, and primary hepatocytes cultured in vitro, we examined the effect of NEFA (0, 0.2, 0.4, 0.8, 1.6, and 3.2 mmol/L on fatty acid metabolism by monitoring the mRNA and protein expression of the following key enzymes: long chain acyl-CoA synthetase (ACSL, carnitine palmitoyltransferase IA (CPT IA, long chain acyl-CoA dehydrogenase (ACADL, and acetyl-CoA carboxylase (ACC. Results: The mRNA and protein expression levels of ACSL and ACADL markedly increased as the concentration of NEFA in the media was increased. The mRNA and protein expression levels of CPT IA were enhanced significantly when the NEFA concentrations increased from 0 to 1.6 mmol/L and decreased significantly when the NEFA concentrations increased from 1.6 to 3.2 mmol/L. The mRNA and protein expression of ACC decreased gradually with increasing concentrations of NEFA. Conclusion: These findings indicate that increased NEFA significantly promote the activation and β-oxidation of fatty acids, but very high NEFA concentrations may inhibit the translocation of fatty acids into mitochondria of hepatocytes. This may explain the development of ketosis or liver lipidosis in dairy cows. CPT IA might be the key control enzyme of the fatty acid oxidation process in hepatocytes.

Haematological and blood biochemical profile in lactating buffaloes in and around Parbhani city

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S. D. Hagawane

Full Text Available Forty buffaloes in early, mid and late lactation with a drop in a milk production were screened for haematological and blood biochemical profile. In early stage of lactation haemoglobin concentration showed lowered trend as compared to recorded means in other groups of lactating buffaloes.  The mean value of TLC in dry pregnant group of buffaloes was 10.05± 0.89 X 103 /cmm showed slightly higher trend than the normal healthy control group. The blood glucose was significantly higher in dry buffaloes (52.72±4.22 mg/dl than the early and late lactating buffaloes (48.23±3.44 mg/dl. During early stage of lactation the serum total protein values (8.36±0.47 g/dl was slightly elevated than the normal healthy control (8.00±0.57 g/dl. The urea nitrogen values differ significantly (P<0.05 amongst different groups of lactating buffaloes. The descending trend in the serum cholesterol concentration in dry pregnant buffaloes compared to lactating buffaloes was observed. There was drop in calcium level during early stage of lactation (8.19±0.83 mg/dl than the normal healthy buffaloes (11.21±0.19 mg/dl. As the stage of lactation progresses the serum calcium level increased. Serum magnesium concentration in various groups of buffaloes did not differ significantly. Early lactation showed highest susceptibility for ketosis and hypocalcaemia. The metabolic disorder associated with hypophosphatemia was significantly high in dry (advance pregnant buffaloes. [Vet World 2009; 2(12.000: 467-469

Retrospective case studies of the efficacy of caprylic triglyceride in mild-to-moderate Alzheimer's disease

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Maynard SD

2013-10-01

Full Text Available Steven Douglas Maynard,1,2 Jeff Gelblum31Union Associated Physicians Clinic, 2Indiana University School of Medicine, Terre Haute, IN, 3Mt Sinai Medical Center of Miami, Aventura Hospital, Aventura, FL, USAAbstract: Under normal conditions, the adult human brain is fueled primarily by glucose. A prominent feature of Alzheimer's disease (AD is region-specific decreases in cerebral glucose metabolism. Ketone bodies are a group of compounds produced from fat stores during periods of low glucose availability that can provide an alternative to glucose for brain metabolism. Consumption of sufficient quantities of caprylic triglyceride (CT increases plasma concentrations of ketone bodies and may be beneficial in conditions of compromised glucose metabolism, such as AD. The present study describes the use of CT in mild-to-moderate AD in routine clinical practice. Case records from eight patients with extensive monitoring of cognitive function using the Mini-Mental State Examination (MMSE and who had received CT for ≥6 months were reviewed. All were outpatients aged ≥50 years, cared for in standard practice, had a diagnosis of probable AD of mild-to-moderate severity (MMSE 14–24, and had received CT for at least 6 months in addition to other approved pharmacotherapy for AD. Response to CT administration as measured by MMSE scores varied by patient. However, the rate of decline in MMSE scores appeared slower than previously published reports for patients treated with pharmacotherapy alone. Profiling of individual patients may provide insight regarding those most likely to benefit from addition of CT to currently approved AD pharmacotherapy.Keywords: ketosis, cognition, Alzheimer's disease, metabolism, glucose

[Evaluation of a new electronic handheld meter for measurement of β-hydroxybutyric acid in dairy cows].

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Mahrt, A; Burfeind, O; Voigtsberger, R; Müller, A; Heuwieser, W

2014-01-01

Subclinical ketosis (SCK), an important disease in lactating dairy cows, is defined as the presence of elevated concentrations of circulating ketone bodies without the development of clinical signs. Therefore, diagnostic methods are limited to the detection of the concentrations of ketone bodies in different body fluids. The objective of this study was to evaluate a recently developed electronic hand- held meter (NovaVet) for the determination of β-hydroxybutyric acid (BHB) in the blood of dairy cows. A total of 155 lactating dairy cows were included in the trial. Blood samples were taken from each cow and analyzed using the BHB meter. The obtained concentrations were compared to the results determined by a commercial laboratory. The Spearman's rank correlation coefficient was determined between the two methods. A Wilcoxon test was performed and a Bland-Altman plot was generated. Test characteristics (sensitivity, specificity, positive and negative predictive value) for established BHB cut points for the diagnosis of SCK were calculated using receiver operating characteristic (ROC) analysis. The two methods were highly correlated (rs = 0.87; p meter (median 1.0 mmol/l; IQR 0.7-1.3 mmol/l) and by the laboratory (median 0.9 mmol/l; IQR 0.7-1.1 mmol/l). Using a cut point of 1.2 mmol/l, sensitivity and specificity of the BHB meter were 97% and 82%, respectively. There was a good agreement between BHB concentrations determined using the BHB meter and the laboratory. Furthermore, the BHB meter displayed good test characteristics. The specificity of 82% results in a number of false-positive results. However, this new device can be recommended for the detection of SCK in cows under practical conditions.

Euglycemic Diabetic Ketoacidosis with Elevated Acetone in a Patient Taking a Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor.

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Andrews, Tory J; Cox, Robert D; Parker, Christina; Kolb, James

2017-02-01

Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose > 500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. Acetone is one of the three main ketone bodies formed during DKA and it may be present at considerable concentrations, contributing to the serum osmolality. Copyright © 2016 Elsevier Inc. All rights reserved.

Short communication: Associations between blood glucose concentration, onset of hyperketonemia, and milk production in early lactation dairy cows.

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Ruoff, J; Borchardt, S; Heuwieser, W

2017-07-01

The objectives of this study were to describe the associations between hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of lactation, to evaluate the effects of body condition score at calving on glucose concentration, and to study the effects of hypoglycemia on milk production. A total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an electronic handheld meter for glucose and β-hydroxybutyrate (BHB), respectively, for a period of 42 d. Hypoglycemia was defined as glucose concentration ≤2.2 mmol/L. Hyperketonemia was defined as a BHB concentration ≥1.2 mmol/L. The onset of HYK was described as early onset (first HYK event within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6 postpartum). The effect of ketosis status on blood glucose within 42 DIM was evaluated using a generalized linear mixed model. No effect was observed of HYK on glucose concentration in primiparous cows. Multiparous cows with early-onset HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic cows. Overall, primiparous cows had a lower prevalence and incidence of hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was associated with higher first test-day milk production and 100 DIM milk production. In conclusion, hypoglycemia mainly occurred in multiparous cows with early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Nutritional Ketosis Condition and Specific Ketogenic Diet, May Benefit Cancer Patients as an Alternative Treatment by Sudden Change in the Metabolic State of Cancer Cells

OpenAIRE

Somayeh Zaminpira; Somayeh Zaminpira

2017-01-01

Cancer disease is the second cause of death in the United States and world-wide. Most Researchers estimate that 595,690 of American people will die from cancer at the end of the year 2017. That means 1,600 deaths/day approximately [1]. Cancer in modern societies is commonly treated with the combination of organ surgery, chemotherapy and radiotherapy. Many kinds of diet strategies have been experimented. However, none of them have been particularly effective. Interestingly, the...

Effects of treatment of periparturient dairy cows with recombinant bovine somatotropin on health and productive and reproductive parameters.

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Silva, P R B; Soares, H F; Braz, W D; Bombardelli, G D; Clapper, J A; Keisler, D H; Chebel, R C

2017-04-01

of metritis (HO-control = 26.2, HO-rbST125 = 16.6, JS-control = 19.9, JS-rbST125 = 13.3%) compared with control cows. Ketosis incidence tended to be higher for rbST125 cows (HO-control = 9.4, HO-rbST125 = 11.3, JS-control = 8.5, JS-rbST125 = 13.4%) compared with control cows. The interaction between treatment and herd tended to affect yield of ECM during the first 30 DIM because HO cows treated with rbST during the periparturient period had greater yield than control HO cows (HO-control = 35.5 ± 1.0 vs. HO-rbST125 = 39.4 ± 1.0 kg/d), but treatment with rbST did not affect yield of ECM of JS cows (JS-control = 26.7 ± 0.6 vs. JS-rbST125 = 27.8 ± 0.6 kg/d). Treatment of periparturient dairy cows with 125 mg of rbST decreased the incidence of uterine disorders in HO and JS cows and increased yield of ECM during the first 30 DIM among HO cows, despite slightly increasing the incidence of ketosis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals

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Dorian S Houser

2013-11-01

Full Text Available Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris, which fasts from food and water for periods of up to three months. During this time, ~90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM. All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures

The effect of maternal fasting during Ramadan on preterm delivery: a prospective cohort study.

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Awwad, J; Usta, I M; Succar, J; Musallam, K M; Ghazeeri, G; Nassar, A H

2012-10-01

To determine the effect of fasting during the month of Ramadan on the rate of preterm delivery (PTD). A prospective cohort study of women with singleton pregnancies who elected to fast and matched controls. Four medical centres in Beirut, Lebanon. Women presenting for prenatal care (20-34 weeks of gestation) during the month of Ramadan, September 2008. Data were collected prospectively. The frequency of PTD was evaluated in relation to the duration of fasting and the stage of gestation at the time of fasting. The primary endpoint was the percentage of pregnant women who had PTD, defined as delivery before 37 completed weeks of gestation. A total of 468 women were approached, of whom 402 were included in the study. There were no differences in smoking history and employment. There was no difference in the proportion of women who had PTD at Ramadan-fasted group and the controls, respectively. The PTD rate was also similar in those who fasted before or during the third trimester. The mean birthweight was lower (3094 ± 467 g versus 3202 ± 473 g, P = 0.024) and the rate of ketosis and ketonuria was higher in the Ramadan-fasted women. On multivariate stepwise logistic regression analysis, fasting was not associated with an increased risk of PTD (odds ratio 0.72; 95% confidence interval 0.34-1.54; P = 0.397). The only factor that had a significant effect on the PTD rate was body mass index (odds ratio 0.43; 95% confidence interval 0.20-0.93; P = 0.033). Fasting during the month of Ramadan does not seem to increase the baseline risk of preterm delivery in pregnant women regardless of the gestational age during which this practice is observed. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

State of the science: VLED (Very Low Energy Diet) for obesity.

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Delbridge, Elizabeth; Proietto, Joseph

2006-01-01

It is often stated, "the faster you lose weight, the faster it is regained ". A review of existing literature does not support such a statement--indeed if anything the reverse is true. The origins of this erroneous view are the misconceptions that weight regain is a simple matter of bad dietary and social habits and that it takes time to change these, that physiological adaptations to rapid weight loss are different to those of gradual weight loss and that weight regain is simply due to a return to old habits. Indeed there are many advantages to rapid weight loss achieved with the use of a modern very low energy diet, including the fact that rapid weight loss is a motivating factor, that the mild ketosis that occurs not only suppresses hunger, but also slows protein loss and that adherence is easier with a structured dietary regime. VLEDs are dietary preparations that provide all nutritional requirements together with between 1845 and 3280 KJ (450 and 800 Kcal) per day. An individual takes this meal replacement three times daily as a substitute for breakfast, lunch and dinner. In addition, a bowl of non-starchy vegetables once daily provides some fibre and helps to satisfy the social aspect of eating. A teaspoon of oil on the vegetables contracts the gall bladder to minimise the risk of gall stone formation. Since weight loss, at whatever rate, results in physiological adaptations leading to weight regain, careful attention must be paid to the period after the VLED regime is completed. Lifestyle modification, diet and exercise are instituted optimally with behaviour modification. If, despite the subject's best efforts, weight regain occurs, an appetite suppressant is advisable to help control the drive to eat.

A comparative study of the metabolic profile, insulin sensitivity and inflammatory response between organically and conventionally managed dairy cattle during the periparturient period.

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Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

2014-09-01

The number of organically managed cattle (OMC) within the European Union has increased tremendously in the last decade. However, there are still some concerns about animals under this farming system meeting their dietary requirements for milk production. The aim of this study was to compare the metabolic adaptations to the onset of lactation in three different herds, one conventional and two organic ones. Twenty-two conventionally managed cattle (CMC) and 20 from each organic farm were sampled throughout the periparturient period. These samplings were grouped into four different stages: (i) far-off dry, (ii) close-up dry, (iii) fresh and (iv) peak of lactation and compared among them. In addition, the results of periparturient animals were also compared within each management type with a control group (animals between the 4th and 5th months of pregnancy). Metabolic profiles were used to assess the health status of the herds, along with the quantification of the acute phase proteins haptoglobin and serum amyloid A, insulin and the calculation of different surrogate indices of insulin sensitivity. Generalised linear mixed models with repeated measurements were used to study the effect of the stage, management type or their interaction on the serum variables studied. The prevalence of subclinical ketosis was higher in OMC, although they showed better insulin sensitivity, a lower degree of inflammation and less liver injury, without a higher risk of macromineral deficiencies. Therefore, attention should be paid on organic farms to the nutritional management of cows around the time of calving in order to prevent the harmful consequences of excessive negative energy balance. Moreover, it must be taken into account that most of the common practices used to treat this condition in CMC are not allowed on a systematic basis in OMC.

The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins.

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Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Kim, Ji-Eun; Kim, Seung-Chul; Jeung, Eui-Bae; Lee, Geun-Shik; Hwang, Dae-Youn; An, Beum-Soo

2015-07-01

Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Innovative dairy cow management to improve resistance to metabolic and infectious diseases during the transition period.

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Lacasse, P; Vanacker, N; Ollier, S; Ster, C

2018-02-01

The incidence of metabolic and infectious diseases varies greatly during the lactation cycle. Most new cases of clinical mastitis appear at the beginning of lactation, and the incidence increases with the level of milk production. In addition to mastitis, many other infectious diseases become clinically apparent during the first 2weeks of lactation. During this time, cows are in a negative energy balance and must mobilize body reserves to balance the deficit between food energy intake and energy required for milk production. The relationships between energy deficit and metabolic diseases, such as ketosis and hepatic lipidosis, are well known. Furthermore, cows in energy deficit have a weakened immune system and are therefore more susceptible to infections. There is now good evidence that the increase in circulating non-esterified fatty acids impairs immune cell functions. Therefore, management approaches that reduce the negative energy balance and the increase in non-esterified fatty acids at the beginning of lactation are likely to improve resistance to infection. Improving the nutrient supply through periparturient nutritional management has been the subject of considerable research. However, another way to reduce the imbalance between nutrient supply and demand is to temporarily decrease the latter. In this review, we examine how management strategies such as conjugated linoleic acid feeding, prepartum milking, or limiting postpartum milk production could be used to reduce metabolic perturbations and immunosuppression during the transition period. At this stage, it appears that reducing the amount of milk harvested postpartum by means of partial milking in the first days after calving is the most promising approach to reduce metabolic stress and immunosuppression without compromising the productivity of high-yielding dairy cows. Copyright © 2017. Published by Elsevier Ltd.

Short communication: Prepartum plasma insulin-like growth factor-I concentrations based on day of insemination are lower in cows developing postpartum diseases.

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Piechotta, M; Sander, A K; Kastelic, J P; Wilde, R; Heppelmann, M; Rudolphi, B; Schuberth, H J; Bollwein, H; Kaske, M

2012-03-01

Because peripartal production diseases are prevalent in dairy cows, early recognition is crucial. Several studies reported metabolic variables as risk predictors for subsequent diseases. To improve on-farm testing and application of those methods, the sampling procedure should take into account variation in gestation length. Furthermore, additional variables indicating cows at risk of any production disease should be sought. Therefore, the objective was to characterize differences between cows with and without postpartum production disease (retained fetal membranes, ketosis, hypocalcemia, abomasal displacement, metritis, mastitis) by prepartum measurement of serum nonesterified fatty acid (NEFA) and plasma insulin-like growth factor (IGF)-I concentrations relative to the artificial insemination (AI) that established pregnancy. Blood was collected from 41 Holstein Friesian cows on 235 to 241, 242 to 248, 249 to 255, 256 to 262, 263 to 269, 270 to 276, 277 to 283, and 284 to 290 d after AI. Health status was assessed daily for 3 wk after calving; 25 cows (66%) had at least one production disease. Cows developing postpartum diseases had higher mean serum NEFA concentrations (450 ± 26 μmol/L; mean ± SE) and lower plasma IGF-I concentrations (78 ± 6 ng/mL) prepartum compared with healthy cows (259 ± 19 μmol/L and 117 ± 8 ng/mL, respectively). In conclusion, because of substantial variation among cows in gestation length, blood samples should be collected and studies performed on risk prediction relative to AI rather than expected date of calving. As the somatotropic axis is one of the key regulators of metabolic adaption for onset of lactation, IGF-I might be a useful variable to differentiate between cows susceptible to production diseases and cows that are able to adapt adequately within the transition period and remain healthy. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Invited review: Opportunities for genetic improvement of metabolic diseases.

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Pryce, J E; Parker Gaddis, K L; Koeck, A; Bastin, C; Abdelsayed, M; Gengler, N; Miglior, F; Heringstad, B; Egger-Danner, C; Stock, K F; Bradley, A J; Cole, J B

2016-09-01

Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors, and status of genetic evaluations were examined for (1) ketosis, (2) displaced abomasum, (3) milk fever, and (4) tetany, as these are the most prevalent metabolic diseases where published genetic parameters are available. The reported incidences of clinical cases of metabolic disorders are generally low (less than 10% of cows are recorded as having a metabolic disease per herd per year or parity/lactation). Heritability estimates are also low and are typically less than 5%. Genetic correlations between metabolic traits are mainly positive, indicating that selection to improve one of these diseases is likely to have a positive effect on the others. Furthermore, there may also be opportunities to select for general disease resistance in terms of metabolic stability. Although there is inconsistency in published genetic correlation estimates between milk yield and metabolic traits, selection for milk yield may be expected to lead to a deterioration in metabolic disorders. Under-recording and difficulty in diagnosing subclinical cases are among the reasons why interest is growing in using easily measurable predictors of metabolic diseases, either recorded on-farm by using sensors and milk tests or off-farm using data collected from routine milk recording. Some countries have already initiated genetic evaluations of metabolic disease traits and currently most of these use clinical observations of disease. However, there are opportunities to use clinical diseases in addition to predictor traits and genomic information to strengthen genetic evaluations for metabolic health in the future. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report.

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Moser, Othmar; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Koehler, Gerd; Eckstein, Max L; Bracken, Richard M; Hofmann, Peter

2017-06-30

Therapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses. A Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L -1 , p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises. People with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis.

Potential Utilization of Automatic Cows Weighing for Evaluation of Health and Nutritional Condition of Herd

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Šárka Podlahová

2011-10-01

Full Text Available Weight of cows affects a large number of factors. Regular weighing and data processing can detect differences that may indicate disorders requiring nursing interventions, e.g. nutritional deficiencies, incorrect fetal development and health problems. The current weighing systems operate as stationary - the animal is fixed, identified and weighed. However, the procedure is time consuming and operation, and that is way this system is used minimally. That implies the need of complete automation of all activities associated with the weighing, which enables introduction of pass – through weight. The aim of this thesis was to develop a methodology for evaluating health and nutritional status of the herd based on data from an automated system for weighing a live weight of dairy cows. There was used in the weighing unit for milking robots Astronaut A3 (Lely company to obtain weight data of individual cows. There were selected dairy cows with the longest period of lactation or already drying off, and especially dairy cows with various health problems for study. Limiting values of weight changes were established after assembling a general equation of mass curve. In the sphere of the diseases there was manifested only ketosis in the weight curve with a loss of 10.2 kg / day (38% weight loss. Additionally, the completion of growth during the first 2 periodes of lactations and weight gain due to advanced pregnancy were confirmed. The maximum daily weight difference recorded in healthy animals was 7 %, equivalent to 40 - 45 kg. The results of the study will be applied for compiling algorithm that will be implemented in the complete management system of cattle breeding, monitoring the dairy cows every day and highlight possible deviations exceeding of physiological changes in weight.

Alternative management of diabetic ketoacidosis in a Brazilian pediatric emergency department

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Savoldelli Roberta D

2010-06-01

Full Text Available Abstract DKA is a severe metabolic derangement characterized by dehydration, loss of electrolytes, hyperglycemia, hyperketonemia, acidosis and progressive loss of consciousness that results from severe insulin deficiency combined with the effects of increased levels of counterregulatory hormones (catecholamines, glucagon, cortisol, growth hormone. The biochemical criteria for diagnosis are: blood glucose > 200 mg/dl, venous pH 3 mmol/L and presence of ketonuria. A patient with DKA must be managed in an emergency ward by an experienced staff or in an intensive care unit (ICU, in order to provide an intensive monitoring of the vital and neurological signs, and of the patient's clinical and biochemical response to treatment. DKA treatment guidelines include: restoration of circulating volume and electrolyte replacement; correction of insulin deficiency aiming at the resolution of metabolic acidosis and ketosis; reduction of risk of cerebral edema; avoidance of other complications of therapy (hypoglycemia, hypokalemia, hyperkalemia, hyperchloremic acidosis; identification and treatment of precipitating events. In Brazil, there are few pediatric ICU beds in public hospitals, so an alternative protocol was designed to abbreviate the time on intravenous infusion lines in order to facilitate DKA management in general emergency wards. The main differences between this protocol and the international guidelines are: intravenous fluid will be stopped when oral fluids are well tolerated and total deficit will be replaced orally; if potassium analysis still indicate need for replacement, it will be given orally; subcutaneous rapid-acting insulin analog is administered at 0.15 U/kg dose every 2-3 hours until resolution of metabolic acidosis; approximately 12 hours after treatment initiation, intermediate-acting (NPH insulin is initiated at the dose of 0.6-1 U/kg/day, and it will be lowered to 0.4-0.7 U/kg/day at discharge from hospital.

A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

Science.gov (United States)

Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

2013-11-01

Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.

Medium-chain triglycerides in infant formulas and their relation to plasma ketone body concentrations.

Science.gov (United States)

Wu, P Y; Edmond, J; Auestad, N; Rambathla, S; Benson, J; Picone, T

1986-04-01

A mild ketosis is known to prevail in the mother, fetus, and newborn infant during the 3rd trimester and in the early neonatal period. It has been shown that during an equivalent period in the rat ketone bodies are readily oxidized and serve as key substrates for lipogenesis in brain. Since medium-chain triglycerides are known to be ketogenic, preterm infants may benefit from dietary medium-chain triglycerides beyond the point of enhanced fat absorption. Our objective was to determine the ketogenic response in preterm infants (gestational age: 33 +/- 0.8 wk) fed three different isocaloric formulas by measuring the concentrations of 3-hydroxybutyrate and acetoacetate in the plasma of these infants. At the time of entrance to the study the infants were receiving 110 kcal/kg/24 h. Study I (11 infants): the infants were fed sequentially in the order; PM 60/40 (PM), Special Care Formula (SCF), and Similac 20 (SIM). In SCF greater than 50% of the fat consists of medium-chain length fatty acids while PM and SIM contain about 25%. The concentration of 3-hydroxybutyrate in plasma was significantly higher when infants were fed SCF than PM and SIM [0.14 +/- 0.03, 0.06 +/- 0.01, and 0.05 +/- 0.01 mM, respectively (p less than 0.01)]. Study II (12 infants); the infants were fed SCF, then SIM, or the reverse. The concentration of acetoacetate in plasma was 0.05 +/- 0.01 and 0.03 +/- 0.01 mM when infants were fed SCF and SIM, respectively (0.1 greater than p greater than 0.05). The concentrations of 3-hydroxybutyrate in plasma were similar to those measured in study I for the respective formulas.(ABSTRACT TRUNCATED AT 250 WORDS)

Presentación de un caso de aplicación de la dieta cetogénica en la epilepsia refractaria Presentation of a case of ketogenic diet application to refractory epilepsy

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Ligia M Marcos Plasencia

2007-12-01

Full Text Available Se presenta el caso de un paciente del sexo masculino, de 2 años de edad, que padece síndrome de West y que ha recibido tratamiento con múltiples drogas antiepilépticas sin obtener resultados alentadores ni en las crisis ni en su desarrollo psicomotor, seriamente afectado. Se establece el régimen de alimentación cetogénico de instalación progresiva, sin período de ayuno inicial, y se observa un cambio clínico en el paciente a partir de que se logran niveles de cetosis, constatados por la aparición de cuerpos cetónicos en la orina. Los cambios clínicos consisten en la disminución del número de crisis diarias y de su intensidad, en la posibilidad de suspender una de las drogas antiepilépticas que usaba, y en el aumento del nivel de vigilia del paciente. Se concluye que no se debe renunciar a esta alternativa de tratamiento en los casos de epilepsia refractaria.The case of a 2-year-old male patient suffering from West syndrome that had been treated with multiple antiepileptic drugs without encouraging results, neither in the seizures, nor in his psychomotor development, which was seriously affected, was reported. A progressive ketogenic diet was established without initial fasting, and it was observed a clinical change in the patient, since ketosis levels were attained and confirmed by the appearance of ketone bodies in urine. The clinical changes consisted in the reduction of the number of daily seizures and their intensity, in the possibility of stopping the use of one of the antiepileptic drugs, and in the increase of the level of sleeplessness of the patient. It was concluded that this treatment alternative should not be rejected in the cases of refractory epilepsy.

Adenosine A1 Receptor Antagonism Abolished the Anti-seizure Effects of Exogenous Ketone Supplementation in Wistar Albino Glaxo Rijswijk Rats

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Zsolt Kovács

2017-07-01

Full Text Available The state of therapeutic ketosis can be achieved by using the ketogenic diet (KD or exogenous ketone supplementation. It was suggested previously that the adenosinergic system may be involved in the mediating effect of KD on suppressing seizure activity in different types of epilepsies, likely by means of adenosine A1 receptors (A1Rs. Thus, we tested in the present study whether exogenous ketone supplements (ketone ester: KE, 2.5 g/kg/day; ketone salt/KS + medium chain triglyceride/MCT: KSMCT, 2.5 g/kg/day applied sub-chronically (for 7 days by intragastric gavage can modulate absence epileptic activity in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij rats. The number of spike-wave discharges (SWDs significantly and similarly decreased after both KE and KSMCT treatment between 3rd and 7th days of gavage. Moreover, blood beta-hydroxybutyrate (βHB levels were significantly increased alike after KE and KSMCT gavage, compared to control levels. The SWD number and βHB levels returned to the baseline levels on the first day without ketone supplementation. To determine whether A1Rs can modify ketone supplement-evoked changes in absence epileptic activity, we applied a non-pro-epileptic dose of a specific A1R antagonist DPCPX (1,3-dipropyl-8-cyclopentylxanthine (intraperitoneal/i.p. 0.2 mg/kg in combination with KSMCT (2.5 g/kg/day, gavage. As expected, DPCPX abolished the KSMCT-evoked decrease in SWD number. Thus, we concluded that application of exogenous ketone supplements may decrease absence epileptic activity in WAG/Rij rats. Moreover, our results suggest that among others the adenosinergic system, likely via A1Rs, may modulate the exogenous ketone supplements-evoked anti-seizure effects.

Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes.

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Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

2018-01-01

Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes.

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Laura R Saslow

Full Text Available We compared the effects of two diets on glycated hemoglobin (HbA1c and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%. We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR consistent with guidelines from the American Diabetes Association (n = 18 or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16. We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04. Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03; 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05. The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09. Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.

Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes

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Shiqi Zhang

2018-03-01

Full Text Available Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1, an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c and its target genes, diacylglycerol acyltransferase (DGAT 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL and CGI-58 for adipose triglyceride lipase (ATGL, thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α, interleukin 1 beta (IL-1β, and interleukin 6 (IL-6 induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

Initiating insulin therapy in children and adolescents with type 1 diabetes mellitus

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Subhash Kumar Wangnoo

2015-01-01

Full Text Available The primary clinical goals to be achieved with insulin initiation are elimination of ketosis and hyperglycemia with prevention of chronic complications. Insulin therapy is the mainstay in management of type 1 diabetes, which should be aimed at achieving good glycemic control, with achievement of hemoglobin A1c (HbA1c <7.5%, pre-meal self-monitored blood glucose (SMBG of 90-130 mg/dL, bed time SMBG of 100-140 mg/dL, mean blood glucose level of 120-160 mg/dL and no ketonuria. Two classes of insulin are available for use in T1DM viz. bolus/prandial insulins (rapid-acting insulins and short-acting insulins and basal insulins (intermediate-acting insulin and long-acting insulin. Insulin glargine and glulisine can be used in children above 6 years, lispro in children above 3 years and detemir and aspart in children above 2 years. The caution for hypoglycemia should be exercised while prescribing them. Degludec is currently not approved for pediatric use. The initial insulin regimen should comprise of ≥2 daily bolus and ≥1 basal insulin injections. Insulin intensification would be required if the initial regimen fails, which can be achieved by increasing frequency of long and rapid acting insulin analogues. The American Diabetes Association guidelines recommend HbA1c targets of <8.0% for children <6 years of age, ≤7.5% for children 6 to 12 years of age, and ≤7.0% for adolescents, 12-18 years of age. However, the evidence is now in favor of a single target HbA1c of ≤7.5% for all children and adolescents <19 years of age.

Clinical and Diagnostic Aspects of Diabetic Ketoacidosis

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Z.P. Nizhynska-Аstapenko

2016-05-01

Full Text Available Background. Leading criteria for laboratory diagnosis and determination of diabetic ketoacidosis severity are considered to be the levels of glucose, blood pH and blood bicarbonate. Technological capabilities of a family doctor are very limited. Therefore, knowledge of detailed clinical symptoms will help the physician to establish correctly a provisional diagnosis and refer a patient to a specialized institution. The aim of our study was to determine the prevalence and special features of certain clinical symptoms and basic laboratory parameters in order to establish the severity level of diabetic ketoacidosis (DKA and to reveal certain correlation between clinical symptoms and laboratory changes in the blood in patients with DKA. Materials and methods. The study involved 123 patients with acute critical decompensated diabetes aged from 9 to 65 years old. We studied the clinical symptoms, measured biochemical changes in blood, blood gas and acid-base state. Results. There was not determined the correlation between severity of diabetic ketoacidosis and clinical parameters and acid-base balance in patients. There were determined the peculiarities electrolyte changes and the emergence gas metabolic changes on the cell level under ketosis, which further deepened with the development of ketoacidosis. The results of the study indicate the need for a comparison of clinical symptoms and laboratory parameters of pathogenic treatment, taking into account the cumulative data. These recommendations in the protocols are often attached to a single laboratory value and can not always fully comply with the severity of the condition. Conclusions. Blood gas is the most sensitive criterion of metabolic changes in case of diabetic ketoacidosis. The level of blood potassium can be used as an indicator of DKA severity. The level of blood potassium at admission to hospital does not really reflect its deficiency in the tissues.

Breath acetone as a potential marker in clinical practice.

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Ruzsányi, Veronika; Péter Kalapos, Miklós

2017-06-01

In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

The effects of energy concentration in roughage and allowance of concentrates on performance, health and energy efficiency of pluriparous dairy cows during early lactation.

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Schmitz, Rolf; Schnabel, Karina; von Soosten, Dirk; Meyer, Ulrich; Spiekers, Hubert; Rehage, Jürgen; Dänicke, Sven

2018-04-01

The aim of this study was to investigate the effects of different energy supplies from roughage and concentrates on performance, health and energy efficiency during early lactation. For this purpose an experiment was conducted containing 64 pluriparous German Holstein cows from 3 weeks prepartum until 16 weeks postpartum. During dry period all cows received an equal dry cow ration. After calving, cows were assigned in a 2 × 2 factorial arrangement to one of four groups, receiving either a moderate (MR, 6.0 MJ NE L ) or a high (HR, 6.4 MJ NE L ) energy concentration in roughage and furthermore moderate (MC, 150 g/kg energy-corrected milk (ECM)) or high amounts of concentrates (HC, 250 g/kg ECM) on dry matter (DM) basis, which were allocated from an automatic feeding system. Higher allocation of concentrates resulted in an increase of DM intake at expense of roughage intake. HC cows had a higher milk yield than MC cows, whereas ECM was higher in HR cows due to a decrease of milk fat yield in MR groups. Energy balance and body condition score were elevated in HC cows, but no differences occurred in development of subclinical ketosis. Furthermore, energy efficiency variables were lower in HC groups because the greater energy intake was not associated with a considerable elevation of milk yield. Consistency of faeces did not indicate digestive disorders in any of the treatment groups although the faecal manure score was significantly lower in HR groups. Our results underline the importance of a high energy uptake from roughage, which can contribute to an adequate performance and beneficial efficiency, especially at lower amounts of concentrates in ration. Feeding concentrates on an average amount of 9.4 kg/d compared to 6.4 kg/d on DM basis improved the energy balance in our trial, but without consequences for metabolic blood variables and general health of the cows.

Livestock disease threats associated with intensification of pastoral dairy farming.

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Lean, Ij; Westwood, Ct; Playford, Mc

2008-12-01

This paper provides an overview of the changes in the pasture-based dairy systems of New Zealand and Australia that may influence the health of cattle. There are relatively few available data that can be used to quantify the effects of increased intensification of milk production on the health of cattle. There is evidence that increased production increases the risk of mastitis and culling for udder health. Increased risks of mastitis with treatment with somatotropin support these findings; however, the risk of mastitis may decrease with increased milking frequency. Larger herds with greater stocking density should increase the risk for infectious disease, but evidence to support this contention is sparse. Very intensive grazing patterns associated with higher grass yields achieved using better cultivars and greater use of fertilisers favour nematode parasites. There is some evidence of anthelmintic resistance in both nematodes and liver fluke. Veterinarians will need to be aware of the potential for these to reduce the productivity of cattle. There have been benefits of improved nutrition on the efficiency of energy use for dairy production. Diseases such as bloat and ketosis appear to be of lower prevalence. It also appears that mineral nutrition of pasture-fed cattle is being better addressed, with gains in the control of milk fever, hypomagnesaemia and trace-element deficiencies. However, acidosis is a condition with a high point prevalence in pasture-based dairy systems where cows are fed supplements; one study in Australia found a point prevalence of approximately 11% of cows with acidosis. There is evidence from this study that the neutral detergent fibre (NDF) in pasture-based diets may need to be higher than 30% of the diet to maintain rumen stability. Laminitis and acidosis are different conditions with a similar pathogenesis, specifically highly fermentable diets. The prevalence of lameness was 28% in herds in Australia, suggesting that this condition

Prediction of insemination outcomes in Holstein dairy cattle using alternative machine learning algorithms.

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Shahinfar, Saleh; Page, David; Guenther, Jerry; Cabrera, Victor; Fricke, Paul; Weigel, Kent

2014-02-01

When making the decision about whether or not to breed a given cow, knowledge about the expected outcome would have an economic impact on profitability of the breeding program and net income of the farm. The outcome of each breeding can be affected by many management and physiological features that vary between farms and interact with each other. Hence, the ability of machine learning algorithms to accommodate complex relationships in the data and missing values for explanatory variables makes these algorithms well suited for investigation of reproduction performance in dairy cattle. The objective of this study was to develop a user-friendly and intuitive on-farm tool to help farmers make reproduction management decisions. Several different machine learning algorithms were applied to predict the insemination outcomes of individual cows based on phenotypic and genotypic data. Data from 26 dairy farms in the Alta Genetics (Watertown, WI) Advantage Progeny Testing Program were used, representing a 10-yr period from 2000 to 2010. Health, reproduction, and production data were extracted from on-farm dairy management software, and estimated breeding values were downloaded from the US Department of Agriculture Agricultural Research Service Animal Improvement Programs Laboratory (Beltsville, MD) database. The edited data set consisted of 129,245 breeding records from primiparous Holstein cows and 195,128 breeding records from multiparous Holstein cows. Each data point in the final data set included 23 and 25 explanatory variables and 1 binary outcome for of 0.756 ± 0.005 and 0.736 ± 0.005 for primiparous and multiparous cows, respectively. The naïve Bayes algorithm, Bayesian network, and decision tree algorithms showed somewhat poorer classification performance. An information-based variable selection procedure identified herd average conception rate, incidence of ketosis, number of previous (failed) inseminations, days in milk at breeding, and mastitis as the most

INTERNAL MILIEAU OF DAIRY COWS AT THE BEGINNING OF LACTATION AND ITS INFLUENCE ON COMPOSITION OF RAW MILK

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Tušimová Eva

2015-02-01

Full Text Available The aim of this work was to evaluate selected blood biochemical parameters and milk composition of dairy cows at the beginning of lactation and to observe the correlations between blood and milk parameters. In total, 15 Holstein cows at the beginning of lactation were chosen. Blood and milk samples were collected. Energetic (glucose - GLU, d-beta-hydroxybutyrate - D-BHB, triglycerides - TG, nitrogenous (total proteins - TP, UREA, hepatic (aspartate aminotransferase - AST, alanine aminotransferase - ALT, gamma-glutamyltransferase - GGT, alkaline phosphatase - ALP, bilirubin - BILI, cholesterol - CHOL and mineral (sodium - Na, potassium - K, chlorides - Cl-, calcium – Ca, phosphorus – P, magnesium - Mg profiles were determined in the blood serum. Levels of lactose, fat, proteins and minerals (sodium - Na, potassium – K, calcium – Ca, phosphorus – P, magnesium - Mg were determined in milk. Most of the parameters outside physiological limits were found among mineral and hepatic profile. Levels of calcium, phosphorus and sodium were decreased in comparison to reference values. Average concentration of urea was also lower. On the other hand, increase of aspartate aminotransferase and gamma-glutamyltransferase were observed. Levels of lactose (4.82 g.100g-1, fat (4.21 g.100g-1, protein (3.14 g.100g-1 and calcium (4.82 g.l-1 in milk complied with Slovak national standard (STN 57 0529. In our study, ratio of fat to protein lower than 0.75 was observed in 13 % of cows (risk of ketosis and higher than 1.4 in 40 % (NEB. Strong negative correlation between serum cholesterol and milk fat (-0.716; P<0.01 and middle strong negative correlation between cholesterol and milk protein (-0.397; P<0.01 were observed. ALT affected negatively amount of phosphorus in milk (-0.417; P<0.001, which complied with demineralization of the organism and following restriction of liver detoxification activity. On the other hand, strong positive correlation was observed

Structured triglycerides were well tolerated and induced increased whole body fat oxidation compared with long-chain triglycerides in postoperative patients.

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Sandström, R; Hyltander, A; Körner, U; Lundholm, K

1995-01-01

It has been proposed, on the basis of animal experiments, that medium-chain triglycerides (MCT) may exert more favorable effects on whole body metabolism of injured animals than long-chain triglycerides (LCT). Therefore, the present study was designed to evaluate whether structured triglycerides are associated with increased whole body fat oxidation without promotion of ketogenesis in postoperative patients. A structured lipid emulsion (73403 Pharmacia, Sweden) containing medium- and long-chain fatty acids, esterified randomly to glycerol in a triglyceride structure, was used. Whole body fat oxidation was determined by indirect calorimetry in the postoperative period. Patients were randomized to receive structured lipids 1 day followed by LCT (Intralipid, Pharmacia) the next day or vice versa during 6 postoperative days. In part 1 of the study patients received fat at 1.0 g/kg per day in the presence of 80% of the basal requirement of nonprotein calories. In part 2 patients received fat at 1.5 g/kg per day in the presence of 120% of the nonprotein caloric requirement. Amino acids were always provided at 0.15 g N/kg per day. Structured lipids were not associated with any side effects, were rapidly cleared from the plasma compartment, and were rapidly oxidized without any significant hyperlipidemia or ketosis. Provision of structured lipids in the presence of excess of nonprotein calories (part 2) caused a significantly higher whole body fat oxidation (2.4 +/- 0.05 g/kg per day) compared with LCT provision (1.9 +/- 0.06 g/kg per day) (p structured triglycerides were associated with increased whole body fat oxidation in stressed postoperative patients, which is in line with the original metabolic and biochemical concept for structured triglycerides. The study provided evidence to support that structured lipids may represent a next generation of IV fat emulsions that may be clinically advantageous compared with conventional LCT emulsions in certain clinical conditions.

Events occurring during the previous lactation, the dry period, and peripartum as risk factors for early lactation mastitis in cows receiving 2 different intramammary dry cow therapies.

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Pinedo, P J; Fleming, C; Risco, C A

2012-12-01

The objective of this study was to investigate the association between mastitis events occurring during the previous lactation, the dry period, and the peripartum period on the incidence of early lactation mastitis in cows receiving ceftiofur hydrochloride or penicillin dihydrostreptomycin as intramammary dry cow antibiotic therapy. Cows (n=402) from 2 large dairy farms in Central Florida were enrolled in the study at the time of dry-off processing and were randomly assigned to 1 of 2 dry cow therapies: ceftiofur hydrochloride or penicillin dihydrostreptomycin. Composite milk samples were collected at dry-off and after calving for bacteriological examination and somatic cell count. Peripartal health disorders were monitored during the first 30 d of lactation and included calving difficulty, metritis, ketosis, and left displaced abomasum. Milk production and individual somatic cell scores (SCS) were recorded monthly by the Dairy Herd Improvement Association. The main outcome variables were the risk of clinical mastitis during the first 30 and 60 d of lactation, and the risk of subclinical mastitis at the first 2 monthly Dairy Herd Improvement Association tests after calving (up to 70 d in milk). Additionally, the SCS and the presence of mastitis pathogens in milk at dry-off and at calving were analyzed. Explanatory variables consisted of events occurring during the previous lactation, at dry-off and during the dry period, at calving, and within the first 30 d after calving. Multiple events occurring during the previous lactation had a significant effect on the incidence of mastitis in the subsequent lactation. These events included low milk yield, intermediate lactation length, clinical mastitis, and lactation SCS average. Similarly, intramammary infections with environmental bacteria at dry-off increased the chances of clinical mastitis the first month after calving. Dry-off therapy had a significant effect on mastitis incidence; cows treated with ceftiofur

Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice.

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Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Wlaz, Piotr; Czuczwar, Stanislaw J; Gasior, Maciej

2017-04-01

Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

Effects of pathogen-specific clinical mastitis on probability of conception in Holstein dairy cows.

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Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

2014-11-01

The objective of this study was to estimate the effects of pathogen-specific clinical mastitis (CM), occurring in different weekly intervals before or after artificial insemination (AI), on the probability of conception in Holstein cows. Clinical mastitis occurring in weekly intervals from 6 wk before until 6 wk after AI was modeled. The first 4 AI in a cow's lactation were included. The following categories of pathogens were studied: Streptococcus spp. (comprising Streptococcus dysgalactiae, Streptococcus uberis, and other Streptococcus spp.); Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level that can be detected from our microbiological procedures) observed in the culture sample and cases with contamination (≥ 3 pathogens in the sample); and other pathogens [including Citrobacter, yeasts, Trueperella pyogenes, gram-negative bacilli (i.e., gram-negative organisms other than E. coli, Klebsiella spp., Enterobacter, and Citrobacter), Corynebacterium bovis, Corynebacterium spp., Pasteurella, Enterococcus, Pseudomonas, Mycoplasma, Prototheca, and others]. Other factors included in the model were parity (1, 2, 3, 4 and higher), season of AI (winter, spring, summer, autumn), day in lactation of first AI, farm, and other non-CM diseases (retained placenta, metritis, ketosis, displaced abomasum). Data from 90,271 AI in 39,361 lactations in 20,328 cows collected from 2003/2004 to 2011 from 5 New York State dairy farms were analyzed in a generalized linear mixed model with a Poisson distribution. The largest reductions in probability of conception were associated with CM occurring in the week before AI or in the 2 wk following AI. Escherichia coli and Klebsiella spp. had the greatest adverse effects on probability of conception. The probability of conception for a cow with any combination of characteristics may be calculated based on the parameter estimates. These

Obesity and youth diabetes: distinguishing characteristics between islet cell antibody positive vs. negative patients over time.

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Rivera-Vega, Michelle Y; Flint, Amanda; Winger, Daniel G; Libman, Ingrid; Arslanian, Silva

2015-08-01

Obese youth clinically diagnosed with type 2 diabetes mellitus (T2DM) frequently have evidence of islet cell autoimmunity. We investigated the clinical and biochemical differences, and therapeutic modalities among autoantibody positive (Ab+) vs. autoantibody negative (Ab-) youth at the time of diagnosis and over time in a multi-provider clinical setting. Chart review of 145 obese youth diagnosed with T2DM from January 2003 to July 2012. Of these, 70 patients were Ab+ and 75 Ab-. The two groups were compared with respect to clinical presentation, physical characteristics, laboratory data, and therapeutic modalities at diagnosis and during follow up to assess the changes in these parameters associated with disease progression. At presentation, Ab+ youth with a clinical diagnosis of T2DM were younger, had higher rates of ketosis, higher hemoglobin A1c (HbA1c) and glucose levels, and lower insulin and c-peptide concentrations compared with the Ab- group. The Ab- group had a higher body mass index (BMI) z-score and cardiometabolic risk factors at diagnosis and such difference remained over time. Univariate analysis revealed that treatment modality had no effect on BMI in either group. Generalized estimating equations for longitudinal data analysis revealed that (i) BMI z-score and diastolic blood pressure (DBP) were significantly affected by duration of diabetes; (ii) systolic blood pressure (SBP) and ALT were affected by changes in BMI z-score; and (iii) changes in HbA1c had an effect on lipid profile and cardiometabolic risk factors regardless of antibody status. Irrespective of antibody status and treatment modality, youth who present with obesity and diabetes, show no improvement in obesity status over time, with the deterioration in BMI z-score affecting blood pressure (BP) and ALT, but the lipid profile being mostly impacted by HbA1c and glycemic control. Effective control of BMI and glycemia are needed to lessen the future macrovascular complications irrespective

Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

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Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

Low Birthweight, Rapid Weight Gain and Metabolic Syndrome in Adolescence: An Illustrative Case Report

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Onyiriuka Alphonsus N.

2015-12-01

Full Text Available A 16-year-old boy whose diabetes mellitus was diagnosed 3 months previously in a private hospital but was not placed on medication. The presenting complaints were fast breathing for 24 hours, weakness for 2 hours, and unresponsiveness to calls for 0.5 hours. His father was obese with type 2 diabetes mellitus and died 8 months earlier from cardiac arrest. His birthweight was low, 2.2kg. At first presentation, his weight, BMI and blood pressure were 60kg (25th-50th percentile, 19.4kg/m2 (25thpercentile and 110/70mmHg (systolic BP 50th percentile, diastolic BP 50th-90th percentile, respectively. He was managed for diabetic ketoacidosis and was discharged on subcutaneous premixed insulin, 1 Unit/kg/day. At point of discharge, weight and BP were 60.5 kg and 120/70 mmHg, respectively. The patient defaulted but presented again 6 months later at the age of 17 years. At second presentation, his weight, BMI and BP were 89 kg (95th percentile, 27.5 kg/m2 (90th-95th percentile and 180/80 mmHg (systolic 99th percentile; diastolic 90th percentile, respectively. His waist circumference was 98.7cm (> 90th percentile. We had no record of previous waist circumference. His lipid profile showed low HDL-cholesterol 0.7252 mmol/L [(28mg/dl; <5thpercentile]. His fasting blood glucose and HbA1C were 6.5 mmol/L (117mg/dl and 34 mol/mol (5.3%, respectively. A diagnosis of metabolic syndrome in a patient with ketosis-prone type 2 diabetes was made. He was referred to the pediatric cardiologist for management of his hypertension. He defaulted again and was lost to follow up. Conclusion: This report illustrates the association of low birth weight and rapid weight gain with metabolic syndrome in adolescence.

Trial Protocol: Randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking

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Hajek Peter

2010-10-01

Full Text Available Abstract Background Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD, individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. Methods This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/m2, daily smokers (CO > 10 ppm; with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks,15 mg(2 weeks,10 mg(2 weeks. The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months. Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of

Ethnoveterinary medicines used for ruminants in British Columbia, Canada

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Lans, Cheryl; Turner, Nancy; Khan, Tonya; Brauer, Gerhard; Boepple, Willi

2007-01-01

Background The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. Methods In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. Results There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production.Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and Symphytum officinale. Hedera

Norwegian mastitis control programme

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Østerås O

2009-04-01

Full Text Available Abstract This paper describes the methods and results of the Norwegian Mastitis Control Program implemented in 1982. The program has formed an integral part of the Norwegian Cattle Health Services (NCHS since 1995. The NCHS also have specific programs for milk fever, ketosis, reproduction and calf diseases. The goal of the program is to improve udder health by keeping the bulk milk somatic cell count (BMSCC low, to reduce the use of antibiotics, to keep the cost of mastitis low at herd level and improve the consumers' attitude to milk products. In 1996, a decision was made to reduce the use of antibiotics in all animal production enterprises in Norway by 25% within five years. Relevant data has been collected through the Norwegian Cattle Herd Recording System (NCHRS; including health records since 1975 and somatic cell count (SCC data since 1980. These data have been integrated within the NCHRS. Since 2000, mastitis laboratory data have also been included in the NCHRS. Data on clinical disease, SCC and mastitis bacteriology have been presented to farmers and advisors in monthly health periodicals since 1996, and on the internet since 2005. In 1996, Norwegian recommendations on the treatment of mastitis were implemented. Optimal milking protocols and milking machine function have been emphasised and less emphasis has been placed on dry cow therapy. A selective dry cow therapy program (SDCTP was implemented in 2006, and is still being implemented in new areas. Research demonstrates that the rate of clinical mastitis could be reduced by 15% after implementing SDCTP. The results so far show a 60% reduction in the clinical treatment of mastitis between 1994 and 2007, a reduction in BMSCC from 250,000 cells/ml to 114,000 cells/ml, and a total reduction in the mastitis cost from 0.23 NOK to 0.13 NOK per litre of milk delivered to the processors, corresponding to a fall from 9.2% to 1.7% of the milk price, respectively. This reduction is attributed to

Lipid mobilization, immune function and the paradigm of vitamin E in transition cows.

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Ioannis Politis

2016-06-01

Full Text Available The number of metabolic disorders that dairy cows have to cope during the transition to lactation can be divided in three main categories. The first category includes disorders related to abnormal energy metabolism (ketosis, fatty liver, acidosis. The second and the third categories include disorders related to mineral metabolism (milk fever and disorders related directly or indirectly to impaired immune function (mastitis, metritis, retained placenta, respectively. Among the many physiological changes during the transition period, perhaps the most crucial, is an increase in the concentration of plasma non-esterified fatty acids (NEFA. A portion of this increase in NEFA is obligatory and it is under hormonal control while another portion is the result of a situation known as negative energy balance (difference between energy consumed and energy spent. In this presentation I will present data from a collaborative study between the University of Milan and the Agricultural University of Athens which proves that negative correlations exist between blood concentrations of NEFA and β-hydroxybutyrate with α-tocopherol. The adipose tissue contains two main categories of cells: adipocytes and immunocompetent cells mainly monocytes/macrophages. Our research has tested the hypothesis that a cross-talk exists between adipocytes and monocytes/macrophages and this cross-talk is mediated by fatty acids released by adipocytes especially during the transition period. Results indicate that all fatty acids tested (myristic, palmitic, palmitoleic, stearic and oleic upregulate the expression of numerous pro-inflammatory genes by both monocytes but neutrophils, as well. The longer the carbon chain, the most potent is the effect.  Another hypothesis that we have tested is that vitamin E can interfere and block the cross talk between adipocytes and immunocompetent cells. Against this notion, α-tocopherol does not interfere with the effect of fatty acids on

Trial Protocol: randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking.

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Lycett, Deborah; Hajek, Peter; Aveyard, Paul

2010-10-07

Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD), individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/m2), daily smokers (CO > 10 ppm); with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks),15 mg(2 weeks),10 mg(2 weeks)). The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP)) engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR) aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months.Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of urinary ketones measured weekly. Daily

Importance of low carbohydrate diets in diabetes management

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Hall RM

2016-03-01

Full Text Available Rosemary M Hall, Amber Parry Strong, Jeremy D KrebsCentre for Endocrine, Diabetes and Obesity Research, Capital and Coast District Health Board, Wellington, New Zealand Abstract: Dietary strategies are fundamental in the management of diabetes. Historically, strict dietary control with a low carbohydrate diet was the only treatment option. With increasingly effective medications, the importance of dietary change decreased. Recommendations focused on reducing dietary fat to prevent atherosclerotic disease, with decreasing emphasis on the amount and quality of carbohydrate. As the prevalence of obesity and diabetes escalates, attention has returned to the macronutrient composition of the diet. Very low carbohydrate diets (VLCD's have demonstrated effective initial weight loss and improvement in glycemic control, but difficult long-term acceptability and worsening lipid profile. Modifications to the very low carbohydrate (VLC have included limiting saturated fat and increasing carbohydrate (CHO and protein. Reducing saturated fat appears pivotal in reducing low-density lipoprotein (LDL cholesterol and may mitigate adverse effects of traditional VLCD's. Increased dietary protein enhances satiety, reduces energy intake, and improves glycemic homeostasis, but without sustained improvements in glycemic control or cardiovascular risk over and above the effect of weight loss. Additionally, recent studies in type 1 diabetes mellitus suggest promising benefits to diabetes control with low carbohydrate diets, without concerning effects on ketosis or hypoglycemia. Dietary patterns may highlight pertinent associations. For example, Mediterranean-style and paleolithic-type diets, low in fat and carbohydrate, are associated with reduced body weight and improved glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM. A feature of these dietary patterns is low refined CHO and sugar and higher fiber, and it is possible that increasing sugar

Norwegian mastitis control programme

Science.gov (United States)

2009-01-01

This paper describes the methods and results of the Norwegian Mastitis Control Program implemented in 1982. The program has formed an integral part of the Norwegian Cattle Health Services (NCHS) since 1995. The NCHS also have specific programs for milk fever, ketosis, reproduction and calf diseases. The goal of the program is to improve udder health by keeping the bulk milk somatic cell count (BMSCC) low, to reduce the use of antibiotics, to keep the cost of mastitis low at herd level and improve the consumers' attitude to milk products. In 1996, a decision was made to reduce the use of antibiotics in all animal production enterprises in Norway by 25% within five years. Relevant data has been collected through the Norwegian Cattle Herd Recording System (NCHRS); including health records since 1975 and somatic cell count (SCC) data since 1980. These data have been integrated within the NCHRS. Since 2000, mastitis laboratory data have also been included in the NCHRS. Data on clinical disease, SCC and mastitis bacteriology have been presented to farmers and advisors in monthly health periodicals since 1996, and on the internet since 2005. In 1996, Norwegian recommendations on the treatment of mastitis were implemented. Optimal milking protocols and milking machine function have been emphasised and less emphasis has been placed on dry cow therapy. A selective dry cow therapy program (SDCTP) was implemented in 2006, and is still being implemented in new areas. Research demonstrates that the rate of clinical mastitis could be reduced by 15% after implementing SDCTP. The results so far show a 60% reduction in the clinical treatment of mastitis between 1994 and 2007, a reduction in BMSCC from 250,000 cells/ml to 114,000 cells/ml, and a total reduction in the mastitis cost from 0.23 NOK to 0.13 NOK per litre of milk delivered to the processors, corresponding to a fall from 9.2% to 1.7% of the milk price, respectively. This reduction is attributed to changes in attitude and

Ethnoveterinary medicines used for ruminants in British Columbia, Canada

Directory of Open Access Journals (Sweden)

Brauer Gerhard

2007-02-01

Full Text Available Abstract Background The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. Methods In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. Results There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production.Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and

Administração de somatotropina bovina no período pré-parto sobre parâmetros produtivos, sanitários e reprodutivos da primeira lactação de vacas holandesas Bovine somatotropin administration during pre-delivery period to productive, sanitary and reproductive parameters of holstein cows' first lactation

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Laerte Dagher Cassoli

2002-04-01

Full Text Available Para avaliar a administração de somatotropina bovina (bST no período pré-parto, sobre o desempenho na primeira lactação, foram utilizadas 18 novilhas gestantes, de modo que 9 receberam injeções subcutâneas de 500mg de bST nos dias 21 e 9 antes da data prevista para o parto. Os animais foram alimentados com dieta total, 2 vezes ao dia, e os dados coletados foram relativos a parâmetros sanitários, produtivos e reprodutivos na primeira lactação. A administração de bST não afetou os parâmetros sanitários (retenção de placenta, metrite, deslocamento de abomaso, febre do leite e cetose e reprodutivo (cisto folicular. Entretanto, o uso de bST no pré-parto levou à variação de escore de condição corporal (ECC 65% maior, adiantou o pico de produção de leite em 9,7 dias e diminuiu os dias em lactação em 21,8 dias em relação ao controle (P The effects of pre-delivery administration of bovine somatotropin (bST on first lactation performance were evaluated in this study, which involved eighteen Holstein pregnant heifers. Nine animals were supplemented with subcutaneous injections of 500 mg of bST, on days 21 and 9 prior expected delivery, and 9 were not supplemented (control group. Animals were fed total mixed ration, twice daily. Data evaluated in this experiment were related to sanitary, reproductive and productive parameters during first lactation. Administration of bST did not affect parameters related to sanity (retained placenta, metritis, displacement abomasum, milk fever, ketosis, reproduction (follicular cysts. However, heifers supplemented with bST showed changes of body condition score 65% greater, anticipated milk production peak in 9.7 days and decreased number of days in lactation in 21,8 days, compared to the non-supplemented ones (p < 0.05. Milk production peak and milk production corrected for 305 days were not affected by bST administration.

Fresh-cow handling practices and methods for identification of health disorders on 45 dairy farms in California.

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Espadamala, A; Pallarés, P; Lago, A; Silva-Del-Río, N

2016-11-01

The aim of the present study was to describe fresh-cow handling practices and techniques used during fresh cow evaluations to identify postpartum health disorders on 45 dairy farms in California ranging from 450 to 9,500 cows. Fresh cow practices were surveyed regarding (a) grouping and housing, (b) scheduling and work organization, (c) screening for health disorders, and (d) physical examination methods. Information was collected based on cow-side observations and responses from fresh cow evaluators. Cows were housed in the fresh cow pen for 3 to 14 (20%), 15 to 30 (49%), or >31 (31%) d in milk. Fresh cow evaluations were performed daily (78%), 6 times a week (11%), 2 to 5 times a week (9%), or were not routinely performed (2%). There was significant correlation between the duration of fresh cow evaluations and the number of cows housed in the fresh pen. Across all farms, the duration of evaluations ranged from 5 to 240 min, with an average of 16 s spent per cow. During fresh cow checks, evaluators always looked for abnormal vaginal discharge, retained fetal membranes, and down cows. Dairies evaluated appetite based on rumen fill (11%), reduction of feed in the feed bunk (20%), rumination sensors (2%), or a combination of these (29%). Milk yield was evaluated based on udder fill at fresh cow checks (40%), milk flow during milking (11%), milk yield records collected by milk meters (2%), or a combination of udder fill and milk meters (5%). Depressed attitude was evaluated on 64% of the dairies. Health-monitoring exams for early detection of metritis were implemented on 42% of the dairies based on rectal examination (13%), rectal temperature (22%), or both (7%). Dairies implementing health-monitoring exams took longer to perform fresh cow evaluations. Physical examination methods such as rectal examination, auscultation, rectal temperature evaluation, and cow-side ketosis tests were used on 76, 67, 38, and 9% of dairies, respectively. Across dairies, we found large

Dairy cow disability weights.

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McConnel, Craig S; McNeil, Ashleigh A; Hadrich, Joleen C; Lombard, Jason E; Garry, Franklyn B; Heller, Jane

2017-08-01

Over the past 175 years, data related to human disease and death have progressed to a summary measure of population health, the Disability-Adjusted Life Year (DALY). As dairies have intensified there has been no equivalent measure of the impact of disease on the productive life and well-being of animals. The development of a disease-adjusted metric requires a consistent set of disability weights that reflect the relative severity of important diseases. The objective of this study was to use an international survey of dairy authorities to derive disability weights for primary disease categories recorded on dairies. National and international dairy health and management authorities were contacted through professional organizations, dairy industry publications and conferences, and industry contacts. Estimates of minimum, most likely, and maximum disability weights were derived for 12 common dairy cow diseases. Survey participants were asked to estimate the impact of each disease on overall health and milk production. Diseases were classified from 1 (minimal adverse effects) to 10 (death). The data was modelled using BetaPERT distributions to demonstrate the variation in these dynamic disease processes, and to identify the most likely aggregated disability weights for each disease classification. A single disability weight was assigned to each disease using the average of the combined medians for the minimum, most likely, and maximum severity scores. A total of 96 respondents provided estimates of disability weights. The final disability weight values resulted in the following order from least to most severe: retained placenta, diarrhea, ketosis, metritis, mastitis, milk fever, lame (hoof only), calving trauma, left displaced abomasum, pneumonia, musculoskeletal injury (leg, hip, back), and right displaced abomasum. The peaks of the probability density functions indicated that for certain disease states such as retained placenta there was a relatively narrow range of

The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study

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Wesley C. Kephart

2018-01-01

Full Text Available Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio were divided into a control group (CTL; n = 5 and a KD group (n = 7. KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA and ultrasound, resting energy expenditure (REE, blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD (p = 0.053. DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% (p = 0.068, and vastus lateralis thickness values decreased in the KD group by ~8% (p = 0.065. Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD (p = 0.048. Between-group changes in REE, one-repetition maximum (1-RM back squat, 400 m run times, and VO2peak were similar between groups. While our n-sizes were limited, these preliminary data suggest

The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study

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Kephart, Wesley C.; Pledge, Coree D.; Roberson, Paul A.; Mumford, Petey W.; Romero, Matthew A.; Mobley, Christopher B.; Young, Kaelin C.; Lowery, Ryan P.; Wilson, Jacob M.; Huggins, Kevin W.; Roberts, Michael D.

2018-01-01

Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD) on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio) were divided into a control group (CTL; n = 5) and a KD group (n = 7). KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA) and ultrasound, resting energy expenditure (REE), blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB) levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD (p = 0.053). DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% (p = 0.068), and vastus lateralis thickness values decreased in the KD group by ~8% (p = 0.065). Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD (p = 0.048). Between-group changes in REE, one-repetition maximum (1-RM) back squat, 400 m run times, and VO2peak were similar between groups. While our n-sizes were limited, these preliminary data suggest that

Avaliação do perfil metabólico, nutricional e efeitos adversos de crianças com epilepsia refratária em uso da dieta cetogênica Assessment of serum biochemistry, nutritional status and adverse effects of children with refractory epilepsy using the ketogenic diet

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Sueli Rizzutti

2006-10-01

Full Text Available OBJETIVO: Avaliar os efeitos adversos, o perfil metabólico e o crescimento pôndero-estatural de crianças com crises epilépticas de difícil controle, as quais foram submetidas a dieta cetogênica. MÉTODOS: Selecionaram-se 23 pacientes na faixa etária de 2 até 17 anos com epilepsia de difícil controle medicamentoso, sendo 43,5% (n=10 do sexo masculino e 56,5% (n=13 do sexo feminino, provenientes do Setor de Neuropediatria da Disciplina de Neurologia da Universidade Federal de São Paulo. Foram submetidos a dieta cetogênica e acompanhados por um período mínimo de um ano. Dois pacientes não conseguiram manter a cetose por falta de adesão dos pais à dieta. RESULTADOS: Os efeitos adversos encontrados foram reversíveis, incluindo hiperlipidemia, obstipação (17,4%, náuseas e vômitos (43,4%, sonolência (47,8%, infecções intercorrentes (3,0%, recusa da dieta (13,0% e epistaxe (4,3%. O crescimento pôndero-estatural não foi afetado, tendo o peso e a estatura seguido o percentil adequado. CONCLUSÃO: A dieta cetogênica pode constituir-se em uma alternativa segura e efetiva para o tratamento de crianças com epilepsia refratária.OBJECTIVE: The purpose of this research was to evaluate adverse events, serum biochemistry, growth and nutritional status of children with difficult-to-control seizures who were submitted to ketogenic diet. METHODS: Twenty-three patients aging from 2 to 17 years with refractory epilepsies, where 43.5% (n=10 were males and 56.5% (n=13 females from the Sector of Neuropediatrics, Discipline of Neurology of the Universidade Federal de São Paulo, were treated with the ketogenic diet and followed up for at least 1 year. Two patients were not able to achieve persistent ketosis either because they rejected the diets or their parents did not comply. RESULTS: Adverse events were all reversible and included hyperlipidemia, constipation (17.4%, nausea and vomiting (43.4%, drowsiness (47.8%, intercurrent infections (3

Pathogen-specific effects on milk yield in repeated clinical mastitis episodes in Holstein dairy cows.

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Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

2014-03-01

The objective of this study was to estimate the effects of clinical mastitis (CM) cases due to different pathogens on milk yield in Holstein cows. The first 3 CM cases in a cow's lactation were modeled. Eight categories of pathogens were included: Streptococcus spp.; Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level detectable by our microbiological procedures) observed in the culture sample, and cases with contamination (≥ 3 pathogens in the sample); other pathogens that may be treated with antibiotics (included Citrobacter, Corynebacterium bovis, Enterobacter, Enterococcus, Pasteurella, Pseudomonas; "other treatable"); and other pathogens not successfully treated with antibiotics (Trueperella pyogenes, Mycoplasma, Prototheca, yeasts; "other not treatable"). Data from 38,276 lactations in cows from 5 New York State dairy herds, collected from 2003-2004 until 2011, were analyzed. Mixed models with an autoregressive correlation structure (to account for correlation among the repeated measures of milk yield within a lactation) were estimated. Primiparous (lactation 1) and multiparous (lactations 2 and 3) cows were analyzed separately, as the shapes of their lactation curves differed. Primiparas were followed for up to 48 wk of lactation and multiparas for up to 44 wk. Fixed effects included parity, calving season, week of lactation, CM (type, case number, and timing of CM in relation to milk production cycle), and other diseases (milk fever, retained placenta, metritis, ketosis, displaced abomasum). Herd was modeled as a random effect. Clinical mastitis was more common in multiparas than in primiparas. In primiparas, Streptococcus spp. occurred most frequently as the first case. In multiparas, E. coli was most common as the first case. In subsequent cases, CM cases with no specific growth or contamination were most common in both parity groups. The hazard of

Diagnostic performance of cytology for assessment of hepatic lipid content in dairy cattle.

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Fry, M M; Yao, B; Ríos, C; Wong, C; Mann, S; McArt, J A A; Nydam, D V; Leal Yepes, F A; Viesselmann, L; Geick, A; Goldin, K; Jordan, A; Behling-Kelly, E

2018-02-01

The objective of our study was to characterize the diagnostic performance of cytology for assessing hepatic lipid content (HLC) in dairy cows by comparing microscopic evaluation of lipid vacuolation in touch imprint slide preparations of liver biopsies with quantitative measurement of triglyceride concentration ([TG]; mg/mg of wet weight) in paired biopsy samples. Our study also sought to compare the diagnostic performance of liver cytology, plasma nonesterified fatty acid concentration ([NEFA]), and plasma β-hydroxybutyrate concentration ([BHB]) derived from a measurement performed on whole blood, for assessing HLC. Chemical extraction of TG from liver tissue remains the gold standard for quantifying HLC, largely because available blood tests, although useful for detecting some types of pathology, such as increased lipid mobilization, ketosis, or hepatocellular injury, are nonspecific as to etiology. Veterinary practitioners can sample bovine liver for cytological evaluation in a fast, minimally invasive, and inexpensive manner. Thus, if highly predictive of HLC, cytology would be a practical diagnostic tool for dairy veterinarians. In our study, liver biopsy samples from Holstein cows (219 samples from 105 cows: 52 from cows 2 to 20 d prepartum, 105 from cows 0 to 10 d in milk, 62 from cows 18 to 25 d in milk) were used to prepare cytology slides and to quantify [TG] using the Folch extraction method followed by the Hantzch condensation reaction and spectrophotometric measurement. An ordinal scale (0-4) based on amount of hepatocellular cytoplasm occupied by discrete clear vacuoles was used by 3 blinded, independent observers to rank HLC in Wright-Giemsa-stained slides. Interobserver agreement in cytology scoring was good. Corresponding plasma [NEFA] and [BHB] measurements were available for 187 and 195 of the 219 samples, respectively. Liver [TG] correlated more strongly with cytology score than with NEFA or BHB, and receiver operating characteristic curve

High somatic cell counts and changes in milk fat and protein contents around insemination are negatively associated with conception in dairy cows.

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Albaaj, Ahmad; Foucras, Gilles; Raboisson, Didier

2017-01-15

The fertility of dairy cows has decreased dramatically worldwide over the last few decades, and several causes of this trend have been reported. Several studies have associated compromised udder health with deteriorating reproduction performance. Subclinical ketosis (SCK) has also been reported to be a risk factor for decreased conception. The objective of the present study was to describe how SCK might interact with the reported association between udder health and conception in dairy cows. Data from the French Milk Control Program and data on 8,549,667 instances of artificial insemination (AI) and their corresponding preceding and subsequent test-days from 5,979,701 Holstein cows were examined over a 5-year period (2008-2012). The effect of udder health was evaluated through a low (L) or high (H) somatic cell count (SCC) before and after AI using a threshold of 200,000 cells/mL, and transformed into four groups (LL, LH, HL, and HH). Three proxies for defining SCK were proposed based on the milk fat and protein content (or their ratio) before AI. Statistical analysis first included a generalized additive model to help define the optimal threshold values. Next, a logistic regression with a Poisson correction was performed. On average, the risk of conception at first AI was reduced by 14% for LH or HH cows (relative risk [and 95% CI] = 0.86 [0.85-0.87]) when the SCC increased or remained high within 40 days before and after AI, relative to LL group. The reduction of conception success associated with SCK (fat and protein contents changes) varied from 3% to 17% depending on the used SCK proxy. Including the interaction term SCC ∗ SCK clearly showed that the association of increased SCC around AI with conception success was modified by the presence of SCK. A cow that already has SCK and experiences an increase in SCC around or after AI exhibits up to 2 times further decrease in conception success compared with a cow with a high SCC and no SCK. In conclusion

Association between body energy content in the dry period and post-calving production disease status in dairy cattle.

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Smith, G L; Friggens, N C; Ashworth, C J; Chagunda, M G G

2017-09-01

The transition from gestation to lactation is marked by significant physiological changes for the individual cow such that disease incidence is highest in early lactation. Around the time of calving, cows rely on mobilisation of body energy reserves to fill the energy deficit created by an increase in nutrient demands at a time of restricted feed intake. It is well established that monitoring of body energy reserves in lactation is an important component of herd health management. However, despite their influence on future health and productivity, monitoring of body energy reserves in the dry period is often sparse. Further, there is increasing concern that current dry off management is inappropriate for modern cattle and may influence future disease risk. This study aimed to identify candidate indicators of early lactation production disease from body energy data collected in the dry period and production data recorded at the time of dry off. Retrospective analysis was performed on 482 cow-lactations collected from a long-term Holstein-Friesian genetic and management systems project, the Langhill herd in Scotland. Cow-lactations were assigned to one of four health groups based on health status in the first 30 days of lactation. These four groups were as follows: healthy, reproductive tract disorders (retained placenta and metritis), subclinical mastitis and metabolic disorders (ketosis, hypocalcaemia, hypomagnesaemia and left displaced abomasum). ANOVA, employing a GLM was used to determine effects for the candidate indicator traits. Cows which were diagnosed with a reproductive tract disorder in the first 30 days of lactation experienced a significantly greater loss in body energy content, body condition score and weight in the preceding dry period than healthy cows. The rate of change in body energy content during the first 15 days of the dry period was -18.26 MJ/day for cows which developed reproductive tract disorder compared with +0.63 MJ/day for healthy cows

The effect of lameness on the resting behavior and metabolic status of dairy cattle during the transition period in a freestall-housed dairy herd.

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Calderon, D F; Cook, N B

2011-06-01

�-hydroxybutyrate concentration of 1,165 (1,037 to 1,291) μM that was significantly greater than 697 (560 to 834) μM for slightly lame cows and 687 (551 to 824) μM for nonlame cows. In summary, lameness significantly altered the resting behavior of cows during the transition period and was associated with elevated risk for ketosis in the study herd. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part III. Metritis.

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Stangaferro, M L; Wijma, R; Caixeta, L S; Al-Abri, M A; Giordano, J O

2016-09-01

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metritis based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of metritis by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. In this manuscript, the overall performance of HIS to detect cows with all disorders of interest in this study [ketosis, displaced abomasum, indigestion (companion paper, part I), mastitis (companion paper, part II), and metritis] is also reported. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. An HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as an HIS of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The overall sensitivity of HIS was 55% for all cases of metritis (n=349), but it was greater for cows with metritis and another disorder (78%) than for cows with metritis only (53%). Cows diagnosed with metritis and flagged based on HIS had substantial alterations in their rumination, activity, and HIS patterns around CD, alterations of blood markers of metabolic and health status around calving, reduced milk production, and were more likely to exit the herd than cows not flagged based on the HIS and cows without disease, suggesting that cows flagged based on the HIS had a more severe episode of metritis. Including all disorders of interest for this study, the overall sensitivity was 59%, specificity was 98%, positive predictive value was

Efficacy of treatment for hyperglycemic crisis in elderly diabetic patients in a day hospital

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Benaiges D

2014-05-01

Full Text Available D Benaiges,1–3 JJ Chillarón,1–3 MJ Carrera,1,3 F Cots,3,4 J Puig de Dou,1 E Corominas,1 J Pedro-Botet,1–3 JA Flores-Le Roux,1–3 C Claret,1 A Goday,1–3 JF Cano1–3 1Department of Endocrinology and Nutrition, Hospital del Mar, 2Department of Medicine, Universitat Autònoma de Barcelona, 3Institut Hospital del Mar d’Investigacions Mèdiques, 4Epidemiology and Evaluation Department, Parc de Salut Mar, Barcelona, Spain Background: The purpose of this prospective cohort study was to compare the costs of day hospital (DH care for hyperglycemic crisis in elderly diabetic patients with those of conventional hospitalization (CH. Secondary objectives were to compare these two clinical scenarios in terms of glycemic control, number of emergency and outpatient visits, readmissions, hypoglycemic episodes, and nosocomial morbidity. Methods: The study population comprised diabetic patients aged >74 years consecutively admitted to a tertiary teaching hospital in Spain for hyperglycemic crisis (sustained hyperglycemia [>300 mg/dL] for at least 3 days with or without ketosis. The patients were assigned to DH or CH care according to time of admission and were followed for 6 months after discharge. Exclusion criteria were ketoacidosis, hyperosmolar crisis, hemodynamic instability, severe intercurrent illness, social deprivation, or Katz index >D.Results: Sixty-four diabetic patients on DH care and 36 on CH care were included, with no differences in baseline characteristics. The average cost per patient was 1,345.1±793.6 € in the DH group and 2,212.4±982.5 € in the CH group (P<0.001. There were no differences in number of subjects with mild hypoglycemia during follow-up (45.3% DH versus 33.3% CH, P=0.24, nor in the percentage of patients achieving a glycated hemoglobin (HbA1c <8% (67.2% DH versus 58.3% CH, P=0.375. Readmissions for hyperglycemic crisis and pressure ulcer rates were significantly higher in the CH group

Technical note: Validation of a handheld meter for measuring β-hydroxybutyrate concentrations in plasma and serum from dairy cows.

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Pineda, A; Cardoso, F C

2015-12-01

The use of handheld meters for cow-side tests for β-hydroxybutyrate (BHB) concentrations in whole blood has become common. The aim of this study was to compare serum BHB (sBHB) and plasma BHB (pBHB) concentrations analyzed using either a "gold standard" enzymatic laboratory method (LM; Randox Laboratories Ltd., Antrim, UK; cat. no. RB1007) or a handheld meter (PX; Precision Xtra, Abbott Diabetes Care Inc., Alameda, CA). Results from 374 (187 serum and 187 plasma) samples taken from Holstein cows from 11 d before (52 samples) to 5 d after parturition (137 samples) were used for the analysis. Statistical analysis was performed using the MIXED, REG, and LOGISTIC procedures of SAS (v9.4; SAS Institute Inc., Cary, NC). A linear mixed model with repeated measures was fitted for LM and PX. Regression and correlation analyses were completed to estimate the relationship and agreement between the 2 methods. Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were used to evaluate agreement between LM and PX. Cross-validation by randomly splitting the data in model-building and validation sets was performed to estimate and validate the equation that predicted the LM results using PX. Receiver operating characteristic (ROC) curves were used to estimate the sensitivity (Se) and specificity (Sp) of PX at different threshold levels. The CCC was 0.74 for pBHB and 0.68 for sBHB. The 95% confidence interval of agreement of the Bland-Altman plot encompassed 96% of the difference between LM and PX for pBHB and 95% for sBHB. The mean difference for pBHB was -0.50±0.25mmol, and that for sBHB was -0.63±0.41mmol. The highest Se and Sp for PX were achieved when the threshold for ketosis was set to 1.8mmol/L for pBHB and 2.1mmol/L for sBHB. The area under the ROC curve was 0.97 for pBHB and 0.96 for sBHB. The negative bias shown by the Bland-Altman plots suggested that PX yielded higher pBHB and sBHB concentrations than the LM. However, the excellent test

Comparison of pure Holsteins to crossbred Holsteins with Norwegian Red cattle in first and second generations.

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Ezra, E; Van Straten, M; Weller, J I

2016-08-01

A total of 1922 first generation crossbred cows born between 2005 and 2012 produced by inseminating purebred Israeli Holstein cows with Norwegian Red semen, and 7487 purebred Israeli Holstein cows of the same age in the same 50 herds were analyzed for production, calving traits, fertility, calving diseases, body condition score, abortion rate and survival under intensive commercial management conditions. Holstein cows were higher than crossbreds for 305-day milk, fat and protein production. Differences were 764, 1244, 1231 for kg milk; 23.4, 37.4, 35.6 for kg fat, and 16.7, 29.8, 29.8 for kg protein; for parities 1 through 3. Differences for fat concentration were not significant; while crossbred cows were higher for protein concentration by 0.06% to 0.08%. Differences for somatic cells counts were not significant. Milk production persistency was higher for Holstein cows by 5, 8.3 and 8% in parities 1 through 3. Crossbred cows were higher for conception status by 3.1, 3.6 and 4.7% in parities 1 through 3. Rates of metritis for Holsteins were higher than the crossbred cows by 7.8, 4.6 and 3.4% in parities 1 to 3. Differences for incidence of abortion, dystocia, ketosis and milk fever were not significant. Holstein cows were lower than crossbred cows for body condition score for all three parities, with differences of 0.2 to 0.4 units. Contrary to comparisons in other countries, herd-life was higher for Holsteins by 79 days. A total of 6321 Holstein cows born between 2007 and 2011 were higher than 765 progeny of crossbred cows backcrossed to Israeli Holsteins of the same ages for milk, fat and protein production. Differences were 279, 537, 542 kg milk; 10.5, 17.7, 17.0 kg fat and 6.2, 12.9, 13.2 kg protein for parities 1 through 3. Differences for fat concentration were not significant, while backcross cows were higher for protein percentage by 0.02% to 0.04%. The differences for somatic cell score, conception rate, and calving diseases other than metritis, were not

Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women

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Silvestre R

2004-11-01

Full Text Available Abstract Objective To compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK and low-fat (LF diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE in overweight/obese men and women. Design Randomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%. Subjects 15 healthy, overweight/obese men (mean ± s.e.m.: age 33.2 ± 2.9 y, body mass 109.1 ± 4.6 kg, body mass index 34.1 ± 1.1 kg/m2 and 13 premenopausal women (age 34.0 ± 2.4 y, body mass 76.3 ± 3.6 kg, body mass index 29.6 ± 1.1 kg/m2. Measurements Weight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry, and resting energy expenditure (REE were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person. Results Actual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28% and the LF (~58:22:20% were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day compared to the LF (1562 kcal/day diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake. The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during

Diabetes melito do tipo 2 na infância e adolescência: revisão da literatura Type 2 diabetes in children and adolescents: literature review

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Monica Gabbay

2003-06-01

islet-cell auto-antibodies are important clues to diagnostic the T2DM in youth. Five to 25% of these patients can present ketosis at diagnosis. Insulin therapy can be discontinued during the evolution. Compliance to diet and an exercise program essential aspects of the treatment of adolescents. CONCLUSION: as obesity in the young is currently increasing in several developed or developing countries, T2DM in the youth can be consider an emergent problem also in our population.

Better postpartal performance in dairy cows supplemented with rumen-protected methionine compared with choline during the peripartal period.

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Zhou, Z; Vailati-Riboni, M; Trevisi, E; Drackley, J K; Luchini, D N; Loor, J J

2016-11-01

The onset of lactation in dairy cows is characterized by high output of methylated compounds in milk when sources of methyl group are in short supply. Methionine and choline (CHOL) are key methyl donors and their availability during this time may be limiting for milk production, hepatic lipid metabolism, and immune function. Supplementing rumen-protected Met and CHOL may improve overall performance and health of transition cows. The objective of this study was to evaluate the effect of supplemental rumen-protected Met and CHOL on performance and health of transition cows. Eighty-one multiparous Holstein cows were used in a randomized, complete, unbalanced block design with 2×2 factorial arrangement of Met (Smartamine M, Adisseo NA, Alpharetta, GA) and CHOL (ReaShure, Balchem Inc., New Hampton, NY) inclusion (with or without). Treatments (20 to 21 cows each) were control (CON), CON+Met (SMA), CON+CHOL (REA), and CON+Met+CHOL (MIX). From -50 to -21d before expected calving, all cows received the same diet (1.40Mcal of NE L /kg of DM) with no Met or CHOL. From -21d to calving, cows received the same close-up diet (1.52Mcal of NE L /kg of DM) and were assigned randomly to treatments (CON, SMA, REA, or MIX) supplied as top dresses. From calving to 30 DIM, cows were fed the same postpartal diet (1.71Mcal of NE L /kg of DM) and continued to receive the same treatments through 30 DIM. The Met supplementation was adjusted daily at 0.08% DM of diet and REA was supplemented at 60g/d. Incidence of clinical ketosis and retained placenta tended to be lower in Met-supplemented cows. Supplementation of Met (SMA, MIX) led to greater DMI compared with other treatments (CON, REA) in both close-up (14.3 vs. 13.2kg/d, SEM 0.3) and first 30d postpartum (19.2 vs. 17.2kg/d, SEM 0.6). Cows supplemented with Met (SMA, MIX) had greater yields of milk (44.2 vs. 40.4kg/d, SEM 1.2), ECM (44.6 vs. 40.5kg/d, SEM 1.0), and FCM (44.6 vs. 40.8kg/d, SEM 1.0) compared with other (CON, REA) treatments

Cyclic Vomiting Syndrome in Children

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T.V. Sorokman

2016-08-01

improvement in their condition, which manifested clinically in the transition of the II degree dehydration into the I degree, which required reduction of rehydration therapy volume. After 48 hours of treatment, the signs of intoxication syndrome (lethargy, drowsiness, headache were absent in all children. In 80 % of patients, there was a normalization of appetite, the frequency of nausea complaints significantly reduced. On the 5th day of therapy, no children had ketonuria. Conclusions: 1 obviously, there is a correspondence between cyclic vomiting syndrome and primary acetonemic syndrome (cyclic vomiting syndrome = primary acetonemic syndrome; 2 collecting the family history and detailed clinical features of attack-free period is of the significant importance for the diagnosis. The combination of risk factors in family history is one of the criteria for early diagnosis of cyclic vomiting syndrome; 3 during the oral rehydration therapy with the prescription of Rehydron Optim, ketosis completely stops in the vast majority of patients on the 2nd day of treatment; 4 Rehidron Optim has pleasant organoleptic qualities, it is well tolerated by children, and it has an excellent safety profile of application.

Final OptiMIR Scientific and Expert Meeting: From milk analysis to advisory tools (Palais des Congrès, Namur, Belgium, 16-17 April 2015

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Friedrichs, P.

2015-01-01

phenotypic data of the cows and the MIR spectra from the European MR, which enables the detection of relevant phenotypic traits and their reflection in the MIR spectra. Additionally, a standardization has been installed among all instruments of the milk analyzing laboratories involved in the OptiMIR project to ensure a stable prediction over time and a correction of deviations. Due to the monthly standardization process the developed prediction equations can be used in routine on all instruments taking part in the standardization. Different models for the prediction of the pregnancy status, energy balance, the methane emission as well as the detection of ketosis and acidosis have been developed within OptiMIR. It is worth mentioning, that those models predict the status of the animal with different accuracies and that progress on development and implementation differs between the models. Some of the tools developed within OptiMIR are already used in the field and provide dairy farmers with useful information e.g. about the health status or methane emission of a certain cow. The OptiMIR project also resulted in a collaborative planning on an economic interest group formation of the participating MROs. The final OptiMIR scientific and expert meeting disseminates the results obtained through OptiMIR more detailed and also provides an overview of recent advances in the development of management tools for the dairy sector. Initial application of the MIR-based tools has shown their potential for providing dairy farmers with information to improve their herd management in a cost-effective way. However, further research and development is required to finish a greater extend of MIR-based tools so that north-western European stakeholders can acquire competitive advantage in the dairy sector.

Comparing Finger-stick β-Hydroxybutyrate with Dipstick Urine Tests in the Detection of Ketone Bodies

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Baris KURU

2014-06-01

�ntem: İleriye yönelik kesitsel çalışmada, acil serviste serum glikoz düzeyi 150 mg/dL ve üzerinde olan hastaların parmak ucu kan beta-hidroksibütirat, venöz kan gazı ve idrar ketonu ölçümü yapıldı. Bulgular: Bu çalışmaya toplam 265 hasta dâhil edildi. Hastaların yaş ortalaması 62.4±14.9 yıl, %65.7'si kadındı. İdrar ketonu negatif olan 221 hastanın 29'unda (%13.1 parmak ucundan kan ketonu pozitif olarak saptandı. Bu hastaların üçü ağır, altısı orta düzeyli, 20'si hafif düzeyli ketonemikti. Olguların kapiller kan keton düzeyleri ortalaması 0.524±0.9 mmol/L (min.: 0 mmol/L, maks.: 6.7 mmol/L tespit edildi. Sonuç: Acil servise başvuran ve kan glikoz değeri 150 mg/dL üzerindeki hastalar içinde, idrar keton ölçümü yerine kapiller kan keton ölçümünün kullanılması hastaların yönetiminde önemli değişikliğe yol açabilir. Key words: Diabetic ketoacidosis, hydroxybutyrates, ketosis, Anahtar sözcükler: Diyabetik ketoasidoz, hidroksibütirat, ketozis

Study of Blood Metabolites Changes of Purebred Ghezel and Crossbred Arkhar Merinos × Ghezel Ewes during Late Pregnancy

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Leila Ahmadzadeh

2016-11-01

, which may originate from genetic potential of these two groups. These differences revealed that hybrid ewes are more resistant against blood metabolite changes during late pregnancy. Study of fluctuations in the blood metabolites during several stages of pregnancy can help us to determine abnormal metabolic cases and prediction of metabolic disorders such as pregnancy toxemia or ketosis, fatty liver syndrome and disease relating to fetus and ewe metabolism.

Ethical, social, environmental and economic issues in animal agriculture

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Kesavan, P C; Swaminathan, M S [Research Foundation, Third Cross Street, Taramani Institutional Area, Chennai - 600 113 (India); net, mssrfed@vsnl

2003-07-01

environmental balance and social harmony with the forest, coastal and hill communities of various regions of India. The ethical issues from a technological point of view centre around both gene-based and nongene- based technologies to improve the nutrition, health and productivity of the farm animals. In particular, a reference needs to be made to bovine somatotropin (bST), a natural growth hormone secreted by the anterior pituitary in all animals, with a major effect on the regulation of growth and also milk production. Since the quantities of bST obtained from slaughtered animals are quite small, recombinant DNA technology-based r-bST is produced, and widely used in the USA to increase the milk production by 10% to 20%. Exhaustive evaluation tests conducted in the USA have shown that r-bST has no harmful effects in milk, but a high production of milk makes higher demands on animal physiology, and if an adequate food supply is lacking, negative effects are observed on fertility besides other health problems, especially mastitis and ketosis. Presently, neither r-bST, nor adequate nutritious feed is available for millions of dairy cattle in the developing countries. The economic benefits of 'mass production' over 'production by masses' are obvious; further, the access to the r-bST in the 'mass production' system, but not in the system of 'production by masses' could accentuate the economic disparity. The above-said scenario has further ramifications in view of the implications arising from the WTO-related Agreement on Agriculture. With an array of domestic supports, products of 'mass production' could be dumped into developing countries causing a substantial rise in the already high levels of livelihood and food insecurity. Since the r-DNA based technologies for 'pharming' or for human food are not yet applied to farm animals in the developing countries there are no serious concerns of bio-safety, and violation of ethical norms. In the countries, where animals for human food are

[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

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Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

2003-01-01

-meal hyperglycemia of Type 2 diabetes. Epalrestat (Ono Yakuhin Co., 1992) is effective for diabetic neuropathy by reducing the formation of sorbitol. These anti-DM drugs were recently studied and developed in Japan. 4) The Japan Diabetes Society proposed a guideline on diagnostic criteria and treatment of diabetes mellitus (DM) in 1999 and revised it in 2002. DM is classified as insulin-dependent DM (Type l) and non-insulin dependent DM (Type 2). Type 1, juvenile onset DM, requires insulin therapy to prevent ketosis and to sustain life. Treatment of type 2, adult onset DM, is recommended as a step-by-step method, starting with dietary-exercise therapy, followed by oral hypoglycemic drugs and then insulin therapy. DM patients with complications should have a therapy devised to match their circumstances. 5) Epidemiological aspects: The mortality rate of DM compared to the time of drug appearance was traced from 1920 to 2000. The curve goes down slowly in the time frame of World War II, but rises from 1950 to 1970. The elevation could not be suppressed by the appearance of SUs, BGs or improved insulin preparations. The curve runs flat from 1980 to 1990, which might be related to the use of purified insulin or human insulin therapy. The mortality rate of DM indicates that death by hyperglycemic coma and other deaths resulting from complications are excluded. The survey of the principal cause of death by DM during the period of 1981-1990 indicates that the death rate due to hyperglycemic coma is only 1.7% of the total deaths caused by DM. The effect of drug therapy on all of the death resulting from DM is not detected. Hospital visitation and admission rates of the DM patients have been recorded since 1952 in Japan. This curve is rising continuously, and none of the antidiabetic drugs has been able to suppress it. These data show that the antidiabetic drugs relieve DM symptoms through their effective hypoglycemic actions, but that they cannot suppress the mortality rate of DM. It is

Is insulin the preferred treatment for HbA1c >9%?

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Bloomgarden, Zachary

2017-09-01

The algorithms and guidelines of the American Association of Clinical Endocrinologists and the American Diabetes Association recommend that insulin administration be strongly considered for people with type 2 diabetes (T2D) with HbA1c levels exceeding 9.0% and 10%, respectively. Although the caveat is given in both sets of recommendations that this is particularly appropriate when patients are "symptomatic," referring to urinary frequency with increased thirst and appetite, weight loss, and ketosis, the clinical definition of such presentations may be ill-defined, and it is noteworthy that both documents consider insulin to offer particular benefit under such circumstances. However, with multiple options for glycemic treatment, it is of interest to reconsider this argument for insulin use. It should be recalled that in the UK Prospective Diabetes Study, diet alone was associated with a reduction in HbA1c from 9% to 7%. Drug-naïve people with T2D do often show surprisingly strong reductions in HbA1c with metformin-based dual-agent oral treatment approaches; a recent report showed that even with baseline HbA1c >11%, the combination of metformin with a sulfonylurea, pioglitazone, or sitagliptin was associated with reduction in HbA1c from 11.6% to 6.0%. A 32-week study of the combination of rosiglitazone with metformin in patients with mean baseline HbA1c 8.9% showed a mean HbA1c reduction of 2.3%, and an open-label cohort with baseline HbA1c 11.8% had a reduction in HbA1c to 7.8%. With metformin plus sitagliptin, a mean placebo-adjusted HbA1c reduction of 2.1% from a baseline of 8.8% was reported, with those patients with baseline HbA1c >9% having a 2.6% reduction in HbA1c, and an open-label cohort with baseline HbA1c 11.2% having a 2.9% reduction in HbA1c. Similar 2% HbA1c reductions from baseline levels of 9.1% were seen with metformin in initial combination with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin. Although such dual oral agent