Gender differences in factors influencing insulin resistance in elderly hyperlipemic non-diabetic subjects

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Hrebícek Jirí

2002-10-01

Full Text Available Abstract Background The increase in the prevalence of insulin resistance-related metabolic syndrome, a disorder that greatly increases the risk of diabetes, heart attack and stroke, is alarming. One of the most frequent and early symptoms of metabolic syndrome is hypertriglyceridemia. We examined the gender differences between various metabolic factors related to insulin resistance in elderly non-diabetic men and postmenopausal women of comparable age suffering from hypertriglyceridemia, and compared them with healthy subjects of equal age. Results The indexes of insulin resistance HOMA IR and QUICKI were significantly higher in both hyperlipemic men and women than in controls; 95% confidence limits of hyperlipemic subjects did not overlap with controls. In both normolipemic and hyperlipemic men and women serum leptin correlated significantly with insulin resistance, while HDL-cholesterol correlated inversely with HOMA-IR only in women (both normo- and hyperlipemic, and serum tumor necrosis factor α (TNFα only in hyperlipemic women. According to results of multiple regression analysis with HOMA-IR as a dependent variable, leptin played a significant role in determining insulin resistance in both genders, but – aside from leptin – triglycerides, TNFα and decreased HDL-cholesterol were significant determinants in women, while body mass index and decreased HDL-cholesterol were significant determinants in men. The coefficient of determination (R2 of HOMA IR by above mentioned metabolic variables was in women above 60%, in men only about 40%. Conclusion The significant role of serum leptin in determination of insulin resistance in both elderly men and postmenopausal women of equal age was confirmed. However, the study also revealed significant gender differences : in women a strong influence of triglycerides, TNFα and decreased HDL-cholesterol, in men only a mild role of BMI and decreased HDL-cholesterol.

Treatment of Severe Hypertriglyceridemia with Continuous Insulin Infusion

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Yesica Rodríguez Santana

2011-01-01

Full Text Available Severe hypertriglyceridemia (SH represents a therapeutic emergency because of the possibility of developing cardiovascular events and hyperlipemic acute pancreatitis (PA. Most patients with SH suffer primary or genetic abnormality in lipid metabolism in combination with a precipitating factor such as uncontrolled diabetes mellitus, alcoholism, and drug intake. The standard treatment of hypertriglyceridemia (HTG with omega 3 fatty acids and fibrates, along with dietary changes, has no effect on an emergency situation. There are no clinical guidelines to SH, but therapy with insulin, heparin, a combination of both, plasmapheresis, or octreotide have been tested succesfully. We report the case of a 10-year-old girl with clinical acute pancreatitis and diabetic ketoacidosis debut, along with incidental finding of an SH, who had a good outcome after treatment with insulin intravenous infusion.

Laparoscopic bariatric surgery for the treatment of severe hypertriglyceridemia.

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Hsu, Sung-Yu; Lee, Wei-Jei; Chong, Keong; Ser, Kong-Han; Tsou, Jun-Jiun

2015-04-01

It is well established that severe hypertriglyceridemia can lead to pancreatitis. At present, medical treatment for patients with severe hypertriglyceridemia and repeat pancreatitis attacks is not adequate. The aim of this study was to assess the effectiveness of laparoscopic bariatric surgery in these patients. A review of 20 morbidly obese patients with severe hypertriglyceridemia (a triglyceride level of >1000 mg/dL) who received laparoscopic bariatric surgery was performed. The study population comprised 14 males and six females, with an average age of 35.0 years (range 24-52 years), and the mean body mass index was 38.2 kg/m(2) (range 25-53 kg/m(2)). The preoperative mean plasma triglyceride level was 1782.7 mg/dL (range 1043-3884 mg/dL). Four patients had a history of hypertriglyceridemic pancreatitis and 13 patients had associated diabetes. Of the 20 patients, 17 (85%) received gastric bypass, whereas three (15%) received restrictive-type surgery. Laparoscopic access was used in all of the patients. Hypertriglyceridemia in morbidly obese patients was more commonly associated with male sex and a poorly controlled diabetic state. The mean weight reduction was 25.5% 1 year after surgery, with a marked improvement in diabetes management. As early as 1 month following surgery, the plasma mean triglyceride levels had decreased to 254 mg/dL (range 153-519 mg/dL), and this was further reduced to mean levels of 192 mg/dL (range 73-385 mg/dL) 1 year after surgery. One patient developed acute pancreatitis during the perioperative period, but none of the patients suffered an episode of pancreatitis in the follow-up period (from 6 months to 13 years). Bariatric surgery can be successfully used as a metabolic surgery in severe hypertriglyceridemia patients at risk of acute pancreatitis. However, control of triglyceride levels prior to bariatric surgery is indicated. Copyright © 2014. Published by Elsevier Taiwan.

LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus.

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Nocoń-Bohusz, Julita; Wikiera, Beata; Basiak, Aleksander; Śmigiel, Robert; Noczyńska, Anna

2016-02-18

Severe hypertriglyceridemia is a condition associated with extremely high triglycerides (TG) plasma concentrations exceeding 1000mg/dl. This condition may result in mutations in genes encoding lipoprotein lipase (LPL), apolipoprotein C2 (APOC2) and apolipoprotein A5 (APOA5) characterized by an autosomal recessive inheritance pattern. A case report of a patient in which clinical picture of type 1 diabetes mellitus (T1DM) was accompanied by diabetic ketoacidosis (DKA) and severe hypertriglyceridemia. A 2.5-year-old boy was admitted to the hospital with ketoacidosis (pH - 7.0, BE - 20mmol/l, HCO3 10mmol/l), glucose level of 850mg%, hyponatremia (Na 100mmol/l) and hyperlipidemia (TG 13493 mg/dl, TC 734 mg/dl). The administered treatment resulted in nearly normal glycemic values and lipid disturbances normalization. This child was diagnosed with a heterozygous mutation of the LPL gene. Currently with an intensive insulin therapy and correct metabolic control of type 1 diabetes mellitus (T1DM), this patient maintains a normal lipid profile. In patient with T1DM the diagnosis of severe hypertriglyceridemia in the course of ketoacidosis should be based on careful interpretation of laboratory tests results. Moreover genetic tests of the patient and his/her immediate relatives blood samples should be performed. © Polish Society for Pediatric Endocrinology and Diabetology.

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.

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Tenenbaum, Alexander; Klempfner, Robert; Fisman, Enrique Z

2014-12-04

The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG

[Severe hypertriglyceridemia induced acute pancreatitis: a case report and review of the literature].

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Herrera Del Águila, Dwight Denis; Garavito Rentería, Jorge; Linarez Medina, Karen; Lizarzaburu Rodríguez, Víctor

2015-01-01

Hypertriglyceridemia-induced acute pancreatitis occurs in about 1-4% of the cases. It is the third leading cause of pancreatitis after biliary and alcoholic etiology. Hypertriglyceridemia can be caused by primary causes, lipid metabolism disorders and secondary causes. A 32 year old man, born in Huancayo, with a history of diabetes mellitus type 2, severe mixed dyslipidemia with primary hypertriglyceridemia, was admitted to emergency with 10 days of abdominal pain with moderate intensity in epigastrium and left hypochondrium spreading to dorsal region after intake of high-fat meal. 24 hours before admission, pain exacerbates increasing intensity and causing nausea and bilious vomits. Therefore, all laboratory examinations are carried out resulting in hypertriglyceridemia-induced acute pancreatitis. For that reason, an adequate clinical history physical examination associated with laboratory and image examinations are important to consider hypertriglyceridemia as part of the etiology of acute pancreatitis.

Studies of association of AGPAT6 variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes

DEFF Research Database (Denmark)

Snogdal, Lena Sønder; Grarup, Niels; Banasik, Karina

2013-01-01

Type 2 diabetes, obesity and insulin resistance are characterized by hypertriglyceridemia and ectopic accumulation of lipids in liver and skeletal muscle. AGPAT6 encodes a novel glycerol-3 phosphate acyltransferase, GPAT4, which catalyzes the first step in the de novo triglyceride synthesis. AGPA......-deficient mice show lower weight and resistance to diet- and genetically induced obesity. Here, we examined whether common or low-frequency variants in AGPAT6 associate with type 2 diabetes or related metabolic traits in a Danish population.......Type 2 diabetes, obesity and insulin resistance are characterized by hypertriglyceridemia and ectopic accumulation of lipids in liver and skeletal muscle. AGPAT6 encodes a novel glycerol-3 phosphate acyltransferase, GPAT4, which catalyzes the first step in the de novo triglyceride synthesis. AGPAT6...

Does Abdominal Obesity Accelerate the Effect of Hypertriglyceridemia on Impaired Fasting Glucose?

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Lee, Soojin; Chun, Kihong; Lee, Soonyoung; Kim, Daejung

2010-01-01

Purpose This study sought to determine whether abdominal obesity is a risk factor for impaired fasting glucose (IFG) and hypertriglyceridemia and to verify whether moderate effect of abdominal obesity on the relationship between IFG and hypertriglyceridemia in Korea. Materials and Methods Data from the Korean National Health and Nutrition Examination Survey was used for the analysis. The study population included 5,938 subjects aged 20 year old drawn from non-diabetic participants in a health...

Does abdominal obesity accelerate the effect of hypertriglyceridemia on impaired fasting glucose?

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Lee, Soojin; Chun, Kihong; Lee, Soonyoung; Kim, Daejung

2010-05-01

This study sought to determine whether abdominal obesity is a risk factor for impaired fasting glucose (IFG) and hypertriglyceridemia and to verify whether moderate effect of abdominal obesity on the relationship between IFG and hypertriglyceridemia in Korea. Data from the Korean National Health and Nutrition Examination Survey was used for the analysis. The study population included 5,938 subjects aged 20 year old drawn from non-diabetic participants in a health examination survey. The subjects were classified according to the presence of abdominal obesity based on waist circumference, IFG based on their fasting blood glucose level, and hypertriglyceridemia on their fasting triglyceride. The multivariate-adjusted odds ratios for the occurrence of hypertriglyceridemia were 2.91 in the abdominal obesity group as compared with the nonobesity group and 1.31 in subjects with IFG compared with the normoglycemia controls. Abdominal obesity was found to be positively moderated in the interaction between waist circumference and fasting blood sugar. The moderate effect between abdominal obesity and IFG contributes to the development of hypertriglyceridemia in Korea.

Plasma Exchange for the Treatment of Transient Extreme Hypertriglyceridemia Associated with Diabetic Ketoacidosis and Acute Pancreatitis

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Davide Donelli

2018-03-01

Full Text Available Diabetic ketoacidosis (DKA can quite frequently present in association with acute pancreatitis (AP caused by transient severe hypertriglyceridemia (HTG. Here we report the case of a patient presenting with DKA, severe HTG and AP who received urgent plasma exchange for HTG control, and who reached adequate serum triglyceride levels only after appropriate DKA management. The treatment of patients presenting with DKA and coexistent AP associated with severe HTG should focus first on appropriate DKA management. Plasma exchange as a treatment for severe HTG in patients with DKA and AP should be evaluated carefully.

Severe hypertriglyceridemia in Japan: Differences in causes and therapeutic responses.

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Murase, Toshio; Okubo, Minoru; Ebara, Tetsu; Mori, Yasumichi

Severe hypertriglyceridemia (>1000 mg/dL) has a variety of causes and frequently leads to life-threating acute pancreatitis. However, the origins of this disorder are unclear for many patients. We aimed to characterize the causes of and responses to therapy in rare cases of severe hypertriglyceridemia in a group of Japanese patients. We enrolled 121 patients from a series of case studies that spanned 30 years. Subjects were divided into 3 groups: (1) primary (genetic causes); (2) secondary (acquired); and (3) disorders of uncertain causes. In the last group, we focused on 3 possible risks factors for hypertriglyceridemia: obesity, diabetes mellitus, and heavy alcohol intake. Group A (n = 20) included 13 patients with familial lipoprotein lipase deficiency, 3 patients with apolipoprotein CII deficiency, and other genetic disorders in the rest of the group. Group B patients (n = 15) had various metabolic and endocrine diseases. In Group C (uncertain causes; n = 86), there was conspicuous gender imbalance (79 males, 3 females) and most male subjects were heavy alcohol drinkers. In addition, 18 of 105 adult patients (17%) had histories of acute pancreatitis. The cause of severe hypertriglyceridemia is uncertain in many patients. In primary genetic forms of severe hypertriglyceridemia, genetic diversity between populations is unknown. In the acquired forms, we found fewer cases of estrogen-induced hypertriglyceridemia than in Western countries. In our clinical experience, the cause of most hypertriglyceridemia is uncertain. Our work suggests that genetic factors for plasma triglyceride sensitivity to alcohol should be explored. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Estrogen-associated severe hypertriglyceridemia with pancreatitis.

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Aljenedil, Sumayah; Hegele, Robert A; Genest, Jacques; Awan, Zuhier

Estrogen, whether therapeutic or physiologic, can cause hypertriglyceridemia. Hypertriglyceridemia-induced pancreatitis is a rare complication. We report 2 women who developed estrogen-associated severe hypertriglyceridemia with pancreatitis. The first patient developed pancreatitis secondary to hypertriglyceridemia associated with in vitro fertilization cycles. Marked reduction in her triglyceride was achieved with dietary restrictions and fibrate. The second patient developed pancreatitis secondary to hypertriglyceridemia during her pregnancies. She was noncompliant with the treatment; therefore, her triglyceride remained high after delivery. In both patients, no hypertriglyceridemia-associated genes mutations were identified, although the second patient had strong polygenic susceptibility to hypertriglyceridemia. Estrogen-induced severe hypertriglyceridemia with pancreatitis can be a life-threatening condition. Screening in high-risk patients is crucial to prevent subsequent complications. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

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Natasha Gupta

2014-01-01

Full Text Available Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term and was successfully treated with postpartum therapeutic plasma exchange. Patient also developed several other complications related to her substantial hypertriglyceridemia including preeclampsia, chylous ascites, retinal detachment, pleural effusion, and chronic pericarditis. This patient had no previous family or personal history of lipid abnormality and had four successful prior pregnancies without developing gestational hypertriglyceridemia. Such a severe hypertriglyceridemia is usually seen in patients with familial chylomicronemia syndromes where hypertriglyceridemia is exacerbated by the pregnancy, leading to fatal complications such as acute pancreatitis.

[Rare cause for severe hypertriglyceridemia - case 9/2013].

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Kahl, Sabine; Roden, Michael; Mörike, Klaus; Müssig, Karsten

2013-11-01

We report on a 48-year-old female patient with recently developed severe hypertriglyceridemia. Medical history was remarkable for breast cancer with breast-preserving surgery and chemoradiotherapy. The patient has been treated with 20 mg tamoxifen per day for three months. Laboratory results showed hypertriglyeridemia, hypercholesterolemia and lowered HDL-cholesterol. Findings were consistent with a drug-induced hypertriglyceridemia caused by anti-estrogenic therapy with tamoxifen. After consulting the patient's gynaecologist, we discontinued tamoxifen treatment. Thereupon, triglyceride levels fell consistently. There were no signs of pancreatitis, serum amylase and lipase were in the normal range. Patients with pre-diagnosed metabolic disorders, especially dyslipidemia and type 2 diabetes, should undergo regular controls of serum triglycerides during tamoxifen treatment. Also, one should keep in mind that a subacute, severe rise in serum triglyceride levels may be caused, in rare cases, by tamoxifen treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

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Gupta, Natasha; Ahmed, Seema; Shaffer, Lemuel; Cavens, Paula; Blankstein, Josef

2014-01-01

Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term an...

Hypertriglyceridemia Thalassemia Syndrome: Common Disease, Uncommon Association.

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Das, Lipsa; Samprathi, Madhusudan; Shukla, Umesh; Bandyopadhyay, Debapriya; Das, Rashmi Ranjan

2016-07-01

Hypertriglyceridemia has been rarely described with thalassemia, an entity called hypertriglyceridemia-thalassemia syndrome. The authors describe a young infant diagnosed with thalassemia major with severe hypertriglyceridemia. The presence of severe hypertriglyceridemia in this child which rapidly resolved after transfusion, probably suggests a self limited mechanism which may not require therapy. Though hypertriglyceridemia has been reported with hemolytic anemias, the mechanism is unclear. This case illustrates that thalassemia may be associated with hypertriglyceridemia; once familial and secondary causes are ruled out, clinicians may wait for spontaneous resolution before considering specific therapy.

Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus.

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Lampman, R M; Schteingart, D E

1991-06-01

Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

Understanding hypertriglyceridemia in women: clinical impact and management with prescription omega-3-acid ethyl esters

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Thomas D Dayspring

2011-03-01

Full Text Available Thomas D DayspringNorth Jersey Institute of Menopausal Lipidology, Wayne, NJ, USABackground: Elevated triglycerides (TGs are a common lipid disorder in the US and are associated with comorbidities such as pancreatitis, obesity, type 2 diabetes, and metabolic syndrome. TGs are generally elevated in postmenopausal women compared with premenopausal women. Meta-analysis has shown that elevated TGs are associated with an increased risk of coronary heart disease (CHD.Objective: This article provides a general overview of TG metabolism and reviews data on the epidemiology and risk of elevated TGs in women, as pregnancy and menopause, in particular, have been associated with unfavorable changes in the lipoprotein profile, including elevations in TGs. In addition, this review seeks to explain the recommended TG goals and treatment options for hypertriglyceridemia with an emphasis on severe hypertriglyceridemia (TGs ≥ 500 mg/dL and its respective treatment with prescription omega-3-acid ethyl esters (P-OM3.Methods: MedLine was searched for articles published through August 2009 using the terms “hypertriglyceridemia” and “dyslipidemia”, with subheadings for “prevalence”, “women”, “treatment”, “guidelines”, “risk”, and “omega-3 fatty acids”. Publications discussing the epidemiology of hypertriglyceridemia, CHD risk, treatment guidelines for lipid management, or clinical trials involving P-OM3 were selected for review. The reference lists of relevant articles were also examined for additional citations.Results: Hypertriglyceridemia is associated with increased CHD risk. Women, especially those with polycystic ovarian syndrome, type 2 diabetes, or who are postmenopausal, should be monitored regularly for the impact of hypertriglyceridemia on their lipid profile. Cardiovascular risk of TGs can be indirectly assessed by monitoring non-high-density lipoprotein cholesterol (non-HDL-C levels. There are multiple sets of guidelines

[Bezafibrate in an infant with congenital generalized lipodystrophy and severe hypertriglyceridemia].

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Araújo, Rogério Santiago; Ramos, André de Paula Silva; Borges, Máriton de Araújo Sousa

2013-11-01

Congenital generalized lipodystrophy (CGL) with severe hypertriglyceridemia in a children less than 1 year of age is associated with worse metabolic risk. We used data from patient records, as well as extensive literature research to write the manuscript. We report the case of an infant with typical phenotype of CGL and hypertriglyceridemia of 1,360 mg/dL who was treated with bezafibrate at a dose of 30 to 60 mg/day from age 11 months to 5.5 years old, with a measurement of nadir of triglycerides of 55 mg/dL. Clinical evolution and clinical laboratory tests before and after bezafibrate were carried out over 5 years and 6 months. Phenotype was classified as CGL type 2. Despite the efficient control of hypertriglyceridemia and absence of development of diabetes mellitus, the use of bezafibrate did not prevent the onset of hepatic steatosis during evolution. Hypolipidemic therapy with bezafibrate proved effective in maintaining the levels of triglycerides, cholesterol and its fractions at normal levels, and its use was not correlated with severe side effects during the described period.

Management of hypertriglyceridemia induced acute pancreatitis and therapeutic plasmapheresis : Report of nine cases and review of literature.

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Uyar, S; Harmandar, F; Kök, M; Taș, Z; Dolu, S; Tokuç, A; Köker, G; Görar, S; Çekin, A H

2017-01-01

Hypertriglyceridemia is one of the rare causes of the acute pancreatitis. The prevalance of hypertriglyceridemia has increased recently due to the changing eating habits, sedentary lifestyle, alcohol consumption, obesity and concomitant diabetes mellitus. Therefore, the frequency of the acute pancreatitis due to hypertriglyceridemia may increase in coming years. Diagnosis of the acute pancreatitis by hypertriglyceridemia can be overlooked easily and may be very severe if untreated accurately on time. In addition to the standard management of pancreatitis, specific treatment for hypertriglyceridemia that is insulin, heparin and anti-hypertriglyceridemic drugs are used. Therapeutic plasmapheresis is the last treatment option and seems the most effective one in this subject through developing device and membrane technologies when we review the current literature. Not only triglycerides but also proinflammatory cytokines and adhesion molecules that play an active role in pathogenesis are removed by plasmapheresis. So, the effectiveness of treatment appears promising. However, the exact pathophysiology of hypertriglyceridemia-induced pancreatitis could not be fully understood and the majority of published experience comes from the case reports and the benefit of randomized clinical trials is not available. Therefore, there are no data about what are the exact indications and when we start therapeutic plasmapheresis in literature. This manuscript describes our hospital experience with treatment options and analyzes reports published recently about plasmapheresis as a treatment modality for hypertriglyceridemia induced acute pancreatitis. © Acta Gastro-Enterologica Belgica.

Increased amino acids levels and the risk of developing of hypertriglyceridemia in a 7-year follow-up

OpenAIRE

Mook-Kanamori, D. O.; Römisch-Margl, W.; Kastenmüller, G.; Prehn, C.; Petersen, A. K.; Illig, T.; Gieger, C.; Wang-Sattler, R.; Meisinger, C.; Peters, A.; Adamski, J.; Suhre, K.

2014-01-01

Background Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D). Aim We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia. Materials and methods We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for which follow-up data were available also at the KORA F4 7 years later. After exclusion for hypertriglyceridemia...

Recommendations for severe hypertriglyceridemia treatment, are there new strategies?

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Filippatos, Theodosios D; Elisaf, Moses S

2014-01-01

This review considers drug combinations and newer treatment strategies for patients with severe hypertriglyceridemia. Hypertriglyceridemia is associated with an atherogenic metabolic profile and in most studies with increased cardiovascular disease risk. Patients with severe hypertriglyceridemia also have increased incidence of pancreatitis. All types of severe hypertriglyceridemia are associated with a reduction in lipoprotein lipase activity. Patients with severe hypertriglyceridemia and abdominal pain or pancreatitis should be hospitalized and treated with hypolipidemic drugs and, if needed, with insulin/dextrose infusion or therapeutic apheresis. Fibrates are the first-line treatment in patients with severe hypertriglyceridemia. Omega-3 fatty acids and niacin are very useful drugs for patients with hypertriglyceridemia. Statins in high doses exhibit a significant hypotriglyceridemic activity. Drugs that interfere with chylomicron production such as orlistat are also useful for hypertriglyceridemic patients. In most patients with severe hypertriglyceridemia drug combinations are needed to maintain an acceptable triglyceride concentration. Gene therapy is under development for patients with known genetic abnormalities of triglyceride metabolism. Clinicians should be vigilant for the recognition and prompt treatment of patients with severe hypertriglyceridemia aimed to avoid the serious complication of pancreatitis and to reduce their cardiovascular risk.

Interactions of obesity and glucose-stimulated insulin secretion in familial hypertriglyceridemia.

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Maruhama, Y; Abe, R; Okuguchi, F; Oikawa, S; Ohneda, A; Goto, Y

1978-06-01

Plasma lipids and lipoproteins, glucose tolerance, plasma insulin response to glucose load, and liver function were examined in 81 relatives of 12 index cases with primary endogenous hypertriglyceridemia, hyperinsulinemia, and hepatic steatosis, as well as in 90 nonrelatives, including the spouses, as controls. Insulin hypersecretion (with or without glucose intolerance), endogenous hypertriglyceridemia, and abnormal liver function suggesting hepatic steatosis were shown to exist in the relatives mostly in combined fashion. Correlation analysis and stepwise multiple regression analysis revealed that the combined disorder developed on the basis of obesity. The incidence of diabetes mellitus was significantly high in the relatives (14.8 per cent) as compared with the normal Japanese population (3.5 per cent). Although the vertical transmission of the combined disorder was noted in almost all pedigrees, the frequency distribution analysis of insulin response, glucose tolerance, and plasma triglyceride showed the histograms of these variables similarly skewed to the right as compared with those of the controls, with no apparent bimodality. In view of the hitherto suggested role of insulin in triglyceride metabolism, it is concluded that hyperinsulinemia coupled with obesity seems to be the basic trait of this form of familial hypertriglyceridemia and hepatic steatosis, though the mode of transmission remains to be elucidated.

Lomitapide for the treatment of hypertriglyceridemia.

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Brahm, Amanda J; Hegele, Robert A

2016-12-01

Severe genetic forms of hypertriglyceridemia carry a risk of life-threatening pancreatitis and lack available effective treatments. Lomitapide is a microsomal triglyceride transfer protein inhibitor currently approved for treatment of homozygous familial hypercholesterolemia that may be useful in the management of severe hypertriglyceridemia. Areas covered: Published trials of lomitapide that reported plasma triglyceride response were reviewed, as was a case report of a patient with hypertriglyceridemia who was treated for 13 years with lomitapide. ClinicalTrials.gov was also reviewed for any unpublished results and ongoing trials. Expert opinion: Lomitapide demonstrates effective triglyceride lowering and may be a useful treatment for patients with genetic hypertriglyceridemia and recurrent acute pancreatitis who are refractory to traditional treatment. However, long term hepatic safety may be a concern and direct clinical trial-level data are lacking for this indication.

Risk factors of diabetes in North Indians with metabolic syndrome.

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Pratyush, Daliparthy D; Tiwari, Shalbha; Singh, Saurabh; Singh, Surya K

2016-01-01

Metabolic syndrome progresses to diabetes and determinants of this progression like hyperinsulinemia, hypertriglyceridemia and genetic factors have been speculative. The present study was aimed at quantifying the insulin resistance and influence of family history of diabetes in subjects with metabolic syndrome developing prediabetes and diabetes. Consecutive subjects attending the endocrine clinic were evaluated for metabolic syndrome as per definition of International Diabetes Federation, 2005. The family history of diabetes in their first degree relatives was ascertained and Homeostasis model assessment of Insulin resistance (HOMA-IR), Homeostasis model assessment for beta cell function (HOMA-B) and Quantitative insulin sensitivity check index (QUICKI) were calculated in 163 subjects enrolled. HOMA-IR was higher (pmetabolic syndrome+prediabetes or diabetes compared to metabolic syndrome with normal glucose tolerance. HOMA-B was lower and prevalence of prediabetes and diabetes was higher in metabolic syndrome subjects with family history of diabetes than in those without such family history (pmetabolic syndrome having prediabetes and diabetes had more severe insulin resistance than those with metabolic syndrome only. Beta cell dysfunction was remarkable and prevalence of prediabetes was high in metabolic syndrome subjects with family history of diabetes. Both the severity of the insulin resistance and family history of diabetes are therefore proposed to be determinants of diminished Beta cell function leading to diabetes in metabolic syndrome. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Altered Plasma Lysophosphatidylcholines and Amides in Non-Obese and Non-Diabetic Subjects with Borderline-To-Moderate Hypertriglyceridemia: A Case-Control Study

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Jung, Saem; Lee, Sang-Hyun; Lee, Jong Ho

2015-01-01

Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease (CVD). We investigated alterations in plasma metabolites associated with borderline-to-moderate HTG (triglycerides (TG) 150-500 mg/dL). Using UPLC-LTQ-Orbitrap mass spectrometry analysis, the metabolomics profiles of 111 non-diabetic and non-obese individuals with borderline-to-moderate HTG were compared with those of 111 age- and sex-matched controls with normotriglyceridemia (NTG, TG amides, including N-ethyldodecanamide (q = 2.9E-05), N-propyldodecanamide (q = 3.5E-05), palmitoleamide (q = 2.9E-06), and palmitic amide (q = 0.019). The metabolomic profiles of the HTG group also exhibited lower plasma levels of cis-4-octenedioic acid (qamides, and cis-4-octenedioic acid among non-diabetic and non-obese individuals with borderline-to-moderate HTG. These results provide novel insights into the metabolic alterations that occur in the early metabolic stages of HTG. This information may facilitate the design of early interventions to prevent disease progression. PMID:25856314

Saroglitazar for the treatment of dyslipidemia in diabetic patients.

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Joshi, Shashank R

2015-03-01

Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects. Saroglitazar , a dual PPAR-α/γ agonists, is an emerging therapeutic option with its dual benefit on glycemic and lipid parameters. This paper reviews the clinical development of saroglitazar for the management of diabetic dyslipidemia. The efficacy and safety profile of saroglitazar is reviewed in context to currently available therapy like pioglitazone for diabetes and fibrates for hypertriglyceridemia. In addition, this paper also reviews the association between diabetes and dyslipidemia and the role of TG in reducing cardiovascular events. Saroglitazar, a dual PPAR-α/γ agonist, is a potential therapeutic option for the management of diabetic dyslipidemia. It has dual benefit of significant improvement in glycemic parameters (glycated hemoglobin and fasting blood glucose) and significant improvement in dyslipidemia (TGs, apolipoprotein B, non-HDL-C). The results of Phase III clinical trials indicate that saroglitazar is devoid of conventional side effects of fibrates and pioglitazone. Future clinical trials of saroglitazar will further establish its place in the management of diabetes, dyslipidemia and associated cardiovascular risk.

Determining triglyceride reductions needed for clinical impact in severe hypertriglyceridemia.

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Christian, Jennifer B; Arondekar, Bhakti; Buysman, Erin K; Jacobson, Terry A; Snipes, Rose G; Horwitz, Ralph I

2014-01-01

Patients with severe hypertriglyceridemia have an increased risk of cardiovascular disease and pancreatitis. Target triglyceride levels associated with clinical benefit for patients with severe hypertriglyceridemia are not currently known. This study evaluates the association between lower follow-up triglyceride levels and incidence of clinical events for patients with severe hypertriglyceridemia. By using claims data from 2 large US healthcare databases, we conducted a retrospective cohort study and identified 41,210 adults with severe hypertriglyceridemia (triglycerides ≥ 500 mg/dL) between June 2001 and September 2010. The date of the first severe hypertriglyceridemia laboratory result was the index date. Patients were categorized into 1 of 5 triglyceride ranges (severe hypertriglyceridemia with follow-up triglyceride levels severe hypertriglyceridemia with follow-up triglyceride levels 200 to 299 mg/dL and 300 to 399 mg/dL (P severe hypertriglyceridemia with the lowest follow-up triglyceride levels. Copyright © 2014 Elsevier Inc. All rights reserved.

DKA with Severe Hypertriglyceridemia and Cerebral Edema in an Adolescent Boy: A Case Study and Review of the Literature

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Tansit Saengkaew

2016-01-01

Full Text Available A 13-year-old adolescent boy with type 1 diabetes mellitus (1b presented with diabetic ketoacidosis (DKA and cerebral edema. Grossly lipemic serum and lipemia retinals due to extremely high triglyceride (TG level were observed without evidence of xanthoma or xanthelasma. Cerebral edema was treated by appropriate ventilation and mannitol administration. Normal saline was carefully given and regular insulin was titrated according to blood sugar levels. Triglyceride levels were reduced from 9,800 mg/dL to normal range within 9 days after conventional treatment was commenced without antilipid medication. Based on our review of the literature, this is the first reported case of confirmed pediatric DKA with severe hypertriglyceridemia and cerebral edema. In patients with DKA and hypertriglyceridemia, clinicians should be mindful of the possibility of associated acute pancreatitis and cerebral edema.

Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

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Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

2014-01-01

Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

Secondary hypertriglyceridemia in children and adolescents.

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Blackett, Piers R; Wilson, Don P; McNeal, Catherine J

2015-01-01

Secondary dyslipidemia with predominant hypertriglyceridemia may occur as a consequence of both common and rare causes. After accounting for obesity and associated insulin resistance, clinicians should carefully consider other contributing factors and conditions. Genetic background and causative factors prevail during gestation, infancy, and childhood and continue in adults. Elevations in triglyceride (TG) are associated with transfer of TG to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) resulting in lipolysis, HDL degradation, and formation of atherogenic LDL particles. Defining and treating the underlying cause is the first step toward restoring the lipids and lipoproteins to normal, especially in cases with severe hypertriglyceridemia, who are at risk for acute pancreatitis. Disorders involving the liver, kidney, endocrine, and immune systems and medications need to be considered. Rare diseases such as lipodystrophy and glycogen storage disease are particularly challenging, and there have been promising new developments. Treatment depends on the severity; prevention of acute pancreatitis being a priority in severe cases and lifestyle modification being a foundation for general management followed by targeting TG and predictors of coronary artery disease such as LDL cholesterol and non-HDL cholesterol, when they exceed cutpoints. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Clinical characteristics of Japanese patients with severe hypertriglyceridemia.

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Tada, Hayato; Kawashiri, Masa-Aki; Nakahashi, Takuya; Yagi, Kunimasa; Chujo, Daisuke; Ohbatake, Azusa; Mori, Yukiko; Mori, Shunsuke; Kometani, Mitsuhiro; Fujii, Hiroshi; Nohara, Atsushi; Inazu, Akihiro; Mabuchi, Hiroshi; Yamagishi, Masakazu; Hayashi, Kenshi

2015-01-01

Although of interest, few data exist on the clinical characteristics of Japanese patients with an extremely high triglyceride level (≥ 1000 mg/dL). We assessed the clinical characteristics of Japanese patients with an extremely high triglyceride level. We investigated the presence of coronary artery disease, history of pancreatitis, the presence of fatty liver, and the potential causes of elevated triglyceride in Japanese subjects with an extremely high level of fasting triglyceride (≥ 1000 mg/dL) among 70,368 subjects whose serum triglyceride was measured for any reason at Kanazawa University Hospital from April 2004 to March 2014. We identified 215 (0.31%) subjects (mean age, 46 years; male, 170, mean body mass index, 25 kg/m(2)) with severe hypertriglyceridemia. Among them, 4 (1.9%) subjects were classified as type I, 97 (45.1%) subjects were type IV, and 114 (53.0%) subjects were type V hyperlipidemia, according to Fredrickson's classification. Among 215 subjects, 116 subjects (54.0%) drank alcohol, 58 (27.0%) showed heavy intake (≥ 60 g/d), and 64 (29.8%) subjects had diabetes. In total, 59 (27.4%) subjects had transient severe hypertriglyceridemia caused by corticosteroids (N = 19), antidepressant (N = 18), l-asparaginase and steroids for acute lymphoid leukemia (N = 15), hormone replacement therapy for breast cancer (N = 9), β-blocker (N = 5), hypothyroidism (N = 4), pregnancy (N = 4), and panhypopituitarism (N = 2). As many as 119 (55.3%) subjects exhibited fatty liver. Moreover, 12 (5.6%) and 17 (7.9%) subjects had a history of pancreatitis and coronary artery disease, respectively. A variety of situations can cause severe hypertriglyceridemia. We suggest that potential secondary causes should be carefully assessed for such patients. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Comparison of iron status and insulin resistance between non-diabetic offspring of type 2 diabetics and non-diabetic offspring of non-diabetics

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Zafar, U.; Qureshi, H.J.

2015-01-01

Insulin resistance is positively correlated with body iron. It is unclear whether iron is a cause or an outcome of insulin resistance. Insulin resistance precedes type 2 diabetes mellitus. Offspring of type 2 diabetics are insulin resistant as compared to those of the non-diabetics. The present study was designed to compare and correlate insulin resistance with iron parameters (including serum ferritin, transferrin saturation and blood haemoglobin) in non-diabetic offspring of type 2 diabetics and non-diabetic offspring of non-diabetics. Methods: It was a cross-sectional study, conducted on one hundred and twenty male subjects 20-40 years of age. They were divided into two groups, each group having 60 subjects. Group A included non-diabetic offspring of type 2 diabetics, while Group B included non-diabetic offspring of non-diabetics. Fasting blood sample was taken and examined for glucose, haemoglobin, insulin, iron, TIBC and ferritin. Data was analysed by SPSS-17. Results: Insulin resistance and iron parameters were significantly higher (p<0.05) in non-diabetic offspring of type 2 diabetics as compared to those of the non-diabetics. There was significant positive correlation (p=0.027) between insulin resistance and serum iron in non-diabetic offspring of type 2 diabetics. There was also significant positive correlation between insulin resistance and serum iron, transferrin saturation and haemoglobin in non-diabetic offspring of non-diabetics. Conclusion: Non-diabetic offspring of type 2 diabetics have iron load and insulin resistance, that predispose them to the development of type 2 diabetes. (author)

Early plasmapheresis in patients with severe hypertriglyceridemia induced acute pancreatitis

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Nasa, Prashant; Alexander, George; Kulkarni, Amitabh; Juneja, Deven; Sehra, Sudhish; Agarwal, Rajesh; Koul, Kandy

2015-01-01

Hypertriglyceridemia can cause severe diseases such as acute pancreatitis (AP) and coronary artery disease. The routine management of hypertriglyceridemia is dietary restriction of fat and lipid-lowering medications to manage the secondary or precipitating causes of hypertriglyceridemia. However, in cases of AP with severe hypertriglyceridemia (SHTG) (triglycerides [TG] >1000 mg/dl) rapid reduction of TG levels to well below 1000 mg/dl can improve outcome and prevent further episodes of pancr...

Systemic Lupus Erythematosus Associated with Extreme Hypertriglyceridemia

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Chin-Sung Huang

2008-04-01

Full Text Available Only a few cases of hypertriglyceridemia in patients with systemic lupus erythematosus (SLE have been reported. We report a case of a 13-year-old girl suffering from SLE associated with severe hypertriglyceridemia. The persistent hypertriglyceridemia was extremely well tolerated. As a result of steroid treatment, serum triglycerides fell dramatically from a high of 5601 mg/dL to 75 mg/dL despite the patient switching to a free diet. We considered the presence of an autoantibody to lipoprotein lipase and commenced immunosuppression. The role of steroids in completely correcting deficient lipoprotein lipase activity is discussed.

Severe hypertriglyceridemia and hypercholesterolemia accelerating renal injury: a novel model of type 1 diabetic hamsters induced by short-term high-fat / high-cholesterol diet and low-dose streptozotocin.

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He, Liang; Hao, Lili; Fu, Xin; Huang, Mingshu; Li, Rui

2015-04-11

Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-β, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important

Asparaginase-Induced Hypertriglyceridemia Presenting as Pseudohyponatremia during Leukemia Treatment

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Ashley Hinson

2014-01-01

Full Text Available Asparaginase is a chemotherapeutic agent used to induce disease remission in children with acute lymphoblastic leukemia (ALL. We describe the cases of two females with ALL who developed pseudohyponatremia as a presentation of hypertriglyceridemia following asparaginase treatment. Nine similar published cases of asparaginase-induced hypertriglyceridemia and its complications are also discussed. Possible mechanisms of action include inhibition of lipoprotein lipase, decreased hepatic synthesis of lipoprotein, and increased synthesis of VLDL. Effects of asparaginase-induced hypertriglyceridemia range from asymptomatic to transaminasemia, pancreatitis, and life-threatening thrombosis or hyperviscosity syndrome. All cases of hypertriglyceridemia described resolved following cessation of asparaginase treatment ± further treatments.

Subcutaneous NPH Insulin for Severe Hypertriglyceridemia in a Pregnant Patient with Type V Hyperlipoproteinemia: a Case Report

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Mustafa Kemal Balcı

2012-06-01

Full Text Available An increase in triglyceride levels in familial hyperlipidemia during pregnancy has been reported. Severe hypertriglyceridemia can lead to complications such as acute pancreatitis, preeclampsia, maternal and fetal complications. Because of the teratogenic effects associated with fibrate therapy in pregnancy, alternative treatment strategies such as insulin as a rapid and potent activator of lipoprotein lipase are required during pregnancy. We report a case of hypertriglyceridemia in a 33-year-old pregnant woman in whom treatment with merely single one time administration of Neutral Protamine Hagedorn insulin was accompanied by a reduction in the serum triglyceride level; to the best of our knowledge, this has never been reported in the literature. Her triglyceride level was 3616 mg/dL before insulin treatment and 1246 mg/dL after insulin treatment. Although this regimen was used safely and effectively in our patient, comprehensive studies are required to evaluate the effectiveness and safety of subcutaneously intermediate-acting Neutral Protamine Hagedorn insulin for the treatment of severe hypertriglyceridemia in non-diabetic pregnant women.

PROMETHEUS: an observational, cross-sectional, retrospective study of hypertriglyceridemia in Russia.

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Karpov, Yuri; Khomitskaya, Yunona

2015-08-25

Data regarding the prevalence of hypertriglyceridemia in the Russian population are lacking, despite triglyceride (TG)-mediated pathways being causal in cardiovascular disease. The prevalence of mixed dyslipidemia and severe hypertriglyceridemia in the Russian population (PROMETHEUS) was undertaken to address this gap. This was an observational, cross-sectional retrospective study. Data from adults with a full/partial lipoprotein record who had blood analyses done at an INVITRO laboratory in Russia between January 1, 2011 and December 31, 2013 were analyzed. The primary endpoint was the prevalence of hypertriglyceridemia (TG ≥ 1.7 mmol/L); secondary endpoints included prevalence of borderline high, high, and very high TG and severe hypertriglyceridemia, defined as a TG level of 1.7 to hypertriglyceridemia, borderline high TG, high TG, very high TG, and severe hypertriglyceridemia in the full dataset was 29.2, 16.2, 12.9, 0.11, and 0.011%, respectively; corresponding rates in the nested sample were 19.0, 17.2, 0.25, and 0.016%, respectively. TG levels were 16.4% higher in males versus females; males had a greater risk of hypertriglyceridemia (risk ratio 1.25; 95% CI 1.24, 1.26; P hypertriglyceridemia increased with age, peaking at 40-49 years in males (42.8%) and 60-69 years in females (34.4%); a 0.61% increase in TG levels for each year of life was predicted. Hypertriglyceridemia prevalence increased over time. Correlations between TG and LDL-C, HDL-C, TC, and HbA1c (nested sample only) were observed. Almost one-third of Russians have hypertriglyceridemia, but severe disease (TG ≥ 10.0 mmol/L) is rare. Although the risk of hypertriglyceridemia was greater in males versus females, its prevalence increased with age, regardless of sex. TG was associated with HbA1c, LDL-C, HDL-C, and TC.

The study of Insulin Resistance in the Off Springs of Diabetics and Non Diabetic Patients

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Ganesh Manoorkar

2017-12-01

Full Text Available Introduction: Insulin resistance is one of the main cause in the pathogenesis of the development of type- 2 diabetes mellitus. Elevated insulin levels and insulin resistance may be present several years prior to the development of hyperglycaemia. Hence the diagnosis of insulin resistance at the initial stages in risk group people could be used as an effective measure to prevent type 2 diabetes mellitus and its outcome, including reduction in morbidity and mortality. Though type 2 diabetes mellitus has multifactorial aetiology, genetic factor plays an important role in the development of diabetes mellitus. So we have tried to establish relation between genetic factor and insulin resistance by studying the insulin resistance in off springs of diabetics and non diabetics patients. Aims and objectives: Estimation of insulin levels in the off springs (non diabetics of diabetics and non diabetics patients. Comparision of insulin resistance in the off springs (non diabetics of diabetics and non diabetics. To find the relation between insulin resistance and genetic factor. Material and method: This study was carried out in the department of Biochemistry Grant Government Medical College Mumbai. Total 100 non diabetic people were included in the study of age above 30 years. These are divided into two groups as- Group-I includes 50 off springs (Ist degree relatives of non diabetic people. Group-II includes 50 off springs (Ist degree relatives of diabetic people. The fasting plasma glucose and serum insulin levels are estimated in the above two groups. The insulin resistance was calculated by using HOMA-IR model. Result: Fasting plasma glucose, serum insulin level and insulin resistance is significantly increased in group-II people as compared to group-I people. Conclusion: There is a strong relation between genetic factor and insulin resistance which exist prior to the development of diabetes mellitus. The people of group-II are susceptible for the

Ethnic differences in the ability of triglyceride levels to identify insulin resistance.

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Sumner, Anne E; Cowie, Catherine C

2008-02-01

The Metabolic Syndrome is used to predict the onset of coronary artery disease and Type 2 diabetes. As the predictive value of the Metabolic Syndrome has been challenged, alternative syndromes have been developed. All of these syndromes were developed in populations that were predominantly non-Hispanic white (NHW). They include the Enlarged Waist Elevated Triglyceride Syndrome, the Overweight-Lipid Syndrome and the Hypertriglyceridemic Waist Syndrome. The first applies to postmenopausal women, the second to overweight individuals (BMI> or =25 kg/m(2)), and the third to men. Each syndrome uses hypertriglyceridemia as a criterion. However, the definition of hypertriglyceridemia varies by syndrome i.e. TG> or =128 mg/dL for the Enlarged Waist Elevated Triglyceride Syndrome, TG> or =130 mg/dL for the Overweight-Lipid Syndrome, > or =150 mg/dL for the Metabolic Syndrome, and TG> or =176 mg/dL for the Hypertriglyceridemic Waist Syndrome. Insulin resistance and hypertriglyceridemia are highly correlated. But as insulin resistant non-Hispanic blacks (NHB) often have triglyceride (TG) levels below the thresholds set by these syndromes, the ability of either TG or these syndromes to identify high risk NHB is unknown. Using the National Health and Nutrition Examination Survey (NHANES) 1999-2002, our goals were to determine by ethnicity: (1) the prevalence of each of these syndromes; (2) the ability of fasting TG concentrations to identify insulin resistance at cut-off levels established by these syndromes, specifically 130, 150 and 176 mg/dL. Participants were 2804 adults from NHANES 1999-2002. The cohort was divided into tertiles of homeostasis model assessment. Insulin resistance was defined as the upper tertile (> or =2.73). The prevalence of each syndrome was lower in NHB than NHW or Mexican Americans (MA) (all Pidentify individuals at high risk for conditions such as cardiovascular disease and Type 2 diabetes, ethnic differences in TG levels should be considered.

Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline

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Berglund, Lars; Brunzell, John D.; Goldberg, Anne C.; Goldberg, Ira J.; Sacks, Frank; Murad, Mohammad Hassan; Stalenhoef, Anton F. H.

2012-01-01

Objective: The aim was to develop clinical practice guidelines on hypertriglyceridemia. Participants: The Task Force included a chair selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence, e-mail discussion, conference calls, and one in-person meeting. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: The Task Force recommends that the diagnosis of hypertriglyceridemia be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150–999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hypertriglyceridemia (triglycerides of > 1000 mg/dl) be considered a risk for pancreatitis. The Task Force also recommends that patients with hypertriglyceridemia be evaluated for secondary causes of hyperlipidemia and that subjects with primary hypertriglyceridemia be evaluated for family history of dyslipidemia and cardiovascular disease. The Task Force recommends that the treatment goal in patients with moderate hypertriglyceridemia be a non-high-density lipoprotein cholesterol level in agreement with National Cholesterol Education Program Adult Treatment Panel guidelines. The initial treatment should be lifestyle therapy; a combination of diet modification and drug therapy may also be considered. In patients with severe or very severe hypertriglyceridemia, a fibrate should be used as a first-line agent. PMID:22962670

Severe/Extreme Hypertriglyceridemia and LDL Apheretic Treatment: Review of the Literature, Original Findings

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Olga Diakoumakou

2014-01-01

Full Text Available Hypertriglyceridemia (HTG is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase the risk of premature coronary artery disease. HTG may also be due to genetic factors (called primary HTG and particularly the severe/extreme HTG (SEHTG, which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG caused by autoimmune disease. This review considers the causes of SEHTG, and their management including treatment with low density lipoprotein apheresis and analyzes the original findings.

Serum Uric Acid Levels and Risk of Incident Hypertriglyceridemia: A Longitudinal Population-based Epidemiological Study.

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Zheng, Rongjiong; Ren, Ping; Chen, Qingmei; Yang, Tianmeng; Chen, Changxi; Mao, Yushan

2017-09-01

Hypertriglyceridemia is one of lipid metabolism abnormalities; however, it is still debatable whether serum uric acid is a cause or a consequence of hypertriglyceridemia. We performed the study to investigate the longitudinal association between serum uric acid levels and hypertriglyceridemia. The study included 4190 subjects without hypertriglyceridemia. The subjects had annual health examinations for 8 years to assess incident hyperglyceridemia, and the subjects were divided into groups based on the serum uric acid quartile. Cox regression models were used to analyze the risk factors of development hypertriglyceridemia. During follow-up, 1461 (34.9%) subjects developed hypertriglyceridemia over 8 years of follow-up. The cumulative incidence of hypertriglyceridemia was 28.2%, 29.1%, 36.9%, and 45.6% in quartile 1,2,3 and 4, respectively ( P for trend uric acid levels were independently and positively associated with the risk of incident hypertriglyceridemia. Hypertriglyceridemia has become a serious public health problem. This longitudinal study demonstrates that high serum uric acid levels increase the risk of hypertriglyceridemia. © 2017 by the Association of Clinical Scientists, Inc.

Hypertriglyceridemia, a common dyslipidemia of complex definition

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Chiara Trenti

2013-04-01

Full Text Available Background: Hypertriglyceridemia is a common biochemical finding. Depending on the triglyceride levels it can be associated with increased risk of acute pancreatitis and of cardiovascular disease. The most severe forms have a genetic basis. Clinical case: We report a case of a 60-year-old woman with very high triglycerides (800- 3,000 mg/dL and normal cholesterol levels. The patient is a non smoker, on hypolipemic diet, non alcoholic consumer, and on regular physical exercise. Her blood pressure is normal, BMI is 20, waist circumference is 78 cm. Thyroid, renal and hepatic function are normal. She has never had acute pancreatitis or cardiovascular disease. Discussion: The diagnostic and therapeutic management of this case is discussed. Causes of primary (genetic and secondary hypertriglyceridemia are also reviewed, together with clinical features and management on every day practice. We focused on severe hypertriglyceridemia.

Type 2 diabetes mellitus as a disorder of galanin resistance.

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Fang, Penghua; Shi, Mingyi; Zhu, Yan; Bo, Ping; Zhang, Zhenwen

2016-01-01

The increasing prevalence of type 2 diabetes mellitus with its high morbidity and mortality becomes an important health problem. The multifactorial etiology of type 2 diabetes mellitus is relative to many gene and molecule alterations, and increased insulin resistance. Besides these, however, there are still other predisposing and risk factors accounting for type 2 diabetes mellitus not to be identified and recognized. Emerging evidence indicated that defects in galanin function played a crucial role in development of type 2 diabetes mellitus. Galanin homeostasis is tightly relative to insulin resistance and is regulated by blood glucose. Hyperglycemia, hyperinsulinism, enhanced plasma galanin levels and decreased galanin receptor activities are some of the characters of type 2 diabetes mellitus. The discrepancy between high insulin level and low glucose handling is named as insulin resistance. Similarly, the discrepancy between high galanin level and low glucose handling may be denominated as galanin resistance too. In this review, the characteristic milestones of type 2 diabetes mellitus were condensed as two analogical conceptual models, obesity-hyper-insulin-insulin resistance-type 2 diabetes mellitus and obesity-hyper-galanin-galanin resistance-type 2 diabetes mellitus. Both galanin resistance and insulin resistance are correlative with each other. Conceptualizing the etiology of type 2 diabetes mellitus as a disorder of galanin resistance may inspire a new concept to deepen our knowledge about pathogenesis of type 2 diabetes mellitus, eventually leading to novel preventive and therapeutic interventions for type 2 diabetes mellitus. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis.

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Sai-Li Xie

Full Text Available Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL, apolipoprotein C2 (APOC2, apolipoprotein A5 (APOA5, lipase maturation factor 1 (LMF1, and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1 genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis.

Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis

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Huang, Xie-Lin; Chen, Chao; Jin, Rong; Huang, Zhi-Ming; Zhou, Meng-Tao

2015-01-01

Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis. PMID:26079787

Management of Severe Hypertriglyceridemia with Plasmapheresis During Pregnancy

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Gokhan Boyraz

2016-01-01

Full Text Available Although severe hypertriglyceridemia is rarely seen in pregnancy, it may result in acute pancreatitis leading to increased morbidity in both mother and fetus. Restriction of dietary lipid and lipid-lowering medications are the cornerstones of the treatment. Experiences with plasmapheresis are limited. Herein, a pregnant woman with hypertriglyceridemia who was given preconceptional counseling and medical therapy and kept under close observation since the early weeks of gestation, succesfully managed with dietary lipid restriction and especially with serial plasmapheresis is discussed. Her previous pregnancy was remarkable with fetal demise due to acute pancreatitis at 24th weeks of gestation. It is important that the clinicians have a clear understanding of the normal lipid profile during pregnancy, the clinical picture, the potential complications, available treatment options of hypertriglyceridemia particularly during pregnancy.

PEG-asparaginase induced severe hypertriglyceridemia.

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Galindo, Rodolfo J; Yoon, Justin; Devoe, Craig; Myers, Alyson K

2016-04-01

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

Hypertriglyceridemia Induced Pancreatitis (Chylomicronemia Syndrome Treated with Supportive Care

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Emin Uysal

2014-01-01

Full Text Available Hypertriglyceridemia is a rare cause of pancreatitis. In treatment pancreatic rest, lifestyle changes, medications (fibrates, n-3 polyunsaturated fatty acids, and nicotinic acid are essential. Many experimental treatment modalities have been reported as insulin and heparin infusion and plasmapheresis. In this study we present the hypertriglyceridemia-induced pancreatitis treated with supportive care.

Plasmapheresis for Preventing Complication of Hypertriglyceridemia: A Case Report and Review of Literature.

Science.gov (United States)

Costantini, Nicoletta; Mameli, Antonella; Marongiu, Francesco

2016-01-01

Severe hypertriglyceridemia is a common indication for the need of plasma exchange in treatment of hypertriglyceridemic-induced pancreatitis when normal therapies fail to garner a response. Application of plasmapheresis to prevent complication of hypertriglyceridemia is limited because of its cost and availability. We present a case of a 44-year-old man with metabolic syndrome and a medical history of secondary polycythemia in obesity hypoventilation syndrome, whose laboratory tests revealed a triglycerides value of 3965 mg/dL. To prevent the complication of pancreatitis due to hypertriglyceridemia, we performed plasma exchange 3 times when conventional treatments did not sufficiently reduce the high level of triglycerides. A review of the current available literature was therefore conducted to provide an overview of the present data on apheretic treatment for patients with severe hypertriglyceridemia. Several case reports and case series have used plasmapheresis in acute treatment of hypertriglyceridemia pancreatitis related. In our case, the choice of plasmapheresis was applied in prevention of possible complications of hypertriglyceridemia.

Asparaginase-Induced Hypertriglyceridemia Presenting as Pseudohyponatremia during Leukemia Treatment

OpenAIRE

Hinson, Ashley; Newbern, Dorothee; Linardic, Corinne M.

2014-01-01

Asparaginase is a chemotherapeutic agent used to induce disease remission in children with acute lymphoblastic leukemia (ALL). We describe the cases of two females with ALL who developed pseudohyponatremia as a presentation of hypertriglyceridemia following asparaginase treatment. Nine similar published cases of asparaginase-induced hypertriglyceridemia and its complications are also discussed. Possible mechanisms of action include inhibition of lipoprotein lipase, decreased hepatic synthesis...

Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia[S

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Mendoza-Barberá, Elena; Julve, Josep; Nilsson, Stefan K.; Lookene, Aivar; Martín-Campos, Jesús M.; Roig, Rosa; Lechuga-Sancho, Alfonso M.; Sloan, John H.; Fuentes-Prior, Pablo; Blanco-Vaca, Francisco

2013-01-01

During the diagnosis of three unrelated patients with severe hypertriglyceridemia, three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, and p.Asp332ValfsX4] were found without evidence of concomitant LPL, APOC2, or GPIHBP1 mutations. The molecular mechanisms by which APOA5 mutations result in severe hypertriglyceridemia remain poorly understood, and the functional impairment/s induced by these specific mutations was not obvious. Therefore, we performed a thorough structural and functional analysis that included follow-up of patients and their closest relatives, measurement of apoA-V serum concentrations, and sequencing of the APOA5 gene in 200 nonhyperlipidemic controls. Further, we cloned, overexpressed, and purified both wild-type and mutant apoA-V variants and characterized their capacity to activate LPL. The interactions of recombinant wild-type and mutated apoA-V variants with liposomes of different composition, heparin, LRP1, sortilin, and SorLA/LR11 were also analyzed. Finally, to explore the possible structural consequences of these mutations, we developed a three-dimensional model of full-length, lipid-free human apoA-V. A complex, wide array of impairments was found in each of the three mutants, suggesting that the specific residues affected are critical structural determinants for apoA-V function in lipoprotein metabolism and, therefore, that these APOA5 mutations are a direct cause of hypertriglyceridemia. PMID:23307945

Insulin resistance in type 1 diabetes: what is ?double diabetes? and what are the risks?

OpenAIRE

Cleland, S. J.; Fisher, B. M.; Colhoun, H. M.; Sattar, N.; Petrie, J. R.

2013-01-01

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens ma...

Synthesis, characterization, and preclinical evaluation of new thiazolidin-4-ones substituted with p-chlorophenoxy acetic acid and clofibric acid against insulin resistance and metabolic disorder.

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Gowdra, Vasantharaju S; Mudgal, Jayesh; Bansal, Punit; Nayak, Pawan G; Manohara Reddy, Seethappa A; Shenoy, Gautham G; Valiathan, Manna; Chamallamudi, Mallikarjuna R; Nampurath, Gopalan K

2014-01-01

We synthesized twenty thiazolidin-4-one derivatives, which were then characterized by standard chromatographic and spectroscopic methods. From the in vitro glucose uptake assay, two compounds behaved as insulin sensitizers, where they enhanced glucose uptake in isolated rat diaphragm. In high-carbohydrate diet-induced insulin resistant mice, these two thiazolidin-4-ones attenuated hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and glucose intolerance. They raised the plasma leptin but did not reverse the diabetes-induced hypoadiponectinemia. Additionally, compound 3a reduced adiposity. The test compounds were also able to reverse the disturbed liver antioxidant milieu. To conclude, these two novel thiazolidin-4-ones modulated multiple mechanisms involved in metabolic disorders, reversing insulin resistance and thus preventing the development of type-2 diabetes.

Indigenous plant medicines for health care: treatment of Diabetes mellitus and hyperlipidemia.

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Parikh, Nisha H; Parikh, Palak K; Kothari, Charmy

2014-05-01

Medicinal plants have played an important role in treating and preventing a variety of diseases throughout the world. Metabolic syndrome had become a global epidemic, defined as a cluster of three of five criteria: insulin resistance and glucose intolerance, abdominal obesity, hypertension, low high-density cholesterol, and hypertriglyceridemia. The current review focuses on Indian medicinal plant drugs and plants used in the treatment of diabetes and hyperlipidemia. Though there are various approaches to reduce the ill-effects of diabetes and hyperlipidemia and its secondary complications, plant-based drugs are preferred due to lesser side effects and low cost. The current review focuses on twenty-three medicinal plants used in the treatment of Diabetes mellitus and nine medicinal plants used in the treatment of hyperlipidemia. The wealth of knowledge on medicinal plants points to a great potential for research and the discovery of new drugs to fight diseases, including diabetes and hyperlipidemia. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Hypertriglyceridemia-induced pancreatitis created by oral estrogen and in vitro fertilization ovulation induction

OpenAIRE

Lee, Jee; Goldberg, Ira J.

2008-01-01

Hypertriglyceridemia is one of the known causes of pancreatitis. Estrogen treatment can aggravate hypertriglyceridemia by increasing very low density lipoprotein secretion and reducing hepatic triglyceride lipase. In this paper, we present 3 patients who developed severe hypertriglyceridemia with conditions that increased estrogen. Two patients were found to have genetic lipoprotein lipase deficiency and were treated with birth control pills. The third was a patient with polycystic ovary dise...

Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients

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Figueiredo Márcio J

2011-03-01

Full Text Available Abstract Background Hypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance could be a common root for RHTN (resistant hypertension or RHTN plus type 2 diabetes (T2D comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D, and its relationship with serum adiponectin concentration. Methods Twenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years were evaluated using the following parameters: BMI (body mass index, biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV in time and frequency domains stratified into three periods: 24 hour, day time and night time. Results Both groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone and night periods (sympathetic > parasympathetic tone. T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m2 - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04, lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04 and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r

Liver cirrhosis and diabetes: Risk factors, pathophysiology, clinical implications and management

Institute of Scientific and Technical Information of China (English)

Diego Garcia-Compean; Joel Omar Jaquez-Quintana; Jose Alberto Gonzalez-Gonzalez; Hector Maldonado-Garza

2009-01-01

About 30% of patients with cirrhosis have diabetes mellitus (DM). Nowadays, it is a matter for debate whether type 2 DM in the absence of obesity and hypertriglyceridemia may be a risk factor for chronic liver disease. DM,which develops as a complication of cirrhosis, is known as "hepatogenous diabetes". Insulin resistance in muscular and adipose tissues and hyperinsulinemia seem to be the pathophysiologic bases of diabetes in liver disease. An impaired response of the islet β-cells of the pancreas and hepatic insulin resistance are also contributory factors. Non-alcoholic fatty liver disease, alcoholic cirrhosis, chronic hepatitis C (CHC) and hemochromatosis are more frequently associated with DM. Insulin resistance increases the failure of the response to treatment in patients with CHC and enhances progression of fibrosis. DM in cirrhotic patients may be subclinical.Hepatogenous diabetes is clinically different from that of type 2 DM, since it is less frequently associated with microangiopathy and patients more frequently suffer complications of cirrhosis. DM increases the mortality of cirrhotic patients. Treatment of the diabetes is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs. This manuscript will review evidence that exists in relation to: type 2 DM alone or as part of the metabolic syndrome in the development of liver disease;factors involved in the genesis of hepatogenous diabetes;the impact of DM on the clinical outcome of liver disease; the management of DM in cirrhotic patients and the role of DM as a risk factor for the occurrence and exacerbation of hepatocellular carcinoma.

Prevalence of dyslipidemia in patients with type-2 diabetes mellitus

International Nuclear Information System (INIS)

Siddiqui, S.A.; Shabbir, I.; Sherwani, M.U.I.K.; Hussain, R.

2011-01-01

Background: The dyslipidaemia associated with type-2 diabetes is associated with raised plasma triglycerides, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels and is a risk factor of cardiovascular disease. Objectives: To assess the lipid abnormalities in patients with type-2 diabetes. Study design and settings: A cohort study carried out at Diabetic Clinic of PMRC Research Centre, FJMC, Lahore, Pakistan. Patients and Methods Eight years case records of type-2 diabetic patients seen at the research centre from 1999-2006 were reviewed. The research centre is a specialized centre for diagnosing and treating diabetes mellitus. All the patients were recruited for their follow up check up and laboratory investigations for dislipidemia. Adult treatment panel III guidelines for dyslipidaemia were followed. A 12 hours fasting blood sample was collected from each patient for serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose as well as glycosylated hemoglobin (HbA1c) by using standard methods at Biochemistry laboratory of the research centre. LDL-C/ HDL-C ratios, Very low-density lipoprotein cholesterol (VLDL-C) and body mass index was calculated after anthropometery body mass index (BMI) less than or equal to 25 was considered as overweight while less than or equal 30 obese. HbA1c 40 mg/dl were seen in 67%. Raised VLDL-C (above 40 mg/dl) was seen in 32.9% cases. The group with high LDL and VLDL is at risk of developing cardiovascular disease. Hypertriglyceridaemia was found in 55% and hypercholesterolaemia in 45.4% cases. Obesity as indicated by body mass index was found in 53.7% patients. Statistically significant association of hypercholesterolemia, hypertriglyceridemia, hypo HDL cholesterolemia and VLDL-C was found with advancing age while only hypertriglyceridemia and VLDL-C showed a positive

Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

Science.gov (United States)

Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

2016-04-01

High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone. Georg Thieme Verlag KG Stuttgart · New York.

Helicobacter pylori Infection and Insulin Resistance in Diabetic and Nondiabetic Population

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Jamshid Vafaeimanesh

2014-01-01

Full Text Available Helicobacter pylori (HP is a common worldwide infection with known gastrointestinal and nongastrointestinal complications. One of the gastrointestinal side effects posed for this organism is its role in diabetes and increased insulin resistance. The aim of this study was to evaluate the association between HP and insulin resistance in type 2 diabetic patients and nondiabetics. This cross-sectional study was carried out from May to December 2013 on 211 diabetic patients referred to diabetes clinic of Shahid Beheshti Hospital of Qom and 218 patients without diabetes. HP was evaluated using serology method and insulin resistance was calculated using HOMA-IR. The prevalence of H. pylori infection was 55.8% and 44.2% in diabetics and nondiabetics (P=0.001. The study population was divided into two HP positive and negative groups. Among nondiabetics, insulin resistance degree was 3.01±2.12 and 2.74±2.18 in HP+ and HP− patients, respectively P=0.704. Oppositely, insulin resistance was significantly higher in diabetic HP+ patients rather than seronegative ones (4.484±2.781 versus 3.160±2.327, P=0.013. In diabetic patients, in addition to higher prevalence of HP, it causes a higher degree of insulin resistance.

Hypertriglyceridemia-associated Acute Pancreatitis with Chylous Ascites in Pregnancy

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Shih-Chang Chuang

2006-01-01

Full Text Available Both cholesterol and triglyceride levels in serum increase progressively during pregnancy. Hypertrigly-ceridemia is a well-recognized cause of acute pancreatitis, while pancreatitis-associated chylous ascites has rarely been reported. We report a 28-year-old female with coexistence of hypertriglyceridemia, acute pancreatitis, and chylous ascites during pregnancy. After emergency cesarean section, she was treated with nil per os, intravenous hydration, antibiotics, and analgesics as required. Due to the development of positive peritonitis 5 days later, an exploratory laparotomy was performed. Surgical interventions included pancreatic necrosec-tomy, right hemicolectomy and ileostomy, cholecystostomy, gastrostomy, and feeding jejunostomy. Postoperative treatment included antibiotics, total parenteral nutrition, and then low-fat diet with medium-chain triglyceride supplementation. She was discharged on the 43rd day after surgery and was free of symptoms during 6 months of follow-up. Ileocolostomy was performed 6 months after discharge. Fasting lipid profile should be regularly monitored during pregnancy due to the association of hypertriglyceridemia with development of acute pancreatitis in the mother.

Synthesis, Characterization, and Preclinical Evaluation of New Thiazolidin-4-ones Substituted with p-Chlorophenoxy Acetic Acid and Clofibric Acid against Insulin Resistance and Metabolic Disorder

Directory of Open Access Journals (Sweden)

Vasantharaju S. Gowdra

2014-01-01

Full Text Available We synthesized twenty thiazolidin-4-one derivatives, which were then characterized by standard chromatographic and spectroscopic methods. From the in vitro glucose uptake assay, two compounds behaved as insulin sensitizers, where they enhanced glucose uptake in isolated rat diaphragm. In high-carbohydrate diet-induced insulin resistant mice, these two thiazolidin-4-ones attenuated hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and glucose intolerance. They raised the plasma leptin but did not reverse the diabetes-induced hypoadiponectinemia. Additionally, compound 3a reduced adiposity. The test compounds were also able to reverse the disturbed liver antioxidant milieu. To conclude, these two novel thiazolidin-4-ones modulated multiple mechanisms involved in metabolic disorders, reversing insulin resistance and thus preventing the development of type-2 diabetes.

Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

Science.gov (United States)

Chen, Chung-Yuan; Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yaun-Jinn; Hsiao, Pi-Jung; Shin, Shyi-Jang

2015-02-10

Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54±51.69 vs. 86.58±63.4 (p≤0.001), 43.98±44.09 vs. 64.52±45.06 (p=0.002), 43.86±35.75 vs. 62.72±51.2 (p=0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of -13.981 (95% confidence interval (CI) -27.587, -0.374), -26.847 (95% CI -37.562, -16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of -2.947 (p=0.004), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. Dengue patients with diabetes tended to have more severe

Secondary acute pancreatitis to hypertriglyceridemia: presentation of two clinical cases

International Nuclear Information System (INIS)

Jimenez Forero, Sonia Jeanneth; Roa Saavedra, Ximena; Villalba, Maria Claudia

2008-01-01

The acute pancreatitis is a reversible inflammatory process. Hypertriglyceridemia as etiology of the acute pancreatitis reaches frequencies between 1,3 to 11% according to literature when the triglycerides levels of reach values over 1000 mg/dl nevertheless hypertriglyceridemia is observed in 12 to 39% of the acute pancreatitis like factor associate. The objective of the medical treatment is to increase the activity of lipoproteinlipasa and to increase the degradation of vhylomicrones; diminishing therefore the serum triglycerides values of a levels smaller to 500 even to less of 200 mg/dl if is possible with different strategies among of them the insulin. In the present article, we presented two clinical cases of severe pancreatitis induced by hypertriglyceridemia, handled with therapy of insulin infusion with suitable evolution and clinical answer given by significant diminution of the levels of triglycerides, 48 hours post treatment

Heterozygous CAV1 frameshift mutations (MIM 601047 in patients with atypical partial lipodystrophy and hypertriglyceridemia

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Alston Lindsay

2008-01-01

Full Text Available Abstract Background Mice with a deleted Cav1 gene encoding caveolin-1 develop adipocyte abnormalities and insulin resistance. From genomic DNA of patients with atypical lipodystrophy and hypertriglyceridemia who had no mutations in any known lipodystrophy gene, we used DNA sequence analysis to screen the coding regions of human CAV1 (MIM 601047. Results We found a heterozygous frameshift mutation in CAV1, designated I134fsdelA-X137, in a female patient who had atypical partial lipodystrophy, with subcutaneous fat loss affecting the upper part of her body and face, but sparing her legs, gluteal region and visceral fat stores. She had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis. In addition, she had some atypical features, including congenital cataracts and neurological findings. Her father was also heterozygous for this mutation, and had a similar pattern of fat redistribution, hypertriglyceridemia and congenital cataracts, with milder neurological involvement. An unrelated patient had a different heterozygous frameshift mutation in the CAV1 gene, designated -88delC. He also had a partial lipodystrophy phenotype, with subcutaneous fat loss affecting the arms, legs and gluteal region, but sparing his face, neck and visceral fat stores. He also had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis; however he had no clinically apparent neurological manifestations. The mutations were absent from the genomes of 1063 healthy individuals. Conclusion Thus, very rare CAV1 frameshift mutations appear to be associated with atypical lipodystrophy and hypertriglyceridemia.

Novel LMF1 Nonsense Mutation in a Patient with Severe Hypertriglyceridemia

OpenAIRE

Cefalù, Angelo B.; Noto, Davide; Arpi, Maria Luisa; Yin, Fen; Spina, Rossella; Hilden, Hannele; Barbagallo, Carlo M.; Carroccio, Antonio; Tarugi, Patrizia; Squatrito, Sebastiano; Vigneri, Riccardo; Taskinen, Marja-Riitta; Péterfy, Miklós; Averna, Maurizio R.

2009-01-01

Context: Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X).

Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High-Fructose Diet

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Da-Wei Huang

2018-01-01

Full Text Available This study investigated the ameliorative effect of gallic acid (GA on hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high-fructose diet (HFD-induced diabetic rats. The previous results showed that orally administered GA (30 mg/kg body weight for four weeks significantly reduced the levels of plasma glucose and triglyceride (TG in HFD rats. GA also markedly decreased the perirenal adipose tissues weight of HFD rats in present study (p < 0.05. Western blot assay indicated that GA restored expression of insulin signaling-related proteins, such as insulin receptor (IR, protein kinase C-zeta (PKC-ζ, and glucose transporter-4 (GLUT4 in the perirenal adipose tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related proteins, such as phosphofructokinase (PFK and pyruvate kinase (PK, and increased the expression of lipolysis-related proteins, such as adipose triglyceride lipase (ATGL, which is involved in lipolysis in the perirenal adipose tissues of HFD rats. This study revealed that GA may alleviate hypertriglyceridemia and fat accumulation through enhancing glycolysis and lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also suggest the potential of GA in preventing the progression of diabetes mellitus (DM complications.

Insulin resistance and serum parameters of iron status in type 2 diabetics

International Nuclear Information System (INIS)

Zafar, U.

2011-01-01

Background: Type 2 diabetes mellitus (T2DM) is a predominant public health concern worldwide, accounting for 90% of the cases of diabetes globally. Pathogenesis of T2DM involves insulin resistance, defective insulin secretion and increased glucose production by the liver. Subclinical haemochromatosis has been considered as one of the probable causes of insulin resistance and diabetes mellitus. The aim of this study was to determine and correlate insulin resistance and serum parameters of iron status (serum ferritin and transferrin saturation) in type 2 diabetics. Methods: It was a correlational study. This study was conducted on sixty male patients with type 2 diabetes mellitus. Fasting blood sample was taken from each subject and analysed for glucose, haemoglobin, insulin, iron, Total Iron Binding Capacity (TIBC) and ferritin. Insulin resistance was determined by HOMA-IR index. Transferrin saturation was calculated from serum iron and TIBC. Data was analysed using SPSS-17. Results: There was significant positive correlation between insulin resistance and transferrin saturation, but there was no significant correlation of insulin resistance with blood haemoglobin, serum iron and serum ferritin in type 2 diabetics. Conclusion: Correlation between insulin resistance and transferrin saturation reveals that iron has negative impact on insulin sensitivity in type 2 diabetics. (author)

Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review.

Science.gov (United States)

Kuchay, Mohammad Shafi; Farooqui, Khalid J; Bano, Tarannum; Khandelwal, Manoj; Gill, Harmandeep; Mithal, Ambrish

2017-01-01

Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

Type V hypertriglyceridemia in children, a therapeutic challenge in pediatrics

Science.gov (United States)

Mărginean, Cristina Oana; Meliţ, Lorena Elena; Dobreanu, Minodora; Mărginean, Maria Oana

2017-01-01

Abstract Rationale: Hypertriglyceridemia is defined as a level of triglycerides above 150 mg/dL. The complex causes and classification of hypertriglyceridemia lead to difficulties in the diagnosis and management of this condition. Patient concerns: We present the case of a 15 years and 6 months old female teenager, admitted in our clinic for the following complaints: severe abdominal pain predominantly in the lateral left quadrant, nausea, vomiting, and the lack of stools for 2 days. The clinical exam showed: impaired general status, painful abdomen at superficial and deep palpation in the left and upper abdominal quadrants, the absence of stools for 2 days. Diagnoses: The laboratory parameters revealed leukocytosis with neutrophilia, thrombocytopenia, high level of serum amylase and triglycerides, and increased inflammatory biomarkers. The imagistic investigations showed ascites and paralytic ileus. Interventions: The management was burdened by the side-effects of hypolipidemic drugs impairing the liver function and leading to rhabdomyolysis, but eventually the patient's outcome was good. Outcomes: Type V hyperlipoproteinemia is a rare condition accounting for approximately 5% of the cases. The risk for acute pancreatitis is well-known to be associated with hypertriglyceridemia, even though in rare cases. Lessons: The prognosis of hypertriglyceridemia is pediatrics is burdened not only by the long-term risk factors associated to the diseases itself, but also by the negative effects of long-term hypolipidemic treatment. PMID:29390422

Evaluation of hypertriglyceridemia using non-fasting health checkup data in a Japanese population.

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Takahara, Mitsuyoshi; Katakami, Naoto; Kaneto, Hideaki; Noguchi, Midori; Shimomura, Iichiro

2013-01-01

Some employees have difficulty undergoing health checkups in the workplace in a fasting state. However, hypertriglyceridemia is usually diagnosed based on fasting triglyceride (TG) measurements. The current study investigated the performance of non-fasting health checkup data for predicting hypertriglyceridemia in a Japanese population. We recruited a total of 1,959 Japanese employees who had their fasting TG levels reexamined after undergoing initial health checkups under either a fasting (the fasting population; n= 856) or non-fasting state (the non-fasting population; n= 1103). Hypertriglyceridemia was defined as a fasting TG level of ≥ 1.7 mmol/l. The area under the receiver operating characteristic (ROC) curve of the initial TG measurements for reexamination-detected hypertriglyceridemia was 0.85 in the fasting population and 0.83 in the non-fasting population. The area under the ROC curve of the initial TG measurements in the non-fasting population was not inferior to that of the multivariate model where other non-fasting health checkup data were added. The optimal non-fasting TG cutoff point was 2.0 mmol/l. The cutoff point was further lowered when the population was limited to patients undergoing health checkups four or more hours after their last meal and when the prevalence of hypertriglyceridemia in the population was simulated to be reduced. The non-fasting workplace TG measurements by themselves exhibited a tolerable performance for predicting hypertriglyceridemia. The optimal cutoff point in Japanese employees appears to be lower than 2.3 mmol/l, the recently proposed Western cutoff point.

Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia

DEFF Research Database (Denmark)

Beigneux, Anne P; Miyashita, Kazuya; Ploug, Michael

2017-01-01

lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides, and severe hypertriglyceridemia (chylomicronemia). During the characterization of a monoclonal antibody-based immunoassay......-rich lipoproteins and causing severe hypertriglyceridemia. (Funded by the National Heart, Lung, and Blood Institute and the Leducq Foundation.)........ Three of the six patients had systemic lupus erythematosus. One of these patients who had GPIHBP1 autoantibodies delivered a baby with plasma containing maternal GPIHBP1 autoantibodies; the infant had severe but transient chylomicronemia. Two of the patients with chylomicronemia and GPIHBP1...

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

Science.gov (United States)

Aye, Myint Myint; Kilpatrick, Eric S; Aburima, Ahmed; Wraith, Katie S; Magwenzi, Simbarashe; Spurgeon, B; Rigby, Alan S; Sandeman, Derek; Naseem, Khalid M; Atkin, Stephen L

2014-02-28

Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814.

Periodontitis and Insulin Resistance: Casual or Causal Relationship?

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Abhijit N. Gurav

2012-12-01

Full Text Available Insulin resistance (IR is now considered as a chronic and low level inflammatory condition. It is closely related to altered glucose tolerance, hypertriglyceridemia, abdominal obesity, and coronary heart disease. IR is accompanied by the increase in the levels of inflammatory cytokines like interleukin-1 and 6, tumor necrosis factor-α. These inflammatory cytokines also play a crucial part in pathogenesis and progression of insulin resistance. Periodontitis is the commonest of oral diseases, affecting tooth investing tissues. Pro-inflammatory cytokines are released in the disease process of periodontitis. Periodontitis can be attributed with exacerbation of IR. Data in the literature supports a "two way relationship" between diabetes and periodontitis. Periodontitis is asymptomatic in the initial stages of disease process and it often escapes diagnosis. This review presents the blurred nexus between periodontitis and IR, underlining the pathophysiology of the insidious link. The knowledge of the association between periodontitis and IR can be valuable in planning effectual treatment modalities for subjects with altered glucose homeostasis and diabetics. Presently, the studies supporting this association are miniscule. Further studies are mandatory to substantiate the role of periodontitis in the deterioration of IR.

LEPTIN RESISTANCE AND TYPE 2 DIABETES

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O. M. Oleshchuk

2017-07-01

Full Text Available Leptin is one of adipocyte-secreted hormones. It signals to the brain and other tissues about the status of body energy reserves. Circulating leptin levels are directly proportional to the amount of the body fat. Leptin concentration increases when surfeit and decreases during fasting. Obese patients are hyperleptinemic compared with thin persons and they are tolerant to the central hypothalamic effects of leptin. The reduced sensitivity toward exogenous and endogenous leptin is commonly referred to as leptin resistance. Alterations in the signaling of the long isoform of the leptin receptor play the crucial role in leptin resistance. Surfeit may induce leptin resistance and other metabolic sequelae of obesity. Leptin insensitivity and insulin resistance play a major role in the development of type 2 diabetes. Metformin remains the preferred first-line pharmacologic agent for the treatment of type 2 diabetes. It reduces hepatic glucose production, increases glucose uptake in peripheral tissue and can lead to weight loss. Metformin decreases both insulin and leptin concentration, restores the sensitivity to these hormones. But some studies have shown poor relationship between metformin action and leptin level. And the mechanism of metformin action on leptin resistance remains unclear. Thus, these issues should be studied as well as polymorphisms in genes encoding metformin action.

Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.

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Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Valenti, Vincenza; Ingrassia, Valeria; Giammanco, Antonina; Panno, Maria D; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

2015-12-01

Cyclic AMP responsive element-binding protein 3-like 3 (CREB3L3) is a novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which hypertriglyceridemia displayed an autosomal dominant pattern of inheritance. The proband was a 49-year-old woman with high plasma triglycerides (≤1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation in this family, we analyzed the candidate genes of recessive and dominant forms of primary hypertriglyceridemia by direct sequencing. The sequencing of CREB3L3 gene led to the discovery of a novel minute frame shift mutation in exon 3 of CREB3L3 gene, predicted to result in the formation of a truncated protein devoid of function (c.359delG-p.K120fsX20). Heterozygosity for the c.359delG mutation resulted in a severe phenotype occurring later in life in the proband and her brother and a good response to diet and a hypotriglyceridemic treatment. The same mutation was detected in a 13-year-old daughter who to date is normotriglyceridemic. We have identified a novel pathogenic mutation in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable pattern of penetrance. © 2015 American Heart Association, Inc.

Altered plasma lysophosphatidylcholines and amides in non-obese and non-diabetic subjects with borderline-to-moderate hypertriglyceridemia: a case-control study.

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Sae Young Lee

Full Text Available Hypertriglyceridemia (HTG is a risk factor for atherosclerotic cardiovascular disease (CVD. We investigated alterations in plasma metabolites associated with borderline-to-moderate HTG (triglycerides (TG 150-500 mg/dL. Using UPLC-LTQ-Orbitrap mass spectrometry analysis, the metabolomics profiles of 111 non-diabetic and non-obese individuals with borderline-to-moderate HTG were compared with those of 111 age- and sex-matched controls with normotriglyceridemia (NTG, TG <150 mg/dL. When compared to the NTG control group, the HTG group exhibited higher plasma levels of lysophosphatidylcholines (lysoPCs, including C14:0 (q = 0.001 and C16:0 (q = 1.8E-05, and several amides, including N-ethyldodecanamide (q = 2.9E-05, N-propyldodecanamide (q = 3.5E-05, palmitoleamide (q = 2.9E-06, and palmitic amide (q = 0.019. The metabolomic profiles of the HTG group also exhibited lower plasma levels of cis-4-octenedioic acid (q<1.0E-9 and docosanamide (q = 0.002 compared with those of the NTG controls. LysoPC 16:0 and palmitoleamide emerged as the primary metabolites able to discriminate the HTG group from the NTG group in a partial least-squares discriminant analysis and were positively associated with the fasting triglyceride levels. We identified alterations in lysoPCs, amides, and cis-4-octenedioic acid among non-diabetic and non-obese individuals with borderline-to-moderate HTG. These results provide novel insights into the metabolic alterations that occur in the early metabolic stages of HTG. This information may facilitate the design of early interventions to prevent disease progression.

Diabetes Mellitus Increases Severity of Thrombocytopenia in Dengue-Infected Patients

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Chung-Yuan Chen

2015-02-01

Full Text Available Background: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54 ± 51.69 vs. 86.58 ± 63.4 (p ≤ 0.001, 43.98 ± 44.09 vs. 64.52 ± 45.06 (p = 0.002, 43.86 ± 35.75 vs. 62.72 ± 51.2 (p = 0.012. Diabetes mellitus, death, dengue shock syndrome (DSS and dengue hemorrhagic fever (DHF and increased glutamic-pyruvate transaminase (GPT levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of −13.981 (95% confidence interval (CI −27.587, −0.374, −26.847 (95% CI −37.562, −16.132, and 0.054 (95% CI 0.015, 0.094 respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of −2.947 (p = 0.004, 2.801 (p = 0.005, and −3.568 (p ≤ 0.001, respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

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Magee, M J; Bloss, E; Shin, S S; Contreras, C; Huaman, H Arbanil; Ticona, J Calderon; Bayona, J; Bonilla, C; Yagui, M; Jave, O; Cegielski, J P

2013-06-01

Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (pdiabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Hospital Management of Severe Hypertriglyceridemia in Children.

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Valaiyapathi, Badhma; Ashraf, Ambika P

2017-01-01

Severe Hypertriglyceridemia (HTG), i.e., plasma triglyceride levels exceeding 1000 mg/dL, is one of the established causes of acute pancreatitis and severe abdominal pain. There are no established pediatric guidelines regarding treatment of children and adolescents with severe HTG. To review the pathophysiology and etiology of severe HTG in the pediatric age group, and to discuss management options. Severe HTG is usually due to deficient or absent Lipoprotein Lipase (LPL) activity, which can be due to primary genetic etiology or secondary causes triggering HTG in those with underlying genetic susceptibility. Hospitalization is indicated for patients with severe HTG who are symptomatic with abdominal pain or pancreatitis, in those with uncontrolled diabetes requiring insulin, or, in those with substantial elevations of plasma TG. Fasting followed by fat free diet until plasma TG declines to severe pancreatitis, shock or multi-organ failure. Medications such as fibrates and omega-3 fatty acids are not effective if LPL activity is absent or when plasma TG is >1800 mg/dL. Medications only have an adjunct role in the management. Low fat diet, lifestyle changes, weight loss, control of secondary causes, and patient education form the mainstay of management once the patient is discharged. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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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.

[Concept Analysis for Psychological Insulin Resistance in Korean People with Diabetes].

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Song, Youngshin

2016-06-01

The purpose of this study was to define the concept for psychological insulin resistance in the Korean population with diabetes. The Hybrid model was used to perform the concept analysis of psychological insulin resistance. Results from both the theoretical review with 26 studies and a field study including 19 participants with diabetes were included in final process. The preceding factors of psychological insulin resistance were uncontrolled blood glucose and change in daily life. The concept of psychological insulin resistance was found to have three categories with 8 attributes such as emotional factors (negative feeling), cognitive factors (low awareness and knowledge, low confidence for self-injection) and supportive factors (economic burden, dependency life, embarrassing, feeling about supporters, feeling of trust in, vs mistrust of health care providers). The 8 attributes included 30 indicators. The psychological insulin resistance of population with diabetes in Korea was defined as a complex phenomenon associated with insulin therapy that can be affected by emotional factors, cognitive factors, and supportive relational factors. Based on the results, a tool for measuring psychological insulin resistance of Koreans with diabetes and effective programs for enhancing insulin adherence should be developed in future studies.

Alloxan-induced and Insulin-resistant Diabetes Mellitus affect ...

African Journals Online (AJOL)

The purpose of this study was to determine the effects of diabetes mellitus and insulin resistance on semen parameters, histology of reproductive organs and serum concentrations of testosterone and luteinizing hormone (LH). Male Sprague-Dawley rats weighing 180 - 200g were made diabetic by intravenous injection of ...

[Severe hypertriglyceridemia : Diagnostics and new treatment principles].

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Kassner, U; Dippel, M; Steinhagen-Thiessen, E

2017-08-01

Severe hypertriglyceridemia is defined at a plasma triglyceride (TG) concentration of >885 mg/dl and may result - in particular when clinical symptoms appear before the age of 40 - from "large variant" mutations in genes which influence the function of the lipoprotein lipase (LPL). For diagnosis, secondary factors have to be excluded and treated before further genetic tests are considered. Typical symptoms in almost all patients are recurrent, sometimes severe abdominal pain attacks, which can result in acute pancreatitis, the most important, sometimes life-threatening complication. To minimize the risk of severe pancreatitis, the aim is to maintain the plasma TG concentration hypertriglyceridemia have an increased cardiovascular risk. To lower this is the primary treatment goal here. Treatment mainly consists of a life-long, strict fat- and carbohydrate-restricted diet and the abstention from alcohol. Omega‑3-Fatty acids and fibrates can be used to lower plasma TG levels. Recently, new gene therapy approaches for LPL-deficient patients have become available in Germany.

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

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Basar, Rafet; Uzum, Ayse Kubat; Canbaz, Bulent; Dogansen, Sema Ciftci; Kalayoglu-Besisik, Sevgi; Altay-Dadin, Senem; Aral, Ferihan; Ozbey, Nese Colak

2013-05-01

During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

Determinants of Intravascular Resistance in Indian Diabetic Nephropathy Patients: A Hospital-Based Study

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Anubhav Thukral

2011-01-01

Full Text Available Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.

[Severely increased serum lipid levels in diabetic ketoacidosis - case report].

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Stefansson, Hrafnkell; Sigvaldason, Kristinn; Kjartansson, Hilmar; Sigurjonsdottir, Helga Águsta

2017-01-01

Severe hypertriglyceridemia is a known, but uncommon complication of diabetic ketoacidosis. We discuss the case of a 23-year-old, previously healthy, woman who initially presented to the emergency department with abdominal pain. Grossly lipemic serum due to extremely high triglyceride (38.6 mmol/L) and cholesterol (23.2 mmol/L) levels were observed with a high blood glucose (23 mmol/L) and a low pH of 7.06 on a venous blood gas. She was treated successfully with fluids and insulin and had no sequale of pancreatitis or cerebral edema. Her triglycerides and cholesterol was normalized in three days and she was discharged home on insulin therapy after five days. Further history revealed a recent change in diet with no meat, fish or poultry consumption in the last 12 months and concomitantly an increase in carbohydrate intake which might have contributed to her extremely high serum lipid levels. This case demonstrates that clinicians should be mindful of the different presentations of diabetic ketoacidosis. Key words: diabetic ketoacidosis, hypertriglyceridemia, hyperlipidemia, vegan diet, carbohydrate diet. Correspondence: Hrafnkell Stefansson, hrafnkell.stefans@gmail.com.

Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia

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Aguilar-Salinas, Carlos A.; Tusie-Luna, Teresa; Pajukanta, Päivi

2014-01-01

Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explains the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia. PMID:24768220

Prevalence of dyslipidemia in patients with type-2 diabetes mellitus

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Siddiqui, S A; Shabbir, I; Sherwani, M U.I.K.; Hussain, R [Fatima Jinnah Medical College, Lahore (Pakistan). Dept. of Research Centre

2011-01-15

32.9% cases. The group with high LDL and VLDL is at risk of developing cardiovascular disease. Hypertriglyceridaemia was found in 55% and hypercholesterolaemia in 45.4% cases. Obesity as indicated by body mass index was found in 53.7% patients. Statistically significant association of hypercholesterolemia, hypertriglyceridemia, hypo HDL cholesterolemia and VLDL-C was found with advancing age while only hypertriglyceridemia and VLDL-C showed a positive association with duration of diabetes. A significant association of hyperglycemia (raised HbA1c) was seen with hypertriglyceridemia and high LDL-C along with high body mass index i.e. obesity. Conclusions: Hypertriglyceridemia, high LDL-C and VLDL-C, low HDL-C levels and obesity were the pattern of dyslipidemia found in our diabetic population. (author)

Laparoscopic bariatric surgery for the treatment of severe hypertriglyceridemia

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Sung-Yu Hsu

2015-04-01

Conclusion: Bariatric surgery can be successfully used as a metabolic surgery in severe hypertriglyceridemia patients at risk of acute pancreatitis. However, control of triglyceride levels prior to bariatric surgery is indicated.

Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)

DEFF Research Database (Denmark)

Bingley, Polly J; Mahon, Jeffrey L; Gale, Edwin A M

2008-01-01

OBJECTIVE: Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers......-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox...... glucose tolerance test (P insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0...

Severe hypertriglyceridemia with pancreatitis: thirteen years' treatment with lomitapide.

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Sacks, Frank M; Stanesa, Maxine; Hegele, Robert A

2014-03-01

Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia. The patient had been hospitalized many times for pancreatitis since age 15 years. Her serum triglyceride level averaged 3900 mg/dL while she received therapy with approved lipid drugs. She is homozygous for a coding mutation (P234L) in lipoprotein lipase, leaving her unable to metabolize triglycerides in chylomicrons and very low density lipoproteins (VLDL). Lomitapide reduces the secretion of chylomicrons and VLDL. Lomitapide, which was started when she was 44 years old after near-fatal pancreatitis, lowered her fasting triglyceride level from greater than 3000 mg/dL to a mean (SD) of 903 (870) mg/dL while she received 30 mg/d and to 524 (265) mg/dL while she received 40 mg/d; eliminated chronic abdominal pain; and prevented pancreatitis. However, fatty liver, present before treatment, progressed to steatohepatitis and fibrosis after 12 to 13 years. Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.

Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease.

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Karalliedde, Janaka; Gnudi, Luigi

2016-02-01

Diabetes mellitus (DM) is increasingly recognized as a heterogeneous condition. The individualization of care and treatment necessitates an understanding of the individual patient's pathophysiology of DM that underpins their DM classification and clinical presentation. Classical type-2 diabetes mellitus is due to a combination of insulin resistance and an insulin secretory defect. Type-1 diabetes is characterized by a near-absolute deficiency of insulin secretion. More recently, advances in genetics and a better appreciation of the atypical features of DM has resulted in more categories of diabetes. In the context of kidney disease, patients with DM and microalbuminuria are more insulin resistant, and insulin resistance may be a pathway that results in accelerated progression of diabetic kidney disease. This review summarizes the updated classification of DM, including more rarer categories and their associated renal manifestations that need to be considered in patients who present with atypical features. The benefits and limitations of the tests utilized to make a diagnosis of DM are discussed. We also review the putative pathways and mechanisms by which insulin resistance drives the progression of diabetic kidney disease. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Environmental determinants of type 1 diabetes: a role for overweight and insulin resistance.

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Islam, Sadia T; Srinivasan, Shubha; Craig, Maria E

2014-11-01

Rates of type 1 diabetes are rising globally, with a decreasing proportion of high-risk genotypes and twin concordance rates below 50%. Therefore, environmental factors such as viruses, nutrition and overweight have been examined as putative aetiological agents. The accelerator hypothesis proposes that overweight and insulin resistance are central to both type 1 and type 2 diabetes and may explain, in part, the rise in type 1 diabetes incidence. The temporal rise in body mass index at type 1 diabetes onset and the observation that pre-diabetic children are heavier and more insulin resistant than their peers suggests convergence of type 1 and type 2 diabetes phenotypes. The influence of insulin resistance may begin in utero, although the aetiological role of birthweight in type 1 diabetes remains unclear. Further research to elucidate the role of these modifiable risk factors in today's obesogenic environment may provide future potential for diabetes prevention. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Managing hypertriglyceridemia in children with systemic lupus erythematosus: Two sides of the same coin.

Science.gov (United States)

Basu, Biswanath; Babu, Binu George; Bhattacharyya, Suman

Hypertriglyceridemia is common in children with systemic lupus erythematosus (SLE). A retrospective analysis of the baseline clinical-pathological presentation and treatment outcome (status of lipid profiles) was performed in two children with SLE, who presented with extreme hypertriglyceridemia over a follow-up period of four weeks. The children were treated with prednisolone, mycophenolate mofetil (MMF), hydroxychloroquine and hypolipidemic agents, depending on their disease status. On serial follow-up, the first child showed a significantly raised serum triglyceride level after receiving one week of oral prednisolone therapy. Anti-lipoprotein-lipase (LPL) autoantibody was absent. Lipid profile levels of this child gradually improved after replacing oral prednisolone with another immunosuppressant, namely MMF. The second child presented with extreme hypertriglyceridemia with positive anti-LPL autoantibody. She responded to plasmapheresis followed by increasing the dose of immunosuppressant. So, extreme hypertriglyceridemia in children with SLE may be steroid induced or due to presence of anti-LPL auto antibody. Management should be individualized depending on the etiology. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Severe gestational hypertriglyceridemia: A practical approach for clinicians

Science.gov (United States)

Wong, Bertha; Ooi, Teik C

2015-01-01

Severe gestational hypertriglyceridemia is a potentially life threatening and complex condition to manage, requiring attention to a delicate balance between maternal and fetal needs. During pregnancy, significant alterations to lipid homeostasis occur to ensure transfer of nutrients to the fetus. In women with an underlying genetic predisposition or a secondary exacerbating factor, severe gestational hypertriglyceridemia can arise, leading to devastating complications, including acute pancreatitis. Multidisciplinary care, implementation of a low-fat diet with nutritional support, and institution of a hierarchical therapeutic approach are all crucial to reduce maternal and fetal morbidity. To avoid maternal pancreatitis, close surveillance of triglycerides throughout pregnancy with elective hospitalization for refractory cases is recommended. Careful dietary planning is required to prevent neural and retinal complications from fetal essential fatty acid deficiency. Questions remain about the safety of fibrates and plasmapheresis in pregnancy as well as the optimal timing for induction and delivery of these women. PMID:27512474

Severe Hypertriglyceridemia - Induced Pancreatitis During Pregnancy

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Handan Çelik

2008-08-01

scan of abdomen was normal, with no evidence of cholelithiasis but there was perisplenic fluid accumulation. A diagnosis of acute pancreatitis secondary to hypertriglyceridemia was made. With early conservative treatment the patient’s condition was effectively improved and she was discharged from the hospital 8 days later. After 12 weeks, cesarean section was performed due to previous cesarean section. She was discharged home three days later with her baby.

Lipid profile abnormalities in Type II diabetics with and without microalbuminura

International Nuclear Information System (INIS)

Qadoos, A.; Javaid, Q.U.A.; Shahzad, A.; Toor, I.

2017-01-01

To find the frequency of microalbuminemia in type II diabetic patients and to determine the frequency of different abnormalities of lipid profile in Type II diabetic patients with and without microalbuminuria. Methodology: Total 344 patients of type-II diabetes mellitus of both genders between the age of 35-70 years were enrolled in the study from Lahore General Hospital, Lahore, Pakistan. Blood sample for lipid profile was collected after 12 hours of fasting and spot mid stream early morning urine sample was collected in laboratory for microalbuminuria detection. Results: Out of 344 cases, 151 (43.90%) were male and 193 (56.10%) were females with male to female ratio of 2:1. 132 (38.37%) cases were between 35-50 years of age while 212 (61.63%) between 51-70 years of age (mean 53.18+9.32). Frequency of microalbuminuria was recorded in 32.56% (n=112) cases. Out of 112 cases of microalbuminuria, Hypertriglyceridemia was seen in 98 (87.5%) cases, increased LDL-C in 102 (91%) while decreased HDL-C was found in 95 (84.8%) cases (p=0.000). Out of 232 cases of without microalbuminuria, hypertriglyceridemia was found in 143 (61%) cases, increased LDL-C in 151 (65%) and decreased HDL-C was seen in 169 (72.8%) cases. Frequency of microalbuminuria was seen more in age group of 51-75 years (n=65) with disease duration of more than 3 years (n=71), HbA1c 6 (n=69) and BMI more than 30. Conclusion: The frequency of hypertriglyceridemia, increased LDL-C and decreased HDL-C is higher in type II diabetic patients with microalbuminuria as compare to patients without microalbuminuria and is dependent on advanced age, duration of disease and BMI. (author)

Systematic review of hypertriglyceridemia-induced acute pancreatitis: A more virulent etiology?

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Carr, Rosalie A; Rejowski, Benjamin J; Cote, Gregory A; Pitt, Henry A; Zyromski, Nicholas J

2016-01-01

We sought to define the severity and natural history of hypertriglyceridemia induced acute pancreatitis (HTG-AP), specifically whether HTG-AP causes more severe AP than that caused by other etiologies. Systematic review of the English literature. Thirty-four studies (15 countries; 1972-2015) included 1340 HTG-AP patients (weighted mean prevalence of 9%). The median admission triglyceride concentration was 2622 mg/dl (range 1160-9769). Patients with HTG have a 14% weighted mean prevalence of AP. Plasmapheresis decreased circulating triglycerides, but did not conclusively affect AP mortality. Only 7 reports (n = 392 patients) compared severity of HTG-AP to that of AP from other etiologies. Of these, 2 studies found no difference in severity, while 5 suggested that HTG-AP patients may have increased severity compared to AP of other etiology. 1) hypertriglyceridemia is a relatively uncommon (9%) cause of acute pancreatitis; however, patients with hypertriglyceridemia have a high (14%) incidence of acute pancreatitis; 2) plasmapheresis may offer specific therapy unique to this patient population; and 3) data specifically comparing the severity of HTG-AP with AP caused by other etiologies are heterogeneous and scarce. Copyright © 2016. Published by Elsevier B.V.

Assessment of urinary tract infection and their resistance to antibiotics in diabetic and non-diabetic patients

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Nureen Zahra

2016-09-01

Full Text Available Diabetic patients are more susceptible to urinary tract infections (UTIs than non-diabetic patients and due to the development of multidrug resistant uropathogenic strains, the choice of antibacterial agents is being limited. The study was undertaken to determine the influence of diabetes mellitus on the uropathogens and antibiotic sensitivity pattern among patients with UTIs. A cross-sectional study was conducted in which total of 400 patients were studied out of which 150 were diabetics and 250 were non-diabetics. Patients with negative urine culture (n = 240 were excluded from the study and 160 patients with positive culture of UTIs of which 80 were diabetics and 80 were non-diabetics, included in this study. Clinical data were obtained from individual study participant with informed written consent using pre-tested questionnaire. According to the clean-catch procedure, midstream urine samples were collected and cultured for the diagnosis and susceptibility of bacteriuria. Out of 160 uropathogenic isolates, E. coli was found as a leading pathogen i.e. 46.25% followed by Candida spp. 30.62%, S. Faecalis 15.62%, P. aeruginosa 3.13%, Pneumococcus. 1.25%, MSSA 1.25%, MRSA 0.63%, Proteus spp. 0.63% and Vancomycin resistant enterococcus spp. 0.63%. The results indicated that prevalence of UTIs was significantly higher in diabetic patients than in non-diabetic subjects. E. coli was found to be the most common isolate. It was observed that UTIs in diabetic patients was more in female diabetic patients than in male patients. Investigation of bacteriuria in diabetic patients for UTIs is an important tool for the treatment and prevention of renal complications.

Effect of Creosote Bush-Derived NDGA on Expression of Genes Involved in Lipid Metabolism in Liver of High-Fructose Fed Rats: Relevance to NDGA Amelioration of Hypertriglyceridemia and Hepatic Steatosis.

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Haiyan Zhang

Full Text Available Nordihydroguaiaretic acid (NDGA, the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS, lowering blood glucose, free fatty acids (FFA and triglyceride (TG levels in several models of dyslipidemia, as well as improving body weight (obesity, insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36, and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors. Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt, AMPK activity (P-AMPK, MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1. These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

A prospective 4-year study of insulin resistance and adipokines in morbidly obese diabetic and non-diabetic patients after gastric banding.

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Urbanavicius, Vaidotas; Juodeikis, Zygimantas; Dzenkeviciute, Vilma; Galkine, Aiste; Petrulioniene, Zaneta; Sapoka, Virginijus; Brimiene, Vilma; Vitkus, Dalius; Brimas, Gintautas

2017-06-01

There are insufficient data regarding the changes in adipokine levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non-diabetic patients and their effects on insulin resistance and type 2 diabetes remission. To assess leptin, adiponectin, and insulin resistance changes after LAGB in diabetic and non-diabetic morbidly obese patients. One hundred and three patients (37 with and 66 without type 2 diabetes) underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin, adipokine levels and insulin resistance were evaluated preoperatively, and 1 and 4 years after LAGB. The mean patient age was 45.9 ±11.7 years and mean preoperative body mass index was 47.5 ±7.3 kg/m 2 . A total of 80 of 103 patients (77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin levels decreased significantly in both groups at 1 year, but after 4 years this was noted only in non-diabetic patients. After 1 year adiponectin levels increased significantly only in non-diabetic patients (p = 0.003) and remained almost the same at 4 years. A significant decrease in insulin resistance was noted in both groups 1 year after LAGB and diabetes remission was observed in 23 (62.1%) patients. There was a negative correlation between preoperative insulin resistance and adiponectin levels throughout the follow-up period. Leptin levels positively correlated with BMI throughout the study period (baseline r = 0.45; p < 0.001; after 1 year r = 0.71; p < 0.001; after 4 years r = 0.68; p < 0.001). There was no significant correlation between leptin and adiponectin concentrations preoperatively or after 1 year; however, at 4 years it was significant (r = 0.27; p < 0.02). The most significant metabolic changes occurred within 1 year after LAGB. The 4-year follow-up revealed stabilization in metabolic indices rather than significant improvement.

Autoimmune severe hypertriglyceridemia induced by anti-apolipoprotein C-II antibody.

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Yamamoto, Hiroyasu; Tanaka, Minoru; Yoshiga, Satomi; Funahashi, Tohru; Shimomura, Iichiro; Kihara, Shinji

2014-05-01

Among type V hyperlipoproteinemias, only one-fourth of the patients have genetic defects in lipoprotein lipase (LPL) or in its associated molecules; the exact mechanism in other patients is usually unknown. The aim of the study was to report a case of severe hypertriglyceridemia induced by anti-apolipoprotein (apo) C-II autoantibody and to clarify its pathogenesis. A 29-year-old Japanese woman presented with severe persistent hypertriglyceridemia since the age of 20 years. The past history was negative for acute pancreatitis, eruptive xanthomas, or lipemia retinalis. LPL mass and activities were normal. Plasma apo C-II levels were extremely low, but no mutation was observed in APOC2. Apo C-II protein was detected in the serum by immunoprecipitation and Western blotting. Large amounts of IgG and IgM were incorporated with apo C-II protein coimmunoprecipitated by anti-apo C-II antibody. IgG, but not IgM, purified from the serum prevented interaction of apo C-II with lipid substrate and diminished LPL hydrolysis activity. We identified anti-apo C-II antibody in a myeloma-unrelated severe hypertriglyceridemic patient. In vitro analysis confirmed that the autoantibody disrupted the interaction between apo C-II and lipid substrate, suggesting the etiological role of anti-apo C-II antibody in severe hypertriglyceridemia in this patient.

Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report.

Science.gov (United States)

Kido, Kazuhiko; Evans, Rickey A; Gopinath, Anil; Flynn, Jeremy D

2018-02-01

Hypertriglyceridemia and hyperlipidemia are the most remarkable metabolic complications seen with long-term sirolimus therapy. We report the case of a 36-year-old woman status post bilateral lung transplantation on a maintenance immunosuppression regimen of sirolimus, tacrolimus, and prednisone who presented with status migrainosus, chest pain, abdominal discomfort, and triglyceride levels greater than 4425 mg/dL. In previously reported cases of severe hypertriglyceridemia that developed on maintenance sirolimus therapy, plasmapheresis has been utilized as an early strategy to rapidly lower triglycerides in order to minimize the risk of acute complications such as pancreatitis, but our case was managed medically without plasmapheresis. The most recent triglyceride was down to 520 mg/dL 2 months after discontinuation of sirolimus. We estimate the probability of this reaction to sirolimus as probable based on a score of 5 points on the Naranjo scale. This is the first case report to our knowledge that highlights the sole use of oral lipid-lowering drug agents to treat severe hypertriglyceridemia secondary to sirolimus without the use of plasmapheresis. Sirolimus-induced severe hypertriglyceridemia can be managed with oral lipid-lowering agents without plasmapheresis. Clinician needs to be aware of the importance of baseline and regular triglyceride monitoring in patients on sirolimus.

Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

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Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil); Oliveira, Antônio Cesar Cabral de; Wichi, Rogério Brandão [Departamento de Educação Física - UFS, São Cristóvão, SE (Brazil); Santos, Márcio Roberto Viana, E-mail: marciorvsantos@bol.com.br [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil)

2014-07-15

Resistance exercise effects on cardiovascular parameters are not consistent. The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

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Marcelo Mendonça Mota

2014-07-01

Full Text Available Background: Resistance exercise effects on cardiovascular parameters are not consistent. Objectives: The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods: Wistar rats were divided into three groups: control group (n = 8; sedentary diabetic (n = 8; and trained diabetic (n = 8. Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results: A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2% and an increase in the trained diabetic group (95 ± 3% without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05 in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05 in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg as compared to the sedentary diabetic group. Conclusions: Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

International Nuclear Information System (INIS)

Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos; Oliveira, Antônio Cesar Cabral de; Wichi, Rogério Brandão; Santos, Márcio Roberto Viana

2014-01-01

Resistance exercise effects on cardiovascular parameters are not consistent. The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats

Effects of Resistance Training on Serum Level of Reproductive Hormones and Sperm Parameters in Type 2 Diabetes Rats

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Mohammad Parastesh

2016-11-01

Full Text Available Abstract Background: Diabetes mellitus is associated with reductions in fertility indices. Resistance training, on the other hand, through reducing the adverse effects of diabetes, exerts a positive impact on diabetic individuals. The aim of the present study was to examine the effects of ten weeks of resistance training on serum levels of reproductive hormones and sperm parameters in Wistar rats with diabetes mellitus type 2. Materials and Methods:In this experimental study, 36 Wistar rats with mean weight of 200±50 were ran-domly assigned to healthy control, diabetic control and diabetic training groups. The diabetic resistance training group received ten weeks of resistance training (climbing up the ladder following the induction of diabetes. Twenty-four hours after the last training session, left epididymis of the rats was examined for studying sperm parameters and blood serum samples were examined for evaluating reproductive hormones. Data were analyzed using one-way ANOVA and Turkey’s Post Hoc test at 0.05%. Results: Ten weeks of resistance training induced significant increases in serum testosterone and FSH levels in the resistance training group in comparison to the diabetic group (p<0.007.Resistance training did not have any significant effects on serum LH levels in the resistance training group compared to the diabetic control group. In ad-dition, sperm parameters (sperm count, survival rate and motility presented significant improvements compared to the diabetic group(p<0.05. Conclusion: Resistance training can improve sperm parameters, including sperm count, survival rate and motility, through increasing serum testosterone, LH and FSH levels (reproductive hormones in rats with diabetes mellitus type 2.

Dietary counselling effectively improves lipid levels in patients with endogenous hypertriglyceridemia: emphasis on weight reduction and alcohol limitation

NARCIS (Netherlands)

de Man, F. H.; van der Laarse, A.; Hopman, E. G.; Gevers Leuven, J. A.; Onkenhout, W.; Dallinga-Thie, G. M.; Smelt, A. H.

1999-01-01

To evaluate the short-term effect of dietary counselling in patients with endogenous hypertriglyceridemia and evaluate the effects of advised nutrient changes. A prospective dietary intervention study in patients with endogenous hypertriglyceridemia from January I st 1988 to December 31 st 1996

Effect of adrenomedullin gene delivery on insulin resistance in type 2 diabetic rats

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Hoda Y. Henein

2011-01-01

Full Text Available Type 2 diabetes mellitus is one of the common metabolic disorders that ultimately afflicts large number of individuals. Adrenomedullin (AM is a potent vasodilator peptide; previous studies reported development of insulin resistance in aged AM deficient mice. In this study, we employed a gene delivery approach to explore its potential role in insulin resistance. Four groups were included: control, diabetic, non-diabetic injected with the AM gene and diabetic injected with the AM gene. One week following gene delivery, serum glucose, insulin, triglycerides, leptin, adiponectin and corticosterone were measured as well as the insulin resistance index (HOMA-IR. Soleus muscle glucose uptake and RT-PCR of both AM and glucose transporter-4 (GLUT 4 gene expressions were assessed. A single tail vein injection of adrenomedullin gene in type 2 diabetic rats improved skeletal muscle insulin responsiveness with significant improvement of soleus muscle glucose uptake, HOMA-IR, serum glucose, insulin and triglycerides and significant increase in muscle GLUT 4 gene expression (P < 0.05 compared with the non-injected diabetic rats. The beneficial effects of AM gene delivery were accompanied by a significant increase in the serum level of adiponectin (2.95 ± 0.09 versus 2.33 ± 0.17 μg/ml in the non-injected diabetic group as well as a significant decrease in leptin and corticosterone levels (7.51 ± 0.51 and 262.88 ± 10.34 versus 10.63 ± 1.4 and 275.86 ± 11.19 ng/ml respectively in the non-injected diabetic group. The conclusion of the study is that AM gene delivery can improve insulin resistance and may have significant therapeutic applications in type 2 diabetes mellitus.

The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

DEFF Research Database (Denmark)

Perry, Rachel J; Samuel, Varman T.; Petersen, Kitt Mia Falck

2014-01-01

Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding...... of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol...... activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes....

Assesment of propolis supplementation on insulin resistance in diabetic patients

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nazli samadi

2017-05-01

Full Text Available Introduction: Diabetes mellitus is a common endocrine disease . The number of people with diabetes over the last twenty years has doubled . Asia as a result of rapid economic growth , as the center of the epidemic in the world . Iran is among the countries with a high prevalence of diabetes mellitus . Use of medicinal plants as adjunctive therapy along with medication always been original . In recent years the tendency of patients to alternative therapies and traditional medicine has increased. Methods : Among patients referred to clinics of University of Medical Sciences, Yazd, Iran , 67 people were selected and randomly divided into two groups,intervention or placebo. Patients in the intervention group received 3 tablets of 300 mg bee propolis and in the control group received placebo . The study lasted 12 weeks . Serum insulin and insulin resistance index were evaluated at the beginning and end of the study. Results: 57 patients completed the study . The average demographic characteristics , anthropometric indices , serum insulin and insulin resistance index at the beginning and end of the study between the two groups showed no significant difference. Conclusion : In this study , supplementation with bee propolis for 12 weeks , on the serum insulin and indices of insulin resistance in patients with type II diabetes is not effective . Further studies are needed to make a final decision.

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia.

Science.gov (United States)

Ahn, Hyeon Yeong; Kim, Minjoo; Chae, Jey Sook; Ahn, Young-Tae; Sim, Jae-Hun; Choi, Il-Dong; Lee, Sang-Hyun; Lee, Jong Ho

2015-08-01

Previous studies have indicated that supplementation with probiotics might improve lipid metabolism. The objective of the study was to evaluate the effect of supplementation with probiotic strains Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 on triglyceride (TG) and apolipoprotein A-V (apo A-V) levels. A randomized, double-blinded, placebo-controlled study was conducted with 128 non-diabetic subjects with hypertriglyceridemia. Over a 12-week test period, the probiotic group consumed 2 g/day of a powdered supplement containing L. curvatus HY7601 and L. plantarum KY1032, whereas the placebo group consumed a powder lacking probiotics. After the treatment, the probiotic group showed an 18.3% (P  C genotype. The consumption of two probiotic strains for 12 weeks reduced TGs and increased the apo A-V and LDL particle size in hypertriglyceridemic subjects. This effect was more pronounced in subjects with higher levels of fasting TGs regardless of their APOA5 -1131T > C genotype. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinical and laboratory parameters in adult diabetics with and without calcific shoulder periarthritis.

Science.gov (United States)

Mavrikakis, M E; Sfikakis, P P; Kontoyannis, S A; Antoniades, L G; Kontoyannis, D A; Moulopoulou, D S

1991-10-01

The clinical and laboratory parameters of calcific shoulder periarthritis (CSP) were examined in 900 patients with type II diabetes mellitus as well as in 350 age- and sex-matched control subjects. A threefold increased prevalence of CSP in diabetics compared with the control group was associated with the presence of longstanding and poorly controlled diabetes, hypercholesterolemia, and hypertriglyceridemia suggesting pronounced diabetic angiopathy, as well as with minor trauma and hypomagnesemia. Aging and serum calcium concentrations were not related to the presence of CSP. Thirty-two percent of diabetics with CSP were symptomatic; 15% of them presented with severe pain and restriction of shoulder movement. These findings confirm a close pathogenetic interrelation between CSP and diabetes mellitus.

Hypertriglyceridemia: the future of genetics to guide individualized therapeutic strategies

NARCIS (Netherlands)

Bernelot Moens, Sophie J.; Hassing, Carlijne H.; Nieuwdorp, Max; Stroes, Erik S. G.; Dallinga-Thie, Geesje M.

2013-01-01

The use of genetic information to explore and treat diseases is ever-expanding, varying from the use of classical approaches for monogenetic disorders to the growing genome-wide association studies to understand more complex traits. In hypertriglyceridemia, development has progressed rapidly. We

The ddY mouse: a model of postprandial hypertriglyceridemia in response to dietary fat

Science.gov (United States)

Yamazaki, Tomomi; Kishimoto, Kyoko; Ezaki, Osamu

2012-01-01

Postprandial hyperlipidemia (lipemia) is a risk factor for atherosclerosis. However, mouse models of postprandial hyperlipidemia have not been reported. Here, we report that ddY mice display marked postprandial hypertriglyceridemia in response to dietary fat. In ddY mice, the fasting serum total triacylglyceride (TG) concentration was 134 mg/dl, which increased to 571 mg/dl after an intragastric safflower oil load (0.4 ml/mouse). In C57BL/6J mice, these concentrations were 57 and 106 mg/dl, respectively. By lipoprotein analysis, ddY mice showed increases in chylomicron- and VLDL-sized TG fractions (remnants and VLDL) after fat load. In C57BL/6J mice, post-heparin plasma LPL activity after fat load was increased 4.8-fold relative to fasting. However, in ddY mice, the increase of LPL activity after fat load was very small (1.2-fold) and not significant. High fat feeding for 10 weeks led to obesity in ddY mice. A difference in LPL amino acid composition between C57BL/6J and ddY mice was detected but was deemed unlikely to cause hypertriglyceridemia because hypertriglyceridemia was not evident in other strains harboring the ddY-type LPL sequence. These findings indicate that postprandial hypertriglyceridemia in ddY mice is induced by decreased LPL activity after fat load and is associated with obesity induced by a high-fat diet. PMID:22735545

Analysis of the effect of diabetes type 2 duration on beta cell secretory function and insulin resistance

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Popović Ljiljana

2006-01-01

Full Text Available Diabetes type 2 is a chronic metabolic disorder. Pathogenesis of diabetes type 2 results from the impaired insulin secretion, impaired insulin action and increased endogenous glucose production. Diabetes evolves through several phases characterized by qualitative and quantitative changes of beta cell secretory function. The aim of our study was to analyze the impact of diabetes duration on beta cell secretory function and insulin resistance. The results indicated significant negative correlation of diabetes duration and fasting insulinemia, as well as beta cell secretory function assessed by HOMA β index. Our study also found significant negative correlation of diabetes duration and insulin resistance assessed by HOMA IR index. Significant positive correlation was established between beta cell secretory capacity (fasting insulinemia and HOMA β and insulin resistance assessed by HOMA IR index, independently of diabetes duration. These results indicate that: beta cell secretory capacity, assessed by HOMA β index, significantly decreases with diabetes duration. In parallel with decrease of fasting insulinemia, reduction of insulin resistance assessed by HOMA IR index was found as well.

Assessing Psychological Insulin Resistance in Type 2 Diabetes

DEFF Research Database (Denmark)

Holmes-Truscott, Elizabeth; Pouwer, F; Speight, Jane

2017-01-01

PURPOSE OF REVIEW: This study aims to examine the operationalisation of 'psychological insulin resistance' (PIR) among people with type 2 diabetes and to identify and critique relevant measures. RECENT FINDINGS: PIR has been operationalised as (1) the assessment of attitudes or beliefs about...

The effective fraction isolated from Radix Astragali alleviates glucose intolerance, insulin resistance and hypertriglyceridemia in db/db diabetic mice through its anti-inflammatory activity.

Science.gov (United States)

Hoo, Ruby Lc; Wong, Janice Yl; Qiao, Cf; Xu, A; Xu, Hx; Lam, Karen Sl

2010-08-24

Macrophage infiltration in adipose tissue together with the aberrant production of pro-inflammatory cytokines has been identified as the key link between obesity and its related metabolic disorders. This study aims to isolate bioactive ingredients from the traditional Chinese herb Radix Astragali (Huangqi) that alleviate obesity-induced metabolic damage through inhibiting inflammation. Active fraction (Rx) that inhibits pro-inflammatory cytokine production was identified from Radix Astragali by repeated bioactivity-guided high-throughput screening. Major constituents in Rx were identified by column chromatography followed by high-performance liquid chromatography (HPLC) and mass-spectrometry. Anti-diabetic activity of Rx was evaluated in db/db mice. Treatment with Rx, which included calycosin-7-β-D-glucoside (0.9%), ononin (1.2%), calycosin (4.53%) and formononetin (1.1%), significantly reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and MCP-1) in human THP-1 macrophages and lipopolysaccharide (LPS)-induced activation of NF-κB in mouse RAW-Blue macrophages in a dose-dependent manner. Chronic administration of Rx in db/db obese mice markedly decreased the levels of both fed and fasting glucose, reduced serum triglyceride, and also alleviated insulin resistance and glucose intolerance when compared to vehicle-treated controls. The mRNA expression levels of inflammatory cell markers CD68 and F4/80, and cytokines MCP-1, TNF-α and IL-6 were significantly reduced in epididymal adipose tissue while the alternatively activated macrophage marker arginase I was markedly increased in the Rx-treated mice. These findings suggest that suppression of the inflammation pathways in macrophages represents a valid strategy for high-throughput screening of lead compounds with anti-diabetic and insulin sensitizing properties, and further support the etiological role of inflammation in the pathogenesis of obesity-related metabolic disorders.

The effective fraction isolated from Radix Astragali alleviates glucose intolerance, insulin resistance and hypertriglyceridemia in db/db diabetic mice through its anti-inflammatory activity

Directory of Open Access Journals (Sweden)

Hoo Ruby LC

2010-08-01

Full Text Available Abstract Background Macrophage infiltration in adipose tissue together with the aberrant production of pro-inflammatory cytokines has been identified as the key link between obesity and its related metabolic disorders. This study aims to isolate bioactive ingredients from the traditional Chinese herb Radix Astragali (Huangqi that alleviate obesity-induced metabolic damage through inhibiting inflammation. Methods Active fraction (Rx that inhibits pro-inflammatory cytokine production was identified from Radix Astragali by repeated bioactivity-guided high-throughput screening. Major constituents in Rx were identified by column chromatography followed by high-performance liquid chromatography (HPLC and mass-spectrometry. Anti-diabetic activity of Rx was evaluated in db/db mice. Results Treatment with Rx, which included calycosin-7-β-D-glucoside (0.9%, ononin (1.2%, calycosin (4.53% and formononetin (1.1%, significantly reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and MCP-1 in human THP-1 macrophages and lipopolysaccharide (LPS-induced activation of NF-κB in mouse RAW-Blue macrophages in a dose-dependent manner. Chronic administration of Rx in db/db obese mice markedly decreased the levels of both fed and fasting glucose, reduced serum triglyceride, and also alleviated insulin resistance and glucose intolerance when compared to vehicle-treated controls. The mRNA expression levels of inflammatory cell markers CD68 and F4/80, and cytokines MCP-1, TNF-α and IL-6 were significantly reduced in epididymal adipose tissue while the alternatively activated macrophage marker arginase I was markedly increased in the Rx-treated mice. Conclusion These findings suggest that suppression of the inflammation pathways in macrophages represents a valid strategy for high-throughput screening of lead compounds with anti-diabetic and insulin sensitizing properties, and further support the etiological role of inflammation in the pathogenesis of

Rare and common variants in LPL and APOA5 in Thai subjects with severe hypertriglyceridemia: A resequencing approach.

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Khovidhunkit, Weerapan; Charoen, Supannika; Kiateprungvej, Arunrat; Chartyingcharoen, Palm; Muanpetch, Suwanna; Plengpanich, Wanee

2016-01-01

Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors. Few data exist on the genetics of severe hypertriglyceridemia in Asian populations. To examine the genetic variants of 3 candidate genes known to influence triglyceride metabolism, LPL, APOC2, and APOA5, which encode lipoprotein lipase, apolipoprotein C-II, and apolipoprotein A-V, respectively, in a large group of Thai subjects with severe hypertriglyceridemia. We identified sequence variants of LPL, APOC2, and APOA5 by sequencing exons and exon-intron junctions in 101 subjects with triglyceride levels ≥ 10 mmol/L (886 mg/dL) and compared with those of 111 normotriglyceridemic subjects. Six different rare variants in LPL were found in 13 patients, 2 of which were novel (1 heterozygous missense variant: p.Arg270Gly and 1 frameshift variant: p.Asp308Glyfs*3). Four previously identified heterozygous missense variants in LPL were p.Ala98Thr, p.Leu279Val, p.Leu279Arg, and p.Arg432Thr. Collectively, these rare variants were found only in the hypertriglyceridemic group but not in the control group (13% vs 0%, P severe hypertriglyceridemia. A common p.Gly185Cys APOA5 variant, in particular, was quite prevalent and potentially contributed to hypertriglyceridemia in this group of patients. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Spontaneous diabetes mellitus in captive Mandrillus sphinx monkeys: a case report.

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Pirarat, N; Kesdangsakolwut, S; Chotiapisitkul, S; Assarasakorn, S

2008-06-01

Case history The two obese mandrills (Mandrillus sphinx) showed clinical signs of depression, anorexia, hyperglycemia, hypertriglyceridemia, glucosuria, proteinuria and ketonuria. Septic bed sore wounds were noted on both fore and hind limbs. Results Histopathological study revealed severe islet amyloidosis in both mandrills. Immunohistochemical study using polyclonal anti-cat amylin antibody confirmed derivation of the islet amyloid from islet amyloid polypeptide (IAPP). Cardiomyopathy and myocardial fibrosis were also evident. Conclusions The present study documents diabetes mellitus in two obese mandrills. Diabetes in these animals had features very similar type 2 diabetes mellitus of humans, including the development of severe, IAPP-derived islet amyloidosis. The mandrill may, therefore, serve as an animal model of human type 2 diabetes mellitus.

Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy.

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Zuckerwise, Lisa C; Werner, Erika F; Pettker, Christian M; McMahon-Brown, Erin K; Thung, Stephen F; Han, Christina S

2012-08-01

Increased insulin requirements in pregnancy can hinder attainment of glycemic control in diabetic patients. U-500 insulin is a concentrated form of regular insulin that can be a valuable tool in the treatment of patients with severe insulin resistance. A 24-year-old woman with pregestational diabetes mellitus experienced increasing insulin requirements during pregnancy, peaking at 650 units daily. The frequent, large-volume injections of standard-concentration insulin were poorly tolerated by the patient and resulted in nonadherence. She subsequently achieved glycemic control on thrice-daily U-500 insulin. Pregnancy exacerbates insulin resistance in diabetic patients, and these patients may require high doses of insulin. U-500 insulin is an effective alternative for patients with severe insulin resistance and should be considered for pregnant women with difficulty achieving glycemic control.

Effect of insulin resistance on intracellular signal transduction of vessels in diabetic

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Cen Rongguang; Wei Shaoying; Mo Xingju

2003-01-01

To investigate the relationship between the insulin resistance (IR) and the intracellular signal transduction of vessels, changes in fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), inositol triphosphate (IP 3 ), protein kinase C(PKC) and intracellular total calcium concentration in 31 diabetic patients were compared with those of 39 normal controls. The levels of FBG, FINS, TG and TC in diabetic patients were significantly higher than those of normal controls (P 3 and PKC in diabetic patients were significantly lower than those of normal controls (P<0.01). The results suggest that there is a causal relation between insulin resistance and abnormalities of cellular calcium metabolism and intracellular signal transduction of vessels

Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

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Ito, Matthew K

2015-10-01

Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Changes of plasma angiogenic factors during chronic resistance exercise in type 1 diabetic rats

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Esfahani, S.P.; Gharakhanlou, R.

2012-01-01

Objective: Exercise has several beneficial effects on cardiovascular system. However, the exact mechanism is unclear. The purpose of this study was to evaluate the effects of chronic resistance exercise on some plasma angiogenic factors in type 1 diabetic rats. Methodology: Thirty male Wistar rats were divided into three groups of control, diabetic and diabetic trained (n = 10 each). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). The rats in the trained group undertook one training session per day, 3 days/week, for 4 weeks. Blood samples were taken and the concentrations of plasma glucose, lipid profile, nitric oxide (NO), vascular endothelial growth factor (VEGF) and soluble form of VEGF receptor-1 (sFlt-1) were determined. Results: We found a significant reduction in plasma NO concentrations in diabetic rats compared to the controls (p 0.05). There were no significant differences in plasma VEGF and sFlt-1 concentrations between diabetic sedentary and trained groups (p > 0.05). Moreover, VEGF/sFlt-1 ratios in diabetic animals were lower than the control group and resistance exercise could not increase this ratio in diabetic animals (p > 0.05) Conclusion: Resistance exercise could not change plasma VEGF, sFlt-1 and VEGF/sFlt-1 ratio. However, it increased plasma NO concentrations in diabetic animals. More studies are needed to determine the effects of this type of exercise on the angiogenesis process. (author)

Diabetes and early postpartum methicillin-resistant Staphylococcus aureus infection in US hospitals

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Parriott, Andrea M.; Arah, Onyebuchi A.

2013-01-01

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) infection in postpartum women is not well characterized. Because diabetes is a risk factor for some infections, we sought to characterize the relationship between diabetes and invasive MRSA infections in women admitted to US

Relationship between blood pressure and insulin resistance in patients with gestational diabetes

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Kan Shujuan; Zhang Sujuan

2008-01-01

Objective: To study the relationship existe between blood pressure level and degree of insulin resistance in patients with gestational diabetes. Methods: Ninety-five cases of gestational diabetes were diagnosed among 350 pregnant women. Of them, 55 were found to be hypertensive and 40 were normotensive. Fasting, 1,2, 3h post-prandial (75g glucose) blood sugar (with peroxidase method) levels and fasting insulin (with RIA) levels were measured in these patients and 85 normal pregnant women (as control). Results: Fasting, 1, 2, 3h post 75g glucose blood sugar and fasting insulin levels in the 55 hypertensive diabetics were significantly higher than those in the normotensives and controls (P<0.05). The calculated insulin sensitivity indices were significantly lower (P also < 0.05). Conclusion: A higher insulin resistance existed in hypertensive gestational diabetics which might be a risk factor of developing hypertension. (authors)

Effect of resistance training on plasma nitric oxide and asymmetric dimethylarginine concentrations in type I diabetic rats

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Parivash Shekarchizadeh Esfahani

2013-01-01

Conclusion: Elevated ADMA level in diabetic animals can normalize during resistance exercise. Reduced ADMA level and increased NO level following resistance training might improve cardiovascular risk in diabetic subjects.

Evaluation and treatment of hypertriglyceridemia: an endocrine society clinical practice guideline.

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Berglund, L.; Brunzell, J.D.; Goldberg, A.C.; Goldberg, I.J.; Sacks, F.M.; Murad, M.H.; Stalenhoef, A.F.H.

2012-01-01

Objective: The aim was to develop clinical practice guidelines on hypertriglyceridemia. Participants: The Task Force included a chair selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional experts in the field, and a methodologist. The authors received no corporate

Hypertriglyceridemia

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Brahm, Amanda; Hegele, Robert A.

2013-01-01

Hypertriglyceridemia (HTG) is commonly encountered in lipid and cardiology clinics. Severe HTG warrants treatment because of the associated increased risk of acute pancreatitis. However, the need to treat, and the correct treatment approach for patients with mild to moderate HTG are issues for ongoing evaluation. In the past, it was felt that triglyceride does not directly contribute to development of atherosclerotic plaques. However, this view is evolving, especially for triglyceride-related fractions and variables measured in the non-fasting state. Our understanding of the etiology, genetics and classification of HTG states is also evolving. Previously, HTG was considered to be a dominant disorder associated with variation within a single gene. The old nomenclature includes the term “familial” in the names of several hyperlipoproteinemia (HLP) phenotypes that included HTG as part of their profile, including combined hyperlipidemia (HLP type 2B), dysbetalipoproteinemia (HLP type 3), simple HTG (HLP type 4) and mixed hyperlipidemia (HLP type 5). This old thinking has given way to the idea that genetic susceptibility to HTG results from cumulative effects of multiple genetic variants acting in concert. HTG most is often a “polygenic” or “multigenic” trait. However, a few rare autosomal recessive forms of severe HTG have been defined. Treatment depends on the overall clinical context, including severity of HTG, concomitant presence of other lipid disturbances, and the patient's global risk of cardiovascular disease. Therapeutic strategies include dietary counselling, lifestyle management, control of secondary factors, use of omega-3 preparations and selective use of pharmaceutical agents. PMID:23525082

Hypertriglyceridemia

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Amanda Brahm

2013-03-01

Full Text Available Hypertriglyceridemia (HTG is commonly encountered in lipid and cardiology clinics. Severe HTG warrants treatment because of the associated increased risk of acute pancreatitis. However, the need to treat, and the correct treatment approach for patients with mild to moderate HTG are issues for ongoing evaluation. In the past, it was felt that triglyceride does not directly contribute to development of atherosclerotic plaques. However, this view is evolving, especially for triglyceride-related fractions and variables measured in the non-fasting state. Our understanding of the etiology, genetics and classification of HTG states is also evolving. Previously, HTG was considered to be a dominant disorder associated with variation within a single gene. The old nomenclature includes the term “familial” in the names of several hyperlipoproteinemia (HLP phenotypes that included HTG as part of their profile, including combined hyperlipidemia (HLP type 2B, dysbetalipoproteinemia (HLP type 3, simple HTG (HLP type 4 and mixed hyperlipidemia (HLP type 5. This old thinking has given way to the idea that genetic susceptibility to HTG results from cumulative effects of multiple genetic variants acting in concert. HTG most is often a “polygenic” or “multigenic” trait. However, a few rare autosomal recessive forms of severe HTG have been defined. Treatment depends on the overall clinical context, including severity of HTG, concomitant presence of other lipid disturbances, and the patient's global risk of cardiovascular disease. Therapeutic strategies include dietary counselling, lifestyle management, control of secondary factors, use of omega-3 preparations and selective use of pharmaceutical agents.

The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia.

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Backes, James; Anzalone, Deborah; Hilleman, Daniel; Catini, Julia

2016-07-22

Hypertriglyceridemia (triglycerides > 150 mg/dL) affects ~25 % of the United States (US) population and is associated with increased cardiovascular risk. Severe hypertriglyceridemia (≥ 500 mg/dL) is also a risk factor for pancreatitis. Three omega-3 fatty acid (OM3FA) prescription formulations are approved in the US for the treatment of adults with severe hypertriglyceridemia: (1) OM3FA ethyl esters (OM3EE), a mixture of OM3FA ethyl esters, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Lovaza®, Omtryg™, and generics); (2) icosapent ethyl (IPE), EPA ethyl esters (Vascepa®); and (3) omega-3 carboxylic acids (OM3CA), a mixture of OM3FAs in free fatty acid form, primarily EPA, DHA, and docosapentaenoic acid (Epanova®). At approved doses, all formulations substantially reduce triglyceride and very-low-density lipoprotein levels. DHA-containing formulations may also increase low-density lipoprotein cholesterol. However, this is not accompanied by increased non-high-density lipoprotein cholesterol, which is thought to provide a better indication of cardiovascular risk in this patient population. Proposed mechanisms of action of OM3FAs include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation. OM3CA bioavailability (area under the plasma concentration-time curve from zero to the last measurable concentration) is up to 4-fold greater than that of OM3FA ethyl esters, and unlike ethyl esters, the absorption of OM3CA is not dependent on pancreatic lipase hydrolysis. All three formulations are well tolerated (the most common adverse events are gastrointestinal) and demonstrate a lack of drug-drug interactions with other lipid-lowering drugs, such as statins and fibrates. OM3FAs appear to be an effective treatment option for patients with severe hypertriglyceridemia.

Nonalcoholic Fatty Liver Disease and Associated Metabolic Risks of Hypertension in Type 2 Diabetes: A Cross-Sectional Community-Based Study

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Xiaoying Ding

2017-01-01

Full Text Available The mechanisms facilitating hypertension in diabetes still remain to be elucidated. Nonalcoholic fatty liver disease (NAFLD, which is a higher risk factor for insulin resistance, shares many predisposing factors with diabetes. However, little work has been performed on the pathogenesis of hypertension in type 2 diabetes (T2DM with NAFLD. The aim of this study is to investigate the prevalence of hypertension in different glycemic statuses and to analyze relationships between NAFLD, metabolic risks, and hypertension within a large community-based population after informed written consent. A total of 9473 subjects aged over 45 years, including 1648 patients with T2DM, were enrolled in this cross-sectional study. Clinical and biochemical parameters of all participants were determined. The results suggested that the patients with prediabetes or T2DM were with higher risks to have hypertension. T2DM with NAFLD had significantly higher levels of blood pressure, triglyceride, uric acid, and HOMA-IR than those without NAFLD. Data analyses suggested that hypertriglyceridemia [OR = 1.773 (1.396, 2.251], NAFLD [OR = 2.344 (1.736, 3.165], hyperuricemia [OR = 1.474 (1.079, 2.012], and insulin resistance [OR = 1.948 (1.540, 2.465] were associated with the higher prevalence of hypertension independent of other metabolic risk factors in type 2 diabetes. Further studies are needed to focus on these associations.

Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study

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Francis Gordon A

2011-09-01

Full Text Available Abstract Background Severe hypertriglyceridemia (HTG is one cause of acute pancreatitis, yet the level of plasma triglycerides likely to be responsible for inducing pancreatitis has not been clearly defined. Methods and Results A retrospective cohort study was conducted on patients presenting non-acutely to the Healthy Heart Program Lipid Clinic at St. Paul's Hospital with a TG level > 20 mM (1772 mg/dl between 1986 and 2007. Ninety-five patients with TG > 20 mM at the time of referral were identified, in who follow up data was available for 84. Fifteen patients (15.8%, with a mean outpatient TG level of 38.1 mM, had a history of acute pancreatitis. Among 91 additional patients with less severe HTG, none had a history of pancreatitis when TG were between 10 and 20 mM. Among patients with TG > 20 mM on presentation, 8 (8.5%, with a mean TG level of 67.8 mM, exhibited eruptive xanthomata. A diet high in carbohydrates and fats (79% and obesity (47.6% were the two most frequent secondary causes of HTG at initial visit. By 2009, among patients with follow up data 53% exhibited either pre-diabetes or overt Type 2 diabetes mellitus. Upon referral only 23 patients (24% were receiving a fibrate as either monotherapy or part of combination lipid-lowering therapy. Following initial assessment by a lipid specialist this rose to 84%, and remained at 67% at the last follow up visit. Conclusions These results suggest hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitis unless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and fats, and obesity are the main secondary causes of HTG, and that fibrates are frequently overlooked as the drug of first choice for severe HTG.

The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus and associated risk factors among adults living in a rural Koladiba town, northwest Ethiopia.

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Worede, Abebaw; Alemu, Shitaye; Gelaw, Yalemzewod Assefa; Abebe, Molla

2017-07-06

Diabetes mellitus is becoming a big public health challenge, particularly in developing countries like Ethiopia. It is a manageable disease if early screening and follow up is made. However, as studies in Ethiopia are limited and unorganized, determining the magnitude of prediabetes and diabetes and identifying associated risk factors is quite essential. A community-based, cross-sectional study was conducted from February to April 2015 among adults (aged ≥20 years) in a rural Koladiba town. A multistage sampling technique was used to select a total of 392 study participants. Data were collected after a fully informed written consent was obtained from each participant. Demographic, behavioral, and clinical data were collected using a well-structured questionnaire. Multivariable logistic regression models were fitted to control the effect of confounders. Adjusted odds ratios (AOR) with their 95% confidence intervals (95% CI) were computed to measure associations. A p value of fasting glucose and undiagnosed diabetes mellitus were 12% (95% CI 9-16) and 2.3% (95% CI 1.1-4), respectively, in Koladiba. Overweight (AOR: 4.257, 95% CI 1.345-13.476), obesity (AOR: 5.26, 95% CI 1.138-24.316), hypertriglyceridemia (AOR: 2.83, 95% CI 1.451-5.521), and systolic hypertension (AOR: 3.858, 95% CI 1.62-9.189) were found to be independently associated with impaired fasting glucose. Positive family history of diabetes also showed a marginal association with impaired fasting glucose (p = 0.057). Male sex (p = 0.012) and hypertriglyceridemia (p = 0.030) were associated with undiagnosed diabetes mellitus. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus are found to be significant. Obesity, hypertriglyceridemia, and systolic hypertension are independently associated with impaired fasting glucose among adults. We recommend that the community be aware of healthy life style, early screening, and maintain continuous follow up.

Is hypertriglyceridemia a prognostic factor in sepsis?

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Cetinkaya A

2014-02-01

Full Text Available Ali Cetinkaya,1 Abdulsamet Erden,1 Deniz Avci,1 Hatice Karagoz,1 Samet Karahan,1 Mustafa Basak,1 Kadir Bulut,1 Vedat Gencer,1 Hasan Mutlu2 1Internal Medicine Department, Kayseri Training and Research Hospital, Kayseri, Turkey; 2Medical Oncology Department, Acibadem Kayseri Hospital, Kayseri, Turkey Introduction: Sepsis and septic shock are important causes of mortality in intensive care unit patients, hence early diagnosis and therapy are important in management of their treatment. The available information on sepsis patients is not enough to recommend or to discard the routine evaluation of triglyceride (TG levels at the onset of sepsis. The aim of this study was to investigate the association of hypertriglyceridemia and clinical outcome (or mortality in patients with severe sepsis. Materials and methods: Between January 1 and December 31, 2011, a total of 84 patients with sepsis from the intensive internal care unit at the Kayseri Training and Research Hospital, Kayseri, Turkey, were investigated retrospectively. Sepsis was defined according to the American College of Chest Physicians/Society of Critical Care Medicine/European Society of Intensive Care Medicine consensus conference definitions. For each patient, survival was recorded at the end of the last day of hospitalization as dead or alive. The TG values were taken retrospectively from the records, which were performed routinely for each patient with sepsis at the time of diagnosis. TG >150 mg/dL was considered as hypertriglyceridemia. Results: The percentages of male and female patients were 44% and 56%, respectively. The mean age of patients was 71.49±11.071 years. The percentage of patients with TG values more than 150 mg/dL was 81% (25/31 in the non-survivor group and 19% (6/31 in the survivor group. There was a significant difference regarding TG values between groups (P=0.039. Discussion: It was observed in this study that patients in the intensive care unit with sepsis had high

[Aspects of the antimicrobial resistence profile in infections with Escherichia coli and Klebsiella pneumoniae in diabetic patients].

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Petrovici, Cristina G; Dorobăţ, Carmen; Matei, Mioara; Teodor, Andra; Luca, V; Miftode, Egidia

2011-01-01

Infections in diabetic patient remains an important cause of morbidity and mortality, triggering and maintaining a prolonged metabolic imbalance. Emergence of extented spectrum beta-lactmase (ESBL) in Escherichia coli and Klebsiella pneumoniae is a major concern, because of the atypical manner infection acts in this group of imunodepressed patients and also for the limited therapeutic solutions. For this reason we have evaluated the profile of antimicrobial resistance of these pathogens in both diabetic and non diabetic patients. The aim of this study was to evaluate, in a retrospective case control study, the antibiotic susceptibility pattern in isolates of E. coli and Klebsiella spp. from different biological products in 49 diabetics and 150 non-diabetics admitted in The Clinical Hospital of Infectious Diseases Iaşi over a period of two years. Most of strains of E. coli and Klebsiella spp. ESBL positive were found in uroculture. Significant differences in E. coli resistance rate between diabetics and nondiabetics were noted for amoxicillin-clavulanic acid and ciprofloxacin (31,4% vs.13,98%, p=0,04, respectively 52,9% vs. 24,46%, p=0,004). More isolates of ESBL positive K. pneumoniae were found in diabetic patients (50% vs. 24%). Ciprofloxacin resistance of K. pneumoniae was significantly higher in diabetics (75% vs 39%; p=0,05). There was no resistance in E. coli and K. pneumoniae isolates to imipenem in the diabetic group. The high resistance rate to quinolones and 3rd generation cefalosporins limits their use for the treatment of Escherichia coli and K. pneumoniae infections. Other alternatives for empiric therapy in community and nosocomial-acquired infections in diabetic patient remains carbapenems, aminoglycosides and colimycin.

The Effect of Resistance Training on Cardio-Metabolic Factors in Males with Type 2 Diabetes

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Ghalavand

2014-10-01

Full Text Available Background Diabetes is one of the most important metabolic diseases in the world and exercise is a common advice to manage diabetes and reduce its complications. Objectives The aim of this study was to investigate the effect of resistance training on blood glucose, blood pressure and resting heart rate in males with type 2 diabetes. Materials and Methods In this semi-experimental study, 20 males with type 2 diabetes with mean age of 46 ± 3.4 years old who met the inclusion criteria were selected. The participants were randomly assigned into resistance training (n = 10 and control (n = 10 groups. Resistance exercise training program was performed for eight weeks, three sessions per week. Cardiovascular and biochemical parameters were measured before and after the intervention. To analyze the measured parameters changes t-test was used at P ≤ 0.05 significance level. Results After eight weeks, a significant decrease in fasting blood sugar (P = 0.002, glycosylated hemoglobin (P = 0.025 and systolic blood pressure (P = 0.022 was observed in the resistance group. In addition, there was a significant difference in blood sugar (P = 0.003 and glycosylated hemoglobin (P = 0.031 between the two groups. Conclusions Findings of this study confirmed the positive influence of resistance training to control blood glucose and blood pressure in males with type 2 diabetes.

Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

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Goto, Yoshinori; Nishimura, Ryosei; Nohara, Atsushi; Mase, Shintaro; Fujiki, Toshihiro; Irabu, Hitoshi; Kuroda, Rie; Araki, Raita; Ikawa, Yasuhiro; Maeba, Hideaki; Yachie, Akihiro

2016-08-01

A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.

Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

International Nuclear Information System (INIS)

Salhanick, A.I.; Amatruda, J.M.

1988-01-01

Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, the authors investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable [ 14 C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus

Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and Diabetes: A Review

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Nabilatul Hani Mohd-Radzman

2013-01-01

Full Text Available Insulin resistance is a key factor in metabolic disorders like hyperglycemia and hyperinsulinemia, which are promoted by obesity and may later lead to Type II diabetes mellitus. In recent years, researchers have identified links between insulin resistance and many noncommunicable illnesses other than diabetes. Hence, studying insulin resistance is of particular importance in unravelling the pathways employed by such diseases. In this review, mechanisms involving free fatty acids, adipocytokines such as TNFα and PPARγ and serine kinases like JNK and IKKβ, asserted to be responsible in the development of insulin resistance, will be discussed. Suggested mechanisms for actions in normal and disrupted states were also visualised in several manually constructed diagrams to capture an overall view of the insulin-signalling pathway and its related components. The underlying constituents of medicinal significance found in the Stevia rebaudiana Bertoni plant (among other plants that potentiate antihyperglycemic activities were explored in further depth. Understanding these factors and their mechanisms may be essential for comprehending the progression of insulin resistance towards the development of diabetes mellitus.

Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome

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Clement, L.C.; Mace, C.; Avila-Casado, C.; Joles, J.A.; Kersten, A.H.; Chugh, S.S.

2014-01-01

The molecular link between proteinuria and hyperlipidemia in nephrotic syndrome is not known. We show in the present study that plasma angiopoietin-like 4 (Angptl4) links proteinuria with hypertriglyceridemia through two negative feedback loops. In previous studies in a rat model that mimics human

Gender difference and relationship of insulin resistance with microalbuminuria type-2 diabetes

International Nuclear Information System (INIS)

Ahmed, S.; Ahmad, A.

2010-01-01

To determine the relationship of insulin resistance with microalbuminuria in patients of type-2 Diabetes mellitus and observe gender difference if any. Study Design: A cross-sectional study. Place and Duration of Study: Diabetes Clinic of Combined Military Hospital, Malir Cantt, from April to August 2007. Methodology: One hundred and fifty five patients of type-2 Diabetes mellitus were included in the study who had either microalbuminuria or normo albuminuria. Body mass index, waist circumference and blood pressure were recorded. Fasting venous blood sample was collected for plasma glucose (FPG), serum insulin, total and HDL cholesterol, triglycerides, creatinine and HbA1c. Urine albumin excretion was determined using urine albumin to creatinine ratio. Insulin resistance was calculated from fasting plasma glucose and serum insulin levels, using homeostatic model assessment of insulin resistance (HOMA-IR). Correlation and association testing was carried out with significance at p < 0.05. Results: Microalbuminuria was found to be significantly correlated with HOMA-IR (r = 0.33, p < 0.001), serum insulin (r = 0.28, p = < 0.001), body mass index (r = 0.18, p = 0.02) and waist circumference (r = 0.21, p = 0.008). This correlation was more significant in women (n = 85, r = 0.48, p = < 0.0001) as compared to men (n = 70, r = 0.14, p = 0.12). The correlation between HOMA-IR and urine albumin excretion remained highly significant (p = 0.001) after controlling for gender, age, duration of diabetes, waist circumference, hypertension, triglycerides and HbA1c. Conclusion: Urinary albumin excretion in patients of type-2 diabetes is strongly associated with insulin resistance and related cardiovascular risk factors. This association appears to be stronger in women than the men, in our population. (author)

Prevalence of insulin resistance in siblings of type 2 diabetics of north west punjabi population.

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Kaur, Sukhraj; Mahajan, Mridula; Bal, B S

2014-08-01

Insulin resistance a physiological condition is marked by hyperglycemia and failure of cells to respond to normal action thus hyperinsulinemia. It is prevalent in individuals having genetic predisposition and family history of type 2 diabetes mellitus. Physically inactive individuals having sedentary life style are also at a risk of developing insulin resistance. The present study was planned to observe the prevalence of insulin resistance or pre diabetes in various age groups of North West Punjabi population. A total of 400 families comprising of 1159 offsprings of diabetic patients and siblings amongst each were included in the present study. All these 400 families had history of type 2 diabetes mellitus in the present or past generation. Written consent was taken from the head of the family for inclusion in the study. Fasting samples were collected and analysed for Glucose, Glycosylated Hb, complete lipid profile, Insulin and c-peptide. Body mass index, waist hip ratio and HOMA-IR were calculated. Comparison of mean of various parameters was done using student t-test. Analysis of variance (ANOVA) was applied for comparison between groups followed by Bonferroni post hoc analysis. Pearson's correlation method was used for quantitative variables. Statistical significance was defined as p18-35 years were more prone to insulin resistance as compared to other age groups. Insulin resistance at a young age of 18-35 years predisposes these individuals to coronary events. Females in reproductive years are more prone to insulin resistance or pre diabetes as compared to males of the same age group.

Icosapent ethyl: a review of its use in severe hypertriglyceridemia.

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Kim, Esther S; McCormack, Paul L

2014-12-01

Icosapent ethyl (Vascepa®) is a high-purity ethyl ester of eicosapentaenoic acid (EPA) that is de-esterified to EPA following oral administration. Both EPA and docosahexaenoic acid (DHA) are long-chain omega-3 fatty acids that have been associated with triglyceride (TG)-lowering. However, DHA has been associated with increased low-density lipoprotein cholesterol (LDL-C) levels. Icosapent ethyl contains ≥96 % of the EPA ethyl ester, does not contain DHA, and is approved in the USA for use as an adjunct to diet to lower TG levels in adult patients with severe (≥500 mg/dL [≥5.65 mmol/L]) hypertriglyceridemia. In a pivotal phase III trial, oral icosapent ethyl 4 g/day significantly decreased the placebo-corrected median TG levels by 33.1 %. It did not increase LDL-C, had favorable effects on other lipid parameters, and had a tolerability profile similar to that of placebo. Therefore, icosapent ethyl is an effective and well-tolerated agent for the treatment of severe hypertriglyceridemia in adults.

p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients

DEFF Research Database (Denmark)

Brown, Audrey E; Palsgaard, Jane; Borup, Rehannah

2015-01-01

Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic cultured myotubes, which is in keeping with a retained genetic/epigenetic defect of insulin action. We investigated differences in gene...... expression during differentiation between diabetic and control muscle cell cultures. Microarray analysis was performed using skeletal muscle cell cultures established from type 2 diabetic patients with a family history of type 2 diabetes and clinical evidence of marked insulin resistance and nondiabetic...... significantly, it did not improve insulin-stimulated glucose uptake. Increased cytokine expression driven by increased p38 MAPK activation is a key feature of cultured myotubes derived from insulin-resistant type 2 diabetic patients. p38 MAPK inhibition decreased cytokine expression but did not affect...

The relationship between vitronectin and hepatic insulin resistance in type 2 diabetes mellitus.

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Cao, Yan; Li, Xinyu; Lu, Chong; Zhan, Xiaorong

2018-05-18

The World Health Organization (WHO) estimates that approximately 300 million people will suffer from diabetes mellitus by 2025. Type 2 diabetes mellitus (T2DM) is much more prevalent. T2DM comprises approximately 90% of diabetes mellitus cases, and it is caused by a combination of insulin resistance and inadequate compensatory insulin secretory response. In this study, we aimed to compare the plasma vitronectin (VN) levels between patients with T2DM and insulin resistance (IR) and healthy controls. Seventy patients with IR and 70 age- and body mass index (BMI)-matched healthy controls were included in the study. The insulin, Waist-to-Hip Ratio (WHR), C-peptide (CP) and VN levels of all participants were examined. The homeostasis model of assessment for insulin resistence index (HOMA-IR (CP)) formula was used to calculate insulin resistance. The levels of BMI, fasting plasma gluose (FPG), 2-hour postprandial glucose (2hPG), glycated hemoglobins (HbA1c), and HOMA-IR (CP) were significantly elevated in case group compared with controls. VN was found to be significantly decreased in case group. (VN Mean (Std): 8.55 (2.92) versus 12.88 (1.26) ng/mL p insulin resistance in patients with T2DM.

Empagliflozin decreases remnant-like particle cholesterol in type 2 diabetes patients with insulin resistance.

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Hattori, Sachiko

2017-11-28

Remnant lipoproteins are thought to be atherogenic. Remnant-like particle cholesterol (RLP-C), which reflects the levels of various kinds of remnant lipoproteins in the blood, has a significant correlation with insulin resistance. In the present study, we measured the effect of empagliflozin (EMPA) on the levels of RLP-C, and investigated whether EMPA-mediated change in RLP-C is associated with a change in insulin resistance in type 2 diabetes patients who have insulin resistance. Patients were allocated to receive a placebo (n = 51) or EMPA (n = 58) as an add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. EMPA significantly decreased glycated hemoglobin, bodyweight, systolic blood pressure, plasma triglycerides, liver transaminases and estimated glomerular filtration rate, and increased high-density lipoprotein cholesterol. Furthermore, EMPA decreased RLP-C and homeostatic model assessment of insulin resistance. In the placebo group, there were no significant changes in these factors except for slight increases in liver transaminases. Multiple regression analysis showed that the change in homeostatic model assessment of insulin resistance (P = 0.0102) and the change in alanine aminotransferase (P = 0.0301) were significantly associated with the change in RLP-C in the EMPA group. The change in RLP-C significantly correlated with the change in homeostatic model assessment of insulin resistance (Pearson correlation coefficient 0.503, 95% confidence interval 0.199-0.719; P = 0.00241). EMPA decreases RLP-C levels, which is closely associated with amelioration of insulin sensitivity in diabetes patients who have insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Effect of Resistance Exercise Training Associated with Skeletal Muscle Hypertrophy on Serum Pro-Inflammatory Cytokines in STZ-induced Diabetes

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Mahdieh Molanouri Shamsi

2016-06-01

Full Text Available Skeletal muscle atrophy is associated with type 1 diabetes. Effects of resistance exercise training associated with skeletal muscle hypertrophy on serum inflammatory cytokines was exactly not clarified. Protein levels of inflammatory cytokines IL-6, TNF-α, and interleukin-1beta (IL-1β in serum of healthy and streptozotocin (STZ- induced diabetic rats subjected to resistance exercise training were assessed in this study. Rats were divided into the control, training, control diabetic and diabetic training groups. Training groups performed the resistance training consisted of climbing a 1 m ladder with increasing weight added to the tail. Proteins levels of IL-6, TNF-α and IL-1β in serum were measured by the ELIZA method. The results of this study indicated that resistance training induced skeletal muscle hypertrophy in diabetic samples (P<0.05. Also, Resistance training decrease IL-6 protein levels in serum. Inflammatory cytokines could act as stress factors in diabetes. It seems that this kind of exercise training individually could not change cytokines levels in serum.

The Relationship Between Osteomyelitis Complication and Drug-Resistant Infection Risk in Diabetic Foot Ulcer: A Meta-analysis.

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Chen, Yin; Ding, Hui; Wu, Hua; Chen, Hong-Lin

2017-09-01

In this study, we aimed to investigate the relationship between osteomyelitis complications and drug-resistant infection risk in diabetic foot ulcer. Searches of MEDLINE and ISI databases were performed for the studies. Odds ratios (ORs) for drug-resistant infection incidence were calculated for diabetic foot ulcer patients with or without osteomyelitis complications. Eleven studies (12 cohorts) with 1526 patients were included in this study. Meta-analysis showed that the summary OR was 3.343 (95% CI = 2.355-4.745; Z = 6.75, P analysis by only pooled the adjusted ORs showed that the result was robust (the summary OR = 4.081, 95% CI = 2.471-6.739). Subgroup analysis by drug-resistant type showed that the summary OR was 4.391 (95% CI = 2.287-8.394) for methicillin-resistant infection subgroup, and 2.693 (95% CI = 1.882-3.851) for multidrug-resistant infection subgroup. The meta-regression showed that drug-resistant incidence ( t = -0.90, P = .389) and published year ( t = -0.11, P = .913) were not related with the OR changes. In conclusion, our meta-analysis indicates that osteomyelitis complications are related with drug-resistant infection risk in diabetic foot ulcer. We suggest bone culture-based narrow-spectrum antibiotic therapy for osteomyelitis for prevention drug-resistant infection in diabetic foot ulcer.

Diabetic retinopathy is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

International Nuclear Information System (INIS)

Anan, Futoshi; Takayuki, Masaki; Takahashi, Naohiko; Nakagawa, Mikiko; Eshima, Nobuoki; Saikawa, Tetsunori; Yoshimatsu, Hironobu

2009-01-01

Diabetic retinopathy (DR) and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This preliminary study was therefore designed to test the hypothesis that DR is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. Seventy persons were diagnosed to have type 2 diabetes in the examination from June 2004 to May 2006. The study group consisted of 29 type 2 diabetic patients with DR (age: 58±6 years, mean±standard deviation (s.d.)) and 41 type 2 diabetic patients with no DR (NDR) (n=41, 58±5 years). Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma norepinephrine concentration and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphic findings. DR patients had lower BRS, early and delayed 123 I-MIBG myocardial uptake values and higher percent washout rate (WR) of 123 I-MIBG than the NDR patients. With respect to metabolic findings, DR patients had higher fasting plasma insulin concentration (P 123 I-MIBG (P 123 I-MIBG are independently associated with DR in Japanese patients with type 2 diabetes mellitus. (author)

Pegaspargase Induced Hypertriglyceridemia Resulting in Severe Fatal Pancreatitis

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Neil Vyas

2015-01-01

Full Text Available Pegaspargase is used to treat acute lymphocytic leukemia (ALL. Pegaspargase definitely has its benefits in treating ALL; however we cannot lose sight of one of its very rare but potentially deadly complications, acute pancreatitis. Clinicians should monitor triglycerides while the patient is on treatment with Pegaspargase and suspect acute pancreatitis if the patient develops abdominal pain. If pancreatitis occurs, therapy should be stopped immediately and not reinstituted. For patients with hypertriglyceridemia without pancreatitis, discontinuation of therapy should be considered.

Topicality of the problem of combined course of multi-drug resistant pulmonary tuberculosis with diabetes mellitus

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O. M. Raznatovska

2017-08-01

Full Text Available According to the World Health Organization, today in the world among the infectious chronic diseases one of the leading places and causes of death is multi-drug resistant tuberculosis of the lungs, and chronic non-communicable diseases – diabetes mellitus. The situation is complicated by the fact that the number of patients with combined course of these two heavy separate illnesses that complicate each other increases. It is established that with increasing severity of diabetes mellitus, tuberculosis process in the lungs becomes more complicate and deteriorates, and vice versa, the specific process complicates the course of diabetes mellitus, contributing to the development of diabetic complications. Against this background, the effectiveness of treatment of patients suffering from multi-drug resistant tuberculosis of the lungs in our country remains very low, mainly due to the toxic adverse reactions to antimycobacterial drugs of the reserve line, and in the case of adding diabetes mellitus, it deteriorates even more. The aim of this study was to review the scientific literature to determine the relevance of the study of combined course of multi-drug resistant tuberculosis of the lungs with diabetes mellitus and perspectives of innovative methods of diagnosis of diabetes mellitus. Early diagnosis of pre-diabetes, and autoimmune diseases will allow the use of timely correction techniques that prevents the development of diabetes mellitus, depending on its type, and in the future the development of serious irreversible processes, allow timely applying appropriate methods of correction of the revealed violations. Results. Very little amount of work is dedicated to the problem of combined course of multi-drug resistant tuberculosis of the lungs with diabetes mellitus, regardless of its type, the theme is relevant for today, in Ukraine there are no data regarding its study. This combined course of very difficult in the treatment diseases requires

SERUM MAGNESIUM, LIPID PROFILE AND GLYCATED HAEMOGLOBIN IN DIABETIC RETINOPATHY

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Sunanda Vusikala

2016-07-01

Full Text Available BACKGROUND Diabetic retinopathy is one of the important microvascular complications of diabetes mellitus of long duration. Alterations in trace metals like magnesium and lipid profile was observed in diabetic retinopathy with hyperglycaemic status. AIM The study was taken up to assess the role of magnesium, lipid profile and glycated haemoglobin in diabetic retinopathy. MATERIALS AND METHODS A total of 80 subjects between 40-65 years were included in the study. Group 1 includes 20 age and sex matched healthy controls. Group 2 includes 30 cases of Diabetes mellitus without retinopathy. Group 3 includes 30 cases of Diabetes mellitus with retinopathy. RESULTS Magnesium was found to be significantly low in the diabetic group with retinopathy. Serum cholesterol and triglycerides were significantly elevated in the diabetic group with retinopathy. Fasting and Postprandial plasma glucose and glycated haemoglobin (HbA1c levels confirmed the glycaemic status of each of the groups. CONCLUSIONS Hypomagnesemia, hypercholesterolaemia, hypertriglyceridemia was observed in diabetic retinopathy along with increased levels of glycated haemoglobin in our study.

Serum levels of fractalkine are associated with markers of insulin resistance in gestational diabetes.

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Ebert, T; Hindricks, J; Kralisch, S; Lossner, U; Jessnitzer, B; Richter, J; Blüher, M; Stumvoll, M; Fasshauer, M

2014-08-01

Fractalkine has recently been introduced as an adipokine that improves glucose tolerance. Regulation of fractalkine in gestational diabetes, as well as its association with markers of obesity, glucose and lipid metabolism, inflammation and renal function, has not been elucidated. Circulating fractalkine was quantified by enzyme-linked immunosorbent assay in 74 women with gestational diabetes and 74 healthy, pregnant control subjects matched for age, BMI, and gestational age. Median (interquartile range) levels of fractalkine were not significantly different between the two groups [gestational diabetes: 2.24 (2.16) μg/l; control: 2.45 (1.38) μg/l] (P = 0.461). In multivariate linear regression analysis, fractalkine remained independently associated with homeostasis model assessment of insulin resistance (β = -0.253, P = 0.002) and the proinflammatory adipokine progranulin (β = 0.218, P = 0.007). Circulating fractalkine is not different between women with gestational diabetes and control subjects, but the adipokine is independently associated with markers of insulin resistance and proinflammatory progranulin in pregnancy. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes with diabetic nephropathy depending on the stage of chronic kidney disease

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2012-06-01

Full Text Available Aim: to study the role and relationship of lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes mellitus (DM2 with diabetic nephropathy (DN, depending on the stage of chronic kidney disease (CKD. Materials and Methods: a total of 240 patients with type 2 diabetes in the early stages of DN and CKD were studied. Results: in patients with type 2 diabetes development of DN was associated with an increased level of proinflammatory cytokines and lipid abnormalities (hypertriglyceridemia. We found a negative correlation between the level of triglycerides (TG and glomerular filtration rate (GFR (r = -0,43 and a direct correlation between the level of IL-6 and TG (r = 0,48. Conclusions: increased levels of proinflammatory cytokines and triglycerides increase the risk of development and progression of DN and CKD.

Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

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Sharifah Intan Qhadijah Syed Ikmal

2013-01-01

Full Text Available Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

Serum fetuin-A associates with type 2 diabetes and insulin resistance in Chinese adults.

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Aiyun Song

2011-04-01

Full Text Available Previous studies have demonstrated that fetuin-A is related to insulin resistance among subjects with normal glucose tolerance but not patients with type 2 diabetes. There are limited data available concerning fetuin-A and insulin resistance in Chinese. We aimed to study the association of fetuin-A with insulin resistance among participants with or without type 2 diabetes in a large sample size of adults aged 40 and older.A community-based cross-sectional study was performed among 5,227 Chinese adults. The average age of our study was 61.5±9.9 years. Serum fetuin-A concentrations were not significantly different between male and female (296.9 vs. 292.9 mg/l, p = 0.11. Compared with the lowest quartile, the highest quartile of serum fetuin-A revealed a significant higher proportion of type 2 diabetic patients (34.8% vs. 27.3%, p<0.0001. In the multinomial logit models, the risk of type 2 diabetes was associated with each one quartile increase of serum fetuin-A concentrations when referenced not only to normal glucose tolerance (OR 1.24, 95% CI 1.07-1.43, p = 0.004 but also to impaired glucose regulation (OR 1.25, 95% CI 1.08-1.44, p = 0.003, respectively, after adjustment for age, sex, community, current smoking, and current drinking. The logistic regression analysis showed that fetuin-A were associated with elevated HOMA-IR and fasting serum insulin both among the participants with or without type 2 diabetes in the full adjusted analysis. There was no significant association between elevated serum fetuin-A concentrations and impaired glucose regulation (all p≥0.12.Higher fetuin-A concentrations were associated with type 2 diabetes and insulin resistance in middle aged and elderly Chinese.

Explaining psychological insulin resistance in adults with non-insulin-treated type 2 diabetes

DEFF Research Database (Denmark)

Holmes-Truscott, Elizabeth; Skinner, Timothy Chas; Pouwer, F

2016-01-01

to the model. CONCLUSIONS: Psychological insulin resistance may reflect broader distress about diabetes and concerns about its treatment but not general beliefs about medicines, depression or anxiety. Reducing diabetes distress and current treatment concerns may improve attitudes towards insulin as a potential......AIMS: To investigate the contribution of general and diabetes-specific emotional wellbeing and beliefs about medicines in the prediction of insulin therapy appraisals in adults with non-insulin-treated type 2 diabetes. METHODS: The sample included Diabetes MILES-Australia cross-sectional survey...... diabetes medications (BMQ Specific); negative insulin therapy appraisals (ITAS); depression (PHQ-9); anxiety (GAD-7), and diabetes distress (DDS-17). Factors associated with ITAS Negative scores were examined using hierarchical multiple regressions. RESULTS: Twenty-two percent of the variance in ITAS...

Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

Science.gov (United States)

Miyaguchi, S; Satoh, J; Takahashi, K; Sakata, Y; Nakazawa, T; Miyazaki, J; Toyota, T

2001-01-01

Systemic administration of human lymphotoxin-alpha (hLT-alpha) made NOD mice resistant not only to spontaneous autoimmune type 1 diabetes mellitus but also to cyclophosphamide (CY)-induced diabetes and diabetes transfer by diabetic NOD spleen cells (triple resistance). In this study we analyzed the mechanisms of hLT-alpha-induced resistance, focusing on (1) hLT-alpha-induced resistance in the pancreatic beta cell, (2) CY-resistant suppressor cells, (3) suppression of induction or function of effector cells for beta cell destruction, or (4) others. To examine the first possibility in vitro, a NOD-derived beta cell line (MIN6N) was pretreated with hLT-alpha and then mixed with diabetic NOD spleen cells and MIN6N cell viability was measured. Treatment with hLT-alpha did not protect MIN6N cells but rather enhanced cytotoxicity. Next NOD-scid mice were pretreated with hLT-alpha and then transferred with diabetic NOD spleen. All the recipients developed diabetes. These results excluded the first possibility. The second possibility was also excluded by a cotransfer experiment, in which diabetic NOD spleen cells were cotransferred to NOD-scid mice with nontreated or hLT-alpha-treated nondiabetic NOD spleens. There was no significant difference in diabetes incidence between the two groups. To observe the third possibility, spleen cells of hLT-alpha-treated triple-resistant NOD mice were transferred to NOD-scid mice. Diabetes developed in the recipients, although the onset of diabetes was slightly delayed. Finally, hLT-alpha-treated triple-resistant NOD mice developed diabetes 1 week after daily IL-12 treatment. In summary, hLT-alpha administration made NOD mice resistant to effector cells for beta cell destruction. This resistance was induced in NOD, but not in NOD-scid, mice, indicating that lymphocytes were obligatory for the resistance. However, it was not mediated by transferable suppressor cells. Because effector cells were present in hLT-alpha-treated NOD spleen and

Severe hypertriglyceridemia and colchicine intoxication following suicide attempt

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Lev S

2017-11-01

Full Text Available Shaul Lev,1 David Snyder,2 Carmil Azran,3 Victor Zolotarsky,1 Arik Dahan4 1Intensive Care Unit, Rabin Medical Center, Petah-Tikva, 2Sackler School of Medicine NY/American Program, Tel-Aviv University, Tel Aviv, 3Clinical Pharmacy, Herzliya Medical Center, Herzliya, 4Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract: Colchicine overdose is uncommon but potentially life threatening. Due to its serious adverse systemic effects, overdose must be recognized and treated. We report a case of an 18-year-old female who ingested 18 mg (~0.4 mg/kg of colchicine in a suicide attempt. The patient’s clinical manifestations included abdominal cramps, vomiting, pancytopenia, hypocholesterolemia, and rhabdomyolysis. Two unique manifestations of toxicity in this patient were profound and persistent, severe hypertriglyceridemia and electrolyte imbalance, mainly hypophosphatemia, with no other evident cause except the colchicine intoxication. Following intensive supportive treatment, including ventilator support, N-acetylcysteine, granulocyte colony stimulating factor, electrolyte repletion, and zinc supplementation, the patient made a complete recovery. Colchicine intoxication is a severe, life-threatening situation that should be followed closely in intensive care units. Severe changes in body functions can rapidly develop, as previously described in the literature. To our knowledge, this extremely elevated triglyceride level has never been reported without the administration of propofol, and requires further evaluation. Keywords: colchicine, intoxication, hypophosphatemia, hypertriglyceridemia 

Nutritional correlates and dynamics of diabetes in the Nile rat (Arvicanthis niloticus: a novel model for diet-induced type 2 diabetes and the metabolic syndrome

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Maslova Ekaterina

2010-04-01

, whereas blood glucose and the perirenal fat pad, as well as liver and kidney weight, were positively related to early-onset diabetes. Rats weaned early (4-5 wks and challenged with a high-fat Western-type diet developed diabetes faster, and body fat accumulation was more apparent, whereas food restriction curtailed it. Conclusion The Nile rat fed typical rodent diets develops hyperinsulinemia that precedes hyperglycemia (insulin resistance leading to diet-induced type 2 diabetes associated with hypertriglyceridemia, hypercholesterolemia, and hypertension. Dietary modulation affected growth rate (weight gain and central adiposity to impact disease progression. This rodent model represents a novel system of gene-diet interactions affecting energy utilization that can provide insight into the prevention and treatment of the type 2 diabetes and Metabolic Syndrome.

[Effect of metabolic uncontrolled diabetes mellitus (DM) on the resistance index of renal (IR) Interlobar arteries assessed with pulsed Doppler].

Science.gov (United States)

Muraira-Cárdenas, Luis Cesar; Barrios-Pérez, Martín

2016-01-01

Diabetes mellitus is a chronic degenerative disease characterized by elevated hyperglycemia, triggering a series of processes and culminating in chronic, uncontrolled, cellular and vascular damage in different organs. To assess whether the elevated glycosylated hemoglobin, microalbuminuria, and the time evolution of more than 10 years of diabetes mellitus are associated with elevated resistance index of the interlobar renal arteries assessed with pulsed Doppler in patients with metabolic uncontrolled diabetes mellitus. Transversal-analytical, observational, prospective study that included diabetic patients attending UMAE abdominal ultrasound in 25 of IMSS, from October 15, 2014 to November 15, 2014, which was performed for pulsed Doppler index resistance of vascular interlobar renal arteries and was collected from electronic medical records: age, sex, glycated hemoglobin, and microalbuminuria. The association between metabolic uncontrolled diabetes mellitus was analyzed with the elevation of resistance index by χ(2) test or Fisher, being significant with a value of p diabetes were examined, with an average age of 52.3 ± 14.2 years, 41 were older than 50 years (65.0%), 26 with hypertension (41.2%), 32 with higher levels of glycated hemoglobin 7 (50.8%), 35 with normoalbuminuria (55.6%), 28 with microalbuminuria (44.4%), and 39 with a time evolution of diabetes of more than 10 years (61.9%). We observed a statistically significant difference between microalbuminuria and increased duration of diabetes mellitus with high resistance index. The alterations in renal microvasculature conditioned by the occurrence of microalbuminuria in diabetic nephropathy and the duration of diabetes are strongly associated with higher resistance index.

Association between insulin resistance and risk of complications in children and adolescents with type 1 diabetes.

Science.gov (United States)

Krochik, Andrea G; Botto, Marianela; Bravo, Mónica; Hepner, Mirta; Frontroth, Juan P; Miranda, Miguel; Mazza, Carmen

2015-01-01

It has been hypothesized that insulin resistance may be involved in the development of type 1 diabetes complications and early diagnosis would be important for their prevention. Our aim was to study insulin resistance in our population of children with type 1 diabetes and to identify associated early risk factors for micro- and macrovascular complications. A descriptive, cross-sectional study was conducted including 150 children with type 1 diabetes. Anthropometric, bioelectric impedance, carotid Doppler ultrasonography, electromyography, and conduction velocity studies were performed. Baseline plasma glucose, lipid profile, uric acid, plasma thyrotropin, glycosylated hemoglobin A1C, and microalbuminuria were assessed. More insulin-resistant patients were defined as those having an estimated glucose disposal rate (eGDR) value below the first quartile. Clinically manifest microvascular complications were not found in any of the patients. More insulin-resistant patients had a greater sub scapular fold thickness, a higher incidence of obesity (12% vs. 1.7% p 0.007), higher fructosamine levels (496 vs. 403 p19, and a higher incidence of altered lipid metabolism (70% vs. 39% p 0.0007). In the subgroup of patients with lower eGDR there were more children with lipid disorders, obesity, and worse diabetic control, which, if not corrected, may lead to development of micro- and macrovascular complications. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

[Multiple organ failure complicating a severe acute necrotising pancreatitis secondary of a severe hypertriglyceridemia: a case report].

Science.gov (United States)

Degardin, J; Pons, B; Ardisson, F; Gallego, J-P; Thiery, G

2013-09-01

We report the case of a 42-year-old man admitted for a multi-organ failure with a coma, a hemodynamic instability, a respiratory distress syndrome, an acute renal failure and a thrombocytopenia. The blood samples highlighted a milky serum and allowed to diagnose an acute pancreatitis associated with a major dyslipidemia: hypertriglyceridemia 11,800 mg/dL and hypercholesterolemia 1195 mg/dL. The CT-scans do not reveal any cerebral abnormalities but highlighted pancreatic lesions without biliary obstruction. A multi-organ failure complicating a severe acute pancreatitis secondary of a major hypertriglyceridemia was mentioned. Despite the absence of clear guidelines, a session of plasma exchange was started in emergency. Symptomatic treatment with protective ventilation, vasopressors, continuous heparin and insulin was continued. The clinical and biological course was good in parallel of the normalization of lipid abnormalities. The patient was discharged at day 17 with a lipid-lowering therapy. We discuss the various treatments available for the management of acute pancreatitis complicating a severe hypertriglyceridemia and their actual relevance in the absence of clear recommendations. Copyright © 2013. Published by Elsevier SAS.

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant.

Science.gov (United States)

Indumathi, C K; Lewin, S; Ayyar, Vageesh

2011-07-01

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

OpenAIRE

C K Indumathi; S Lewin; Vageesh Ayyar

2011-01-01

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs - Effects of metformin at isoenergetic feeding in a type 2-like diabetic pig model

NARCIS (Netherlands)

Koopmans, S.J.; Mroz, Z.; Dekker, R.A.; Corbijn, H.; Ackermans, M.; Sauerwein, H.

2006-01-01

Insulin-mediated glucose metabolism was investigated in streptozotocin (STZ)¿treated diabetic pigs to explore if the STZ-diabetic pig can be a suitable model for insulin-resistant, type 2 diabetes mellitus. Pigs (40 kg) were meal-fed with a low-fat (5%) diet. Hyperinsulinemic (1, 2, and 8 mU kg¿1

Antidiabetic and Renoprotective Effects of Cladophora glomerata Kützing Extract in Experimental Type 2 Diabetic Rats: A Potential Nutraceutical Product for Diabetic Nephropathy

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Chutima Srimaroeng

2015-01-01

Full Text Available Cladophora glomerata extract (CGE has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1 and 3 (Oat3, using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model.

Antidiabetic and renoprotective effects of Cladophora glomerata Kützing extract in experimental type 2 diabetic rats: a potential nutraceutical product for diabetic nephropathy.

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Srimaroeng, Chutima; Ontawong, Atcharaporn; Saowakon, Naruwan; Vivithanaporn, Pornpun; Pongchaidecha, Anchalee; Amornlerdpison, Doungporn; Soodvilai, Sunhapas; Chatsudthipong, Varanuj

2015-01-01

Cladophora glomerata extract (CGE) has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM) rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1) and 3 (Oat3), using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model.

Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training.

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Molanouri Shamsi, M; Hassan, Z H; Gharakhanlou, R; Quinn, L S; Azadmanesh, K; Baghersad, L; Isanejad, A; Mahdavi, M

2014-05-01

Skeletal muscle atrophy is associated with type-1 diabetes. Skeletal muscle is the source of pro- and anti-inflammatory cytokines that can mediate muscle hypertrophy and atrophy, while resistance exercise can modulate both muscle mass and muscle cytokine expression. This study determined the effects of a 5-week resistance exercise training regimen on the expression of muscle cytokines in healthy and streptozotocin-induced diabetic rats, with special emphasis on interleukin-15 (IL-15), a muscle-derived cytokine proposed to be involved in muscle hypertrophy or responses to stress. Induction of diabetes reduced muscle weight in both the fast flexor hallucis longus (FHL) and slow soleus muscles, while resistance training preserved FHL muscle weight in diabetic rats. IL-15 protein content was increased by training in both FHL and soleus muscles, as well as serum, in normal and diabetic rats. With regard to proinflammatory cytokines, muscle IL-6 levels were increased in diabetic rats, while training decreased muscle IL-6 levels in diabetic rats; training had no effect on FHL muscle IL-6 levels in healthy rats. Also, tumor necrosis factor-alpha (TNF-α) and IL-1β levels were increased by diabetes, but not changed by training. In conclusion, we found that in diabetic rats, resistance training increased muscle and serum IL-15 levels, decreased muscle IL-6 levels, and preserved FHL muscle mass.

Association of Oxidative Stress and Obesity with Insulin Resistance in Type 2 Diabetes Mellitus.

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Das, P; Biswas, S; Mukherjee, S; Bandyopadhyay, S K

2016-01-01

Oxidative stress occurs due to delicate imbalance between pro-oxidant and anti oxidant forces in our system. It has been found to be associated with many morbidities but its association with obesity and insulin resistance is still controversial. Here in our study we examined 167 patients of recent onset type 2 diabetes mellitus and 60 age sex matched non-diabetic control. Body Mass Index (BMI), abdominal circumference, fasting blood glucose, serum insulin and plasma Malondealdehyde (MDA, marker for oxidative stress) were measured in them. On the basis of BMI, subjects were divided into obese (BMI≥25) and non obese (BMIobese and non-obese sub groups. Insulin resistance score showed positive correlation with BMI, abdominal circumference, and plasma MDA, strength of association being highest with abdominal circumference. Plasma MDA was found to have positive correlation with physical parameters. Study concludes that, obesity mainly central type may predispose to insulin resistance and oxidative stress may be a crucial factor in its pathogenesis. Thus, oxidative stress may be the connecting link between obesity and type 2 diabetes mellitus, two on going global epidemics.

High Prevalence of Obesity, Hypertension, Hyperlipidemia, and Diabetes Mellitus in Japanese Outpatients with Schizophrenia: A Nationwide Survey.

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Sugai, Takuro; Suzuki, Yutaro; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Ozeki, Yuji; Matsuda, Hiroshi; Sugawara, Norio; Yasui-Furukori, Norio; Minami, Yoshitake; Okamoto, Kurefu; Sagae, Toyoaki; Someya, Toshiyuki

2016-01-01

Patients with schizophrenia have significantly shorter life expectancy than the general population, and a problem they commonly face is an unhealthy lifestyle, which can lead to obesity and metabolic syndrome. There is a very clear need to determine the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus which are components of metabolic syndrome in patients with schizophrenia, but there has been a paucity of large-scale studies examining this situation in Japan. The aim of our study was to address this need. We conducted a large-scale investigation of the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus using a questionnaire in 520 outpatient facilities and 247 inpatient facilities of the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7,655 outpatients and 15,461 inpatients with schizophrenia. The outpatients had significantly higher prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus than the inpatients. The prevalence of hypo-HDL cholesterolemia was higher in inpatients than outpatients. Age-specific analysis showed the prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus among outpatients to be 2- to 3-fold higher than among inpatients. In individuals aged ≥60 years, the prevalence of obesity and DM among outpatients was about 3-fold higher than among inpatients. Japanese outpatients with schizophrenia were more likely to have physical risk such as obesity, hypertension, hyperlipidemia, and diabetes mellitus than inpatients. The physical risk to patients with schizophrenia may be affected by environmental parameters, such as type of care. The physical risk to Japanese patients with schizophrenia demands greater attention.

The relationship between insulin resistance and the change of cytosol free calcium concentration in gestational diabetes mellitus

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Li Pu; Zheng Lei; Cen Rongguang; Song Yangxiu

2004-01-01

To investigate the relationship between the insulin resistance (IR) and abnormalities of cellular calcium metabolism in gestational diabetes mellitus, the changes in the [Ca 2+ ]i and the insulin receptor tyrosine kinase activity in circulating erythrocytes of 32 cases gestational diabetes were compared with those of 47 normal pregnant and 43 non pregnant women. The level of [Ca 2+ ]i in circulating erythrocyte in gestational diabetes mellitus women was significantly higher than that in the pregnant and non pregnant women (P 2+ ]i in circulating erythrocytes in gestational diabetes mellitus was positively correlated with fasting blood glucose and fasting insulin, negatively with the insulin receptor tyrosine kisase activity (P 2+ ]i level during the gastational period might be one of the possible factor in the insulin resistance of gestaional diabetes mellitus. (authors)

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

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C K Indumathi

2011-01-01

Full Text Available Berardinelli Seip congenital lipodystrophy (BSCL is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

Heritability, parental transmission and environment correlation of pediatric-onset type 2 diabetes mellitus and metabolic syndrome-related traits.

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Miranda-Lora, América L; Vilchis-Gil, Jenny; Molina-Díaz, Mario; Flores-Huerta, Samuel; Klünder-Klünder, Miguel

2017-04-01

To estimate the heritability, parental transmission and environmental contributions to the phenotypic variation in type 2 diabetes mellitus and metabolic syndrome-related traits in families of Mexican children and adolescents. We performed a cross-sectional study of 184 tri-generational pedigrees with a total of 1160 individuals (99 families with a type 2 diabetes mellitus proband before age 19). The family history of type 2 diabetes mellitus in three generations was obtained by interview. Demographic, anthropometric, biochemical and lifestyle information was corroborated in parents and offspring. We obtained correlations for metabolic traits between relative pairs, and variance component methods were used to determine the heritability and environmental components. The heritability of early-onset of type 2 diabetes mellitus was 0.50 (p1.0e-7). The heritability was greater than 0.5 for hypertension, hypoalphalipoproteinemia, hypercholesterolemia, body mass index, waist circumference, blood pressure, 2-h insulin, and cholesterol (p1). In contrast, we observed a high environmental correlation (>0.50) for blood pressure, HbA1c and HDL-cholesterol after multivariate adjustment (ptype 2 diabetes mellitus and insulin resistance, were significantly correlated only through the mother and others, such as hypertriglyceridemia, were significantly correlated only through the father. This study demonstrates that type 2 diabetes mellitus and metabolic syndrome-related traits are highly heritable among Mexican children and adolescents. Furthermore, several cardiometabolic factors have strong heritability and/or high environmental contributions that highlight the complex architecture of these alterations. Copyright © 2017 Elsevier B.V. All rights reserved.

Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream.

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Eric J Brunner

2008-08-01

Full Text Available Raised C-reactive protein (CRP is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study. Homeostasis model assessment-insulin resistance (HOMA-IR and hemoglobin A1c (HbA1c were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92. The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11. Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88. Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls using three SNPs in tight linkage disequilibrium with our

Resistance Training in Type 2 Diabetic Patients Improves Uric Acid Levels

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R. Sousa Moisés S.S.

2014-12-01

Full Text Available Resistance training (RT can provide several benefits for individuals with Type 2 diabetes. The aim of this study was to investigate the effects of resistance training on the strength levels and uric acid (UA concentration in individuals with Type 2 diabetes. The study included 68 patients (57.7±9.0 years that participated in an organized program of RT for 12 weeks. The volunteers were divided into two groups: an experimental group (EG; n=34 that performed the resistance training program consisting of seven exercises executed in an alternating order based on segments; and a control group (CG; n=34 that maintained their normal daily life activities. Muscle strength and uric acid were measured both pre- and post-experiment. The results showed a significant increase in strength of the subjects in the EG for all exercises included in the study (p<0.001. Comparing the strength levels of the post-test, intergroup differences were found in supine sitting (p<0.001, leg extension (p<0.001, shoulder press (p<0.001, leg curl (p=0.001, seated row (p<0.001, leg press (p=0.001 and high pulley (p<0.001. The measured uric acid was significantly increased in both experimental and control groups (p<0.001 and p=0.001, respectively. The intergroup comparison showed a significant increase for the EG (p=0.024. We conclude that the training program was effective for strength gains despite an increase in uric acid in Type 2 diabetics.

Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice

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Liu, Zhi-Qin; Liu, Ting; Chen, Chuan; Li, Ming-Yan; Wang, Zi-Yu; Chen, Ruo-song; Wei, Gui-xiang; Wang, Xiao-yi; Luo, Du-Qiang

2015-01-01

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathways, and its increased activity and expression are implicated in the pathogenesis of insulin resistance. Therefore, the inhibition of PTP1B is anticipated to become a potential therapeutic strategy to treat T2DM. Fumosorinone (FU), a new natural product isolated from insect fungi Isaria fumosorosea, was found to inhibit PTP1B activity in our previous study. Herein, the effects of FU on insulin resistance and mechanism in vitro and in vivo were investigated. FU increased the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, and also reduced blood glucose and lipid levels of type 2 diabetic KKAy mice. FU decreased the expression of PTP1B both in insulin-resistant HepG2 cells and in liver tissues of diabetic KKAy mice. Furthermore, FU increased the phosphorylation of IRβ, IRS-2, Akt, GSK3β and Erk1/2 in insulin-resistant HepG2 cells, as well as the phosphorylation of IRβ, IRS-2, Akt in liver tissues of diabetic KKAy mice. These results showed that FU increased glucose uptake and improved insulin resistance by down-regulating the expression of PTP1B and activating the insulin signaling pathway, suggesting that it may possess antidiabetic properties. - Highlights: • Fumosorinone is a new PTP1B inhibitor isolated from insect pathogenic fungi. • Fumosorinone attenuated the insulin resistance both in vitro and in vivo. • Fumosorinone decreased the expression of PTP1B both in vitro and in vivo. • Fumosorinone activated the insulin signaling pathway both in vitro and in vivo

Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice

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Liu, Zhi-Qin [College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002 (China); College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality control of Hebei province, Hebei University, Baoding 071002 (China); Liu, Ting; Chen, Chuan [College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002 (China); Li, Ming-Yan; Wang, Zi-Yu; Chen, Ruo-song; Wei, Gui-xiang; Wang, Xiao-yi [College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality control of Hebei province, Hebei University, Baoding 071002 (China); Luo, Du-Qiang, E-mail: duqiangluo999@126.com [College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002 (China)

2015-05-15

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathways, and its increased activity and expression are implicated in the pathogenesis of insulin resistance. Therefore, the inhibition of PTP1B is anticipated to become a potential therapeutic strategy to treat T2DM. Fumosorinone (FU), a new natural product isolated from insect fungi Isaria fumosorosea, was found to inhibit PTP1B activity in our previous study. Herein, the effects of FU on insulin resistance and mechanism in vitro and in vivo were investigated. FU increased the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, and also reduced blood glucose and lipid levels of type 2 diabetic KKAy mice. FU decreased the expression of PTP1B both in insulin-resistant HepG2 cells and in liver tissues of diabetic KKAy mice. Furthermore, FU increased the phosphorylation of IRβ, IRS-2, Akt, GSK3β and Erk1/2 in insulin-resistant HepG2 cells, as well as the phosphorylation of IRβ, IRS-2, Akt in liver tissues of diabetic KKAy mice. These results showed that FU increased glucose uptake and improved insulin resistance by down-regulating the expression of PTP1B and activating the insulin signaling pathway, suggesting that it may possess antidiabetic properties. - Highlights: • Fumosorinone is a new PTP1B inhibitor isolated from insect pathogenic fungi. • Fumosorinone attenuated the insulin resistance both in vitro and in vivo. • Fumosorinone decreased the expression of PTP1B both in vitro and in vivo. • Fumosorinone activated the insulin signaling pathway both in vitro and in vivo.

Achieving ADA/ISPAD clinical guideline goals is associated with higher insulin sensitivity and cardiopulmonary fitness in adolescents with type 1 diabetes: Results from RESistance to InSulin in Type 1 ANd Type 2 diabetes (RESISTANT) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with Type 1 Diabetes (EMERALD) Studies.

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Bjornstad, Petter; Cree-Green, Melanie; Baumgartner, Amy; Coe, Gregory; Reyes, Yesenia Garcia; Schäfer, Michal; Pyle, Laura; Regensteiner, Judith G; Reusch, Jane Eb; Nadeau, Kristen J

2018-05-01

Most youth with type 1 diabetes do not meet the American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body mass index (BMI). We hypothesized that ISPAD/ADA goal achievement would be associated with better insulin sensitivity (IS) and cardiopulmonary fitness. IS was quantified as glucose infusion rate (GIR) from a hyperinsulinemic-euglycemic clamp in youth with type 1 diabetes from the RESistance to InSulin in Type 1 ANd Type 2 diabetes (RESISTANT) (n = 86) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with Type 1 Diabetes (EMERALD) (n = 41) cohorts (n = 127; age 15.7 ± 2.2 years, 52% girls). Cardiopulmonary fitness was measured as peak oxygen consumption (VO 2 peak/kg) during upright (RESISTANT) or supine (EMERALD) cycle ergometry and were stratified by cycle type. Goal achievement was defined as HbA1c 35 mg/dL, triglycerides ADA/ISPAD goal achievement was associated with greater IS and cardiopulmonary fitness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The correlation of adiponectin, IL-6 with insulin resistance and macrovascular lesion in type 2 diabetes

International Nuclear Information System (INIS)

Shi Bimin; Cheng Xingbo

2006-01-01

Objective: To investigate the serum level changes of adiponectin and IL-6 and their relation with macrovascular complications in patients with type 2 diabetes before and after thiazolidinediones intervention. Methods: Serum adiponectin and IL-6 level were examined using ELISA method in 16 patients with obese type 2 diabetes, 24 patients with diabetes with normal body weight, and 14 controls. Their body mass index (BMI) and HOMA-IR were calculated and the internal membrane thickness (IMT) of carotid artery was also observed. These indexes were reexamined after thiazolidinediones (Avandia) intervention and correlation analysis was performed. Results: A decreased serum concentration of adiponectin and an elevated level of IL-6 and HOMA-IR were found in diabetes group especially in those with obesity (P<0.01). Serum adiponectin was negatively correlated with HOMA-IR, BMI, IL-6 and IMT while IL-6 was positively correlated with the above-mentioned indexes. After treatment with thiazolidinediones, the insulin resistance state and adponectin and IL-6 were significantly improved especially in those with obesity (P<0.05, P<0.01). Conclusion: Adiponectin is closed correlated with obesity (P<0.05, P<0.01). Conclusion: Adiponectin is closed correlated with obesity, insulin resistance and macrovascular lesions. IL-6 may be involved in the mechanism of insulin resistance in type 2 diabetes patients especially in the obese diabetes group. In addition to enhance the sensitivity of insulin, thiazolidinediones may play a potential role in anti-inflammation, anti-atherosclerosis and immuno-regulation. (authors)

Type V hypertriglyceridemia in children, a therapeutic challenge in pediatrics: A case report and a review of the literature.

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Mărginean, Cristina Oana; Meliţ, Lorena Elena; Dobreanu, Minodora; Mărginean, Maria Oana

2017-12-01

Hypertriglyceridemia is defined as a level of triglycerides above 150 mg/dL. The complex causes and classification of hypertriglyceridemia lead to difficulties in the diagnosis and management of this condition. We present the case of a 15 years and 6 months old female teenager, admitted in our clinic for the following complaints: severe abdominal pain predominantly in the lateral left quadrant, nausea, vomiting, and the lack of stools for 2 days. The clinical exam showed: impaired general status, painful abdomen at superficial and deep palpation in the left and upper abdominal quadrants, the absence of stools for 2 days. The laboratory parameters revealed leukocytosis with neutrophilia, thrombocytopenia, high level of serum amylase and triglycerides, and increased inflammatory biomarkers. The imagistic investigations showed ascites and paralytic ileus. The management was burdened by the side-effects of hypolipidemic drugs impairing the liver function and leading to rhabdomyolysis, but eventually the patient's outcome was good. Type V hyperlipoproteinemia is a rare condition accounting for approximately 5% of the cases. The risk for acute pancreatitis is well-known to be associated with hypertriglyceridemia, even though in rare cases. The prognosis of hypertriglyceridemia is pediatrics is burdened not only by the long-term risk factors associated to the diseases itself, but also by the negative effects of long-term hypolipidemic treatment. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes

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Aldo Ferreira-Hermosillo

2015-01-01

Full Text Available Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n=61, 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance.

Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance

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Wu, Mengrui; Kim, Teayoun; Jariwala, Ravi H.; Garvey, W. John; Luo, Nanlan; Kang, Minsung; Ma, Elizabeth; Tian, Ling; Steverson, Dennis; Yang, Qinglin; Fu, Yuchang

2016-01-01

In the current study, we used muscle-specific TRIB3 overexpressing (MOE) and knockout (MKO) mice to determine whether TRIB3 mediates glucose-induced insulin resistance in diabetes and whether alterations in TRIB3 expression as a function of nutrient availability have a regulatory role in metabolism. In streptozotocin diabetic mice, TRIB3 MOE exacerbated, whereas MKO prevented, glucose-induced insulin resistance and impaired glucose oxidation and defects in insulin signal transduction compared with wild-type (WT) mice, indicating that glucose-induced insulin resistance was dependent on TRIB3. In response to a high-fat diet, TRIB3 MOE mice exhibited greater weight gain and worse insulin resistance in vivo compared with WT mice, coupled with decreased AKT phosphorylation, increased inflammation and oxidative stress, and upregulation of lipid metabolic genes coupled with downregulation of glucose metabolic genes in skeletal muscle. These effects were prevented in the TRIB3 MKO mice relative to WT mice. In conclusion, TRIB3 has a pathophysiological role in diabetes and a physiological role in metabolism. Glucose-induced insulin resistance and insulin resistance due to diet-induced obesity both depend on muscle TRIB3. Under physiological conditions, muscle TRIB3 also influences energy expenditure and substrate metabolism, indicating that the decrease and increase in muscle TRIB3 under fasting and nutrient excess, respectively, are critical for metabolic homeostasis. PMID:27207527

Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low-Density Lipoprotein Cholesterol Levels.

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Kitagami, Masayuki; Yasuda, Ryuta; Toma, Naoki; Shiba, Masato; Nampei, Mai; Yamamoto, Yoko; Nakatsuka, Yoshinari; Sakaida, Hiroshi; Suzuki, Hidenori

2017-08-01

Dyslipidemia is a well-known risk factor for carotid stenosis progression, but triglycerides have attracted little attention. The aim of this study was to assess if serum triglycerides affect progression of carotid stenosis in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. This is a retrospective study in a single hospital consisting of 71 Japanese patients with internal carotid artery stenosis greater than or equal to 50% and normal serum LDL-C levels who underwent angiographic examination with or without the resultant carotid artery stenting or endarterectomy from 2007 to 2011, and were subsequently followed up for 4 years. Clinical factors including fasting serum triglyceride values were compared between the progression (≥10% increase in degree of carotid stenosis on ultrasonography) and the nonprogression groups. During 4 years, 15 patients (21.1%) had carotid stenosis progression on either side. Cox regression analysis demonstrated that symptomatic cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR, 6.228; P = .011) were associated with subsequent progression of carotid stenosis. Kaplan-Meier plots demonstrated that the progression-free survival rate was significantly higher in patients without hypertriglyceridemia and intracranial arteriosclerotic stenosis at baseline. Among patients with moderate to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an important risk factor for progression of carotid stenosis irrespective of surgical treatments. It would be worthwhile to test if triglyceride-lowering medications suppress carotid stenosis progression. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene.

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Soto, Angela Ganan; McIntyre, Adam; Agrawal, Sungeeta; Bialo, Shara R; Hegele, Robert A; Boney, Charlotte M

2015-09-04

Lipoprotein Lipase (LPL) deficiency is a rare autosomal recessive disorder with a heterogeneous clinical presentation. Several mutations in the LPL gene have been identified to cause decreased activity of the enzyme. An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. Genomic DNA analysis identified lipoprotein lipase deficiency due to compound heterozygosity including a novel p.Q240H mutation in exon 5 of the lipoprotein lipase (LPL) gene. His severe hypertriglyceridemia, including xanthomas, resolved with dietary long-chain fat restriction. We describe a novel mutation of the LPL gene causing severe hypertriglyceridemia and report the response to treatment. A review of the current literature regarding LPL deficiency syndrome reveals a few potential new therapies under investigation.

Genetic disassociation of autoimmunity and resistance to costimulation blockade-induced transplantation tolerance in nonobese diabetic mice.

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Pearson, Todd; Markees, Thomas G; Serreze, David V; Pierce, Melissa A; Marron, Michele P; Wicker, Linda S; Peterson, Laurence B; Shultz, Leonard D; Mordes, John P; Rossini, Aldo A; Greiner, Dale L

2003-07-01

Curing type 1 diabetes by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. Most islet allotransplant tolerance induction protocols have been tested in nonobese diabetic (NOD) mice, and most have failed. Failure has been attributed to the underlying autoimmunity, assuming that autoimmunity and resistance to transplantation tolerance have a common basis. Out of concern that NOD biology could be misleading in this regard, we tested the hypothesis that autoimmunity and resistance to transplantation tolerance in NOD mice are distinct phenotypes. Unexpectedly, we observed that (NOD x C57BL/6)F(1) mice, which have no diabetes, nonetheless resist prolongation of skin allografts by costimulation blockade. Further analyses revealed that the F(1) mice shared the dendritic cell maturation defects and abnormal CD4(+) T cell responses of the NOD but had lost its defects in macrophage maturation and NK cell activity. We conclude that resistance to allograft tolerance induction in the NOD mouse is not a direct consequence of overt autoimmunity and that autoimmunity and resistance to costimulation blockade-induced transplantation tolerance phenotypes in NOD mice can be dissociated genetically. The outcomes of tolerance induction protocols tested in NOD mice may not accurately predict outcomes in human subjects.

Cholera toxin subunit B peptide fusion proteins reveal impaired oral tolerance induction in diabetes-prone but not in diabetes-resistant mice.

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Presa, Maximiliano; Ortiz, Angela Zarama; Garabatos, Nahir; Izquierdo, Cristina; Rivas, Elisa I; Teyton, Luc; Mora, Conchi; Serreze, David; Stratmann, Thomas

2013-11-01

The cholera toxin B subunit (CTB) has been used as adjuvant to improve oral vaccine delivery in type 1 diabetes. The effect of CTB/peptide formulations on Ag-specific CD4(+) T cells has remained largely unexplored. Here, using tetramer analysis, we investigated how oral delivery of CTB fused to two CD4(+) T-cell epitopes, the BDC-2.5 T-cell 2.5 mi mimotope and glutamic acid decarboxylase (GAD) 286-300, affected diabetogenic CD4(+) T cells in nonobese diabetic (NOD) mice. When administered i.p., CTB-2.5 mi activated 2.5 mi(+) T cells and following intragastric delivery generated Ag-specific Foxp3(+) Treg and Th2 cells. While 2.5 mi(+) and GAD-specific T cells were tolerized in diabetes-resistant NODxB6.Foxp3(EGFP) F1 and nonobese resistant (NOR) mice, this did not occur in NOD mice. This indicated that NOD mice had a recessive genetic resistance to induce oral tolerance to both CTB-fused epitopes. In contrast to NODxB6.Foxp3(EGFP) F1 mice, oral treatment in NOD mice lead to strong 2.5 mi(+) T-cell activation and the sequestration of these cells to the effector-memory pool. Oral treatment of NOD mice with CTB-2.5 mi failed to prevent diabetes. These findings underline the importance of investigating the effect of oral vaccine formulations on diabetogenic T cells as in selected cases they may have counterproductive consequences in human patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lack of plasma albumin impairs intravascular lipolysis and explains the associated free fatty acids deficiency and hypertriglyceridemia

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Oliveira Helena CF

2010-12-01

Full Text Available Abstract Background Abnormalities in lipid metabolism and transport are hallmarks in analbuminemic Nagase rats (NAR and humans. Triglyceridemia is nearly 3- to 5-fold higher in female NAR than in control Sprague-Dawley rats (SDR. Also, NAR present with a severe plasma free fatty acid (FFA deficit. There are conflicting results regarding the mechanisms underlying NAR hypertriglyceridemia. Objective We aimed at investigating whether liver lipogenesis and triglyceride secretion rates into the plasma contribute to the hypertriglyceridemia in NAR. We also studied whether heparin or albumin administration would release the hypothesized lipolysis inhibition in NAR. Methods The incorporation of tritiated water into lipids and the linear accumulation rate of plasma triglycerides after Triton WR1339 injection were the measures of liver lipogenesis and triglyceride secretion rates. Results Lipogenesis (596 ± 40 vs. 929 ± 124 μmol 3H2O/g/h and triglyceride (4.25 ± 1.00 vs. 7.04 ± 1.68 mg/dL/min secretion rates were slower (P ≤ 0.05 in fasted NAR than in control SDR. The injection of either heparin or albumin elicited an increase in NAR plasma FFA levels over time. FFA levels reached control levels 90 min after the albumin administration, increasing from 0.36 ± 0.05 to 1.34 ± 0.16 mEq/L (P ≤ 0.05. These results indicate that the lack of plasma albumin inhibits intravascular lipolysis and causes the FFA deficit observed in NAR. Conclusion NAR hepatic triglyceride synthesis and output do not contribute to NAR hypertriglyceridemia. We propose that the lack of albumin diminishes intravascular lipolysis which reduces the plasma triglyceride removal rate and explain both NAR hypertriglyceridemia and FFA deficiency.

Effect of Andrographis paniculata Extract on Triglyceride Levels of the Patients with Hypertriglyceridemia: A Randomized Controlled Trial.

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Phunikhom, Kutcharin; Khampitak, Kovit; Aromdee, Chantana; Arkaravichien, Tarinee; Sattayasai, Jintana

2015-07-01

Hypertriglyceridemia is one of the risk factors for cardiovascular disease, and reduction oftriglyceride (TG) level is recommended in clinical practice guidelines for the treatment. Recently, andrographolide, a main active compound of Andrographispaniculata has been shown to possess hypolipidemic effects in animals. To investigate the TG-lowering effects of A. paniculata extract (APE) in patients with hypertriglyceridemia (TG ≥ 150 mg/dL) using gemfibrozil treatment as the reference. A randomized controlled clinical trial was carried out in sixty subjects with hypertriglyceridemia. They were divided into three groups and treated with low dose of APE (APE-L, andrographolide 71.64-72.36 mg/day), high dose of APE (APE-H, andrographolide 119.64-120.36 mg/day), and gemfibrozil 300 mg/day. The treatments were conducted for 8 weeks. Guidance on lifestyle modifications was provided. The primary endpoint was the mean difference ± SD (95% CI) in TG levels (baseline from the end of treatment), which were -3 ± 125.6 (-59.1, 58.5), 41.6 ± 86.3 (1.2, 82), and 57.1 ± 94.9 (12.7, 101.6) in the APE-L, APE-H, and gemfibrozil groups, respectively. APE-H 120 mg/day and gemfibrozil 300 mg/day caused a significant reduction of TG level (P = 0.0442 and 0.0145, respectively) when compared to the baseline. There was no notable difference in the safety or tolerability among the treatment groups. In patients with modest hypertriglyceridemia with lifestyle intervention, APE-H reduced the TG level comparable to the effect of gemfibrozil 300 mg/day. APE treatment was as tolerable as gemfibrozil treatment. Hence, Andrographis paniculata might be used as an alternative medicine in treating hypertriglyceridemic patients.

Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway

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Zhou, Jun, E-mail: hustzhj@hust.edu.cn; Xu, Gang; Bai, Zhaoshuai; Li, Kaicheng; Yan, Junyan; Li, Fen; Ma, Shuai; Xu, Huibi; Huang, Kaixun, E-mail: hxxzrf@hust.edu.cn

2015-12-15

Recent evidence suggests a potential pro-diabetic effect of selenite treatment in type 2 diabetics; however, the underlying mechanisms remain elusive. Here we investigated the effects and the underlying mechanisms of selenite treatment in a nongenetic mouse model of type 2 diabetes. High-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice were orally gavaged with selenite at 0.5 or 2.0 mg/kg body weight/day or vehicle for 4 weeks. High-dose selenite treatment significantly elevated fasting plasma insulin levels and insulin resistance index, in parallel with impaired glucose tolerance, insulin tolerance and pyruvate tolerance. High-dose selenite treatment also attenuated hepatic IRS1/Akt/FoxO1 signaling and pyruvate kinase gene expressions, but elevated the gene expressions of phosphoenolpyruvate carboxyl kinase (PEPCK), glucose 6-phosphatase (G6Pase), peroxisomal proliferator-activated receptor-γ coactivator 1α (PGC-1α) and selenoprotein P (SelP) in the liver. Furthermore, high-dose selenite treatment caused significant increases in MDA contents, protein carbonyl contents, and a decrease in GSH/GSSG ratio in the liver, concurrent with enhanced ASK1/MKK4/JNK signaling. Taken together, these findings suggest that high-dose selenite treatment exacerbates hepatic insulin resistance in mouse model of type 2 diabetes, at least in part through oxidative stress-mediated JNK pathway, providing new mechanistic insights into the pro-diabetic effect of selenite in type 2 diabetes. - Highlights: • Selenite exacerbates hepatic insulin resistance in HFD/STZ-induced diabetic mice. • Selenite elevates hepatic gluconeogenesis and reduces glycolysis in diabetic mice. • Selenite exacerbates hepatic oxidative stress and triggers JNK signaling pathway. • Selenite elevates hepatic selenoprotein P expression in diabetic mice.

Selenite exacerbates hepatic insulin resistance in mouse model of type 2 diabetes through oxidative stress-mediated JNK pathway

International Nuclear Information System (INIS)

Zhou, Jun; Xu, Gang; Bai, Zhaoshuai; Li, Kaicheng; Yan, Junyan; Li, Fen; Ma, Shuai; Xu, Huibi; Huang, Kaixun

2015-01-01

Recent evidence suggests a potential pro-diabetic effect of selenite treatment in type 2 diabetics; however, the underlying mechanisms remain elusive. Here we investigated the effects and the underlying mechanisms of selenite treatment in a nongenetic mouse model of type 2 diabetes. High-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice were orally gavaged with selenite at 0.5 or 2.0 mg/kg body weight/day or vehicle for 4 weeks. High-dose selenite treatment significantly elevated fasting plasma insulin levels and insulin resistance index, in parallel with impaired glucose tolerance, insulin tolerance and pyruvate tolerance. High-dose selenite treatment also attenuated hepatic IRS1/Akt/FoxO1 signaling and pyruvate kinase gene expressions, but elevated the gene expressions of phosphoenolpyruvate carboxyl kinase (PEPCK), glucose 6-phosphatase (G6Pase), peroxisomal proliferator-activated receptor-γ coactivator 1α (PGC-1α) and selenoprotein P (SelP) in the liver. Furthermore, high-dose selenite treatment caused significant increases in MDA contents, protein carbonyl contents, and a decrease in GSH/GSSG ratio in the liver, concurrent with enhanced ASK1/MKK4/JNK signaling. Taken together, these findings suggest that high-dose selenite treatment exacerbates hepatic insulin resistance in mouse model of type 2 diabetes, at least in part through oxidative stress-mediated JNK pathway, providing new mechanistic insights into the pro-diabetic effect of selenite in type 2 diabetes. - Highlights: • Selenite exacerbates hepatic insulin resistance in HFD/STZ-induced diabetic mice. • Selenite elevates hepatic gluconeogenesis and reduces glycolysis in diabetic mice. • Selenite exacerbates hepatic oxidative stress and triggers JNK signaling pathway. • Selenite elevates hepatic selenoprotein P expression in diabetic mice.

Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension

DEFF Research Database (Denmark)

Stolzenburg Oxlund, Christina; Cangemi, Claudia; Henriksen, J E

2015-01-01

Diabetic patients with hypertension are at particularly high risk of vascular damage and consequently cardiovascular and renal disease. Fibulin-1, an extracellular matrix glycoprotein, is increased in arterial tissue and plasma from individuals with type 2 diabetes. This study aimed to evaluate...... whether antihypertensive treatment with spironolactone changes plasma fibulin-1 levels. In a multicenter, double-blind, randomized, placebo-controlled study, 119 patients with type 2 diabetes and resistant hypertension were included. A dose of spironolactone 25 mg or matching placebo was added to previous....... Treatment with low-dose spironolactone reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. This supports the hypothesis that the antihypertensive effect of the mineralocorticoid receptor blocker in part may be due to regression of vascular remodeling....

Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women

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Iskra Bitoska

2016-02-01

CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause.

Decreased distensibility of resistance vessels of the skin in type 1 (insulin-dependent) diabetic patients with microangiopathy

DEFF Research Database (Denmark)

Kastrup, J; Nørgaard, T; Parving, H H

1987-01-01

The distensibility of the resistance vessels of the skin at the dorsum of the foot was determined in 11 long-term type 1 (insulin-dependent) diabetic patients with nephropathy and retinopathy, nine short-term type 1 diabetic patients without clinical microangiopathy and in nine healthy non-diabetic...... during head-up tilt was only 24% in diabetic subjects with and 48% in diabetic patients without clinical microangiopathy, compared with 79% in normal non-diabetic subjects (P less than 0.0005 and P less than 0.05, respectively). An inverse correlation between microvascular distensibility and degree...

Obesity, insulin resistance, and type 1 diabetes mellitus.

Science.gov (United States)

Polsky, Sarit; Ellis, Samuel L

2015-08-01

To summarize recent studies about obesity, insulin resistance, and type 1 diabetes mellitus (T1DM). Overweight and obesity continue to be prevalent among individuals with T1DM. Obesity rates appear to have reached a plateau among children with T1DM in some parts of the world. The risk for development of T1DM is increased by obesity and may occur at an earlier age among obese individuals with a predisposition. Obesity increases the risk for comorbidities among individuals with T1DM, especially metabolic syndrome, and microvascular and macrovascular diseases. Metformin, glucagon-like peptide-1 agonist therapy, sodium glucose cotransporter-2 inhibitor therapy, and bariatric surgery may be beneficial therapies for glucose control, comorbidity management, and obesity among adults with T1DM. Insulin resistance may be improved among obese individuals with T1DM by biguanides (metformin) and glucagon-like peptide-1 agonists (exenatide). We review the last 18 months of literature on obesity, insulin resistance, and T1DM to highlight new epidemiologic results and treatments.

The -1131T>C polymorphism in the apolipoprotein A5 gene is related to hypertriglyceridemia in Taiwanese aborigines.

Science.gov (United States)

Huang, Meng-Chuan; Wang, Tsu-Nai; Wang, Huan-Sen; Sung, Yi-Ching; Ko, Ying-Chin; Chiang, Hung-Che

2008-04-01

The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T>C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T>C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride > or = 150 mg/dL was defined as the hypertriglyceridemia group and triglyceride Japanese and Han Chinese, but was higher than that in Caucasians. In a multiple logistic model adjusted for possible confounders, C allele-containing variants were independently associated with greater risks (CT genotype: OR = 3.28, 95% CI = 1.43-7.56; CC genotype: OR = 5.86, 95% CI = 2.15-15.99) of hypertriglyceridemia than the TT genotype (p fashion (for trend, p C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.

Insulin resistance and cognitive performance in type 2 diabetes : The Maastricht study

NARCIS (Netherlands)

Geijselaers, Stefan L C; Sep, Simone J S; Schram, Miranda T; van Boxtel, Martin P J; Henry, Ronald M A; Verhey, Frans R J; Kroon, Abraham A; Schaper, Nicolaas C; Dagnelie, Pieter C; van der Kallen, Carla J H; Stehouwer, Coen D A; Biessels, Geert Jan

AIMS: Type 2 diabetes, hyperinsulinemia, and insulin resistance are associated with cognitive impairment. Experimental studies indicate that insulin signaling in the brain is related to cognitive performance. Here we evaluated whether insulin-related variables contribute to the variance in cognitive

Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes

NARCIS (Netherlands)

H. Yaghootkar (Hanieh); C. Lamina (Claudia); R.A. Scott (Robert); Z. Dastani (Zari); M.-F. Hivert (Marie-France); L.L. Warren (Liling); A. Stancáková (Alena); S.G. Buxbaum (Sarah); L.-P. Lyytikäinen (Leo-Pekka); P. Henneman (Peter); Y. Wu (Ying); C.Y.Y. Cheung (Chloe); J.S. Pankow (James); A.U. Jackson (Anne); S. Gustafsson (Stefan); J.H. Zhao (Jing Hua); C. Ballantyne (Christie); W. Xie (Weijia); R.N. Bergman (Richard); M. Boehnke (Michael); F. El Bouazzaoui (Fatiha); F.S. Collins (Francis); S.H. Dunn (Sandra); J. Dupuis (Josée); N.G. Forouhi (Nita); C.J. Gillson (Christopher); A.T. Hattersley (Andrew); J. Hong (Jaeyoung); M. Kähönen (Mika); J. Kuusisto (Johanna); L. Kedenko (Lyudmyla); F. Kronenberg (Florian); A. Doria (Andrea); T.L. Assimes (Themistocles); E. Ferrannini (Ele); T. Hansen (Torben); K. Hao (Ke); H. Häring (Hans); J.W. Knowles (Joshua); C.M. Lindgren (Cecilia); J.J. Nolan (John); J. Paananen (Jussi); O. Pedersen (Oluf); T. Quertermous (Thomas); U. Smith (Ulf); T. Lehtimäki (Terho); C.-T. Liu (Ching-Ti); R.J.F. Loos (Ruth); M.I. McCarthy (Mark); A.D. Morris (Andrew); R.S. Vasan (Ramachandran Srini); T.D. Spector (Timothy); T.M. Teslovich (Tanya); J. Tuomilehto (Jaakko); J.A.P. Willems van Dijk (Ko); J. Viikari (Jorma); N. Zhu (Na); C. Langenberg (Claudia); E. Ingelsson (Erik); R.K. Semple (Robert); A. Sinaiko (Alan); C.N.A. Palmer (Colin); M. Walker (Mark); K.S.L. Lam (Karen); B. Paulweber (Bernhard); K.L. Mohlke (Karen); C.M. van Duijn (Cornelia); O. Raitakari (Olli); A. Bidulescu (Aurelian); N.J. Wareham (Nick); M. Laakso (Markku); D. Waterworth (Dawn); D.A. Lawlor (Debbie); J.B. Meigs (James); J.B. Richards (Brent); T.M. Frayling (Timothy)

2013-01-01

textabstractAdiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used

Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine.

Science.gov (United States)

Hiel, Sophie; Neyrinck, Audrey M; Rodriguez, Julie; Pachikian, Barbara D; Bouzin, Caroline; Thissen, Jean-Paul; Cani, Patrice D; Bindels, Laure B; Delzenne, Nathalie M

2018-04-25

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 ( Apoc3 , inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.

Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine

Directory of Open Access Journals (Sweden)

Sophie Hiel

2018-04-01

Full Text Available Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse. We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing and apolipoprotein C3 (Apoc3, inhibitor of lipoprotein lipase in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.

Influence of multidrug resistant organisms on the outcome of diabetic foot infection

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Nese Saltoglu

2018-05-01

Full Text Available Objectives: We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms. Methods: We included the patients with diabetic foot infections (DFI from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge. Results: In total, 791 patients with DFI were included, 531(67% were male, median age was 62 (19–90. Severe infection was diagnosed in 85 (11% patients. Osteomyelitis was diagnosed in 291(36.8% patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%, P. aeruginosa (19% and E. coli (12%. Methicillin resistance (MR rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+ Gram negative bacteria (GNB was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8% were re-hospitalized. Of the 791 patiens, 127 (16% had major amputation, and 24 (3% patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, CI: 1.82–38.15, p = 0.006, isolation of Klebsiella spp. (OR:7.7, CI: 1.24–47.96, p = 0.028, and chronic heart failure (OR: 3, CI: 1.01–9.04, p = 0.05. MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p < 0.001. Conclusion: Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality. Keywords: Diabetic foot infection, MRSA, Klebsiella, Fatality

Article Commentary: Insulin Resistance, Type 2 Diabetes and Chronic Liver Disease. A Deadly Trio

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Amedeo Lonardo

2009-01-01

Full Text Available In this commentary to the paper by Donadon V. et al (Clinical Medicine: Endocrinology and Diabetes. 2009;2:25–33. the association and significance of insulin resistance with chronic liver disease are shortly reviewed and the molecular mechanisms underlying the diabetogenic and oncogenic potentials of advanced liver disease are summarized. Literature studies demonstrate that hepatocellular carcinoma (HCC can be part of the natural history of NASH. HCCs in patients with features of metabolic syndrome as the only risk factor for liver disease have distinct morphological characteristics and mainly occur in the absence of significant fibrosis in the background liver. Moreover, data indicate that the presence of diabetes carries an approximately three to four-fold increased risk of HCC and such a risk is strongly increased by concurrent viral infections. Finally, the relationship between insulin resistance, steatosis and diabetes in NAFLD and HCV infection will be commented, along with the directions for future studies.

Mendelian Randomisation Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

DEFF Research Database (Denmark)

Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A

2013-01-01

Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes but its causal role remains controversial. We used a Mendelian randomisation approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic varian...

Effect of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats

International Nuclear Information System (INIS)

Anwar, M. K.; Hussain, M. M.; Khan, M. A.; Ahmad, T.

2013-01-01

Objective: To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. Group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis. Results: Fasting plasma glucose levels were significantly decreased (p <0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p <0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p <0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine. Conclusions: The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome. (author)

Association between circulating irisin and insulin resistance in non-diabetic adults: A meta-analysis.

Science.gov (United States)

Qiu, Shanhu; Cai, Xue; Yin, Han; Zügel, Martina; Sun, Zilin; Steinacker, Jürgen Michael; Schumann, Uwe

2016-06-01

Exogenous administration of recombinant irisin improves glucose metabolism. However, the association of endogenous circulating (plasma/serum) irisin with insulin resistance remains poorly delineated. This study was aimed to examine this association by meta-analyzing the current evidence without study design restriction in non-diabetic adults. Peer-reviewed studies written in English from 3 databases were searched to December 2015. Studies that reported the association between circulating irisin and insulin resistance (or its reverse, insulin sensitivity) in non-diabetic non-pregnant adults (mean ages ≥18years) were included. The pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity. Of the 195 identified publications, 17 studies from 15 articles enrolling 1912 participants reported the association between circulating irisin and insulin resistance. The pooled effect size was 0.15 (95% CI: 0.07 to 0.22) with a substantial heterogeneity (I(2)=55.5%). This association seemed to be modified by glycemic status (fasting blood glucose ≥6.1mmol/L versus insulin sensitivity (6 studies; r=-0.17, 95% CI: -0.25 to -0.09). Circulating irisin is directly and positively associated with insulin resistance in non-diabetic adults. However, this association is rather small and requires further clarification, in particular by well-designed large epidemiological studies with overall, race-, and sex-specific analyses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Alstr?m Syndrome: Genetics and Clinical Overview

OpenAIRE

Marshall, Jan D; Maffei, Pietro; Collin, Gayle B; Naggert, J?rgen K

2011-01-01

Alstr?m syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinic...

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy.

Science.gov (United States)

Mader, Jessica R; Resch, Zachary T; McLean, Gary R; Mikkelsen, Jakob H; Oxvig, Claus; Marler, Ronald J; Conover, Cheryl A

2013-10-01

We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess the possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout (KO) mice. Renal histopathology was evaluated after 4 months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration to those of diabetic WT mice, indicating that these changes were predominantly age-related. However, thickened Bowman's capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had significantly reduced or no evidence of changes in Bowman's capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT mice compared with Papp-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy.

Aerobic exercise training promotes additional cardiac benefits better than resistance exercise training in postmenopausal rats with diabetes.

Science.gov (United States)

Quinteiro, Hugo; Buzin, Morgana; Conti, Filipe Fernandes; Dias, Danielle da Silva; Figueroa, Diego; Llesuy, Susana; Irigoyen, Maria-Cláudia; Sanches, Iris Callado; De Angelis, Kátia

2015-05-01

The aim of this study was to evaluate the effects of aerobic exercise training or resistance exercise training on cardiac morphometric, functional, and oxidative stress parameters in rats with ovarian hormone deprivation and diabetes. Female Wistar rats (200-220 g) were divided into a sham-operated group (euglycemic sham-operated sedentary [ES]; n = 8) and three ovariectomized (bilateral removal of ovaries) and diabetic (streptozotocin 50 mg/kg IV) groups as follows: diabetic ovariectomized sedentary (DOS; n = 8), diabetic ovariectomized undergoing aerobic exercise training (DOTA; n = 8), and diabetic ovariectomized undergoing resistance exercise training (DOTR; n = 8). After 8 weeks of resistance (ladder) or aerobic (treadmill) exercise training, left ventricle function and morphometry were evaluated by echocardiography, whereas oxidative stress was evaluated at the left ventricle. The DOS group presented with increased left ventricle cavity in diastole and relative wall thickness (RWT), and these changes were attenuated in both DOTA and DOTR groups. Systolic and diastolic function was impaired in the DOS group compared with the ES group, and only the DOTA group was able to reverse this dysfunction. Lipoperoxidation and glutathione redox balance were improved in both trained groups compared with the DOS group. Glutathione peroxidase and superoxide dismutase were higher in the DOTA group than in the other studied groups. Correlations were observed between lipoperoxidation and left ventricle cavity in diastole (r = 0.55), between redox balance and RWT (r = 0.62), and between lipoperoxidation and RWT (r = -0.60). Aerobic exercise training and resistance exercise training promote attenuation of cardiac morphometric dysfunction associated with a reduction in oxidative stress in an experimental model of diabetes and menopause. However, only dynamic aerobic exercise training is able to attenuate systolic and diastolic dysfunction under this condition.

Prevalence of micro- and macrovascular diabetes complications at time of type 2 diabetes diagnosis and associated clinical characteristics

DEFF Research Database (Denmark)

Gedebjerg, Anne; Almdal, Thomas Peter; Berencsi, Klara

2018-01-01

enrolled in the prospective Danish Center for Strategic Research in T2D cohort during 2010-2016. We calculated age- and gender-adjusted prevalence ratios (aPRs) of complications using log-binomial and Poisson regression. RESULTS: In total, 35% (n=2456) T2D patients had diabetic complications around...... diagnosis; 12% (n=828) had microvascular complications, 17% (n=1186) macrovascular complications, and 6% (n=442) had both. HbA1c levels of ≥7% were associated with microvascular complications [HbA1c 7%-8%; aPR: 1.35, 95% confidence interval (CI): 1.12-1.62] but not macrovascular complications [aPR: 0.91, 95......, smoking, elevated CRP levels, and anti-hypertensive therapy. Microvascular complications were associated with high blood pressure, hypertriglyceridemia, and absence of lipid-lowering therapy. CONCLUSIONS: One-third of patients with T2D had diabetes complications around time of diagnosis. Our findings...

Prevalence and Risk Factors of Diabetic Nephropathy in Omani Type 2 Diabetics in Al-Dakhiliyah Region

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Abdulhakeem Hamood Alrawahi

2012-05-01

Full Text Available Objective: To assess the prevalence and risk factors of diabetic nephropathy among Omani type 2 diabetics in Al-Dakhiliyah region of the Sultanate of Oman.Methods: A cross-sectional and a case control study designs were used to assess the prevalence and risk factors respectively. For the prevalence study a sample of 699 diabetic subjects were selected randomly from two polyclinics in Al-Dakhiliyah region; Sumail and Nizwa polyclinics. For the case control study, a sample consisting of 215 cases and 358 controls were randomly selected from those who were included in the cross-sectional study. A well designed questionnaire has been used to collect data regarding the disease and risk factors. Data was analyzed using SPSS19 statistical program.Results: Total prevalence of diabetic nephropathy was calculated as 42.5% (95% C.I: 38.83% - 46.15%. The difference in the prevalence in the two polyclinic catchment area was not significant. The prevalence was significantly higher among males (51.6% compared to females (36.5%. Crude analysis of the risk factors showed significant association between diabetic nephropathy and the following factors; male gender, decreased literacy, long duration of diabetes mellitus, hypertension, retinopathy, neuropathy, family history of diabetic nephropathy, poor glycemic control (high HbA1c, and hypertriglyceridemia. Multivariate analysis showed the following factors to be independent risk factors; male gender, decreased literacy, long duration of diabetes, family history of diabetic nephropathy and poor glycaemic control (high HbA1c.Conclusion: The prevalence of diabetic nephropathy in this study was 42.5% and the significant risk factors associated with it included male gender, decreased literacy, long duration of diabetes, family history of diabetic nephropathy and poor glycemic control (high HbA1c.

Hipertrigliceridemia familiar grave durante a gestação Severe familial hypertriglyceridemia during pregnancy

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Luiz Augusto Casulari

2001-07-01

Full Text Available A presença de hipertrigliceridemia grave durante a gravidez é rara, mas comporta grande possibilidade de desenvolver complicações, como a pancreatite aguda, que coloca em risco a mãe e o feto. Apresentamos o relato da evolução da gestação de uma paciente portadora de hipertrigliceridemia grave que havia apresentado pancreatite aguda dois meses antes da fecundação. Foi tratada durante o pré-natal com dieta e 3,0 g de ácidos graxos de cadeia ômega-3 (ácidos eicosapentaenóico 14% e docosahexaenóico 11,13%. Os níveis de triglicerídeos foram mantidos abaixo de 800 mg/dl, sendo este limite considerado seguro para evitar o desenvolvimento de pancreatite aguda. A gestação evoluiu, sem intercorrências, para parto vaginal, a termo. O recém-nato não apresentou alterações morfológicas ao nascimento. Concluímos que, nesta paciente grávida e portadora de hipertrigliceridemia grave, uma dieta adequada e o emprego de ácidos graxos de cadeia ômega-3 foram eficazes em prevenir a pancreatite aguda. Esta abordagem terapêutica pode ser uma alternativa para as gestantes portadoras de hipertrigliceridemia familiar.Severe hypertriglyceridemia during pregnancy rarely occurs but it frequently produces complications, such as acute pancreatitis, a serious health risk both for the mother and the fetus. The treatment of a patient who had had acute pancreatitis due to hypertriglyceridemia (triglyceridemia = 5100 mg/dl two months before fecundation is presented in this paper. During gestation, bezafibrate was substituted for 3.0 g omega-3 fatty acids (14% eicosapentaenoic and 11.13% docosahexaenoic acids. With this therapy, the triglyceride levels were maintained below 800 mg/dl, which is considered to be the safe limit to avoid acute pancreatitis. No complication occurred during pregnancy, the patient delivered vaginally (40 weeks, and the newborn (3075 g did not present any morphological alterations. We conclude that an adequate diet and the

Fibrinolytic dysfunction in insulin-resistant women with previous gestational diabetes.

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Farhan, S; Winzer, C; Tura, A; Quehenberger, P; Bieglmaier, C; Wagner, O F; Huber, K; Waldhäusl, W; Pacini, G; Kautzky-Willer, A

2006-05-01

Women with a history of gestational diabetes (p-GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease. Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control. All women underwent an oral (OGTT) as well as an intravenous glucose tolerance test (FSIGT). Mathematical model analysis disclosed that 50% (n=37 each) of the p-GDM subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of interest were determined using commercially available test systems. Women with p-GDM and IIS had significantly increased body fat mass (BFM) (Pwomen with p-GDM and NIS and controls, whereas the waist to hip ratio (WHR) was similar in both p-GDM groups but was higher compared with the controls (Pwomen with p-GDM and IIS compared with women with p-GDM and NIS and the controls (Pwomen with IIS had higher PAI-1 levels than lean women with IIS (Pwomen with IIS (Pwomen with IIS independently of their glucose tolerance status (Pwomen with IIS and depends on plasma proinsulin and abdominal obesity. An increase of the PAI-1/SI ratio further characterizes obese insulin-resistant p-GDM women who may be at risk for diabetes and angiopathy.

Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin.

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Balani, Jyoti; Hyer, Steve; Syngelaki, Argyro; Akolekar, Ranjit; Nicolaides, Kypros H; Johnson, Antoinette; Shehata, Hassan

2017-12-01

To examine whether the reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is mediated by changes in insulin resistance. This was a secondary analysis of obese pregnant women in a randomised trial (MOP trial). Fasting plasma glucose and insulin were measured in 384 of the 400 women who participated in the MOP trial. Homeostasis model assessment of insulin resistance (HOMA-IR) was compared in the metformin and placebo groups and in those that developed preeclampsia versus those that did not develop preeclampsia. At 28 weeks, median HOMA-IR was significantly lower in the metformin group. Logistic regression analysis demonstrated that there was a significant contribution in the prediction of preeclampsia from maternal history of chronic hypertension and gestational weight gain, but not HOMA-IR either at randomisation ( p  = 0.514) or at 28 weeks ( p  = 0.643). Reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is unlikely to be due to changes in insulin resistance.

Resistance Training for Diabetes Prevention and Therapy: Experimental Findings and Molecular Mechanisms

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Barbara Strasser

2013-01-01

Full Text Available Type 2 diabetes mellitus (T2D is characterized by insulin resistance, impaired glycogen synthesis, lipid accumulation, and impaired mitochondrial function. Exercise training has received increasing recognition as a cornerstone in the prevention and treatment of T2D. Emerging research suggests that resistance training (RT has the power to combat metabolic dysfunction in patients with T2D and seems to be an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. However, there is limited mechanistic insight into how these adaptations occur. This review provides an overview of the intervention data on the impact of RT on glucose metabolism. In addition, the molecular mechanisms that lead to adaptation in skeletal muscle in response to RT and that are associated with possible beneficial metabolic responses are discussed. Some of the beneficial adaptations exerted by RT include increased GLUT4 translocation in skeletal muscle, increased insulin sensitivity and hence restored metabolic flexibility. Increased energy expenditure and excess postexercise oxygen consumption in response to RT may be other beneficial effects. RT is increasingly establishing itself as an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients.

Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

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Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Teerapornpuntakit, Jarinthorn; Aeimlapa, Ratchaneevan; Chattipakorn, Nipon; Chattipakorn, Siriporn

2018-02-02

Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Insulin resistance in Chinese patients with type 2 diabetes is associated with C-reactive protein independent of abdominal obesity

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Feng Xiaocheng

2010-12-01

Full Text Available Abstract Background There is debate as to whether the association between C-reactive protein (CRP and insulin resistance is independent of body fatness, particularly central obesity. Therefore, the association among CRP, insulin resistance and obesity was analyzed in Chinese patients with type 2 diabetes. Methods The study included 520 Chinese patients diagnosed with type 2 diabetes with CRP levels not exceeding 10 mg/L. The degree of insulin resistance was determined with the homeostasis model assessment of insulin resistance (HOMA-IR. The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4. Results Body mass index (BMI and waist circumference (WC were both higher in Q4, Q3 and Q2 than those in Q1. HOMA-IR was higher in Q2, Q3 and Q4 than that in Q1 (Q1 vs Q4, P Conclusion These findings showed that insulin resistance was associated with CRP levels independent of abdominal obesity in Chinese patients with type 2 diabetes, suggesting that abdominal obesity could only partly explain the link between subclinical inflammation and insulin resistance.

Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

OpenAIRE

de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R

2009-01-01

Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...

Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance?

NARCIS (Netherlands)

Li, Naishi; Fu, Jingyuan; Koonen, Debby P.; Kuivenhoven, Jan Albert; Snieder, Harold; Hofker, Marten H.

Insulin resistance often occurs with dyslipidemia as part of the metabolic syndrome and the current dominant paradigm is that insulin resistance leads to dyslipidemia. However, dyslipidemia may also cause insulin resistance; this was postulated 30 years ago, but has never been substantiated.

The Role of Hypertriglyceridemia in the Development of Atherosclerosis and Endothelial Dysfunction

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Saki Matsumoto

2014-03-01

Full Text Available A hereditary postprandial hypertriglyceridemic rabbit (PHT rabbit is a new dyslipidemic model showing remarkably high plasma triglycerides with only limited elevation of plasma total cholesterol. In PHT rabbits, plasma triglyceride was markedly elevated postprandially compared with healthy Japanese white (JW rabbits. In physiological experiments, the ring preparation of the thoracic aorta was suspended in an organ bath filled with modified Krebs-Henseleit solution, and the developed tension was recorded. Endothelial function was evaluated by acetylcholine-induced vasorelaxation in each preparation with intact endothelium. The acetylcholine-induced endothelium-dependent relaxation was diminished in PHT compared with JW rabbits, suggesting endothelial dysfunction in PHT rabbits. Histological examination was carried out in adipose tissue, liver and aorta. They were fixed in formaldehyde and embedded in paraffin. The tissues were sliced (4 μm and stained using hematoxylin-eosin solution. In the adipose tissue, the visceral fat accumulated, and the size of adipose cells was enlarged in PHT rabbits. The liver of the PHT rabbit was fatty and degenerated. In aorta, increased intimal thickness was observed, suggesting the progression of atherosclerosis in the PHT rabbit. This study suggests the important role of postprandial hypertriglyceridemia in atherosclerosis. By using PHT rabbits, the effects of hypertriglyceridemia on health and diseases could be evaluated precisely.

Dose- and time-dependent association of smoking and its cessation with glycemic control and insulin resistance in male patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry.

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Toshiaki Ohkuma

Full Text Available Cigarette smoking is an important modifiable risk factor for cardiovascular diseases. However, the effect of smoking and its cessation on glycemic control in diabetic patients has not been fully examined yet. The aim of the present study was to examine the association of smoking status with glycemic level and markers of insulin resistance and secretion in patients with type 2 diabetes mellitus.A total of 2,490 Japanese male patients with type 2 diabetes mellitus aged ≥20 years were divided according to smoking status, amount of cigarettes smoked and years since quitting. The associations with glycemic level and markers of insulin resistance and secretion were examined cross-sectionally.HbA1c levels increased progressively with increases in both number of cigarettes per day and pack-years of cigarette smoking compared with never smokers (P for trend = 0.001 and <0.001, respectively, whereas fasting plasma glucose did not. On the other hand, HbA1c, but not fasting plasma glucose, decreased linearly with increase in years after smoking cessation (P for trend <0.001. These graded relationships persisted significantly after controlling for the confounders, including total energy intake, current drinking, regular exercise, depressive symptoms, and BMI. In addition, a homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein also showed similar trends.Smoking and its cessation showed dose- and time-dependent relationship with glycemic control and insulin resistance in patients with type 2 diabetes mellitus. These findings may highlight the importance of smoking cessation in the clinical management of diabetes mellitus.

Titrating lovaza from 4 to 8 to 12 grams/day in patients with primary hypertriglyceridemia who had triglyceride levels >500 mg/dl despite conventional triglyceride lowering therapy

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Glueck Charles J

2012-10-01

Full Text Available Abstract Background Omega-3 fatty acids are important in treatment of severe primary hypertriglyceridemia (HTG. In 15 patients with severe primary HTG (TG >500 mg/dl despite conventional TG lowering therapy, we assessed efficacy-safety of sequential monthly treatment with Lovaza, 4 to 8 to 12 g/day. Methods With TG >500 mg/dl despite Type V diet, hyperinsulinemia and diabetes control, and fibric acids, Lovaza (4 g/d was added for 1 month, and if TG remained >500 mg/dl, increased to 8 g/d for 1 month, and then to 12 g/d for 1 month, and subsequently reduced to 4 g/day for 4 months. Results Primary HTG, median TG 884 mg/dl, 14 men, 1 woman, all white, age 50 ± 7 years, 12 non-diabetic, 3 with stable diabetes control. Weight and diet held stable throughout. In 5 patients, after 1, 2, and 3 months on 4 g/day, TG fell Conclusion Titration of Lovaza from 4 to 8 to 12 g/d safely offers an effective way to lower TG beyond conventional 4 g therapy.

Diabetes, insulin resistance, and metabolic syndrome in horses.

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Johnson, Philip J; Wiedmeyer, Charles E; LaCarrubba, Alison; Ganjam, V K; Messer, Nat T

2012-05-01

Analogous to the situation in human medicine, contemporary practices in horse management, which incorporate lengthy periods of physical inactivity coupled with provision of nutritional rations characterized by inappropriately high sugar and starch, have led to obesity being more commonly recognized by practitioners of equine veterinary practice. In many of these cases, obesity is associated with insulin resistance (IR) and glucose intolerance. An equine metabolic syndrome (MS) has been described that is similar to the human MS in that both IR and aspects of obesity represent cornerstones of its definition. Unlike its human counterpart, identification of the equine metabolic syndrome (EMS) portends greater risk for development of laminitis, a chronic, crippling affliction of the equine hoof. When severe, laminitis sometimes necessitates euthanasia. Unlike the human condition, the risk of developing type 2 diabetes mellitus and many other chronic conditions, for which the risk is recognized as increased in the face of MS, is less likely in horses. The equine veterinary literature has been replete with reports of scientific investigations regarding the epidemiology, pathophysiology, and treatment of EMS. © 2012 Diabetes Technology Society.

Familial hypertriglyceridemia

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The goal of treatment is to control conditions that can raise triglyceride levels. These include obesity , hypothyroidism , and diabetes . Your provider may tell you not to drink alcohol. Certain birth control pills can raise triglyceride levels. ...

Association of serum sparc with insulin resistance in type-2 diabetes mellitus

International Nuclear Information System (INIS)

Nadeem, K.; Ahmed, U.; Arif, H.

2017-01-01

Objective: To determine the association of serum SPARC with insulin resistance in type-2 diabetes. Study Design: Descriptive study. Place and Duration of Study: Physiology department and CREAM lab, Army medical college, Rawalpindi, in collaboration with Military Hospital Rawalpindi, from Feb 2016 to Oct 2016. Material and Methods: Sixty individuals were recruited in this descriptive study. Thirty diagnosed cases of type- 2 DM were included, while thirty age and gender matched healthy individuals were included as controls through non-probability purposive sampling. Controls were labelled as group A, while cases were labelled as group B. Patients with type-1 DM, type-2 DM on insulin therapy, hyperglycemic states other than DM and inflammatory disorders were excluded from the study. Data were collected after informed and written consent. Blood samples were withdrawn under strict aseptic measures and serum was stored at -20 degree C. Serum insulin levels and serum SPARC levels were analyzed by enzyme linked immunosorbent assay (ELISA). Insulin resistance was determined using homeostasis model assessment of insulin resistance (HOMA-IR), and its value >1.5 was considered significant. Results: Fasting insulin levels were significantly higher in group B as compared with group A, supporting the diagnosis of type-2 DM. HOMA-IR values were greater than 1.5 in group B, thus establishing significant insulin resistance. Serum SPARC levels were significantly higher in group B than group A (17.7 ± 1.14 vs 8.7 ± 1.08 ng/ml) with p-value<0.001. Serum SPARC levels showed positive correlation with fasting insulin levels and HOMA-IR values. Conclusion: Our study showed a positive correlation between serum SPARC levels and insulin resistance, which indicates that SPARC plays an important role in the development of insulin resistance in type-2 diabetes mellitus. (author)

Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome.

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Wimalawansa, Sunil J

2018-01-01

The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH) 2 D 3 , especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and

Assessment of the fatty liver index as an indicator of hepatic steatosis for predicting incident diabetes independently of insulin resistance in a Korean population.

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Jung, C H; Lee, W J; Hwang, J Y; Yu, J H; Shin, M S; Lee, M J; Jang, J E; Leem, J; Park, J-Y; Kim, H-K

2013-04-01

Fatty liver disease, especially non-alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance. We examined the clinical and laboratory data of 7860 subjects without diabetes who underwent general routine health evaluations at the Asan Medical Center in 2007 and had returned for follow-up examinations in 2011. Fatty liver index was calculated using an equation that considers serum triglyceride levels, γ-glutamyltransferase, waist circumference and BMI. During a 4-year period, 457 incident diabetes cases (5.8%) were identified. The odds ratios for the development of Type 2 diabetes were significantly higher in the group with a fatty liver index ≥ 60 (fatty liver index-positive) than in the group with a fatty liver index hepatic steatosis is valuable in identifying subjects at high risk for Type 2 diabetes. In addition, fatty liver disease itself contributes to the development of Type 2 diabetes independently of systemic insulin resistance. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Resistance exercise versus aerobic exercise for type 2 diabetes: a systematic review and meta-analysis.

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Yang, Zuyao; Scott, Catherine A; Mao, Chen; Tang, Jinling; Farmer, Andrew J

2014-04-01

Resistance and aerobic exercises are both recommended as effective treatments for people with type 2 diabetes. However, the optimum type of exercise for the disease remains to be determined to inform clinical decision-making and facilitate personalized exercise prescription. Our objective was to investigate whether resistance exercise is comparable to aerobic exercise in terms of effectiveness and safety in people with type 2 diabetes. PubMed, EMBASE, CENTRAL, CINAHL, and SPORTdiscus were systematically searched up to March 2013. The reference lists of eligible studies and relevant reviews were also checked. We used the following criteria to select studies for inclusion in the review: (i) the study was a randomized controlled trial; (ii) the participants were people with type 2 diabetes aged 18 years or more; (iii) the trial compared resistance exercise with aerobic exercise for a duration of at least 8 weeks, with pre-determined frequency, intensity, and duration; and (iv) the trial provided relevant data on at least one of the following: glycaemic control, blood lipids, anthropometric measures, blood pressure, fitness, health status, and adverse events. The assessment of study quality was based on the Cochrane Risk of Bias tool. For effectiveness measures, differences (resistance group minus aerobic group) in the changes from baseline with the two exercises were combined, using a random-effects model wherever possible. For adverse events, the relative risks (resistance group vs. aerobic group) were combined. Twelve trials (n = 626) were included. Following the exercise interventions, there was a greater reduction of glycosylated hemoglobin with aerobic exercise than with resistance exercise (difference 0.18% (1.97 mmol/mol), 95% confidence interval (CI) 0.01, 0.36). This difference became non-significant with sensitivity analysis (p = 0.14). The differences in changes from baseline were also statistically significant for body mass index (difference 0.22, 95% CI 0

The Comparison of Two Methods of Exercise (intense interval training and concurrent resistance- endurance training on Fasting Sugar, Insulin and Insulin Resistance in Women with Mellitus Diabetes

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F Bazyar

2016-05-01

Full Text Available Background & aim: Exercise is an important component of health and an integral approach to the management of diabetes mellitus. The purpose of this study was to compare the effects of intense interval training and concurrent resistance- endurance training on fasting sugar, insulin and insulin resistance in women with mellitus diabetes.   Methods: Fifty-two overweight female diabetic type 2 patients (aged 45-60 years old with fasting blood glucose≥ 126 mg/dl were selected to participate in the present study. Participants were assigned to intense interval training group (N=17, concurrent resistance- endurance training group (N=17 and control group (N=18. The exercises incorporated 10 weeks of concurrent resistance- endurance training and intense interval training. Fasting blood sugar, serum insulin concentrations levels were measured. Concurrent training group trained eight weeks, three times a week of endurance training at 60% of maximum heart rate (MHR and two resistance training sessions per week with 70% of one repetition maximum (1-RM. Intense interval training group trained for eight weeks, three sessions per week for 4 to 10 repeats Wingate test on the ergometer 30s performed with maximum effort. The control group did no systematic exercise. At the end of experiment 42 subjects were succeed and completed the study period, and 10 subjects were removed due to illness and absence in the exercise sessions. Fasting blood sugar and insulin levels 24 hours before and 48 hours after the last training session was measured.   Results: The findings indicated that in periodic fasting, the blood sugar in intensive training group had a marked decrease (p= 0.000 however, the fasting blood sugar of exercise and power stamina groups reduced significantly (p=0.062. The results showed no significant difference between the groups (171/0 p =0.171. Fasting insulin (p <0.001 and insulin resistance (0001/0 = p=0.001 in periodic intensive training group were

Tobacco Use, Insulin Resistance, and Risk of Type 2 Diabetes: Results from the Multi-Ethnic Study of Atherosclerosis.

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Rachel J Keith

Full Text Available Tobacco use is associated with insulin resistance and incident diabetes. Given the racial/ethnic differences in smoking patterns and incident type 2 diabetes our objective was to evaluate the association between tobacco use and insulin resistance (IR as well as incident type 2 diabetes mellitus in a contemporary multiethnic cohort.We studied 5,931 Multi- Ethnic Study of Atherosclerosis (MESA participants who at baseline were free of type 2 diabetes (fasting glucose ≥7.0 mmol/l (126 mg/dl and/or use of insulin or oral hypoglycemic medications categorized by self-reported tobacco status and reclassified by urinary cotinine (available in 58% of participants as never, current or former tobacco users. The association between tobacco use, IR (fasting plasma glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR and incident diabetes over 10 years was evaluated using multivariable linear regression and Cox proportional hazards models, respectively. Mean age of the participants was 62 (±10 years, 46% were male, 41% Caucasian, 12% Chinese, 26% African American and 21% Hispanic/Latino. IR biomarkers did not significantly differ between current, former, and never cigarette users (P >0.10 but showed limited unadjusted differences for users of cigar, pipe and smokeless tobacco (All P <0.05. Fully adjusted models showed no association between dose or intensity of tobacco exposure and any index of IR. When stratified into participants that quit smoking vs. those who continued smoking during the 10-year study there was no difference in serum glucose levels or frequency of diabetes. In fully adjusted models, there was no significant difference in diabetes risk between former or current cigarette smokers compared to never smokers [HR (95% CI 1.02 (0.77,1.37 and 0.81 (0.52,1.26 respectively].In a contemporary multi-ethnic cohort, there was no independent association between tobacco use and IR or incident type 2 diabetes. The role

Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro

DEFF Research Database (Denmark)

Buhl, Kristian B; Stolzenburg Oxlund, Christina; Friis, Ulla G

2014-01-01

diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mm...... of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.......BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2...

Automated ribotyping and antibiotic resistance determining of Bacillus spp from conjunctiva of diabetic patients

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Sertaç Argun Kıvanç

2014-02-01

Conclusion: Diabetic patients seem to be more prone to B. cereus infections than healthy individuals. It would be greatly beneficial to understand and recognize the prevalence of microorganisms and their resistance patterns for better outcome in ocular surgeries.

PRE-DIABETES

OpenAIRE

Akula Annapurna

2013-01-01

Pre-diabetes is a condition where the body's cells begin to show resistance to insulin. Glucose circulates in the blood instead of being used by the cells for energy. Blood sugar levels become elevated. Increased weight, unhealthy diet and a sedentary lifestyle can lead to pre-diabetes. WHAT IS PRE-DIABETES A diagnosis of pre-diabetes means that the cells in your body are becoming resistant to insulin and your blood glucose levels are higher than they should be. Since the levels aren't as hig...

Fine-mapping diabetes-related traits, including insulin resistance, in heterogeneous stock rats

Science.gov (United States)

Holl, Katie L.; Oreper, Daniel; Xie, Yuying; Tsaih, Shirng-Wern; Valdar, William

2012-01-01

Type 2 diabetes (T2D) is a disease of relative insulin deficiency resulting from both insulin resistance and beta cell failure. We have previously used heterogeneous stock (HS) rats to fine-map a locus for glucose tolerance. We show here that glucose intolerance in the founder strains of the HS colony is mediated by different mechanisms: insulin resistance in WKY and an insulin secretion defect in ACI, and we demonstrate a high degree of variability for measures of insulin resistance and insulin secretion in HS rats. As such, our goal was to use HS rats to fine-map several diabetes-related traits within a region on rat chromosome 1. We measured blood glucose and plasma insulin levels after a glucose tolerance test in 782 male HS rats. Using 97 SSLP markers, we genotyped a 68 Mb region on rat chromosome 1 previously implicated in glucose and insulin regulation. We used linkage disequilibrium mapping by mixed model regression with inferred descent to identify a region from 198.85 to 205.9 that contains one or more quantitative trait loci (QTL) for fasting insulin and a measure of insulin resistance, the quantitative insulin sensitivity check index. This region also encompasses loci identified for fasting glucose and Insulin_AUC (area under the curve). A separate <3 Mb QTL was identified for body weight. Using a novel penalized regression method we then estimated effects of alternative haplotype pairings under each locus. These studies highlight the utility of HS rats for fine-mapping genetic loci involved in the underlying causes of T2D. PMID:22947656

Antihyperglycemic Activity of Eucalyptus tereticornis in Insulin-Resistant Cells and a Nutritional Model of Diabetic Mice

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Alis Guillén

2015-01-01

Full Text Available Eucalyptus tereticornis is a plant used in traditional medicine to control diabetes, but this effect has not been proved scientifically. Here, we demonstrated through in vitro assays that E. tereticornis extracts increase glucose uptake and inhibit their production in insulin-resistant C2C12 and HepG2 cells, respectively. Furthermore, in a nutritional model using diabetic mice, the administration of ethyl acetate extract of E. tereticornis reduced fasting glycaemia, improved tolerance to glucose, and reduced resistance to insulin. Likewise, this extract had anti-inflammatory effects in adipose tissue when compared to control diabetic mice. Via bioguided assays and sequential purification of the crude extract, a triterpenoid-rich fraction from ethyl acetate extracts was shown to be responsible for the biological activity. Similarly, we identified the main compound responsible for the antihyperglycemic activity in this extract. This study shows that triterpenes found in E. tereticornis extracts act as hypoglycemic/antidiabetic compounds and contribute to the understanding of their use in traditional medicine.

A novel botanical formula prevents diabetes by improving insulin resistance.

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Kan, Juntao; Velliquette, Rodney A; Grann, Kerry; Burns, Charlie R; Scholten, Jeff; Tian, Feng; Zhang, Qi; Gui, Min

2017-07-05

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease, and the prevalence has increased significantly in recent decades to epidemic proportions in China. Individually, fenugreek (Trigonella foenum graecum) seed, mulberry (Morus alba L.) leaf and American ginseng (Panax quinquefolius) root can improve glycemia in various animal models and humans with impaired glucose metabolism and T2DM. The aim of this study was to design an optimized botanical formula containing these herbal extracts as a nutritional strategy for the prevention of insulin resistance and T2DM. Cell-free α-amylase and α-glucosidase enzyme assays were used to determine inhibitory potential of extracts. Glucose uptake was examined in differentiated human adipocytes using radiolabeled 2-deoxyglucose. Male Sprague Dawley rats were divided and glycemia balanced into 5 groups: two controls (naïve and model) and three doses of the botanical test formula containing standardized fenugreek seed, mulberry leaf and American ginseng extracts (42.33, 84.66 and 169.33 mg/kg BW). Insulin resistance and T2DM was induced by feeding animals a high fat diet and with an alloxan injection. Glucose tolerance was examined by measuring serum glucose levels following an oral glucose load. Fenugreek seed and mulberry leaf dose dependently inhibited α-amylase (IC50 = 73.2 μg/mL) and α-glucosidase (IC50 = 111.8 ng/mL), respectively. All three botanical extracts improved insulin sensitivity and glucose uptake in human adipocytes, which lead to the design of an optimized botanical test formula. In a rat model of insulin resistance and T2DM, the optimized botanical test formula improved fasting serum glucose levels, fasting insulin resistance and the development of impaired glucose tolerance. The reduction in epididymal adipose tissue GLUT4 and PDK1 expression induced by high fat diet and alloxan was blunted by the botanical test formula. A novel botanical formula containing standardized

Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine

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Sophie Hiel; Audrey M. Neyrinck; Julie Rodriguez; Barbara D. Pachikian; Caroline Bouzin; Jean-Paul Thissen; Patrice D. Cani; Laure B. Bindels; Nathalie M. Delzenne

2018-01-01

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We perf...

Factors associated with persistent poorly controlled diabetes mellitus: clues to improving management in patients with resistant poor control.

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Crowley, Matthew J; Holleman, Rob; Klamerus, Mandi L; Bosworth, Hayden B; Edelman, David; Heisler, Michele

2014-12-01

Patients with persistent poorly controlled diabetes mellitus (PPDM), defined as an uninterrupted hemoglobin A1c >8.0% for ≥1 year despite standard care, are at high risk for complications. Additional research to define patient factors associated with PPDM could suggest barriers to improvement in this group and inform the development of targeted strategies to address these patients' resistant diabetes. We analyzed patients with type 2 diabetes from a multi-site randomized trial. We characterized patients with PPDM relative to other patients using detailed survey data and multivariable modeling. Of 963 patients, 118 (12%) had PPDM, 265 (28%) were intermittently poorly controlled, and 580 (60%) were well-controlled. Patients with PPDM had younger age, earlier diabetes diagnosis, insulin use, higher antihypertensive burden, higher low-density lipoprotein cholesterol, and lower statin use relative to well-controlled patients. Among patients with objective adherence data (Veterans Affairs patients), a larger oral diabetes medication refill gap was associated with PPDM. Strategies are needed to target-specific barriers to improvement among patients whose diabetes is resistant to standard diabetes care. Our data suggest that strategies for targeting PPDM should accommodate younger patients' lifestyles, include medication management for insulin titration and comorbid disease conditions, and address barriers to self-management adherence. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Valproic acid reduces insulin-resistance, fat deposition and FOXO1-mediated gluconeogenesis in type-2 diabetic rat.

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Khan, Sabbir; Kumar, Sandeep; Jena, Gopabandhu

2016-06-01

Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage. Insulin-resistance, dyslipidemia and glycemia were evaluated by biochemical estimations, while fat accumulation and structural alteration were assessed by histopathology. Protein expression and insulin signaling were evaluated by western blot and immunohistochemistry. VPA treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, fat deposition in brown adipose tissue, white adipose tissue and liver, which are comparable to metformin treatment. Further, VPA inhibited the gluconeogenesis and glucagon expression as well as restored the histopathological alterations in pancreas and liver. Our findings provide new insights on the anti-diabetic role of VPA in type-2 diabetes mellitus by the modulation of insulin signaling and forkhead box protein O1 (FOXO1)-mediated gluconeogenesis. Since VPA is a well established clinical drug, the detailed molecular mechanisms of the present findings can be further investigated for possible clinical use. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Co-therapy using lytic bacteriophage and linezolid: effective treatment in eliminating methicillin resistant Staphylococcus aureus (MRSA from diabetic foot infections.

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Sanjay Chhibber

Full Text Available BACKGROUND: Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15-30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population. METHODOLOGY: Acute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated. RESULTS AND CONCLUSIONS: A single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis. The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in

Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study.

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Khodaeian, Mehrnoosh; Tabatabaei-Malazy, Ozra; Qorbani, Mostafa; Farzadfar, Farshad; Amini, Peyvand; Larijani, Bagher

2015-11-01

Data regarding the effect of vitamin C (VC) and vitamin E (VE) supplementation on insulin resistance in type 2 diabetes mellitus (T2DM) are controversial. We aimed to systematically review the current data on this topic. All randomized controlled trials (RCTs) conducted to assess the effect of VC and/or VE on insulin resistance in diabetes published in Google Scholar and PubMed web databases until January 2014 were included. Exclusion criteria were studies conducted in animal, type 1 DM, children or pregnant women. Main outcome measure was insulin resistance by homoeostasis model assessment (HOMA) index. According to degree of heterogeneity, fixed- or random-effect model was employed by stata software (11.0). We selected 14 RCTs involving 735 patients with T2DM. VE or mixture-mode supplementation did not have any significant effect on HOMA with a standardized mean difference (SMD): 0·017, 95% CI: -0·376 to 0·411 (P = 0·932); and SMD: -0·035, 95% CI: -0·634 to 0·025 (P = 0·070), respectively, by random-effect model. VC supplement alone did not improve insulin resistance with a SMD: -0·150, 95% CI: -0·494 to 0·194 (P = 0·391), by fixed-effect model. Meta-regression test demonstrated that HOMA index may have not been influenced by the year of publication, dosage or duration of treatment. The sole intake of VC, VE or their combination with other antioxidants could not improve insulin resistance in diabetes. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Local metabolism of glucocorticoids in Prague hereditary hypertriglyceridemic rats – Effect of hypertriglyceridemia and gender

Czech Academy of Sciences Publication Activity Database

Klusoňová, Petra; Pátková, Lenka; Ergang, Peter; Mikšík, Ivan; Zicha, Josef; Kuneš, Jaroslav; Pácha, Jiří

2011-01-01

Roč. 76, č. 12 (2011), s. 1252-1259 ISSN 0039-128X R&D Projects: GA ČR(CZ) GA305/08/0139; GA AV ČR(CZ) KJB500110703 Institutional research plan: CEZ:AV0Z50110509 Keywords : 11beta-hydroxysteroid dehydrogenase * glucocorticoids * hypertriglyceridemia Subject RIV: ED - Physiology Impact factor: 2.829, year: 2011

Metabolic syndrome presenting as abdominal pain

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Mohammed Y Al-Dossary

2017-01-01

Full Text Available Metabolic syndrome represents a sum of risk factors that lead to the occurrence of cardiovascular and cerebrovascular events. The early detection of metabolic syndrome is extremely important in adults who are at risk. Although the physiopathological mechanisms of the metabolic syndrome are not yet clear, insulin resistance plays a key role that could explain the development of type 2 diabetes mellitus in untreated metabolic syndrome patients. Here, we present the case of a 26-year-old male who was diagnosed with metabolic syndrome and severe hypertriglyceridemia after presenting with abdominal pain. Although hypertriglyceridemia and hyperglycemia are the most common predictors of metabolic syndrome, clinicians need to be vigilant for unexpected presentations in patients at risk for metabolic syndrome. This case sheds light on the importance of early detection.

Fasting triglycerides as a predictor of incident diabetes, insulin resistance and β-cell function in a Canadian First Nation.

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Riediger, Natalie D; Clark, Kirsten; Lukianchuk, Virginia; Roulette, Joanne; Bruce, Sharon

2017-01-01

Diabetes prevalence is substantially higher among Canadian First Nations populations than the non-First Nation population. Fasting serum triglycerides have been found to be an important predictor of incident diabetes among non-indigenous populations. However, there is a great need to understand diabetes progression within specific ethnic groups, particularly First Nations populations. The purpose of this study was to test for an association between fasting serum triglycerides and incident diabetes, changes in insulin resistance and changes in β-cell function in a Manitoba First Nation cohort. Study data were from two diabetes screening studies in Sandy Bay First Nation in Manitoba, Canada, collected in 2002/2003 and 2011/2012. The cohort was composed of respondents to both screening studies (n=171). Fasting blood samples and anthropometric, health and demographic data were collected. A generalised linear model with Poisson distribution was used to test for an association between fasting triglycerides and incident diabetes. There were 35 incident cases of diabetes among 128 persons without diabetes at baseline. Participants who developed incident type 2 diabetes were significantly older and had significantly higher body mass index (BMI; p=0.012), total cholesterol (p=0.007), fasting triglycerides (ptriglyceride level was found to be a statistically significant positive predictor of incident diabetes independent of age, sex and waist circumference at baseline. Participants with triglycerides in the highest tertile (≥2.11 mmol/l) had a 4.0-times higher risk of developing incident diabetes compared to those in the lowest tertile (p=0.03). Notably, neither waist circumference nor BMI were significant predictors of incident diabetes independent of age, sex and triglycerides. Fasting triglycerides may be useful as a clinical predictor of insulin resistance and diabetes development among First Nations populations. Unlike other ethnic groups, BMI and waist circumference

Gender differences of dyslipidemia in type 2 diabetics

International Nuclear Information System (INIS)

Gilani, S.Y.H.; Bibi, S.; Ahmed, N.

2010-01-01

Type II diabetic patients are at an increased risk of coronary artery disease and cerebrovascular disease because of deranged lipid metabolism. Female diabetic patients are predominantly at risk. The objective of this cross-sectional study was to determine effects of gender on dyslipidemia of type II diabetic patients. Methods: This study was carried out at Out-Patients Department, Medical A Unit, Ayub Teaching Hospital Abbottabad from May 27, to November 27, 2009. All type II diabetic patients who were above 40 and gave consent were included in the study. Data was collected through a structured proforma. Pattern of dyslipidemia in type II diabetic patients were estimated by computing all the four types of dyslipidemia like hypertriglyceridemia, low HDL, increased serum total cholesterol and increased serum LDL. Results: There were 150 patients with mean age 65.67+- 11.29 years. There were 80 (53.33%) male and 70 (46.7%) female patients. Mean BMI was 28.45 +- 3.30 Kg/m/sup 2/. Mean serum cholesterol level was 3.9 +- 1.31 mmol/L, triglyceride level was 2.98 +- 1.14 mmol/L, LDL level was 3.28 +- 0.85 mmol/L and HDL was 0.95 +- 0.02 mmol/L. Women were more frequent to have low level HDL as compare to men (p 0.05). Conclusion: Female diabetic patients have increased frequency of low level of serum HDL as compared to males. (author)

Prevalence and characteristics of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus nasal colonization among a community-based diabetes population in Foshan, China.

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Lin, Jialing; Xu, Ping; Peng, Yang; Lin, Dongxin; Ou, Qianting; Zhang, Ting; Bai, Chan; Ye, Xiaohua; Zhou, Junli; Yao, Zhenjiang

2017-05-01

Evidence suggests that diabetes might cause an increase in colonization of Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) in community settings. We carried out a cross-sectional study to determine the prevalence and influencing factors of S. aureus and MRSA nasal colonization among a community-based diabetes population, and to identify the characteristics of the isolated strains. A total of 956 participants from 11 community settings were included in the study. Of the 529 diabetes participants, 46 were colonized with S. aureus and 22 were colonized with MRSA. Of the 427 non-diabetes participants, 25 were colonized with S. aureus and 12 were colonized with MRSA. Men (odds ratio 0.45, 95% confidence interval 0.20-0.99, P = 0.047) were less likely to have S. aureus nasal colonization, and those with well-controlled blood glucose (odds ratio 2.04, 95% confidence interval 1.01-4.13, P = 0.047) among the diabetes population were more likely to have S. aureus nasal colonization. The proportion of multidrug-resistant S. aureus strains in the diabetes population (52.17%) was higher than that in the non-diabetes population (28.00%; χ 2 = 3.848, P = 0.050). The most common clonal complex type and Staphylococcal chromosome cassette mec type of MRSA in diabetes population was clonal complex 5 (40.91%) and type IV (27.27%), respectively. The proportion of Panton-Valentine leukocidin gene in MRSA strains was 17.65%. There was great sequence type diversity in MRSA strains. The prevalence of MRSA in the community-based diabetes population was moderate, and the high proportions of multidrug-resistant S. aureus strains and diverse molecular characteristics in the diabetes population should be noticed. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

The-1131T > C Polymorphism in the Apolipoprotein A5 Gene is Related to Hypertriglyceridemia in Taiwanese Aborigines

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Meng-Chuan Huang

2008-04-01

Full Text Available The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T > C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T > C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride ≥150 mg/dL was defined as the hypertriglyceridemia group and triglyceride C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.

Pioglitazone reverses down-regulation of cardiac PPARγ expression in Zucker diabetic fatty rats

International Nuclear Information System (INIS)

Pelzer, Theo; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

2005-01-01

Peroxisome proliferator-activated receptor-γ (PPARγ) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARγ in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARγ agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARγ, glucose transporter-4 and α-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARγ, glut-4, and α-MHC expression levels in diabetic ZDF rats. Cardiac [ 18 F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARγ agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARγ expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin

Influence of multidrug resistant organisms on the outcome of diabetic foot infection.

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Saltoglu, Nese; Ergonul, Onder; Tulek, Necla; Yemisen, Mucahit; Kadanali, Ayten; Karagoz, Gul; Batirel, Ayse; Ak, Oznur; Sonmezer, Cagla; Eraksoy, Haluk; Cagatay, Atahan; Surme, Serkan; Nemli, Salih A; Demirdal, Tuna; Coskun, Omer; Ozturk, Derya; Ceran, Nurgul; Pehlivanoglu, Filiz; Sengoz, Gonul; Aslan, Turan; Akkoyunlu, Yasemin; Oncul, Oral; Ay, Hakan; Mulazımoglu, Lutfiye; Erturk, Buket; Yilmaz, Fatma; Yoruk, Gulsen; Uzun, Nuray; Simsek, Funda; Yildirmak, Taner; Yaşar, Kadriye Kart; Sonmezoglu, Meral; Küçükardali, Yasar; Tuna, Nazan; Karabay, Oguz; Ozgunes, Nail; Sargın, Fatma

2018-05-01

We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms. We included the patients with diabetic foot infections (DFI) from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge. In total, 791 patients with DFI were included, 531(67%) were male, median age was 62 (19-90). Severe infection was diagnosed in 85 (11%) patients. Osteomyelitis was diagnosed in 291(36.8%) patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%), P. aeruginosa (19%) and E. coli (12%). Methicillin resistance (MR) rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+) Gram negative bacteria (GNB) was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8%) were re-hospitalized. Of the 791 patiens, 127 (16%) had major amputation, and 24 (3%) patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, CI: 1.82-38.15, p=0.006), isolation of Klebsiella spp. (OR:7.7, CI: 1.24-47.96, p=0.028), and chronic heart failure (OR: 3, CI: 1.01-9.04, p=0.05). MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p<0.001). Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hypertriglyceridemia and preeclampsia: Its physiological role and up-to-date evidence

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María Paula Martínez Linares

2005-08-01

Full Text Available Preeclampsia is a disease with a highincidence for maternal and fetal morbidity and mortality, mainly indeveloping countries. Although its etiology remains unclear, severalstudies have shown that endothelial cell dysfunction plays an important role in the genesis, development and complications relatedto this disease. Among the different processes, lipid per oxidation is involved in what could be an increase in serum lipid concentrations in pregnant women, especially triglycerides. The aim of this review is to describe the role of lipids in the pathophysiology of preeclampsia and the current evidence about the finding of hypertriglyceridemia and its development.

SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes

DEFF Research Database (Denmark)

Qi, Weier; Li, Qian; Liew, Chong Wee

2017-01-01

. However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. METHODS: We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes. Further, we modulated SHP-1...... expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. RESULTS: Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia...... and decreased arterial SHP-1 expression compared with mice fed a regular diet. Arterial SHP-1 expression was also decreased in Zucker fatty rats, Zucker diabetic fatty rats and in patients with type 2 diabetes. In primary cultured VSMCs, oxidised LDL suppressed SHP-1 expression by activating Mek-1 (also known...

Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics.

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Esteghamati, A; Aryan, Z; Esteghamati, Ar; Nakhjavani, M

2015-04-01

It is not known whether the association of serum 25-hydroxyvitamin D [25(OH)D] with glycemic measurements of individuals without diabetes is similar to those with diabetes or not. This study is aimed to investigate the association of serum 25(OH)D with glycemic markers of diabetics, nondiabetics, and prediabetics. A case-control study was conducted on age and sex matched 1,195 patients with type 2 DM, 121 prediabetics, and 209 healthy controls. Anthropometric variables, lipid profile, glycemic measurements, and serum 25(OH)D levels were recorded. Serum insulin and C-peptide levels were also measured. All glycemic measurements were compared between diabetics and nondiabetics and prediabetics at different vitamin D status. Patients with DM had lower serum 25(OH)D compared to prediabetics and healthy controls. Endogenous insulin production in response to food intake and in fasting was significantly lower in vitamin D deficient patients with DM compared to those with serum 25(OH)D>40 ng/ml. Diabetic women with serum 25(OH)D40 ng/ml. Healthy individuals with serum 25(OH)D<20 ng/ml had signs of insulin resistance as estimated by significant increase of HOMA-IR, HbA1c, and fasting plasma glucose (FPG). In addition, we found that serum 25(OH)D was inversely associated with insulin resistance. Vitamin D deficiency is associated with insulin resistance in nondiabetics, which is independent of obesity. Furthermore, vitamin D deficiency is associated with reduced insulin production in type 2 diabetics, which was mainly observed in men. Accordingly, a gender disparity also exists in association of serum 25(OH)D with glycemic measurements. © Georg Thieme Verlag KG Stuttgart · New York.

Antioxidant, antihyperglycemic, and antidyslipidemic effects of Brazilian-native fruit extracts in an animal model of insulin resistance.

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de Souza Cardoso, Juliane; Oliveira, Pathise Souto; Bona, Natália Pontes; Vasconcellos, Flávia Aleixo; Baldissarelli, Jucimara; Vizzotto, Marcia; Soares, Mayara Sandrielly Pereira; Ramos, Vanessa Plasse; Spanevello, Roselia Maria; Lencina, Claiton Leoneti; Tavares, Rejane Giacomelli; Stefanello, Francieli Moro

2018-12-01

Insulin resistance (IR) plays an important role in the development of many diseases, such as diabetes mellitus. Therefore, the aim of the present study was to evaluate the effects of the extracts from fruits native to Brazil on metabolic parameters and hepatic oxidative markers in an animal model of insulin resistance induced by dexamethasone (DEX). Wistar rats received water or extracts of Eugenia uniflora or Psidium cattleianum, once a day for 21 days. For the last 5 days, the rats received an intraperitoneal injection of saline or DEX. DEX caused a reduction in body weight gain and relative pancreatic weight, as well as glucose intolerance, and an increase in serum glucose and triacylglycerol levels. The extracts were found to prevent hyperglycemia and hypertriglyceridemia. DEX caused an increase in the levels of thiobarbituric acid-reactive substances and reactive oxygen species production in the liver of rats, and both extracts prevented these changes. In addition, hepatic glutathione peroxidase activity was reduced by DEX. However, total thiol content and activities of catalase, superoxide dismutase, and delta-aminolevulinate dehydratase were not altered in any of the tested groups. Fruit extracts of E. uniflora and P. cattleianum exhibited considerable antihyperglycemic, antidyslipidemic, and antioxidant effects, and may be useful in the therapeutic management of alterations due to IR.

Retinol Binding Protein-4 Is Associated with TNF-α and Not Insulin Resistance in Subjects with Type 2 Diabetes Mellitus and Coronary Heart Disease

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Nasser M. Al-Daghri

2009-01-01

Full Text Available We studied the association between RBP4 and various markers related to insulin resistance and diabetic complications as well as inflammatory markers in Saudi population suffering from type 2 diabetes and coronary heart disease. Patients with type 2 diabetes were divided into 3 groups according to the type of treatment and involvement of coronary artery disease. Serum RBP4, TNF-α, insulin, CRP, resistin, leptin and adiponectin were analysed in all samples. RBP4 levels increased significantly in the group of diabetic subjects treated with oral hypoglycemic agents and diabetic patients with coronary heart disease (30.2 ± 11.8; 33.4 ± 13.6 respectively, while there was no significant change in the other group for diabetic subjects on low-carbohydrate diet (25.1 ± 10.9 compared to control group (22.6 ± 9.5. RPB4 levels were positively correlated with TNF-α in the group of diabetic subjects on oral hypoglycemic agents and diabetic patients with coronary heart disease (r = 0.52, P < 0.05; r = 0.58, P < 0.05 respectively. No correlations were found between RBP4 levels and insulin resistance in all studied groups. Our findings suggest that serum RBP4 levels is associated with pro-inflammatory cytokine (TNF-α and is not associated with insulin resistance among patients with type 2 diabetes and coronary heart disease.

The impact of parental history of type 2 diabetes on hyperinsulinemia and insulin resistance in subjects from central Mexico.

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Acevedo-Negrete, Ana Paula; Porchia, Leonardo M; Gonzalez-Mejia, M Elba; Torres-Rasgado, Enrique; Solis-Cano, Dania G; Ruiz-Vivanco, Guadalupe; Pérez-Fuentes, Ricardo

2017-12-01

Hyperinsulinemia and insulin resistance are both associated with the development of Type 2 Diabetes and other pathologies; however, the influence of parental history of Type 2 diabetes (PH-T2D) has yet to be investigated. Therefore, this study was conducted to determine the effect of PH-T2D has on the risk of developing hyperinsulinemia and IR. 1092 subjects (703 non-pregnant females and 389 males) were enrolled for a cross-sectional study. Clinical and biochemical parameters were collected. Subjects were allocated according to their PH-T2D: no parents, one parent, or both parents. Insulin resistance was calculated using the HOMA1 equation (HOMA1-IR). Logistic regression was used to determine the association (odds ratio) between PH-T2D and hyperinsulinemia or insulin resistance. Increasing degrees of PH-T2D were associated with significant increases in fasting plasma glucose, insulin, and HOMA1-IR (p insulin resistance (odds ratio=1.47, 95%CI: 1.08-2.00 and odds ratio=1.77, 95%CI: 1.09-2.87, respectively), when adjusting for age, sex, BMI, fasting plasma glucose, and triglycerides. The presences of PH-T2D significantly increased the risk of developing hyperinsulinemia and insulin resistance. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

Science.gov (United States)

2010-01-01

Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p hypertriglyceridemia. PMID:20429872

Insulin resistance, role of metformin and other noninsulin therapies in pediatric type 1 diabetes

Science.gov (United States)

Type 1 diabetes mellitus (T1DM) in youth is a challenging chronic medical condition. Its management should address not only the glycemic control but also insulin resistance and cardiovascular disease risk factors which are increasingly recognized to be present in youth with TID. Current knowledge on...

Is salivary gland function altered in noninsulin-dependent diabetes mellitus and obesity-insulin resistance?

Science.gov (United States)

Ittichaicharoen, Jitjiroj; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2016-04-01

Salivary gland dysfunction in several systemic diseases has been shown to decrease the quality of life in patients. In non-insulin dependent diabetes mellitus (NIDDM), inadequate salivary gland function has been evidenced to closely associate with this abnormal glycemic control condition. Although several studies demonstrated that NIDDM has a positive correlation with impaired salivary gland function, including decreased salivary flow rate, some studies demonstrated contradictory findings. Moreover, the changes of the salivary gland function in pre-diabetic stage known as insulin resistance are still unclear. The aim of this review is to comprehensively summarize the current evidence from in vitro, in vivo and clinical studies regarding the relationship between NIDDM and salivary gland function, as well as the correlation between obesity and salivary gland function. Consistent findings as well as controversial reports and the mechanistic insights regarding the effect of NIDDM and obesity-insulin resistance on salivary gland function are also presented and discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dietary Patterns, Insulin Resistance, and Incidence of Type 2 Diabetes in the Whitehall II Study

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McNaughton, Sarah A.; Mishra, Gita D.; Brunner, Eric J.

2008-01-01

OBJECTIVE?The aim of this study was to identify a dietary pattern associated with insulin resistance and investigate whether this pattern was prospectively associated with type 2 diabetes. RESEARCH DESIGN AND METHODS?Analysis was based on 7,339 participants of the Whitehall II study. Dietary intake was measured using a 127-item food frequency questionnaire. We used the reduced rank regression method to determine dietary patterns using the homeostasis model assessment of insulin resistance as ...

Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes.

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Duk-Hee Lee

2011-01-01

Full Text Available There is emerging evidence that background exposure to persistent organic pollutants (POPs are important in the development of conditions predisposing to diabetes as well as of type 2 diabetes itself. We recently reported that low dose POPs predicted incident type 2 diabetes in a nested case-control study. The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study.The 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2 sera included 8 organochlorine (OC pesticides, 22 polychlorinated biphenyls (PCBs, and 1 polybrominated biphenyl (PBB. Body mass index (BMI, triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA-IR were study outcomes at 2005-06 (year 20. The evolution of study outcomes during 18 years by categories of serum concentrations of POPs at year 2 was evaluated by adjusting for the baseline values of outcomes plus potential confounders. Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Oxychlordane, trans-nonachlor, and hexachlorobenzene also significantly predicted higher triglycerides. Persistent PCBs with ≥7 chlorides predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 with similar dose-response curves.Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases

The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats.

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Salman, Zenat K; Refaat, Rowaida; Selima, Eman; El Sarha, Ashgan; Ismail, Menna A

2013-08-15

Increasing evidence has established causative links between obesity, chronic inflammation and insulin resistance; the core pathophysiological feature in type 2 diabetes mellitus. This study was designed to examine whether the combination of L-cysteine and metformin would provide additional benefits in reducing oxidative stress, inflammation and insulin resistance in streptozotocin-induced type 2 diabetes in rats. Male Wistar rats were fed a high-fat diet (HFD) for 8 weeks to induce insulin resistance after which they were rendered diabetic with low-dose streptozotocin. Diabetic rats were treated with metformin (300 mg/kg/day), L-cysteine (300 mg/kg/day) and their combination along with HFD for another 2 weeks. Control rats were fed normal rat chow throughout the experiment. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index (HOMA-IR) and serum free fatty acids (FFAs) were measured. Serum levels of the inflammatory markers; monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and nitrite/nitrate were also determined. The liver was isolated and used for determination of malondialdehyde (MDA), reduced glutathione (GSH), caspase-3 and cytochrome c levels. The hypoglycemic effect of the combination therapy exceeded that of metformin and L-cysteine monotherapies with more improvement in insulin resistance. All treated groups exhibited significant reductions in serum FFAs, oxidative stress and inflammatory parameters, caspase-3 and cytochrome c levels compared to untreated diabetic rats with the highest improvement observed in the combination group. In conclusion, the present results clearly suggest that L-cysteine can be strongly considered as an adjunct to metformin in management of type 2 diabetes. © 2013 Elsevier B.V. All rights reserved.

The Role of Hyperglycemia, Insulin Resistance, and Blood Pressure in Diabetes-Associated Differences in Cognitive Performance-The Maastricht Study.

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Geijselaers, Stefan L C; Sep, Simone J S; Claessens, Danny; Schram, Miranda T; van Boxtel, Martin P J; Henry, Ronald M A; Verhey, Frans R J; Kroon, Abraham A; Dagnelie, Pieter C; Schalkwijk, Casper G; van der Kallen, Carla J H; Biessels, Geert Jan; Stehouwer, Coen D A

2017-11-01

To study to what extent differences in cognitive performance between individuals with different glucose metabolism status are potentially attributable to hyperglycemia, insulin resistance, and blood pressure-related variables. We used cross-sectional data from 2,531 participants from the Maastricht Study (mean age ± SD, 60 ± 8 years; 52% men; n = 666 with type 2 diabetes), all of whom completed a neuropsychological test battery. Hyperglycemia was assessed by a composite index of fasting glucose, postload glucose, glycated hemoglobin (HbA 1c ), and tissue advanced glycation end products; insulin resistance by the HOMA of insulin resistance index; and blood pressure-related variables included 24-h ambulatory pressures, their weighted SDs, and the use of antihypertensive medication. Linear regression analyses were used to estimate mediating effects. After adjustment for age, sex, and education, individuals with type 2 diabetes, compared with those with normal glucose metabolism, performed worse in all cognitive domains (mean differences in composite z scores for memory -0.087, processing speed -0.196, executive function and attention -0.182; P values <0.032), whereas individuals with prediabetes did not. Diabetes-associated differences in processing speed and executive function and attention were largely explained by hyperglycemia (mediating effect 79.6% [bootstrapped 95% CI 36.6; 123.4] and 50.3% [0.6; 101.2], respectively) and, for processing speed, to a lesser extent by blood pressure-related variables (17.7% [5.6; 30.1]), but not by insulin resistance. None of the factors explained the differences in memory function. Our cross-sectional data suggest that early glycemic and blood pressure control, perhaps even in the prediabetic stage, may be promising therapeutic targets for the prevention of diabetes-associated decrements in cognitive performance. © 2017 by the American Diabetes Association.

The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology

OpenAIRE

Szymanski, Kimberly M.; Binns, Derk; Bartz, René; Grishin, Nick V.; Li, Wei-Ping; Agarwal, Anil K.; Garg, Abhimanyu; Anderson, Richard G. W.; Goodman, Joel M.

2007-01-01

Lipodystrophy is a disorder characterized by a loss of adipose tissue often accompanied by severe hypertriglyceridemia, insulin resistance, diabetes, and fatty liver. It can be inherited or acquired. The most severe inherited form is Berardinelli-Seip Congenital Lipodystrophy Type 2, associated with mutations in the BSCL2 gene. BSCL2 encodes seipin, the function of which has been entirely unknown. We now report the identification of yeast BSCL2/seipin through a screen to detect genes importan...

Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

OpenAIRE

Wang, Qiuwei; Huang, Ruiping; Yu, Bin; Cao, Fang; Wang, Huiyan; Zhang, Ming; Wang, Xinhong; Zhang, Bin; Zhou, Hong; Zhu, Ziqiang

2013-01-01

OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measur...

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

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Dussaillant Catalina

2012-11-01

Full Text Available Abstract Background Severe hypertriglyceridemia (HTG has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel. Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

APOA5 Q97X mutation identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family.

Science.gov (United States)

Dussaillant, Catalina; Serrano, Valentina; Maiz, Alberto; Eyheramendy, Susana; Cataldo, Luis Rodrigo; Chavez, Matías; Smalley, Susan V; Fuentes, Marcela; Rigotti, Attilio; Rubio, Lorena; Lagos, Carlos F; Martinez, José Alfredo; Santos, José Luis

2012-11-15

Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

Medical nutrition therapy is the essential cornerstone for effective treatment of "refractory" severe hypertriglyceridemia regardless of pharmaceutical treatment: Evidence from a Lipid Management Program.

Science.gov (United States)

Rhodes, Katherine S; Weintraub, Martha; Marchlewicz, Elizabeth H; Rubenfire, Melvyn; Brook, Robert D

2015-01-01

Patients with refractory severe hypertriglyceridemia are at risk of pancreatitis and cardiovascular disease. The role of individualized nutrition therapy in these patients independent of pharmaceutical treatment has not been documented. To document the effect of nutrition intervention on severe hypertriglyceridemia regardless of medication status or prior nutrition counseling. Outcomes of new patients with triglycerides ≥ 500 mg/dL presenting to a Lipid Management Program over a 6-year period were tracked. Patients received comprehensive laboratory assessment, nutrition assessment, and initiation of an individualized diet intervention before seeing the lipidologist. Clinical and behavioral outcomes were recorded. In all, 168 patients (117 men; mean age, 49.03 ± 11.22 years; body mass index, 32.61 ± 5.85 kg/m(2); 110 (65.5%) on lipid-lowering medications) returned for assessment of nutrition intervention. Triglycerides were reduced from median (interquartile range) 961.5 (611.5-1785.3) to 493.0 (337-736.3) mg/dL (P severe hypertriglyceridemia independent of lipid-lowering medication(s) and prior nutrition counseling. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.

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Zeitler, Heike; Balta, Zeynep; Klein, Burkhard; Strassburg, Christian P

2015-08-01

Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia-induced pancreatitis (HTGP). The rationale behind this approach is the depletion of triglycerides and the reduction of inflammatory cytokines. The time span between onset of clinical symptoms and start of plasmapheresis might have an important impact on mortality. Hyperviscosity of patients' plasma represents another special challenge for the applied separation technology. The procedures can be performed either by centrifugal device (CFD) or membrane based (MBS) units. The present study reports the outcome of 10 patients suffering from HTG. The expected mortality of the collective was 25%. Plasmapheresis was started after an average 16.3 h (SD ± 6.7 h) after onset of symptoms. No mortality occurred. Apheresis was statistically equally effective with both devices. A median of 3 sessions reduced the TG level to normal and correlated with patients' improvement. During follow up, three patients developed a pancreatic pseudocyst requiring surgical intervention without further complication. © 2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.

Higher Risk of Abdominal Obesity, Elevated LDL Cholesterol and Hypertriglyceridemia, but not of Hypertension, in People Living with HIV

DEFF Research Database (Denmark)

Gelpi, Marco; Afzal, Shoaib; Lundgren, Jens

2018-01-01

Background: People living with HIV (PLWH) have lower life expectancy than uninfected individuals, partly explained by excess risk of cardiovascular diseases (CVD) and CVD risk factors. We investigated the association between HIV infection and abdominal obesity, elevated LDL cholesterol (LDL...... and underwent blood pressure, waist-, hip-, weight-, and height-measurements. Non-fasting blood samples were obtained from all participants. We assessed whether HIV was independently associated with abdominal obesity, elevated LDL-C, hypertriglyceridemia and hypertension using logistic regression models...... adjusted for known risk factors. Results: HIV infection was associated with higher risk of abdominal obesity (adjusted odds ratio (aOR): 1.92[1.60-2.30]) for a given BMI, elevated LDL-C (aOR: 1.32[1.09-1.59]), hypertriglyceridemia (aOR 1.76[1.49-2.08]), and lower risk of hypertension (aOR: 0.63[0.54 - 0...

Adipokines and Insulin Resistance According to Characteristics of Pregnant Women with Gestational Diabetes Mellitus.

Science.gov (United States)

Jeon, Eon Ju; Hong, Seong Yeon; Lee, Ji Hyun

2017-12-01

The aim of this study was to evaluate adipokines concentration and insulin resistance according to maternal age or obesity at pregnancy and weight change at diagnosed gestational diabetes mellitus (GDM) in pregnant women with GDM. This study included 57 pregnant women who were diagnosed with GDM at 24 to 28 weeks of gestation. The subjects were classified into two or three groups according to pre-pregnancy body mass index (BMI, insulin resistance (HOMA-IR), and HOMA2-%B were increased in the group with pre-pregnancy BMI ≥25 kg/m². Leptin and HOMA-IR were positively correlated with BMI both before pregnancy and at screening for GDM. There were no significant correlations between HOMA-IR and adipokines. HOMA-IR showed positive correlation with HOMA2-%B and negative correlation with HOMA2-%S. Leptin and HOMA-IR at diagnosed GDM were increased in the GDM patients with obesity before pregnancy. They were positively correlated with BMI both before pregnancy and at screening for GDM. The effect of maternal age at pregnancy and weight change during pregnancy at GDM screening on adipokines and insulin resistance might be less pronounced than the effect of maternal obesity. Copyright © 2017 Korean Diabetes Association

The Most Prevalnet Organism in Diabetic Foot Ulcers and Its Drug Sensitivity and Resistance to Different Standard Antibiotics

International Nuclear Information System (INIS)

Nageen, A.

2016-01-01

Objective: To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics. Study Design: Adescriptive and cross-sectional study. Place and Duration of Study: Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012. Methodology: Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted. Results: Staphylococcus aureus was the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients. Conclusion: Staphylococcus aureus was the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole. (author)

Gender differences of dyslipidemia in type 2 diabetics

Energy Technology Data Exchange (ETDEWEB)

Gilani, S Y.H. [Ayub Medical College, Abbottabad (Pakistan). Dept. of Pharmacology; Bibi, S [Ayub Medical College, Abbottabad (Pakistan). Dept. of Physiology; Ahmed, N [Frontier Medical College, Abbottabad (Pakistan). Dept. of Medicine

2010-07-15

Type II diabetic patients are at an increased risk of coronary artery disease and cerebrovascular disease because of deranged lipid metabolism. Female diabetic patients are predominantly at risk. The objective of this cross-sectional study was to determine effects of gender on dyslipidemia of type II diabetic patients. Methods: This study was carried out at Out-Patients Department, Medical A Unit, Ayub Teaching Hospital Abbottabad from May 27, to November 27, 2009. All type II diabetic patients who were above 40 and gave consent were included in the study. Data was collected through a structured proforma. Pattern of dyslipidemia in type II diabetic patients were estimated by computing all the four types of dyslipidemia like hypertriglyceridemia, low HDL, increased serum total cholesterol and increased serum LDL. Results: There were 150 patients with mean age 65.67+- 11.29 years. There were 80 (53.33%) male and 70 (46.7%) female patients. Mean BMI was 28.45 +- 3.30 Kg/m/sup 2/. Mean serum cholesterol level was 3.9 +- 1.31 mmol/L, triglyceride level was 2.98 +- 1.14 mmol/L, LDL level was 3.28 +- 0.85 mmol/L and HDL was 0.95 +- 0.02 mmol/L. Women were more frequent to have low level HDL as compare to men (p<0.05), while no significant difference was found regarding serum cholesterol, serum triglyceride and serum LDL (p>0.05). Conclusion: Female diabetic patients have increased frequency of low level of serum HDL as compared to males. (author)

An Alteration of Lymphocytes Subpopulations and Immunoglobulins Levels in Patients with Diabetic Foot Ulcers Infected Particularly by Resistant Pathogens

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Vladimíra Fejfarová

2016-01-01

Full Text Available The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs especially those infected by resistant microorganisms. Methods. 68 patients treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n=50 and subgroup R by resistant pathogens (n=18. Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p<0.01 and total numbers of lymphocytes (p<0.001 involving B lymphocytes (p<0.01, CD4+ (p<0.01, and CD8+ T cells (p<0.01 and their naive and memory effector cells. Higher levels of IgG (p<0.05 including IgG1 (p<0.001 and IgG3 (p<0.05 were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p<0.05. A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS. Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p<0.01 in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls.

Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial.

Science.gov (United States)

Kastelein, John J P; Maki, Kevin C; Susekov, Andrey; Ezhov, Marat; Nordestgaard, Borge G; Machielse, Ben N; Kling, Douglas; Davidson, Michael H

2014-01-01

Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for ethyl ester forms. The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational pharmaceutical omega-3 free fatty acid (OM3-FFA) containing eicosapentaenoic acid and docosahexaenoic acid. This was a multinational, double-blind, randomized, out-patient study. Men and women with triglycerides (TGs) ≥ 500 mg/dL, but severe hypertriglyceridemia. This trial was registered at www.clinicaltrials.gov as NCT01242527. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The effects of cinnamon on glycemic indexes and insulin resistance in adult male diabetic rats with streptozotocin

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SEbrahim Hosseini

2015-02-01

Full Text Available Background: Diabetes is a common disease that for its treatment and control different methods are recommended such as the use of natural remedies and lifestyle modification. Since the use of herbal medicines have less side effects than many chemical drugs, hence, this study aimed to investigate the effect of cinnamon extract on blood glucose, insulin and insulin resistance in diabetic rats with streptozotocin. Materials and Methods: This experimental study was conducted on 40 adult male rats, that were randomly divided into 4 groups including non diabetic control, diabetic control and two experimental groups receiving doses 60mg/kg of cinnamon extract for 3 and 6 weeks. At the end, by phlebotomizing of rats' heart, blood glucose and insulin were measured and using HOMA score insulin resistance was measured. To be normal data distribution, Kolmogorov-Smirnov test was done and data analyzed by SPSS-20 software and ANOVA and post hoc Tukey tests. Results: The results showed that in the group receiving the cinnamon extract, glycemic and insulin indexes were significantly adjusted. Conclusion: Cinnamon is probably due to have flavonoid and antioxidant compounds with antioxidant by increasing glucose uptake via the different body cells and due to reduction of oxidative stress level led to adjust glycemic and insulin indexes of blood

GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease?

DEFF Research Database (Denmark)

Gaster, M; Staehr, P; Beck-Nielsen, H

2001-01-01

To gain further insight into the mechanisms underlying muscle insulin resistance, the influence of obesity and type 2 diabetes on GLUT4 immunoreactivity in slow and fast skeletal muscle fibers was studied. Through a newly developed, very sensitive method using immunohistochemistry combined...... with morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic...... was reduced to 77% in the obese subjects and to 61% in type 2 diabetic patients compared with the control subjects. We propose that a reduction in the fraction of slow-twitch fibers, combined with a reduction in GLUT4 expression in slow fibers, may reduce the insulin-sensitive GLUT4 pool in type 2 diabetes...

Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats.

Science.gov (United States)

Luo, Cheng; Yang, Hui; Tang, Chengyong; Yao, Gaoqiong; Kong, Lingxi; He, Haixia; Zhou, Yuanda

2015-09-01

Recent studies show that inflammation underlies the metabolic disorders of insulin resistance and type 2 diabetes mellitus. Since kaempferol, a naturally occurring flavonoid, has been described to have potent anti-inflammatory properties, we investigated whether kaempferol could ameliorate insulin resistance through inhibiting inflammatory responses. The model of diabetic rat was induced by 6-week high-fat diet plus streptozotocin. Animals were orally treated with kaempferol (50 or 150 mg/kg) and aspirin (100mg/kg) for 10 weeks. The results showed that kaempferol ameliorated blood lipids and insulin in an dose-dependent manner. Kaempferol effectively restored insulin resistance induced alteration of glucose disposal by using an insulin tolerance test and the euglycemic-hyperinsulinemic clamp method. Western blotting results showed that KPF inhibited the phosphorylation of insulin receptor substrate-1 (IRS-1), IkB kinase α (IKKα) and IkB kinase β (IKKβ). These effects were accompanied with reduction in nucleic and cytosol levels of nuclear factor kappa-β (NF-κB), and further tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels. Aspirin had similar effects. These results provide in vivo evidence that kaempferol-mediated down-regulation of IKK and subsequent inhibition of NF-κB pathway activation may be associated with the reduction of hepatic inflammatory lesions, which is contributing to the improvement of insulin signaling defect in diabetes. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of a mini-trampoline rebound exercise program on insulin resistance, lipid profile and central obesity in individuals with type 2 diabetes.

Science.gov (United States)

Nuhu, Jibril M; Maharaj, Sonill S

2018-04-01

Exercises are important as an adjuvant for managing diabetes but due to fatigue and time constraints, individuals with diabetes may not engage in them. Jumping on a mini-trampoline referred to as rebound exercise is an aerobic activity used for exercise training benefits but only little research is available on its effects in diabetes. The purpose of this study was to determine the effect of mini-trampoline rebound exercise on insulin resistance, lipid profile and central obesity in type 2 diabetics. Sixty non-insulin dependent type 2 diabetics (median age: 39.0 years, median body mass index: 25.2 kg/m2) recruited using convenience sampling were randomized to a rebound exercise group (N.=30) or a control group (N.=30). The control group read health magazines or watched television while the rebound exercise group jumped on a mini-trampoline at moderate intensity for 30 minutes three times per week for 12 weeks. Postrebound exercise, significant improvements in insulin resistance, lipid profile and waist circumference were noted when compared to the control (Ptrampoline rebound exercise is beneficial for individuals with type 2 diabetes and can serve as a useful exercise approach in the management of cardiovascular risk in diabetes.

Liver fat contents, abdominal adiposity and insulin resistance in non-diabetic prevalent hemodialysis patients.

Science.gov (United States)

Chen, Hung-Yuan; Lin, Chien-Chu; Chiu, Yen-Ling; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Wu, Hon-Yen; Peng, Yu-Sen

2014-01-01

The liver fat contents and abdominal adiposity correlate well with insulin resistance (IR) in the general population. However, the relationship between liver fat content, abdominal adiposity and IR in non-diabetic hemodialysis (HD) patients remains unclear. This study aimed to clarify the associations among these factors. This is a cross-sectional, observational study. All patients received abdominal ultrasound for liver fat content. Abdominal adiposity was quantified with the conicity index (Ci) and waist circumference (WC). We checked the homeostasis model assessment for insulin resistance index (HOMA-IR) for IR. A total of 112 patients (60 women) were analyzed. Subjects with higher liver fat contents and WC had higher IR indices. But Ci did not correlate with IR indices. In both the multi-variable linear regression model and the logistic regression model, only higher liver fat content predicted a severe IR status. Liver fat contents have a remarkable correlation with IR; however, abdominal adiposity, measured either by Ci or WC, dose not independently correlate with IR in non-diabetic prevalent HD patients. © 2014 S. Karger AG, Basel.

Effects of the use of assisted reproductive technologies and an obesogenic environment on resistance artery function and diabetes biomarkers in mice offspring.

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Francisco I Ramirez-Perez

Full Text Available Maternal obesity affects the incidence of cardiovascular disease and diabetes in offspring. Also the use of assisted reproductive technologies (ART has been associated with cardiovascular deficiencies in offspring. Obese women often suffer from infertility and use ART to achieve a pregnancy, but the combined effects of maternal obesity and ART on cardiovascular health and incidence of diabetes in the offspring is not known. Here, we report the effects of the use of ART within an obesogenic environment, consisting of feeding a western diet (WD to dams and offspring, on resistance artery function and presence of diabetes biomarkers in juvenile mice offspring. Our results indicate that WD and ART interacted to induce endothelial dysfunction in mesenteric resistance arteries isolated from 7-week-old mice offspring. This was determined by presence of a reduced acetylcholine-induced dilation compared to controls. The arteries from these WD-ART mice also had greater wall cross-sectional areas and wall to lumen ratios indicative of vascular hypertrophic remodeling. Of the diabetes biomarkers measured, only resistin was affected by a WD×ART interaction. Serum resistin was significantly greater in WD-ART offspring compared to controls. Diet and sex effects were observed in other diabetes biomarkers. Our conclusion is that in mice the use of ART within an obesogenic environment interacts to favor the development of endothelial dysfunction in the resistance arteries of juvenile offspring, while having marginal effects on diabetes biomarkers.

Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats.

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Naoki Horii

Full Text Available Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA, a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats. Male 20-week-old type 2 diabetic rats (OLETF were randomly divided into 3 groups: sedentary control, resistance training (3 times a week on alternate days for 8 weeks, or resistance training with continuous infusion of a 5α-reductase inhibitor (n = 8 each group. Age-matched, healthy nondiabetic Long-Evans Tokushima Otsuka (LETO rats (n = 8 were used as controls. The results indicated that OLETF rats showed significant decrease in muscular DHEA, free testosterone, DHT levels, and protein expression of steroidogenic enzymes, with loss of skeletal muscle mass and hyperglycemia, compared to that of LETO rats. However, 8-week resistance training in OLETF rats significantly increased the levels of muscle sex steroid hormones and protein expression of steroidogenic enzymes with a concomitant increase in skeletal muscle mass, improved fasting glucose level, and insulin sensitivity index. Moreover, resistance training accelerated glucose transporter-4 (GLUT-4 translocation and protein kinase B and C-ζ/λ phosphorylation. Administering the 5α-reductase inhibitor in resistance-trained OLETF rats resulted in suppression of the exercise-induced effects on skeletal muscle mass, fasting glucose level, insulin sensitivity index, and GLUT-4 signaling, with a decline in muscular DHT levels. These findings suggest that resistance training

Mechanism linking diabetes mellitus and obesity

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Al-Goblan AS

2014-12-01

Full Text Available Abdullah S Al-Goblan,1 Mohammed A Al-Alfi,1 Muhammad Z Khan2 1Diabetes Center, King Fahad Specialist Hospital, Buraidah, Qassim, Kingdom of Saudi Arabia; 2Sulaiman AlRajhi Colleges, Al Bukairiyah, Kingdom of Saudi Arabia Abstract: Body mass index has a strong relationship to diabetes and insulin resistance. In obese individuals, the amount of nonesterified fatty acids, glycerol, hormones, cytokines, proinflammatory markers, and other substances that are involved in the development of insulin resistance, is increased. The pathogenesis in the development of diabetes is based on the fact that the β-islet cells of the pancreas are impaired, causing a lack of control of blood glucose. The development of diabetes becomes more inevitable if the failure of β-islet cells of the pancreas is accompanied by insulin resistance. Weight gain and body mass are central to the formation and rising incidence of type 1 and type 2 diabetes. This literature review will demonstrate the facts that link obesity with insulin resistance and pancreatic β-cell dysfunction. In conclusion, new approaches in managing and preventing diabetes in obese individuals must be studied and investigated based on the facts. Keywords: diabetes mellitus, obesity, insulin resistance

The effect of Punica granatum L. along with aerobic training on resistin, serum adiponectin and insulin resistance in women with type 2 diabetes

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Ahmad Abdi

2018-04-01

Full Text Available Background: Factors secreted from adipocytes, such as resistin and adiponectin can affect peripheral insulin resistance and type 2 diabetes. Physical activity and pomegranate, which has both anti-inflammatory and antioxidant properties can affect resistin and adiponectin. The aim of this study was to examine the effect of Punica granatum L. along with aerobic training on serum resistin, adiponectin and insulin resistance in women with type 2 diabetes. Materials and Methods: In this study, 33 diabetic women with type 2 diabetes were selected from Babol city and were randomly divided into four groups (control, P. granatum L., training and P. granatum L.+ training. The training groups participated in an aerobic training for six weeks, three sessions a week (60% to 75% of the reserved heart rate and for 25 to 45 min. The control groups of P. granatum L. and P. granatum L. + training were fed 150 mL of P. granatum L. for six weeks (at about 18 p.m. Two days before and after the protocol, blood samples were taken. Results: The results showed that there was no significant difference in the serum resistin levels among the three experimental groups. Also, the results showed a significant difference between adiponectin levels and insulin resistance in four groups. Conclusions: It seems that aerobic training and P. granatum L. and combination of both can have anti-inflammatory and antioxidant effects on reduction of adiponectin and insulin resistance in women with type 2 diabetes.

Association of the hypertriglyceridemic waist phenotype and type 2 diabetes mellitus among adults in China.

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Ren, Yongcheng; Zhang, Ming; Zhao, Jingzhi; Wang, Chongjian; Luo, Xinping; Zhang, Jiatong; Zhu, Tian; Li, Xi; Yin, Lei; Pang, Chao; Feng, Tianping; Wang, Bingyuan; Zhang, Lu; Li, Linlin; Yang, Xiangyu; Zhang, Hongyan; Hu, Dongsheng

2016-09-01

To clarify the association of the hypertriglyceridemic waist phenotype and type 2 diabetes mellitus among adults in China. In the present case-control study, we included 1,685 patients with type 2 diabetes mellitus and 7,141 normal glucose-tolerant controls from the Henan Province of China in 2011. Elevated waist circumference (GW) was defined as ≥90 cm for men and ≥80 cm for women. Hypertriglyceridemia (HT) was defined as >1.7 m mol/L triglycerides (TG) level. The association of hypertriglyceridemic waist phenotype and type 2 diabetes mellitus was investigated by sex, body mass index, physical activity, and family history of diabetes. Cases and controls differed in age, waist circumference (WC), weight, TG level, fasting glucose, body mass index, smoking status, diabetic family history, physical activity and hypertriglyceridemic waist phenotype (P type 2 diabetes mellitus (odds ratio 4.14, 2.42 and 6.23, respectively). Only HTGW was consistently associated with risk of type 2 diabetes mellitus, with or without adjustment. The strongest relationship between HTGW and type 2 diabetes mellitus was for subjects with body mass index 24.0 kg/m(2) (odds ratio 6.54, 95% confidence interval 4.22-10.14) after adjustment for cofounding variables. HTGW was stably and significantly associated with risk of type 2 diabetes mellitus in adult Chinese. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Type 2 diabetes mellitus and its influence in the development of multidrug resistance tuberculosis in patients from southeastern Mexico.

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Pérez-Navarro, Lucia Monserrat; Fuentes-Domínguez, Francisco Javier; Zenteno-Cuevas, Roberto

2015-01-01

To determine the factors associated with the presence of pulmonary tuberculosis in patients with type 2 diabetes mellitus and the effect in the development of drug and multi-drug resistance, in a population with tuberculosis from the southeast of Mexico. This is a case-control study including 409 individuals, 146 with the binomial tuberculosis-type 2 diabetes mellitus and 263 individuals with tuberculosis. Demographic, epidemiological and outcome variables were collected. Risks were calculated. The factors associated with the presence of type 2 diabetes mellitus were age ≥35years, (OR=9.7; CI: 5.2-17.8), previous contact with a person infected with tuberculosis (OR=1.7; CI: 1.1-3.1). Body mass index ≥25 kg/m(2) (OR=2.2; CI: 1.1-4.3), and inherited family history of diabetes (OR=5.4; CI: 3.2-9.2). It was also found that patients with tuberculosis-type 2 diabetes mellitus presented a 4.7-fold (CI: 1.4-11.3) and 3.5-fold (CI: 1.1-11.1) higher risk of developing drug- and multidrug resistance tuberculosis, respectively. By last, individuals with tuberculosis-type 2 diabetes had a 2.3-fold (CI: 1.5-4.1) greater chance of persisting as tuberculosis-positive by the second month of treatment, delaying the resolution of the tuberculosis infection. Type 2 diabetes exerts a strong influence on the presentation and evolution of tuberculosis within the analyzed population and displays remarkable particularities, necessitating the development of dedicated tuberculosis-diabetes surveillance systems that consider the particular epidemiological characteristics of the population affected. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of vitamin D supplementation on fasting plasma glucose, insulin resistance and prevention of type 2 diabetes mellitus in non-diabetics: A systematic review and meta-analysis

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He, Sitian; Yu, Songcheng; Zhou, Zonglei; Wang, Chongjian; Wu, Yongjun; Li, Wenjie

2018-01-01

Increasing epidemiological studies suggest that there is an association between vitamin D deficiency and risk of type 2 diabetes mellitus (T2DM). Therefore, randomized clinical trials (RCTs) have been performed to observe the effect of vitamin D supplementation on preventing T2DM, decreasing fasting plasma glucose (FPG) and improving insulin resistance to confirm the association between vitamin D and T2DM. However, the results of RCTs on controlling FPG level, improving insulin resistance and preventing T2DM in non-diabetics are inconsistent. In the present study, a systematic meta-analysis considering individual variation and intervention strategy was conducted to establish an objective and definitive conclusion. The results suggested that vitamin D supplementation had no significant effect on controlling FPG level, improving insulin resistance or preventing T2DM in non-diabetics in a pooled meta-analysis of 23 articles (containing 28 RCTs). However, stratified analysis indicated that supplementation of vitamin D had differential effects on FPG control, insulin sensitivity improvement and T2DM prevention in individuals with different baseline states: FPG was decreased for those with BMI 2,000 IU/day (P=0.047) and with intervention without calcium (P=0.047). Thus, further trials should focus on individual baselines and the supplementation strategy of vitamin D in the prevention of T2DM. PMID:29725526

The effects of cinnamon on glycemic indexes and insulin resistance in adult male diabetic rats with streptozotocin

OpenAIRE

SEbrahim Hosseini; STaereh Shojaei; SAli Hosseini

2015-01-01

Background: Diabetes is a common disease that for its treatment and control different methods are recommended such as the use of natural remedies and lifestyle modification. Since the use of herbal medicines have less side effects than many chemical drugs, hence, this study aimed to investigate the effect of cinnamon extract on blood glucose, insulin and insulin resistance in diabetic rats with streptozotocin. Materials and Methods: This experimental study was conducted on 40 adult male rats,...

Effect of angiotensin-converting enzyme gene polymorphism at the results of losartan use in the patients with type 2 diabetes mellitus

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T. Yu. Poniatowskaya

2015-03-01

Odessa National Medical University   Summary The article presented is an original investigation where the effects of losartan in patients with hypertension and type 2 diabetes mellitus (T2DM have been evaluated. The effect of therapy has been estimated with the help of gene ACE allelic variant. The dependence of enalapril antihypertensive action and nephroprotective action of ACE polymorphism has been revealed. The results obtained show a different effect on ACE allele variants of lipid metabolism in patients with hypertension and T2DM and complications in the form of hypertriglyceridemia in the patients with DD-genotype.   Key words: type 2 diabetes mellitus, hypertension, I / D polymorphism of the gene ACE, pharmacogenetics, losartan.

Diabetes-Resistant NOR Mice Are More Severely Affected by Streptozotocin Compared to the Diabetes-Prone NOD Mice: Correlations with Liver and Kidney GLUT2 Expressions

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S. Kahraman

2015-01-01

Full Text Available Nonobese Diabetic (NOD mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ. STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly.

Effects of exercise training using resistance bands on glycaemic control and strength in type 2 diabetes mellitus: a meta-analysis of randomised controlled trials.

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McGinley, Samantha K; Armstrong, Marni J; Boulé, Normand G; Sigal, Ronald J

2015-04-01

Resistance exercise using free weights or weight machines improves glycaemic control and strength in people with type 2 diabetes. Resistance band training is potentially less expensive and more accessible, but the effects of resistance band training on glycaemic control and strength in this population are not well understood. This paper aims to systematically review and meta-analyse the effect of resistance band training on haemoglobin A1c (HbA1c) and strength in adults with type 2 diabetes. Database searches were performed in August 2013 (MEDLINE, SPORTDiscus, EMBASE, and CINAHL). Reference lists of eligible articles were hand-searched for additional studies. Randomised trials evaluating the effects of resistance band training in adults with type 2 diabetes on HbA1c or objectively measured strength were selected. Baseline and post-intervention HbA1c and strength were extracted for the intervention and control groups. Details of the exercise interventions and methodological quality were collected. Seven trials met inclusion criteria. Post-intervention-weighted mean HbA1c was nonsignificantly lower in exercise groups compared to control groups [weighted mean difference (WMD) = -0.18 percentage points (-1.91 mmol/mol); P = 0.27]. Post-intervention strength was significantly higher in the exercise groups compared to the control groups in the lower extremities (WMD = 21.90 kg; P diabetes.

Asymptomatic bacteriuria in diabetes mellitus patients in Southwest ...

African Journals Online (AJOL)

%) and Serratia sp (10.8%). Candida sp was isolated more from diabetics than non-diabetics (P = 0.01). There was no significant difference in resistance between diabetics and non-diabetics (P > 0.05). Most isolates showed multiple resistance ...

A study of the pancreatic islet β-cell function and insulin resistance of type2 diabetic gastroparesis

International Nuclear Information System (INIS)

Zou Gang; Shao Hao; Lu Zeyuan; Ding Yuzhen; Chen Guanrong; Fu Juan

2005-01-01

Objective: To study the pancreatic islet β-cell function and insulin resistance of diabetic gastroparesis (DGP). Methods: 31 subjects with normal glucose tolerance (NGT), 32 subjects with impaired glucose tolerance (IGT), 38 subjects with type 2 diabetes mellitus (T2DM) and 31 subjects with DGP were en-rolled in the study, assessed by steamed bread meal tests, the plasma glucose and insulin at 0, 30, 60, 120 and 180 min were respectively measured by using glucose oxidase and radioimmunoassay, investigate the changes of area under insulin cure (INSAUC), Homa-insulin resistance (Homa-IR) index and modified β-cell function index (MBCI). Results: The INSAUC of IGT, T2DM, NGT and DGP fell in turn, there were signif-icantly differences among the groups. The Homa-IR index of NGT, IGT, DGP and T2DM rose in turn, there were significantly differences among the groupsexcept between T2DM and DGP. Conclusions: The pancreatic islet β-cell function of DGP was worse that NGT, IGT and T2DM, and the insulin resistance was stronger than NGT and IGT. (authors)

Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis

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Berglund, Lars; Brunzell, John D.; Goldberg, Anne C.; Goldberg, Ira J.; Stalenhoef, Anton

2013-01-01

While there has been considerable focus on the role and treatment of LDL cholesterol levels, a definitive role of triglycerides in the management of cardiovascular disease has been uncertain. Notably, with increasing triglyceride levels, there is a parallel increase in cholesterol levels carried by triglyceride-rich lipoproteins, which has prompted interest in the use of non-HDL cholesterol levels as a tool guiding interventions. Recent studies have provided evidence for an independent role of triglyceride levels as a cardiovascular risk factor, and recently, an Endocrine Society guideline was published for treatment of hypertriglyceridemia. In contrast to the relative uncertainty regarding triglycerides and cardiovascular disease, a role of very high triglyceride levels as a risk factor for pancreatitis has been well known. The present paper summarizes the underlying evidence for a risk role for triglyceride levels in cardiovascular disease and pancreatitis, current treatment recommendations and areas of future research. PMID:24840268

Nonfasting Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis

DEFF Research Database (Denmark)

Pedersen, Simon B; Langsted, Anne; Nordestgaard, Børge G

2016-01-01

.00 mmol/L-3.99 mmol/L), 3.9 (95% CI, 1.5-10.0; 7.5 events/10 000 person-years) for 354 mg/dL-442 mg/dL (4.00 mmol/L-4.99 mmol/L), and 8.7 (95% CI, 3.7-20.0; 12 events/10 000 person-years) for individuals with triglyceride levels greater than or equal to 443 mg/dL (≥5.00 mmol/L) (trend, P = 6 × 10...... (calculated as weight in kilograms divided by height in meters squared), alcohol intake, and gallstone disease, these results were similar with no statistical evidence of interaction. Conclusions and Relevance: Nonfasting mild-to-moderate hypertriglyceridemia from 177 mg/dL (2 mmol/L) and above is associated...

Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk.

Science.gov (United States)

Thériault, Sébastien; Don-Wauchope, Andrew; Chong, Michael; Lali, Ricky; Morrison, Katherine M; Paré, Guillaume

2016-01-01

We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture

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Park, Kyoungmin; Li, Qian

2016-01-01

The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributing risk factors in diabetes. George L. King, MD, of the Section of Vascular Cell Biology and Complications, Dianne Nunnally Hoppes Laboratory for Diabetes Complications, Joslin Diabetes Center, Harvard Medical School, Boston, MA, received the prestigious award at the American Diabetes Association’s 75th Scientific Sessions, 5–9 June 2015, in Boston, MA. He presented the Edwin Bierman Award Lecture, “Selective Insulin Resistance and the Development of Cardiovascular Disease in Diabetes,” on Sunday, 7 June 2015. This review is focused on the factors and potential mechanisms that are causing various cardiovascular pathologies. In diabetes, insulin’s actions on the endothelium and other vascular cells have significant influence on systemic metabolisms and the development of cardiovascular pathologies. Our studies showed that insulin receptors on the endothelium are important for insulin transport across the endothelial barrier and mediate insulin’s actions in muscle, heart, fat, and the brain. Insulin actions on the vascular cells are mediated by two pathways involving the actions of either IRS/PI3K/Akt or Grb/Shc/MAPK. Insulin’s activation of IRS/PI3K/Akt results in mostly antiatherogenic actions, as this pathway induces activation of eNOS, the expressions of HO-1 and VEGF, and the reduction of VCAM-1. In contrast, insulin’s activation of the Grb/Shc/MAPK pathway mediates the expressions of ET-1 and PAI-1 and migration and proliferation of contractile cells, which have proatherogenic actions. Elevated levels of glucose, free fatty acids, and inflammatory cytokines due to diabetes and insulin resistance selectively inhibit insulin�

Effect of atorvastatin on pancreatic Beta-cell function and insulin resistance in type 2 diabetes mellitus patients: a randomized pilot study.

Science.gov (United States)

Goyal, Aman; Singh, Surender; Tandon, Nikhil; Gupta, Nandita; Gupta, Yogendra Kumar

2014-12-01

Statins are commonly used for the management of dyslipidemia in type 2 diabetes mellitus patients. We hypothesized that atorvastatin could modulate the beta-cell function by altering the levels of proapoptotic and antiapoptotic lipoproteins and could also have an effect on insulin resistance. The aim of the present pilot study was to assess the effect of atorvastatin 10 mg on pancreatic beta-cell function and insulin resistance in patients with hyperlipidemia and type 2 diabetes by using the homeostasis model assessment-2 (HOMA2) index. Fifty-one type 2 diabetes patients receiving oral antidiabetes drugs, not taking statins, with baseline low-density lipoprotein cholesterol between 2.6 mmol/L and 4.1 mmol/L were included. Forty-three patients (21 in placebo group and 22 in atorvastatin group) completed the study and were taken up for final analysis. Fasting blood samples were obtained at baseline and at 12 weeks to determine levels of blood glucose, lipid profile, insulin, C-peptide and glycosylated hemoglobin (A1C). Atorvastatin nonsignificantly increased fasting serum insulin (+14.29%, p=0.18), accompanied by marginal nonsignificant increases in fasting plasma glucose and A1C. There was a decrease in HOMA2 percent beta-cell function (-2.9%, p=0.72) and increase in HOMA2 insulin resistance (+14%, p=0.16) in the atorvastatin group as compared with baseline, but the difference was not statistically significant. Atorvastatin in the dose used failed to produce significant change in pancreatic beta-cell function and insulin resistance in type 2 diabetes patients as assessed by the HOMA2 index. The possible explanations include absence of lipotoxicity at prevailing levels of dyslipidemia at baseline or inadequacy of statin dose used in the study. (Clinical Trials Registry-India: CTRI/2008/091/000099). Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients

DEFF Research Database (Denmark)

Kastrup, J; Nørgaard, T; Parving, H H

1987-01-01

Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects......-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml-1.100 g.min) and without nephropathy and retinopathy (8.5 mmHg ml-1.......100 g.min) compared with non-diabetic subjects (5.2 mmHg ml-1.100 g.min) (p less than 0.001 and p less than 0.005, respectively). Diabetic microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients...

Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus?

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Scott, R; Lintott, C J; Zimmet, P; Campbell, L; Bowen, K; Welborn, T

1999-03-01

Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.

The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.

Science.gov (United States)

Ibrahim, Moustafa Ibrahim; Hamdy, Ahmed; Shafik, Adel; Taha, Salah; Anwar, Mohammed; Faris, Mohammed

2014-05-01

The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus. The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes. A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20-42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21-34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily

The Higher the Insulin Resistance the Lower the Cardiac Output in Men with Type 1 Diabetes During the Maximal Exercise Test.

Science.gov (United States)

Niedzwiecki, Pawel; Naskret, Dariusz; Pilacinski, Stanislaw; Pempera, Maciej; Uruska, Aleksandra; Adamska, Anna; Zozulinska-Ziolkiewicz, Dorota

2017-06-01

The aim of this study was to assess the hemodynamic parameters analyzed in bioimpedance cardiography during maximal exercise in patients with type 1 diabetes differing in insulin resistance. The study group consisted of 40 men with type 1 diabetes. Tissue sensitivity to insulin was assessed on the basis of the glucose disposal rate (GDR) analyzed during hyperinsulinemic-euglycemic clamp. Patients were divided into groups with GDR insulin sensitivity) and GDR ≥4.5 mg/kg/min (G2 group-higher insulin sensitivity). During the exercise test, the heart rate, systolic volume, cardiac output, cardiac index were measured by the impedance meter (PhysioFlow). Compared with the G2 group, the G1 group had a lower cardiac output (CO): during exercise 8.6 (IQR 7.7-10.0) versus 12.8 (IQR 10.8-13.7) L/min; P insulin resistance is associated with cardiac hemodynamic parameters assessed during and after exercise. The higher the insulin resistance the lower the cardiac output during maximal exercise in men with type 1 diabetes.

Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

Science.gov (United States)

Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

2014-10-20

Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

The Correlation of Plasma Levels of Apelin-13 with Insulin Resistance Index and Plasma Leptin of Diabetic Male Rats after 8-Week Aerobic Exercise

Directory of Open Access Journals (Sweden)

Fahimeh Kazemi

2015-09-01

Full Text Available Abstract Background: The physiological role of apelin, an adipokine secreted by adipose tissue, in insulin resistance and type 2 diabetes has been identified. The aim of this study was to determine the correlation of plasma levels of apelin-13 with insulin resistance index (HOMA-IR and plasma leptin of diabetic male rats after 8-week aerobic exercise. Materials and Methods: Peresent study was an experimental study with animal model. Twenty eight diabetic male Wistar rats were divided into 3 groups: Non-diabetic (n=9, control diabetic (n=9 and trained diabetic (n=10. Type 2 diabetes was induced by intraperitoneal injection of nicotinamide and streptozotocin. The trained diabetic rat ran 8-week on treadmill progressively. After the training period, plasma levels of glucose, insulin, leptin and apelin-13 were measured and HOMA-IR was calculated. One-way analysis of variance (ANOVA and Pearson’s correlation were used for analyzing data. p<0.05 was considered to be statistically significant. Results: A significant decrease in plasma levels of glucose, insulin and leptin and HOMA-IR in trained diabetic vs control diabetic rats, a significant increase in plasma levels of apelin in trained diabetic vs non-diabetic and control diabetic rats and a significant negative correlation of plasma levels of apelin with HOMA-IR and plasma leptin in trained diabetic rats was observed. Conclusion: In present study, 8-week aerobic training by improvement of insulin sensitivity (decrease of HOMA-IR and plasma leptin increased plasma levels of apelin-13 in diabetic male rats.

Prevalence and predictors of overweight and insulin resistance in offspring of mothers with gestational diabetes mellitus.

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Boerschmann, Heike; Pflüger, Maren; Henneberger, Lydia; Ziegler, Anette-G; Hummel, Sandra

2010-08-01

Gestational diabetes mellitus (GDM) is associated with high birth weight in the offspring. This may lead to overweight and insulin resistance during childhood. The aim of the study was to assess the impact of GDM on overweight risk and insulin resistance in offspring. BMI measurements were collected at age 2, 8, and 11 years from 232 offspring of mothers with GDM (OGDM) and compared with those from 757 offspring of mothers with type 1 diabetes (OT1D) and 431 offspring of nondiabetic mothers (ONDM) born between 1989 and 2000. Insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) was determined at age 8 and 11 years in 751 children (74 OGDM). Overweight was defined as BMI percentile >or=90; insulin resistance was defined by HOMA-IR. Overweight prevalence was increased in OGDM compared with OT1D and to ONDM throughout childhood (age 11 years 31.1, 15.8, and 15.5%; P = 0.005). Maternal obesity was an important predictor of overweight risk in children (age 11 years odds ratio 7.0 [95% CI 1.8-27.7]; P = 0.006); birth size and maternal smoking during pregnancy were inconsistently associated with and treatment of GDM during pregnancy did not affect overweight risk. HOMA-IR was increased in OGDM compared with offspring of ONDM mothers (P = 0.01, adjusted for sex and age) and was associated with the child's BMI (P = 0.004). Overweight and insulin resistance in children is increased in OGDM compared with OT1D or ONDM. The finding that overweight risk is associated mainly with maternal obesity suggests that familial predisposition contributes to childhood growth in these offspring.

Correlation of insulin resistance with serum C-reactive protein, adiponectin and leptin levels in patients with type 2 diabetes

International Nuclear Information System (INIS)

Duan Yangqiang; Wang Zuobing; Yu Hui

2012-01-01

Objective: To explore the relationship between serum C-reactive protein (CRP), adiponectin (APN), leptin (Leptin) levels, insulin resistance index (HOMA-IR) and type 2 diabetes mellitus (T2DM) disease susceptibility. Methods: The plasma leptin and insulin (FINS) levels in the DM patients were determined by RIA, and the serum ANP levels were determined by ELSIA. The CRP, conventional serum fasting plasma glucose (FPG) levels were determine by automatic biochemistry analyzer. The insulin resistance index (HOMA-IR, FPG x FINS/22.5) was calculated. The result was analyzed with normal healthy control group. Results: The serum CRP and leptin, HOMA-IR levels in T2DM group were significantly higher than that of in control group (P< 0.01), and the serum ANP was significantly lower than in control group (P<0.01). The HOMA-IR in T2DM was positively correlated with serum CRP (r= 0.36, P<0.05) and leptin(r= 0.39, P<0.05), and was negatively correlated with serum APN (r=0.32, P<0.05). Conclusion: The high serum CRP and leptin and low APN levels hyperlipidaemia might be factors for diabetes, and their metabolic disorders may be closely related with insulin resistance in patients with type 2 diabetes. (authors)

Comparative study of telmisartan with pioglitazone on insulin resistance in type 2 diabetic mice

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Khan, A.; Qayyum, A.; Khan, B.T.

2017-01-01

Objective: To evaluate and compare the effects of telmisartan and pioglitazone on peripheral insulin resistance in diabetic mice. Study Design: Randomized control trail. Place and Duration of Study: National Institute of Health, Islamabad and pharmacology dept, Army Medical College, from 17th March to 17th June 2014. Material and Methods: Twenty four BALB/c mice, both male and female, of 35 to 40 grams were used for this study. Animals were randomly divided into four groups. Two were taken as control groups, one was normal control and the other was diabetic control. Two were taken as interventional groups and received either pioglitazone or telmisartan for four weeks after induction of diabetes. Results: After treatment, pioglitazone reduced all the biochemical parameters significantly when compared with diabetic control. Negative correlation between glucose and insulin was changed into positive correlation (r-value, 0.92) with significant p-value (0.015) in pioglitazone treated group, while telmisartan only managed to convert a negative correlation between insulin and glucose into statistically non-significant positive. Conclusion: Telmisartan although reduces glucose levels and improves beta cell mass but the effect is statistically non-significant as compared to pioglitazone. In hypertensive type 2 diabetics a combination of these two drugs may help in reducing the dose of pioglitazone and consequently the cardiovascular adverse effects of pioglitazone. (author)

The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study.

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Li, Yun-Yun; Yang, Xiu-Fen; Gu, Hong; Snellingen, Torkel; Liu, Xi-Pu; Liu, Ning-Pu

2018-01-01

To investigate the relationship between insulin resistance (IR)/β-cell dysfunction and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes mellitus (T2DM), and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index (BMI). Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment (HOMA) method was employed for IR and β-cell function assessment. After excluding those participants who were treated with insulin ( n =352) or had missing data of fasting insulin ( n =96), and further excluding those with poor quality of retinal photographs ( n =10), a total of 1008 subjects were included for the final analysis, 406 (40.3%) were men and 602 (59.7%) were women, age ranging from 34 to 86 (64.87±8.28)y. Any DR (levels 14 and above) was present in 278 (27.6%) subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio (OR) 1.51, 95% confidence interval (CI) 0.87-2.61, P =0.14] or HOMA β-cell (OR 0.71, 95%CI 0.40-1.26, P =0.25). After stratification by BMI, the presence of any DR was associated positively with HOMA IR (OR 2.46, 95%CI: 1.18-5.12, P =0.016), and negatively with HOMA β-cell (OR 0.40, 95%CI: 0.19-0.87, P =0.021) in the group of patients with higher BMI (≥25 kg/m 2 ). In the group of patients with lower BMI (diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes

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You Lim Kim

2012-12-01

Full Text Available BackgroundCentral fat mass (CFM correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes.MethodsTotal of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (KITT and serum adipokines, such as retinol binding protein-4 (RBP4, leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms was defined as CFM, sum of fat mass on the lower extremities (in kilograms as PFM, and sum of CFM and PFM as total fat mass (TFM. PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity.ResultsMedian age was 55.9 years, mean body mass index 27.2 kg/m2, and mean HbA1c level 7.12±0.84%. KITT was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, KITT in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid.ConclusionThese results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.

Plasma phospholipid transfer protein activity is independently determined by obesity and insulin resistance in non-diabetic subjects

NARCIS (Netherlands)

de Vries, Rindert; Kappelle, Paul J. W. H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

2011-01-01

Phospholipid transfer protein (PLTP) is an emerging cardio-metabolic risk factor which is intricately involved in lipoprotein metabolism. Elevated plasma PLTP activity levels are reported in obesity and diabetes mellitus, but the relative contributions of obesity and insulin resistance to plasma

Plasma phospholipid transfer protein activity is independently determined by obesity and insulin resistance in non-diabetic subjects

NARCIS (Netherlands)

de Vries, Rindert; Kappelle, Paul J.W.H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

Background: Phospholipid transfer protein (PLTP) is an emerging cardio-metabolic risk factor which is intricately involved in lipoprotein metabolism. Elevated plasma PLTP activity levels are reported in obesity and diabetes mellitus, but the relative contributions of obesity and insulin resistance

Dyslipidemias in type 2 diabetes mellitus patients in Nnewi South-East Nigeria.

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Jisieike-Onuigbo, N N; Unuigbe, E I; Oguejiofor, C O

2011-01-01

Dyslipidemia has been noted to play an integral role in the pathogenesis and progression of micro and macrovascular complications in diabetes mellitus patients. The complications exemplified by renal vascular and cardiovascular disease cause the most morbidity and mortality in this group of patients. This study is aimed at understanding the pattern of dyslipidemia among type 2 diabetic patients. A total of 108 consenting adult type 2 diabetic patients seen in the medical unit of the Nnamdi Azikiwe University Teaching Hospital Nnewi were evaluated in this crosssectional study. Their fasting lipid profile, fasting blood glucose, weight, height and blood pressure were evaluated. The prevalence of dyslipidemia (at least one abnormal lipid profile) was 90.7%. The 24.1% had single dyslipidemia while 66.6% had combined dyslipidemia. Reduced HDL constituted the highest single abnormality (62%) followed by hypertriglyceridemia (56.5%), hypercholesterolemia (53.7%) and high LDL in (44.4%). The duration of DM was not significantly associated with dyslipidemia (P > 0.05). Dyslipidemia is highly prevalent among type 2 diabetic patients in Nigeria with the majority of the patients having combined dyslipidemia. We recommend that aggressive treatment of lipidemia and hyperglycemia can be instituted to reduce the risk of macro and microvascular complications.

Hypertriglyceridemia: Is there a role for prophylactic apheresis? A case report

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Ana Rita Francisco

Full Text Available Abstract Severe hypertriglyceridemia has been consistently associated with an increased risk of cardiovascular disease and other complications, namely acute pancreatitis. We report a case of a 64 year-old woman with hypertrophic cardiomyopathy and metabolic syndrome with triglyceride level of 3260 mg/dL. Plasma exchange was performed with simultaneous medical treatment to achieve a rapid and effective lowering of triglycerides in order to prevent clinical complications. After three plasmapheresis sessions a marked reduction in triglyceride and total cholesterol levels was observed. Several cases have shown the importance of plasmapheresis in the treatment of acute pancreatitis. We intend to demonstrate the applicability of this technique as primary prophylaxis in the presence of extremely high serum triglyceridemia levels.

Pediatric obesity & type 2 diabetes.

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Dea, Tara L

2011-01-01

This article focuses on (a) identifying obesity and other risk factors for developing type 2 diabetes, (b) differentiating between pediatric type 1 diabetes and type 2 diabetes, and (c) treating pediatric type 2 diabetes. Obesity has significant implications on a child's health, including an increased risk for insulin resistance and progression to type 2 diabetes. Type 2 diabetes in children, characterized by insulin resistance and relative pancreatic b-cell failure due to the increased demand for insulin production, has now reached epidemic proportions. Longitudinal research on pediatric type 2 diabetes, however, is lacking because this epidemic is relatively new. Treatment of type 2 diabetes in children is focused on lifestyle modification with weight management/increased physical activity, and pharmacological management through oral medication or insulin therapy. Because children with type 2 diabetes are at risk for developing diabetes-related complications earlier in life, they need to be closely monitored for comorbidities.

Effect of lipoprotein-associated phospholipase A2 inhibitor on insulin resistance in streptozotocin-induced diabetic pregnant rats.

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Wang, Guo-Hua; Jin, Jun; Sun, Li-Zhou

2018-06-21

This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

The resist diabetes trial: Rationale, design, and methods of a hybrid efficacy/effectiveness intervention trial for resistance training maintenance to improve glucose homeostasis in older prediabetic adults.

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Marinik, Elaina L; Kelleher, Sarah; Savla, Jyoti; Winett, Richard A; Davy, Brenda M

2014-01-01

Advancing age is associated with reduced levels of physical activity, increased body weight and fat, decreased lean body mass, and a high prevalence of type 2 diabetes (T2D). Resistance training (RT) increases muscle strength and lean body mass, and reduces risk of T2D among older adults. The Resist Diabetes trial will determine if a social cognitive theory (SCT)-based intervention improves RT maintenance in older, prediabetic adults, using a hybrid efficacy/effectiveness approach. Sedentary, overweight/obese (BMI: 25-39.9 kg/m(2)) adults aged 50-69 (N = 170) with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) completed a supervised 3-month RT (2×/wk) initiation phase and were then randomly assigned (N = 159; 94% retention) to one of two 6-month maintenance conditions: SCT or standard care. The SCT intervention consisted of faded contacts compared to standard care. Participants continue RT at an approved, self-selected community facility during maintenance. A subsequent 6-month period involves no contact for both conditions. Assessments occur at baseline and months 3 (post-initiation), 9 (post-intervention), and 15 (six months after no contact). Primary outcomes are prediabetes indices (i.e., impaired fasting and 2-hour glucose concentration) and strength. Secondary measures include insulin sensitivity, beta-cell responsiveness, and disposition index (oral glucose and C-peptide minimal model); adherence; body composition; and SCT measures. Resist Diabetes is the first trial to examine the effectiveness of a high fidelity SCT-based intervention for maintaining RT in older adults with prediabetes to improve glucose homeostasis. Successful application of SCT constructs for RT maintenance may support translation of our RT program for diabetes prevention into community settings. Copyright © 2013 Elsevier Inc. All rights reserved.

Resistin: A Potential Biomarker for Periodontitis Influenced Diabetes Mellitus and Diabetes Induced Periodontitis

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Archana Devanoorkar

2014-01-01

Full Text Available Biomarkers are highly specific and sensitive indicators of disease activity. Resistin is a recently discovered adipocytokine, having a potent biomarker quality. Initially resistin was thought to be produced by adipocytes alone; however, emerging evidence suggests that it is also produced in abundance by various cells of the immunoinflammatory system, indicating its role in various chronic inflammatory diseases. Data suggests that resistin plays a role in obesity, insulin resistance, cardiovascular diseases, and periodontitis. Resistin derived its name from the original observation that it induced insulin resistance (resist-in: resist insulin in mice and is downregulated in mature murine adipocytes cultured in the presence of insulin sensitizing drugs like thiazolidinediones. It is well recognized that obesity, is associated with insulin resistance and diabetes. A three-way relationship has been established between diabetes, obesity and periodontitis. Recent evidence also suggests an association between obesity and increased risk for periodontitis. Our previous research showed incremental elevation of resistin with periodontal disease activity and a reduced level of resistin, after periodontal therapy. Thus resistin would be one of the molecular links connecting obesity, periodontitis, and diabetes and may serve as a marker that links periodontal disease with other systemic diseases. A Medline/PubMed search was carried out for keywords “Diabetes Mellitus,” “Periodontitis,” and “Resistin,” and all relevant research papers from 1990 in English were shortlisted and finalized based on their importance. This review provides an insight into the biological action of resistin and its possible role in periodontitis influenced diabetes mellitus and diabetes induced periodontitis.

Despite higher body fat content, Ecuadorian subjects with Laron syndrome have less insulin resistance and lower incidence of diabetes than their relatives.

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Guevara-Aguirre, Jaime; Procel, Patricio; Guevara, Carolina; Guevara-Aguirre, Marco; Rosado, Verónica; Teran, Enrique

2016-06-01

In the present pandemics of obesity and insulin resistant diabetes mellitus (DM), the specific contribution of etiological factors such as shifts in nutritional and exercise patterns, genetic and hormonal, is subject of ongoing research. Among the hormonal factors implicated, we selected obesity-driven insulin resistance for further evaluation. It is known that growth hormone (GH) has profound effects on carbohydrate metabolism. In consequence, we compared the effects of the lack of the counter-regulatory effects of GH, in a group of subjects with GH receptor deficiency (GHRD) due to a mutated GH receptor vs. that of their normal relatives. It was found that, despite their obesity, subjects with GHRD, have diminished incidence of diabetes, lower glucose and insulin concentrations, and lower values of indexes indicative of insulin resistance such as HOMA-IR. The GHRD subjects were also capable of appropriately handling glucose or mixed meal loads despite diminished insulin secretion. These observations allow us to suggest that the association of obesity with increased risk for diabetes appears to be dependent on intact growth hormone signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review.

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Desbois, Anne-Claire; Cacoub, Patrice

2017-03-07

To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk. We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [ i.e ., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)]. HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies. Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.

[Atherogenic dyslipidemia in patients with type 1 diabetes mellitus].

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Chillarón, Juan J; Sales, María P; Flores Le-Roux, Juana A; Castells, Ignasi; Benaiges, David; Sagarra, Enric; Pedro-Botet, Juan

2013-12-07

To assess the prevalence of lipid abnormalities, with special emphasis on atherogenic dyslipidemia and its relationship with chronic complications in patients with type 1 diabetes mellitus (T1DM). Cross-sectional study including all patients aged 18 and over, diagnosed of T1DM attending the outpatient clinic at Hospital del Mar and Hospital de Granollers, in Barcelona, during 2008. Of the 291 enrolled patients, 17.2 and 7.9% had high density lipoproteins (HDL) cholesterol150 mg/dL, respectively. Hypoalphalipoproteinemic patients had a higher prevalence of peripheral neuropathy (28 vs. 7.1%, P<.001), macroalbuminuria (14 vs. 2.5%, P<.001) and higher concentrations of triglycerides (107.5 [55.8] vs. 82.7 [36] mg/dL, P<.0001) compared with those with normal/high HDL cholesterol levels. Hypertriglyceridemia was associated with increasing age (43.6 [11.2] vs. 37.6 [11.8] yr, P<.02), higher prevalence of hypertension (47.8 vs. 22.8%, P<.008), metabolic syndrome (82.6 vs. 22%, P<.001) and microangiopathic complications, lower insulin sensitivity (6.75 [2.1] vs. 8.54 [2.6] mg/Kg(-1)/min(-1), P<.004) compared with the normotriglyceridemic group. One in 5 patients with T1DM has hypoalphalipoproteinemia or hypertriglyceridemia and these conditions are associated with 3 fold-increase microangiopathy. Thus, in these patients glycemic and blood pressure but also lipid profile control must be optimum. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Correlation of blood glucose, serum chemerin and insulin resistance with NAFLD in patients with type 2 diabetes mellitus.

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Zhang, Zhengjun; Wang, Jijun; Wang, Hongmei

2018-03-01

Non-alcoholic fatty liver disease (NAFLD) is a form of clinical syndrome characterized by the fatty degeneration in liver histology and should be further investigated. The aim of the study was to investigate the effects of blood glucose, serum chemerin and insulin resistance on non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus to provide a basis for the prevention and treatment thereof. In total, 300 patients with type 2 diabetes mellitus treated and admitted into the Endocrinology Department of our hospital from June 2015 to June 2017 were enrolled and divided into the simple type 2 diabetes mellitus (group A) and concurrent NAFLD (group B) groups. The sex, age, body mass index (BMI), blood pressure, blood biochemical indexes and chemerin level were compared between the two groups. The patients in group B were further divided into the mild fatty liver (group B1), moderate fatty liver (group B2) and severe fatty liver (group B3) groups. The sex, age, BMI blood pressure, blood biochemical indexes and chemerin level were also compared among the three groups. Finally, the risk factors of type 2 diabetes mellitus complicated by NAFLD were analyzed via logistic regression. The BMI, fasting plasma glucose (FPG), 2 h post-prandial plasma glucose (2hPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-β indexes and serum chemerin level in group B were significantly higher than those in group A (Pdiabetes mellitus complicated by NAFLD is closely associated with severe glucose-lipid metabolism disorder and insulin resistance, and BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin constitute risk factors of concurrent NAFLD.

The effect of 8 weeks of Circuit Resistance Training on metabolic syndrome risk factors and body composition in women over age 50 with diabetes mellitus type 2

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Seyede Amene Azarmehr

2017-10-01

Full Text Available Abstract Introduction: The prevalence of type 2 diabetes mellitus (T2DM increased significantly in the last three decades, and effective strategies to manage and prevent this disease are urgently needed. Physical activity and exercise training is an effective way for metabolic syndrome risk factors in type 2 diabetes mellitus (T2DM patients. However, the effects of Circuit Resistance Training (CRT program on patients T2DM are unknown. The purpose of this study is to investigation the effect of 8 weeks of Circuit resistance training (CRT on metabolic syndrome and body composition in women over age 50 with T2DM. Methods: Twenty women over 50 years old with diabetes Referred to diabetes Center of 17 Shahrivar hospital in Amol and they were divided randomly into two groups; Circuit resistance (n=10 and Control (n=10. Resistance training consisted of 10 stations for 8 weeks and 3 sessions per week (Intensity 60-80% 1RM. Levels of Lipid profile and body composition before and after eight weeks training in both groups were measured. Statistical analysis of the data was carried out by SPSS (v. 22. Results Fasting Blood Sugar (FBS levels (P=0.021, Triglycerides (0.010, high-density lipoprotein cholesterol (0.042, significant decreased in CRT. Also after 8 weeks circuit resistance training, BMI (P= 0.003, WHR (P=0.004 and body fat present (0.019 significant decreased in CRT. Conclusion: According to our results, CRT was an effective approach to improve the Anthropometrics, FBS, lipid profile in women over age 50 with diabetes mellitus type 2. Moreover, CRT did have influence on LDL level.  Keywords: Circuit resistance training, insulin resistance, metabolic syndrome, body composition

"The impact of vitamin C and E, Magnesium and Zinc on glycemic control and insulin resistance in type II diabetic patients "

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Farvid MS

2007-04-01

Full Text Available Background: The present study designed to assess the effect of Mg+Zn, vitamin C+E, and combination of these micronutrients on glycemic control and insulin resistance in type 2 diabetic patients Methods: In a randomized, double-blind, placebo controlled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months; group M: 200 mg and 30 mg Zn (n=16, group V: 200 mg vitamin C and 150 mg vitamin E (n=18, group MV: minerals plus vitamins (n=17, group P: placebo (n=18.Fasting blood glucose, fructosamine, HbA1c and serum insulin were measured at the beginning and at the end of 3 months supplementation. Insulin resistance was calculated by HOMA score. Treatment effects were analyzed by general linear modeling. Results: After 3 months of supplementation fasting blood glucose decreased in MV group (165±46 vs 177±41 mg/dl, p=0.035. There was no significant change in fructoseamin, HbA1c, serum insulin or insulin resistance in treatment groups. Conclusion: The results of the present study provide evidence for the effects of combination of Mg, Zn and vitamin C and E supplementations on improvement of fasting blood glucose but not fructosamine, HbA1c, serum insulin or insulin resistance in type 2 diabetic patients.

Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes

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Rahul Yadav

2017-11-01

Full Text Available PurposeObesity is a major modifiable risk factor for cardiovascular disease. Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients with and without type 2 diabetes (T2DM.ObjectiveTo evaluate changes in lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction following Roux-en-Y bariatric surgery in obese patients with and without diabetes.Materials and methodsLipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction were measured in 37 obese patients with (n = 17 and without (n = 20 T2DM, before and 6 and 12 months after Roux-en-Y bariatric surgery. Two way between subject ANOVA was carried out to study the interaction between independent variables (time since surgery and presence of diabetes and all dependent variables.ResultsThere was a significant effect of time since surgery on (large effect size weight, body mass index (BMI, waist circumference, triglycerides (TG, small-dense LDL apolipoprotein B (sdLDL ApoB, HOMA-IR, CRP, MCP-1, ICAM-1, E-selectin, P-selectin, leptin, and adiponectin. BMI and waist circumference had the largest impact of time since surgery. The effect of time since surgery was noticed mostly in the first 6 months. Absence of diabetes led to a significantly greater reduction in total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol although the effect size was small to medium. There was a greater reduction in TG and HOMA-IR in patients with diabetes with a small effect size. No patients were lost to follow up.ConclusionLipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction improve mostly 6 months after bariatric surgery in obese patients with and without diabetes.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT02169518. https

Association of a microsatellite in FASL to type II diabetes and of the FAS-670G>A genotype to insulin resistance

DEFF Research Database (Denmark)

Nolsøe, R L; Hamid, Y H; Pociot, F

2006-01-01

-cells, Fas expression and concomitant apoptosis owing to a constitutive expression of FasL. FASL and FAS map to loci linked to type II diabetes and estimates of insulin resistance, respectively. We have tested two functional promoter polymorphisms, FAS-670 G>A and FASL-844C>T as well as a microsatellite...... association to type II diabetes for the allele distribution of the FASL microsatellite (P-value 0.02, Bonferroni corrected). The FAS-670G>A was associated with homeostasis model assessment insulin resistance index and body mass index (P-values 0.02 and 0.02). We conclude that polymorphisms of FASL and FAS...

Association Between Free Fatty Acid (FFA and Insulin Resistance: The Role of Inflammation (Adiponectin and high sensivity C-reactive Protein/hs-CRP and Stress Oxidative (Superoxide Dismutase/SOD in Obese Non-Diabetic Individual

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Indriyanti Rafi Sukmawati

2009-12-01

Full Text Available BACKGROUND: Obesity is highly related to insulin resistance, therefore, the increased number of obesity is followed by the increased prevalence of type 2 Diabetes Melitus. Obesity is associated with increased of reactive oxygen species (ROS in muscle, liver and endothelial cells. The increase of ROS would lead to insulin resistance (IR and increased pro-inflammatory protein. FFA plays an important role in IR by inhibiting muscle glucose transport and oxidation via effects on serine/threonine phosphorylation of IRS-1. The aim of this study was discover the existence of SOD, hs-CRP and and adiponectin levels towards the occurrence of insulin resistance which was caused by elevated level of FFA and to discover the interaction between SOD, hs-CRP and adiponectin in non diabetic obese adult male. METHODS: This was observational study with cross sectional design. There were 65 obese male non diabetic subjects and 45 non obese male non diabetic subjects who met the criteria. In this study, measurements were done on body mass index (BMI, fasting glucose, insulin, adiponectin, hs-CRP and SOD. Obese was defined as BMI >25 kg/m2, normal weight was defined as BMI 18.5-23 kh/m2 and Insulin Resistance was defined as HOMA-IR >1. RESULTS: This study showed that Hypoadiponectinemia condition, decreased SOD level and high level of hs-CRP is associated with insulin resistance in obese non diabetic subject. Adiponectin and SOD were correlated negatively with insulin resistance in obese non diabetic (Adiponectin, r=-0.455, p<0.001; SOD, r=-0.262, p=0.003, hs-CRP was positively correlated with insulin resistance in obese non diabetic (r=0.592, p<0.001. FFA levels was increased in obese insulin resistance compared with non obese non insulin resistance. The Odds Ratio of Adiponectin, hs-CRP and SOD in this study was analyzed by logistic binary. The OR for SOD 3.6 (p=0.001, hs-CRP 9.1 (p<0.001 and Adiponectin 7.2 (p<0.001. CONCLUSIONS: This study suggested that FFA

Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

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Wang, Qiuwei; Huang, Ruiping; Yu, Bin; Cao, Fang; Wang, Huiyan; Zhang, Ming; Wang, Xinhong; Zhang, Bin; Zhou, Hong; Zhu, Ziqiang

2013-01-01

The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively. Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, Pinsulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM. Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

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Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

2003-09-01

Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

Whole-exome sequencing reveals GPIHBP1 mutations in infantile colitis with severe hypertriglyceridemia.

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Gonzaga-Jauregui, Claudia; Mir, Sabina; Penney, Samantha; Jhangiani, Shalini; Midgen, Craig; Finegold, Milton; Muzny, Donna M; Wang, Min; Bacino, Carlos A; Gibbs, Richard A; Lupski, James R; Kellermayer, Richard; Hanchard, Neil A

2014-07-01

Severe congenital hypertriglyceridemia (HTG) is a rare disorder caused by mutations in genes affecting lipoprotein lipase (LPL) activity. Here we report a 5-week-old Hispanic girl with severe HTG (12,031 mg/dL, normal limit 150 mg/dL) who presented with the unusual combination of lower gastrointestinal bleeding and milky plasma. Initial colonoscopy was consistent with colitis, which resolved with reduction of triglycerides. After negative sequencing of the LPL gene, whole-exome sequencing revealed novel compound heterozygous mutations in GPIHBP1. Our study broadens the phenotype of GPIHBP1-associated HTG, reinforces the effectiveness of whole-exome sequencing in Mendelian diagnoses, and implicates triglycerides in gastrointestinal mucosal injury.

C-13 NMR spectroscopy of plasma reduces interference of hypertriglyceridemia in the H-1 NMR detection of malignancy

International Nuclear Information System (INIS)

Fossell, E.T.; Hall, F.M.; McDonagh, J.

1991-01-01

The authors have previously described the application of water-suppressed proton nuclear magnetic resonance (H-1 NMR) spectroscopy of plasma for detection of malignancy. Subsequently, hypertriglyceridemia has been identified as a source of false positive results. Here is described a confirmatory, adjunctive technique -analysis of the carbon-13 (C-13) NMR spectrum of plasma- which also identifies the presence of malignancy but is not sensitive to the plasma triglyceride level. Blinded plasma samples from 480 normal donors and 208 patients scheduled for breast biopsy were analyzed by water-suppressed H-1 and C-13 NMR spectroscopy. Triglyceride levels were also measured. Among the normal donors, there were 38 individuals with hypertriglyceridemia of whom 18 had results consistent with malignancy by H-1 NMR spectroscopy. However, the C-13 technique reduced the apparent H-1 false positive rate from 7.0 to 0.6 percent. Similarly, in the breast biopsy cohort, C-13 reduced the false positive rate from 2.8 to 0.9 percent. Furthermore, the accuracy of the combined H-1/C-13 test in this blinded study was greater than 96 percent in 208 patients studied. (author). 27 refs.; 5 figs.; 4 tabs

Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome.

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Stabile, Gaspare; Borrielli, Irene; Artenisio, Alfredo Carducci; Bruno, Lucia Maria; Benvenga, Salvatore; Giunta, Loretta; La Marca, Antonio; Volpe, Annibale; Pizzo, Alfonsa

2014-06-01

Polycystic ovary syndrome (PCOS) is the most common endocrine cause of menstrual irregularities, hirsutism and acne. Women with PCOS present elevated plasma insulin levels, both fasting and after a glucose load, as an indirect evidence of insulin resistance. PCOS women may also present hypertension, low levels of HDL cholesterol, hypertriglyceridemia, visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk. This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women. PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated: menstrual cycle trend, hirsutism and acne, total cholesterolemia and HDL, triglyceridemia, fibrinogenemia, C-reactive protein, oral glucose tolerance test, glycated hemoglobin, FSH, LH, 17OH-progesterone, 17β-estradiol, free and total testosterone, SHBG, DHEA-S, Δ4-androstenedione and adiponectin. Treatment with pioglitazone improves the irregularities of menses and hirsutism. Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases: adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models.

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Ostler, Joseph E; Maurya, Santosh K; Dials, Justin; Roof, Steve R; Devor, Steven T; Ziolo, Mark T; Periasamy, Muthu

2014-03-01

Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db/db and TallyHo mice at prediabetic and overtly diabetic ages. Maximum running speeds and muscle weights were already reduced in prediabetic db/db mice when compared with lean controls and more severely reduced in the overtly diabetic db/db mice. In contrast to db/db mice, TallyHo muscle size dramatically increased and maximum running speed was maintained during the progression from prediabetes to overt diabetes. Analysis of mechanisms that may contribute to decreased muscle weight in db/db mice demonstrated that insulin-dependent phosphorylation of enzymes that promote protein synthesis was severely blunted in db/db muscle. In addition, prediabetic (6-wk-old) and diabetic (12-wk-old) db/db muscle exhibited an increase in a marker of proteasomal protein degradation, the level of polyubiquitinated proteins. Chronic treadmill training of db/db mice improved glucose tolerance and exercise capacity, reduced markers of protein degradation, but only mildly increased muscle weight. The differences in muscle phenotype between these models of type 2 diabetes suggest that insulin resistance and chronic hyperglycemia alone are insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are animal model-dependent.

Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

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Minglong Shao

Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

Deletion of the basement membrane heparan sulfate proteoglycan type XVIII collagen causes hypertriglyceridemia in mice and humans.

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Joseph R Bishop

2010-11-01

Full Text Available Lipoprotein lipase (Lpl acts on triglyceride-rich lipoproteins in the peripheral circulation, liberating free fatty acids for energy metabolism or storage. This essential enzyme is synthesized in parenchymal cells of adipose tissue, heart, and skeletal muscle and migrates to the luminal side of the vascular endothelium where it acts upon circulating lipoproteins. Prior studies suggested that Lpl is immobilized by way of heparan sulfate proteoglycans on the endothelium, but genetically altering endothelial cell heparan sulfate had no effect on Lpl localization or lipolysis. The objective of this study was to determine if extracellular matrix proteoglycans affect Lpl distribution and triglyceride metabolism.We examined mutant mice defective in collagen XVIII (Col18, a heparan sulfate proteoglycan present in vascular basement membranes. Loss of Col18 reduces plasma levels of Lpl enzyme and activity, which results in mild fasting hypertriglyceridemia and diet-induced hyperchylomicronemia. Humans with Knobloch Syndrome caused by a null mutation in the vascular form of Col18 also present lower than normal plasma Lpl mass and activity and exhibit fasting hypertriglyceridemia.This is the first report demonstrating that Lpl presentation on the lumenal side of the endothelium depends on a basement membrane proteoglycan and demonstrates a previously unrecognized phenotype in patients lacking Col18.

A novel APOC2 gene mutation identified in a Chinese patient with severe hypertriglyceridemia and recurrent pancreatitis.

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Jiang, Jingjing; Wang, Yuhui; Ling, Yan; Kayoumu, Abudurexiti; Liu, George; Gao, Xin

2016-01-16

The severe forms of hypertriglyceridemia are usually caused by genetic defects. In this study, we described a Chinese female with severe hypertriglyceridemia caused by a novel homozygous mutation in the APOC2 gene. Lipid profiles of the pedigree were studied in detail. LPL and HL activity were also measured. The coding regions of 5 candidate genes (namely LPL, APOC2, APOA5, LMF1, and GPIHBP1) were sequenced using genomic DNA from peripheral leucocytes. The ApoE gene was also genotyped. Serum triglyceride level was extremely high in the proband, compared with other family members. Plasma LPL activity was also significantly reduced in the proband. Serum ApoCII was very low in the proband as well as in the heterozygous mutation carriers. A novel mutation (c.86A > CC) was identified on exon 3 [corrected] of the APOC2 gene, which converted the Asp [corrected] codon at position 29 into Ala, followed by a termination codon (TGA). This study presented the first case of ApoCII deficiency in the Chinese population, with a novel mutation c.86A > CC in the APOC2 gene identified. Serum ApoCII protein might be a useful screening test for identifying mutation carriers.

Relationship between the serum concentrations of C-reactive protein and parameters of adiposity and insulin resistance in patients with type 2 diabetes mellitus

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Iwasaki, Tomoyuki; Nakajima, Atsushi; Yoneda, Masato; Terauchi, Yasuo

2006-01-01

Serum C-reactive protein (CRP) concentrations have been reported to be associated with body fat, especially visceral fat accumulation, but most studies up to now have been conducted on non-diabetic subjects. In this study, we investigated the association between the serum CRP concentrations and parameters of adiposity and insulin resistance in both Japanese type 2 diabetes patients and non-diabetic subjects. A total of 248 Japanese subjects (140 type 2 diabetes patients and 108 non-diabetic subjects) were enrolled for the study. The degree of insulin resistance was estimated by the homeostasis model assessment (HOMA-R) method. Fat accumulation was evaluated by measuring visceral and subcutaneous fat areas at the level of the umbilicus in abdominal CT scans. To assess hepatic fat content, the ratio of CT attenuation value of the liver to that of the spleen (L/S ratio) was calculated. Serum CRP was found to be significantly correlated with various indices of adiposity, including L/S ratio, visceral fat area (VFA), subcutaneous fat area (SFA), and HOMA-R, in both the diabetic patients and the non-diabetic subjects. After adjustment for five variables (age, gender, serum CRP, HbAlc, and smoking), serum CRP was still significantly correlated with L/S ratio, VFA, SFA, and HOMA-R in the diabetic patients. We also found that changes in serum CRP concentrations were correlated with changes in the VFA and SFA at 1 year after the baseline in 24 diabetic patients. We conclude that serum CRP may be closely related to the degree of liver steatosis and visceral fat accumulation in Japanese type 2 diabetes mellitus patients. (author)

Double Filtration Plasma Apheresis Shortens Hospital Admission Duration of Patients With Severe Hypertriglyceridemia-Associated Acute Pancreatitis.

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Chang, Chiz-Tzung; Tsai, Tsung-Yu; Liao, Hsin-Yi; Chang, Chia-Ming; Jheng, Jyun-Shan; Huang, Wen-Hsin; Chou, Che-Yi; Chen, Chao-Jung

2016-04-01

The treatment effectiveness of double filtration plasma apheresis (DFPP) on severe hypertriglyceridemia-associated acute pancreatitis (STAP) has been questioned because the currently defined serum triglyceride level--1000 mg/dL--is too low for STAP. Given this, we aimed to investigate DFPP effectiveness when we elevated STAP definition to 5000 mg/dL serum triglyceride. We performed nested case-control studies for STAP patients and divided them into groups "with" or "without" DFPP. We further recruited outpatient asymptomatic hypertriglyceridemia patients with STAP history, then divided them into groups "with" or "without" prophylactic DFPP once every 3 to 6 months for 2 years. We observed hospitalization duration and STAP recurrence between patients with and patients without DFPP. Twelve STAP patients receiving DFPP had a median hospitalization of 5 days, whereas 24 patients without DFPP had 10 days (P = 0.009). Six outpatient referrals with STAP history receiving prophylactic DFPP showed no STAP recurrences whereas 6 without DFPP showed 3 recurrences (P = 0.046). For the 25 patients whose serum triglyceride exceeded 5000 mg/dL, 11 receiving DFPP had median hospitalization of 5 days while 14 without DFPP had 11 days (P = 0.012). When applied to serum triglyceride in excess of 5000 mg/dL, DFPP removes oxidized and inflammatory lipoproteins, shortens hospitalization duration, and minimizes STAP recurrence.

Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus

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Vestergaard, H; Rossen, M; Urhammer, S A

1997-01-01

In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine......-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin......-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum...

NTproBNP in insulin-resistance mediated conditions: overweight/obesity, metabolic syndrome and diabetes. The population-based Casale Monferrato Study.

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Baldassarre, Stefano; Fragapani, Salvatore; Panero, Antonio; Fedele, Debora; Pinach, Silvia; Lucchiari, Manuela; Vitale, Anna Rita; Mengozzi, Giulio; Gruden, Gabriella; Bruno, Graziella

2017-09-25

NTproBNP and BNP levels are reduced in obese subjects, but population-based data comparing the pattern of this relationship in the full spectrum of insulin-resistance mediated conditions, overweight/obesity, metabolic syndrome and diabetes, are limited. The study-base were 3244 individuals aged 45-74 years, none of whom had heart failure, 1880 without diabetes and 1364 with diabetes, identified as part of two surveys of the population-based Casale Monferrato Study. All measurements were centralized. We examined with multiple linear regression and cubic regression splines the relationship between NTproBNP and BMI, independently of known risk factors and confounders. A logistic regression analysis was also performed to assess the effect of overweight/obesity (BMI ≥ 25 kg/m 2 ), diabetes and metabolic syndrome on NTproBNP values. Out of the overall cohort of 3244 people, overweight/obesity was observed in 1118 (59.4%) non-diabetic and 917 (67.2%) diabetic subjects, respectively. In logistic regression, compared to normal weight individuals, those with a BMI ≥ 25 kg/m 2 had a OR of 0.70 (95% CI 0.56-0.87) of having high NTproBNP values, independently of diabetes. As interaction between diabetes and NTproBNP was evident (p obesity or metabolic syndrome enhanced fourfold and over the OR of having high NTproBNP levels, while the presence of metabolic syndrome alone had a more modest effect (OR 1.54, 1.18-2.01) even after having excluded individuals with CVD. In the non-diabetic cohort, obesity/overweight and HOMA-IR ≥ 2.0 decreased to a similar extent the ORs of high NTproBNP [0.76 (0.60-0.95) and 0.74 (0.59-0.93)], but the association between overweight/obesity and NTproBNP was no longer significant after the inclusion into the model of HOMA-IR, whereas CRP > 3 mg/dl conferred a fully adjusted OR of 0.65 (0.49-0.86). NT-proBNP levels are lower in overweight/obesity, even in those with diabetes. Both insulin-resistance and chronic low-grade inflammation

Role of macrophage migration inhibitory factor in obesity, insulin resistance, type 2 diabetes, and associated hepatic co-morbidities

NARCIS (Netherlands)

Morrison, M.C.; Kleemann, Robert

2015-01-01

Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate

May the force be with you: why resistance training is essential for subjects with type 2 diabetes mellitus without complications.

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Codella, Roberto; Ialacqua, Marta; Terruzzi, Ileana; Luzi, Livio

2018-05-05

Physical activity, together with diet and pharmacological therapy, represents one of the three cornerstones in type 2 diabetes mellitus treatment and care. The therapeutic appeal of regular physical activity stems from: (i) its non-pharmacological nature; (ii) its beneficial effects on the metabolic risk factors associated with diabetes complications; (iii) its low costs. Evidence accumulated in the last years suggests that aerobic training-endurance training-constitutes a safe modality of intervention, achievable, and effective in diabetes treatment, whenever it is not limited by comorbidities. Aerobic training exerts insulin-mimetic effects and has been shown to lower mortality risk too. Anaerobic, intense physical activity, such as that of strength or power sports disciplines, is not univocally recognized as safe and simple to realize, however, it is important in stimulating energy and glucose metabolism. According to recent evidence, high-intensity training may be prescribed even in the face of cardiovascular diseases, peripheral vascular disease, or osteoarthritis. Some studies have shown resistance training to be more efficient than aerobic exercise in improving glycemic control. This review explores the most up-to-date indications emerging from literature in support of the beneficial effects of strength stimulation and resistance training in patients with type 2 diabetes without complications.

Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus.

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Rahman, Md Mahbubur; Kwon, Han-Sol; Kim, Myung-Jin; Go, Hyeon-Kyu; Oak, Min-Ho; Kim, Do-Hyung

2017-08-01

The objective was to investigate the effects of melatonin and exercise on insulin resistance (IR), hypertension and fatigue syndrome in a rat model of type 2 diabetes mellitus (T2DM). Rats were divided into 5 groups namely normal control (NC), T2DM control group (DC), diabetes plus exercise (DE), diabetes plus oral melatonin supplement (DM) and diabetes plus melatonin and exercise (DME) groups. Melatonin was administered orally 5mg/kg twice daily and 40min swimming/day 5days/week were regimented after diabetes induction. Blood pressure, fasting blood glucose, insulin, IR, serum leptin, lipid profiles, inflammatory cytokines, lipid peroxidation increased significantly (Phypertension, IR, biochemical alteration induced by diabetes and significantly increased exercise performance (Phypertension and exercise performance or fatigue possibly by improving antioxidative activities, hyperlipidemia, inflammatory cytokines via up-regulation of GLUT4, PGC-1 α and mitochondrial biogenesis in T2DM rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Effectiveness of Green Tea or Green Tea Extract on Insulin Resistance and Glycemic Control in Type 2 Diabetes Mellitus: A Meta-Analysis

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Jinyue Yu

2017-08-01

Full Text Available Green tea or green tea extract (GT/GTE has been demonstrated to reduce insulin resistance and improve glycemic control. However, evidence for this health beneficial effect is inconsistent. This systematic review evaluated the effect of GT/GTE on insulin resistance and glycemic control in people with pre-diabetes/type 2 diabetes mellitus (T2DM. Ovid MEDLINE, Embase, AMED, Web of Science, and the Cochrane Library were searched up to April 2017 for randomised controlled trials of participants with pre-diabetes or T2DM, where the intervention was GT/GTE. Meta-analysis was performed to assess the standardised mean difference (SMD in biomarkers of insulin resistance and glycemic control between GT/GTE and placebo groups. Six studies (n=382 were pooled into random-effects meta-analysis. Overall, no differences were found between GT/GTE and the placebo for glycosylated hemoglobin (HbA1c: SMD, −0.32; 95% confidence interval [CI], −0.86 to 0.23, homeostatic model assessment for insulin resistance (HOMA-IR: SMD, 0.10; 95% CI, −0.17 to 0.38, fasting insulin (SMD, −0.25; 95% CI, −0.64 to 0.15, and fasting glucose (SMD, −0.10; 95% CI, −0.50 to 0.30. No evidence support the consumption of GT/GTE could reduce the levels of HbA1c, HOMA-IR, fasting insulin, or fasting glucose in people with pre-diabetes/T2DM. However, the studies included were small and of varying quality.

Relative iron "overload" in offspring of patients with type 2 diabetes mellitus: a new component in the conundrum of insulin resistance syndrome?

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Psyrogiannis, Agathoklis; Kyriazopoulou, Venetsana; Symeonidis, Argiris; Leotsinidis, Michalis; Vagenakis, Apostolos G

2003-01-01

There are a few reports suggesting that subtle disturbances of iron metabolism are frequently found in patients with type 2 diabetes (DM2), but it is not known if these disturbances precede or accompany the diabetic state. We investigated the serum iron indices in 41 offspring of DM2 parents (group I) with normal glucose tolerance, and in 49 offspring whose parents had no history of DM2 and were matched for sex, age, body mass index (BMI), waist to hip ratio (WHR) and blood pressure (group II). Serum iron, ferritin, total iron binding capacity (TIBC), transferrin saturation, serum triglycerides, cholesterol, Apo-B, high density lipoprotein (HDL) and glucose and insulin values during an oral glucose tolerance test were measured. Insulin resistance was assessed using the homeostasis model assessment (HOMA - Insuline resistence index-IRI). In comparison to controls (group II), the offspring of DM2 subjects (group I) had higher fasting serum triglycerides (mean +/- SD 2.25+/-2.08 vs. 1.6+/-0.8 mmol/L, pinsulin in the Area Under the Curve (204.7+/-140.8 v. 153.1 +/- 63.0 microU/ml, pinsulin resistance. Hence, the relative iron "overload" in offspring of type 2 diabetics is present along with insulin resistance and might worsen the hepatic insulin insensitivity already present in these patients.

Differences in low-grade chronic inflammation and insulin resistance in women with previous gestational diabetes mellitus and women with polycystic ovary syndrome.

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Thomann, Robert; Rossinelli, Nadia; Keller, Ulrich; Tirri, Brigitte Frey; De Geyter, Christian; Ruiz, Juan; Kränzlin, Marius; Puder, Jardena J

2008-04-01

Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are both characterized by an increase in insulin resistance. Our goal in the present study was to measure insulin resistance (as estimated by homeostasis model assessment, sex hormone-binding globulin (SHBG) and adiponectin concentrations) and parameters of low-grade inflammation in non-diabetic, non-hyperandrogenic ovulatory women with previous GDM (pGDM) and in non-diabetic women with classic PCOS, characterized by hyperandrogenism and oligo/anovulation. We evaluated 20 women with PCOS, 18 women with pGDM and 19 controls, all matched according to body mass index (BMI). Fasting blood samples were drawn in all women 3-6 days after spontaneous or dydrogesterone-induced withdrawal bleeding. Body fat distribution was assessed using dual-energy X-ray absorptiometry in all women. After adjusting for age and percent body fat, measures of insulin resistance such as SHBG and adiponectin concentrations were decreased and central obesity was increased in women with PCOS and pGDM compared with controls (all p PCOS compared with BMI-matched controls (all p insulin resistance are increased in both women with PCOS and women with pGDM, while low-grade inflammation is increased only in PCOS. PCOS and GDM might represent specific phenotypes of one disease entity with an increased risk of cardiovascular disease, whereby women with PCOS demonstrate an augmented cardiovascular risk profile.

Differences in the associations of anthropometric measures with insulin resistance and type 2 diabetes mellitus between Korean and US populations: Comparisons of representative nationwide sample data.

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Yoon, Yeong Sook; Choi, Han Seok; Kim, Jin Kuk; Kim, Yu Il; Oh, Sang Woo

Variation among ethnic groups in the association between obesity and insulin resistance (IR)/diabetes has been suggested, but studies reported inconsistent results. We evaluated ethnic differences in the association between obesity and insulin resistance (IR)/diabetes. We conducted a cross-sectional analysis using Korea (n=18,845) and the USA (n=4657) National Health and Nutrition Examination Survey(NHANES) 2007-2010. We performed statistical comparisons of AUC-ROC (area under the curve in a receiver operating characteristic curve) values for body mass index (BMI), waist circumference (WC) and homeostasis model assessment of insulin resistance (HOMA-IR) to predict IR or diabetes among different ethnic groups. AUC-ROC values for BMI and WC for predicting IR were highest in Whites (0.8324 and 0.8468) and lowest in Koreans (0.7422 and 0.7367). Whites showed the highest AUC-ROC values for BMI (0.6869) and WC (0.7421) for predicting diabetes, while the AUC-ROC for HOMA-IR was highest in Koreans (0.8861). Linear regression showed significant interactions between ethnicity and the main effects (all Pdiabetes was highest in Whites, while the ability of HOMA-IR to predict diabetes was highest in Koreans. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

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

Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus.

Science.gov (United States)

Chen, Yanmin; Lv, Ping; Du, Mengkai; Liang, Zhaoxia; Zhou, Menglin; Chen, Danqing

2017-07-01

Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats. After then, normal pregnant rats were divided into two groups to receive either apo-RBP4 or vehicle injection. The metabolic parameters and insulin signaling in adipose tissue, skeletal muscle and liver were determined in apo-RBP4 and control groups. Primary human adipocytes were cultured in vitro with different proportions of apo-RBP4 and holo-RBP4 for 24 h. The interaction between RBP4 and STRA6 was assessed by co-immunoprecipitation, and the expression of JAK-STAT pathway and insulin signaling were detected by Western blotting and immunofluorescence. We found increases in serum RBP4 levels and the RBP4:retinol ratio but not in the retinol levels in GDM rats. Exogenous apo-RBP4 injection attenuated insulin sensitivity in pregnant rats. In vitro, a prolonged interaction between RBP4 and STRA6 was observed when apo-RBP4 was present. In response to increased apo-RBP4 levels, cells showed elevated activation of the JAK2/STAT5 cascade and SOCS3 expression, decreased phosphorylation of IR and IRS1, and attenuated GLUT4 translocation and glucose uptake upon insulin stimulation. Apo-RBP4 is a ligand that activates the STRA6 signaling cascade, inducing insulin resistance in GDM.

Renal duplex Doppler ultrasound findings in diabetics

International Nuclear Information System (INIS)

Shim, Hyang Yee; Kim, Young Geun; Kook, Cheol Keu; Yoon, Chong Hyun; Lee, Shin Hyung; Lee, Chang Joon

1993-01-01

The correlation between clinical-laboratory findings and renal duplex Doppler ultrasound findings was studied in 45 patients with diabetes mellitus to see the role of duplex Doppler ultrasound in the detection of diabetic nephropathy. The resistive indices in patients with elevated serum creatinine, BUN, proteinuria, and systolic blood pressure levels were statistically significantly higher than those in patients with normal levels (p<0.05). Also resistive indics in patients with retinopathy were higher than that in patients without retinopathy (p<0.05). But the ultrasound morphologic changes of kidney such as renal length, cortical eye-catching, and corticomedullarycontrast were not well correlated with clinical-laboratory data and resistive index. The resistive index of the kidney in conjunction with clinical-laboratory data in diabetics may be helpful in the evaluation of diabetic nephropathy

Renal duplex Doppler ultrasound findings in diabetics

Energy Technology Data Exchange (ETDEWEB)

Shim, Hyang Yee; Kim, Young Geun; Kook, Cheol Keu; Yoon, Chong Hyun; Lee, Shin Hyung; Lee, Chang Joon [National Medical Center, Seoul (Korea, Republic of)

1993-12-15

The correlation between clinical-laboratory findings and renal duplex Doppler ultrasound findings was studied in 45 patients with diabetes mellitus to see the role of duplex Doppler ultrasound in the detection of diabetic nephropathy. The resistive indices in patients with elevated serum creatinine, BUN, proteinuria, and systolic blood pressure levels were statistically significantly higher than those in patients with normal levels (p<0.05). Also resistive indics in patients with retinopathy were higher than that in patients without retinopathy (p<0.05). But the ultrasound morphologic changes of kidney such as renal length, cortical eye-catching, and corticomedullarycontrast were not well correlated with clinical-laboratory data and resistive index. The resistive index of the kidney in conjunction with clinical-laboratory data in diabetics may be helpful in the evaluation of diabetic nephropathy

Supplementation with Glucosamine Has no Adverse Effects on Glycemic Level and Insulin Resistance in Type 2 Diabetic Patients

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Zohreh Mazloom

2015-10-01

Full Text Available Background: Use of glucosamine as an alternative treatment for osteoarthritis is becoming more frequent, including in those who have diabetes at the same time. The results from in vitro and animal studies propose that glucosamine may inversely affect glucose metabolism. However, the recommended dose of oral glucosamine in healthy people or diabetics did not have such effects consistently. The aim of the present study was to assess the effect of glucosamine on glycemic control and insulin resistance in type 2 diabetic patients. Methods: Fifty-four patients with type 2 diabetes participated in this randomized, double-blind, placebo-controlled study. The participants were assigned to receive 1500 mg glucosamine hydrochloride or placebo for 12 weeks. After determining their baseline characteristics, body mass index and dietary intake components, fasting blood glucose and fasting insulin were measured at weeks of 0, 8, and 12. Indices of insulin function including quantitative insulin sensitivity check index (QUICKI and homeostasis model assessment of insulin resistance (HOMA-IR were calculated by specific formulas. Independent t-test and general linear model repeated measures were used to analyze the data. Results: In the glucosamine group, the means of fasting blood glucose and insulin were 107.31±24.07 mg/dl and 8.75±4.37 μu/ ml, respectively at baseline, which reached 112.38±31.50 and 9.10±4.17 at week 12. In the placebo group, the mean for fasting blood glucose and insulin were 103.84±24.15 and 9.79±4.02 at the beginning of the study, which reached to 111.40±26.43 and 8.58±3.68 at week 12. The results showed that there were no significant differences in fasting blood glucose, insulin, HOMA-IR and QUICKI indices at all the studied time points (weeks of 0, 8 and 12 within or between the groups. Conclusion: Twelve weeks of a normal recommended dose of glucosamine supplements may not have adverse effects on glycemic control and insulin

The Effect of Unsweetened Pomegranate Juice on Insulin Resistance, High Sensitivity C-Reactive Protein and Obesity among Type 2 Diabetes Patients

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Samira Babaeian

2013-04-01

Full Text Available Background & objectives: Diabetes mellitus is one of the prevalent metabolic disorders in the world and mostly it is related to Obesity. Central obesity results in higher risk of diabetes, cardiovascular disease and hyperinsulinemia. Hyperinsulinemia is the main reason of central obesity disorders. Studies have been shown that the fruits, vegetables and drinks are rich in phenolic and antioxidants components may alleviate diabetes diseases. One of these fruits is pomegranate that is rich in flavonoids. Therefore, this study was designed to determine the effect of unsweetened pomegranate juice consumption on insulin resistance, inflammatory factor and anthropometric measures in diabetic patients.   Methods : In this clinical trial, 50 patients with type 2 diabetes aged 30-50 years were recruited into the study and randomly assigned into two groups: (1 intervention group (n=25 who drank 240 ml unsweetened pomegranate juice daily and (2 control group (n=25 who drank 240 ml water daily for two months. Fasting blood glucose, inflammatory factors including hs-CRP, anthropometric measures including weight, height, waist and hip circumference, BMI were determined at the baseline and after 8 weeks. Nutritionist IV program, Independent sample t-test, Paired sample t-test were used for data analyses.   Results : Comparison of fasting blood glucose, HbA1C, body mass index, hs-CRP between the two groups before intervention did not reveal a significant difference. The result of the study showed a significant decrease in insulin resistance, body weight, hip circumstance, waist circumstance in intervention group ( p <0.05 ، p <0.01 ، p <0.05 ، p <0.05 respectively w hereas no significant changes were found for serum glucose, HbA1C, hs-CRP in this group .   Conclusion : These findings indicate the beneficial effect of the daily consumption of unsweetened pomegranate juice on insulin resistance, body weight, waist and hip circumstances.

Insulin resistance predicts early cardiovascular morbidity in men without diabetes mellitus, with effect modification by physical activity.

Science.gov (United States)

Hellgren, Margareta I; Daka, Bledar; Jansson, Per-Anders; Lindblad, Ulf; Larsson, Charlotte A

2015-07-01

to assess how well insulin resistance predicts cardiovascular disease (CVD) in non-diabetic men and women and to explore the influence of physical activity. in this prospective study 2563 men and women without diabetes were examined with an oral glucose tolerance test, anthropometric measurements and blood pressure assessment. Questionnaires about lifestyle and physical activity were completed. Insulin resistance was estimated by fasting concentrations of plasma insulin and by HOMA index for insulin resistance. Participants were followed up for cardiovascular morbidity and mortality during an 8-year period, using information from the National Swedish Inpatient and Mortality registers. at follow-up, HOMAir predicted CVD morbidity in males (50 events) and females (28 events) combined (HRage/sex-adj 1.4, 95% CI 1.1-1.7); however, when stratified by gender HOMAir was predictive solely in men (HRage-adj 1.8, 95% CI 1.3-2.4), whereas no association was found in women (HRage-adj 1.1, 95% CI 0.8-1.5). When stratifying the data for high and low physical activity, the predictive value of insulin resistance became stronger in sedentary men (HRage-adj 2.3, 95% CI 1.5-3.4) but was abolished in men performing moderate to vigorous physical activity (HRage-adj 1.0, 95% CI 0.6-1.6). The results remained when step-wise adjusted also for BMI, ApoB/ApoA1 and hypertension, as well as for smoking, alcohol consumption and education. Outcome for fasting plasma insulin was similar to HOMAir. insulin resistance predicts CVD in the general population; however, men may be more vulnerable to increased insulin resistance than women, and physically inactive men seem to be at high risk. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The Protective Effects of Oral Low-dose Quercetin on Diabetic Nephropathy in Hypercholesterolemic Mice

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Isabele Beserra Santos Gomes

2015-09-01

Full Text Available Aims: Diabetic nephropathy (DN is one of the major causes of end-stage renal disease, and the incidence of DN is increasing worldwide. Considering our previous report indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg demonstrated renoprotective, anti-oxidative and anti-apoptotic effects in the C57BL/6J model of diabetic nephropathy, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE-/-. Methods: DN was induced by streptozotocin (100 mg/kg/day, for 3 days in adult apoE-/-mice. Six weeks later, the mice were divided into the following groups: diabetic apoE-/- mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks, diabetic ApoE-/- mice treated with vehicle (DV and non-treated non-diabetic (ND mice.Results: Quercetin treatment caused a reduction in polyuria (~30%, glycemia (~25%, abolished the hypertriglyceridemia and had significant effects on renal function, including decreased proteinuria (~15% and creatininemia (~30%, which were accompanied by beneficial effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight.Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical and morphological modifications. Thus, this translational study highlights the importance of quercetin as a potential nutraceutical for the management of DN, including in diabetes associated with dyslipidemia.

Correlation of serum vitamin E content with insulin resistance and oxidative stress response in patients with type 2 diabetes mellitus

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Jun Li

2017-08-01

Full Text Available Objective: To study the correlation of serum vitamin E content with insulin resistance and oxidative stress response in patients with type 2 diabetes mellitus. Methods: Patients who were diagnosed with type 2 diabetes mellitus in Xining Second People’s Hospital between February 2016 and February 2017 were selected as T2DM group, healthy volunteers who received physical examination during the same period were selected as control group, oral glucose tolerance test was conducted to detect insulin resistance indexes, and fasting venous blood was collected to detect oxidative stress indicators. Results: Serum VitE, 2 h-Ins, 2 h-CP, Trx, Txnip, SOD and GSH-Px levels of T2DM group were significantly lower than those of control group while F-Ins, F-CP, MDA, AOPP, 8-OHdG, AGEs and LOX-1 levels were significantly higher than those of control group; serum VitE level in T2DM patients was positively correlated with serum 2 h-Ins, 2 h-CP, Trx, Txnip, SOD and GSH-Px levels, and negatively correlated with serum F-Ins, F-CP, MDA, AOPP, 8-OHdG, AGEs and LOX-1 levels. Conclusion: The decrease of serum vitamin E in patients with type 2 diabetes mellitus can lead to the aggravation of insulin resistance and the activation of oxidative stress response.

Association between diabetes mellitus and multi-drug-resistant tuberculosis : a protocol for a systematic review and meta-analysis

NARCIS (Netherlands)

Tegegne, Balewgizie Sileshi; Habtewold, Tesfa Dejenie; Mengesha, Melkamu Merid; Burgerhof, Johannes G M

2017-01-01

INTRODUCTION: Multi-drug-resistant tuberculosis (MDR-TB) has emerged as a challenge to global tuberculosis (TB) control and remains a major public health concern in many countries. Diabetes mellitus (DM) is an increasingly recognized comorbidity that can both accelerate TB disease and complicate its

Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis

NARCIS (Netherlands)

Donga, Esther; Dekkers, Olaf M.; Corssmit, Eleonora P. M.; Romijn, Johannes A.

2015-01-01

Objective: The aim of this study was to perform a systematic review and meta-analysis on insulin resistance in adult patients with type 1 diabetes mellitus compared to healthy controls, assessed by hyperinsulinemic euglycemic clamp studies. Design and methods: We conducted a systematic search of

The SNARE protein SNAP23 and the SNARE-interacting protein Munc18c in human skeletal muscle are implicated in insulin resistance/type 2 diabetes

DEFF Research Database (Denmark)

Boström, Pontus; Andersson, Linda; Vind, Birgitte

2010-01-01

/cytosolic compartment in the patients with the type 2 diabetes. Expression of the SNARE-interacting protein Munc18c was higher in skeletal muscle from patients with type 2 diabetes. Studies in L6 cells showed that Munc18c promoted the expression of SNAP23. CONCLUSIONS: We have translated our previous in vitro results......OBJECTIVE: Our previous studies suggest that the SNARE protein synaptosomal-associated protein of 23 kDa (SNAP23) is involved in the link between increased lipid levels and insulin resistance in cardiomyocytes. The objective was to determine whether SNAP23 may also be involved in the known...... association between lipid accumulation in skeletal muscle and insulin resistance/type 2 diabetes in humans, as well as to identify a potential regulator of SNAP23. RESEARCH DESIGN AND METHODS: We analyzed skeletal muscle biopsies from patients with type 2 diabetes and healthy, insulin-sensitive control...

Sibutramine and L-carnitine compared to sibutramine alone on insulin resistance in diabetic patients.

Science.gov (United States)

Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Gravina, Alessia; Mereu, Roberto; D'Angelo, Angela; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

2010-01-01

To evaluate the effects of one year of treatment with sibutramine plus L-carnitine compared to sibutramine on body weight, glycemic control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-four patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) >8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). There was a decrease in body weight, BMI, HbA(1c), FPI, HOMA-IR, and RBP-4 in both groups, even when the values obtained with sibutramine plus L-carnitine were lower than the values obtained in sibutramine group. There was a faster decrease of FPG, PPG, TC, LDL-C, resistin and Hs-CRP with sibutramine plus L-carnitine even when no differences between the two groups were obtained. Furthermore, only sibutramine plus L-carnitine improved Tg, and visfatin. Sibutramine plus L-carnitine gave a faster improvement of lipid profile, insulin resistance parameters, glycemic control, and body weight compared to sibutramine.

n-3 PUFA Esterified to Glycerol or as Ethyl Esters Reduce Non-Fasting Plasma Triacylglycerol in Subjects with Hypertriglyceridemia

DEFF Research Database (Denmark)

Hedengran, Anne; Szecsi, Pal B; Dyerberg, Jørn

2015-01-01

To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this st......To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective...... of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120...... subjects with non-fasting plasma triacylglycerol levels of 1.7-5.65 mmol/L (150-500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28 % in the AG-PUFA group and 22 % in the EE...

Association of Low-Moderate Arsenic Exposure and Arsenic Metabolism with Incident Diabetes and Insulin Resistance in the Strong Heart Family Study.

Science.gov (United States)

Grau-Perez, Maria; Kuo, Chin-Chi; Gribble, Matthew O; Balakrishnan, Poojitha; Jones Spratlen, Miranda; Vaidya, Dhananjay; Francesconi, Kevin A; Goessler, Walter; Guallar, Eliseo; Silbergeld, Ellen K; Umans, Jason G; Best, Lyle G; Lee, Elisa T; Howard, Barbara V; Cole, Shelley A; Navas-Acien, Ana

2017-12-20

High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity. We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance. We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up. Median ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants. Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives.

Science.gov (United States)

Salzano, Andrea; D'Assante, Roberta; Heaney, Liam M; Monaco, Federica; Rengo, Giuseppe; Valente, Pietro; Pasquali, Daniela; Bossone, Eduardo; Gianfrilli, Daniele; Lenzi, Andrea; Cittadini, Antonio; Marra, Alberto M; Napoli, Raffaele

2018-03-23

Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate. Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

Science.gov (United States)

Moreno, Beatriz; de Faria, Ana Paula; Ritter, Alessandra Mileni Versuti; Yugar, Lara Buonalumi Tacito; Ferreira-Melo, Silvia Elaine; Amorim, Rivadavio; Modolo, Rodrigo; Fattori, André; Yugar-Toledo, Juan Carlos; Coca, Antonio; Moreno, Heitor

2018-05-01

This study aimed to evaluate the effects of glycated hemoglobin (HbA 1c ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA 1c diabetes mellitus: n = 98) and HbA 1c ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA 1c was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA 1c may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function. ©2018 Wiley Periodicals, Inc.

Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia.

Science.gov (United States)

Blair, Hannah A; Dhillon, Sohita

2014-10-01

Omega-3 carboxylic acids (Epanova) [OM3-CA] is the first free fatty acid form of long-chain marine omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid being the most abundant) to be approved by the US FDA as an adjunct to diet to lower triglyceride levels in patients with severe hypertriglyceridemia (≥ 500 mg/dL). Oral OM3-CA has greater bioavailability than ethyl ester forms of omega-3 and, unlike omega-3 acid ethyl esters, does not require co-ingestion of a high-fat meal, as it does not need pancreatic enzyme activity for absorption. In the 12-week EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial, OM3-CA 2 or 4 g/day significantly reduced serum triglyceride levels relative to placebo. Other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and very low-density lipoprotein cholesterol (VLDL-C) levels, were also reduced significantly with OM3-CA relative to placebo. Low-density lipoprotein cholesterol levels were increased significantly with OM3-CA relative to placebo; however, these increases were not accompanied by increases in the circulating concentrations of non-HDL-C, VLDL-C, or apolipoprotein B. OM3-CA was generally well tolerated in this study, with most adverse events being of mild or moderate severity. Although additional comparative data are needed to position OM3-CA with respect to other formulations of omega-3 fatty acids, current evidence suggests that OM3-CA is a useful addition to the treatment options available for patients with severe hypertriglyceridemia.

Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase gene allele with two novel missense variants.

Science.gov (United States)

Kassner, Ursula; Salewsky, Bastian; Wühle-Demuth, Marion; Szijarto, Istvan Andras; Grenkowitz, Thomas; Binner, Priska; März, Winfried; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

2015-09-01

Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union. Therefore the precise molecular diagnosis of familial hyperchylomicronemia may affect treatment decisions. We present a 57-year-old male patient with excessive hypertriglyceridemia despite intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic pancreatitis. Direct DNA sequencing and cloning revealed two novel missense variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) and are likely of functional relevance. No further relevant mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be transmitted in a dominant manner, at least in some families.

Nephrogenic diabetes insipidus with idiopathic Fanconi's syndrome in a child who presented as vitamin D resistant rickets.

Science.gov (United States)

Patra, Soumya; Nadri, Gulnaz; Chowdhary, Harish; Pemde, Harish K; Singh, Varinder; Chandra, Jagdish

2011-10-01

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycaemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium, and magnesium. Whereas diabetes insipidus is a disease of collecting tubules and child mainly presents with dehydration and hypernatremia. Though all the cases published till date were secondary to drugs, myeloma, hematological disorders, etc., we are reporting the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi syndrome. We hypothesized that the NDI may be due to of severe hypokalemia induced tubular dysfunction.

Effectiveness of resistance exercise compared to aerobic exercise without insulin therapy in patients with type 2 diabetes mellitus: a meta-analysis.

Science.gov (United States)

Nery, Cybelle; Moraes, Silvia Regina Arruda De; Novaes, Karyne Albino; Bezerra, Márcio Almeida; Silveira, Patrícia Verçoza De Castro; Lemos, Andrea

Physical exercise has been used to mitigate the metabolic effects of diabetes mellitus. To evaluate the effect of resistance exercise when compared to aerobic exercise without insulin therapy on metabolic and clinical outcomes in patients with type 2 diabetes mellitus. Papers were searched on the databases MEDLINE/PubMed, CINAHL, SPORTDiscus, LILACS, and SCIELO, without language or date of publication limits. Clinical trials that compared resistance exercise to aerobic exercise in adults with type 2 diabetes mellitus who did not use insulin therapy were included. The quality of evidence and risk of bias were assessed using the GRADE system and the Cochrane Risk of Bias tool, respectively. Meta-analysis was also used, whenever possible. Two reviewers extracted the data independently. Eight eligible articles were included in this study, with a total of 336 individuals, with a mean age of 48-58 years. The protocols of aerobic and resistance exercise varied in duration from eight to 22 weeks, 30-60min/day, three to five times/week. Overall the available evidence came from a very low quality of evidence and there was an increase in Maximal oxygen consumption (mean difference: -2.86; 95% CI: -3.90 to -1.81; random effect) for the resistance exercise and no difference was found in Glycated hemoglobin, Body mass index, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Resistance exercise appears to be more effective in promoting an increase in Maximal oxygen consumption in protocols longer than 12 weeks and there is no difference in the control of glycemic and lipid levels between the two types of exercise. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Increased interaction with insulin receptor substrate 1, a novel abnormality in insulin resistance and type 2 diabetes

DEFF Research Database (Denmark)

Caruso, Michael; Ma, Danjun; Msallaty, Zaher

2014-01-01

Insulin receptor substrate 1 (IRS1) is a key mediator of insulin signal transduction. Perturbations involving IRS1 complexes may lead to the development of insulin resistance and type 2 diabetes (T2D). Surprisingly little is known about the proteins that interact with IRS1 in humans under health...... in obesity and T2D in humans, provides new insights into the molecular mechanism of insulin resistance and identifies new targets for T2D drug development....... and disease conditions. We used a proteomic approach to assess IRS1 interaction partners in skeletal muscle from lean healthy control subjects (LCs), obese insulin-resistant nondiabetic control subjects (OCs), and participants with T2D before and after insulin infusion. We identified 113 novel endogenous IRS1...

Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial

NARCIS (Netherlands)

Kastelein, John J. P.; Maki, Kevin C.; Susekov, Andrey; Ezhov, Marat; Nordestgaard, Borge G.; Machielse, Ben N.; Kling, Douglas; Davidson, Michael H.

2014-01-01

Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for ethyl ester forms. The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational pharmaceutical

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats.

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Watts, Tammara; Berti, Irene; Sapone, Anna; Gerarduzzi, Tania; Not, Tarcisio; Zielke, Ronald; Fasano, Alessio

2005-02-22

Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.

Assessing Psychological Insulin Resistance in Type 2 Diabetes: a Critical Comparison of Measures.

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Holmes-Truscott, E; Pouwer, F; Speight, J

2017-07-01

This study aims to examine the operationalisation of 'psychological insulin resistance' (PIR) among people with type 2 diabetes and to identify and critique relevant measures. PIR has been operationalised as (1) the assessment of attitudes or beliefs about insulin therapy and (2) hypothetical or actual resistance, or unwillingness, to use to insulin. Five validated PIR questionnaires were identified. None was fully comprehensive of all aspects of PIR, and the rigour and reporting of questionnaire development and psychometric validation varied considerably between measures. Assessment of PIR should focus on the identification of negative and positive attitudes towards insulin use. Actual or hypothetical insulin refusal may be better conceptualised as a potential consequence of PIR, as its assessment overlooks the attitudes that may prevent insulin use. This paper provides guidance on the selection of questionnaires for clinical or research purpose and the development of new, or improvement of existing, questionnaires.

Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

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Sriwijitkamol, Apiradee; Christ-Roberts, Christine; Berria, Rachele; Eagan, Phyllis; Pratipanawatr, Thongchai; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

2006-03-01

Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

Effects of a treatment with Se-rich rice flour high in resistant starch on enteric dysbiosis and chronic inflammation in diabetic ICR mice.

Science.gov (United States)

Yuan, Huaibo; Wang, Wenjuan; Chen, Deyi; Zhu, Xiping; Meng, Lina

2017-05-01

Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower. Similar results were also found in NRRS-treated mice. In contrast, no significant difference was found between NR-treated and diabetic control groups. The treatments with SRRS and NRRS reduced the faecal pH values of the diabetic mice. Regarding the inflammatory factor levels, lower levels of serum C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-k-gene binding (NF-κB) and leptin (LEP) and higher adiponutrin (ADPN) levels were found in the SRRS and NRRS-treated mice compared with the diabetic and NR-treated mice. In addition, the CRP, IL-6 and NF-κB levels in the SRRS-treated mice were significantly reduced compared with those observed in the NRRS-treated mice. The reverse transcription-PCR (RT-PCR) results showed that the SRRS and NRRS-treated mice presented higher expression levels of orphan G protein-coupled receptor 41 (GPR41) and orphan G protein-coupled receptor 43 (GPR43) proteins compared with diabetic mice and NR-treated mice. These results indicate that treatments with rice high in RS exert beneficial effects by improving enteric dysbiosis and chronic inflammation. In addition, selenium and RS may exert synergistic effects on chronic inflammation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Diabetes in Cushing Disease.

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Mazziotti, G; Formenti, A M; Frara, S; Maffezzoni, F; Doga, M; Giustina, A

2017-05-01

This review focuses on the pathophysiological and clinical aspects of diabetes mellitus occurring in patients with Cushing disease (CD). Insulin resistance and impairment in insulin secretion are both involved in the pathogenesis of glucocorticoid-induced diabetes. Correction of glucocorticoid excess does not always resolve abnormalities of glucose homeostasis, and correction of hyperglycaemia is specifically required. In fact, insulin resistance may persist even after correction of glucocorticoid excess and diabetes needs to be treated for long term. On the other hand, emerging drugs used in the treatment of CD, such as the novel somatostatin analog pasireotide, may have direct effects on glucose homeostasis regardless of control of cortisol excess. Diabetes mellitus is a frequent and early complication of CD with important diagnostic, prognostic and therapeutic implications. Specifically, diagnosis of CD in patients with diabetes may be difficult due to potential misinterpretation of markers of cortisol hypersecretion. Moreover, diabetes mellitus is often difficult to be controlled in CD requiring a careful and dedicated therapeutic approach. Finally, the coexistence of diabetes may influence the therapeutic decision making in CD, since drugs used in this setting may variably influence glucose homeostasis regardless of control of hypercortisolism.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

Science.gov (United States)

Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

2011-12-01

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

Relationship between insulin resistance and blood lipid and sport in patients with type II diabetes mellitus complicated with hypertension%2型糖尿病合并高血压患者胰岛素低抗

Institute of Scientific and Technical Information of China (English)

谭丽艳; 杨红玉; 柴国禄; 沈凌元

2001-01-01

Objective To study the relationship between insulin resistance and blood pressure and blood lipid in patients with type II diabetes mellitus complicated with hypertension.Methods The serum concentration of fasting glucose,insulin,lipids and the level of blood pressure were measured in 56 patients with type II diabetes mellitus complicated with hypertension.Results The insulin sensitivity index(ISI) decreased in patients with type II diabetes mellitus complicated with hypertension compared with the patients with type II diabetes mellitus with normal blood pressure(P< 0.05).A negative correlation with hypertension was found between ISI and SBP,DBP,TG,ApoB in patients with type II diabetes mellitus complicated with hypertension(P<0.05).There was a positive correlation between ISI and HDL in patients with type II diabetes mellitus complicated with hypertension(P<0.05).Conclusion Insulin resistance presents in patients of type II diabetes mellitus complicated with hypertension.Insulin resistance is the major cause of hypertension and lipid metabolic disturbance in patients with type II diabetes mellitus complicated with hypertension.

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

International Nuclear Information System (INIS)

Naidoo, C.

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

Energy Technology Data Exchange (ETDEWEB)

Naidoo, C

1986-01-01

Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, /sup 125/I-insulin binding to the solubilized erythrocyte membrane receptor and /sup 125/I-insulin binding to fibroblasts in culture.

[Associations of insulin resistance and pancreatic beta-cell function with plasma glucose level in type 2 diabetes].

Science.gov (United States)

Nian, Xiaoping; Sun, Gaisheng; Dou, Chunmei; Hou, Hongbo; Fan, Xiuping; Yu, Hongmei; Ma, Ling; He, Bingxian

2002-06-10

To investigate the influence of insulin resistance and pancreatic beta-cell function on plasma glucose level in type 2 diabetes so as to provide theoretical basis for reasonable selection of hypoglycemic agents. The plasma non-specific insulin (NSINS), true insulin (TI) and glucose in eight-one type 2 diabetics, 38 males and 43 females, with a mean age of 53 years, were examined 0, 30, 60 and 120 minutes after they had 75 grams of instant noodles. The patients were divided into two groups according to their fasting plasma glucose (FPG): group A (FPG = 8.89 mmol/L). The insulin resistance was evaluated by HOMA-IR, the beta-cell function was evaluated by HOMA-beta formula and the formula deltaI(30)/deltaG(30) = (deltaI(30)-deltaI(0))/(deltaG(30)-deltaG(0)). The insulin area under curve (INSAUC) was evaluated by the formula INSAUC=FINS/2+INS(30)+INS(60)+INS(120)/2. The mean FPG was 6.23 mmol/L in group A and 12.6 mmol/L in group B. PG2H was 11.7 mmol/L in group A and 19.2 mmol/L in group B. The TI levels in group B at 0, 30, 60, 120 min during standard meal test were significantly higher than those in group A: 6.15 +/- 1.06 vs 4.77 +/- 1.06, 9.76 +/- 1.1 vs 5.88 +/- 1.1,14.68 +/- 1.11 vs 6.87 +/- 1.1 and 17.13 +/- 1.12 vs 8.0 +/- 1.1 microU/dl (all P< 0.01). The NSINS showed the same trend. The insulin resistance in group B was 1.5 times that in group A. With the insulin resistance adjusted, the beta cell function in group A was 5 to 6 times that in group B. The INSAUC in group A was 1.66 times larger than that in group B, especially the INSAUC for true insulin (2 times larger). The contribution of insulin resistance and beta cell function to PG2H was half by half in group A and 1:8 in group B. beta cell function calculated by insulin (Homa-beta) explained 41% of the plasma glucose changes in group A and 54% of the plasma glucose changes in group B. The contribution of insulin deficiency to plasma glocose was 3.3.times that of insulin resistance in group A and was 9

Management of severe hypertriglyceridemia in the hospital: a review.

Science.gov (United States)

Schaefer, Eric W; Leung, Alicia; Kravarusic, Jelena; Stone, Neil J

2012-01-01

For hospitalists, hypertriglyceridemia (HTG) is more than cardiovascular risk. Severe HTG occurs when serum triglycerides rise above 1000 mg/dL, and it carries a risk of abdominal pain and pancreatitis. The etiology of severe HTG is usually a combination of genetic and secondary factors. A detailed history with attention to family history, medications, and alcohol consumption can often lead to the cause. Physical examination findings may stretch across multiple organ systems. Patients with severe HTG should be admitted to the hospital for aggressive medical therapy if they develop symptoms such as abdominal pain or pancreatitis. Asymptomatic patients with severe HTG who have significant short-term risk for developing symptoms require urgent consultation that may lead to a brief hospitalization to address exacerbating factors. Treatment of severe HTG includes a combination of pharmacologic agents and a restriction on dietary triglyceride intake. If oral medications fail to adequately lower triglyceride levels, intravenous insulin and in rare cases therapeutic plasma exchange may be required. To prevent recurrent severe HTG, the patient should be counseled about adherence to long-term medications and lifestyle changes. Copyright © 2011 Society of Hospital Medicine.

History of Diabetes Insipidus.

Science.gov (United States)

Valenti, Giovanna; Tamma, Grazia

2016-02-01

Under physiological conditions, fluid and electrolyte homoeostasis is maintained by the kidney adjusting urine volume and composition according to body needs. Diabetes Insipidus is a complex and heterogeneous clinical syndrome affecting water balance and characterized by constant diuresis, resulting in large volumes of dilute urine. With respect to the similarly named Diabetes Mellitus, a disease already known in ancient Egypt, Greece and Asia, Diabetes Insipidus has been described several thousand years later. In 1670s Thomas Willis, noted the difference in taste of urine from polyuric subjects compared with healthy individuals and started the differentiation of Diabetes Mellitus from the more rare entity of Diabetes Insipidus. In 1794, Johann Peter Frank described polyuric patients excreting nonsaccharine urine and introduced the term of Diabetes Insipidus. An hystorical milestone was the in 1913, when Farini successfully used posterior pituitary extracts to treat Diabetes Insipidus. Until 1920s the available evidence indicated Diabetes Insipidus as a disorder of the pituitary gland. In the early 1928, De Lange first observed that some patients with Diabetes Insipidus did not respond to posterior pituitary extracts and subsequently Forssman and Waring in 1945 established that the kidney had a critical role for these forms of Diabetes Insipidus resistant to this treatment. In 1947 Williams and Henry introduced the term Nephrogenic Diabetes Insipidus for the congenital syndrome characterized by polyuria and renal concentrating defect resistant to vasopressin. In 1955, du Vigneaud received the 1955 Nobel Prize in chemistry for the first synthesis of the hormone vasopressin representing a milestone for the treatment of Central Diabetes Insipidus.

Genetic markers of insulin resistance in gestational diabetes

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Tatiana Vasil'evna Sebko

2009-12-01

Full Text Available Aim. To search for genetic markers of insulin resistance and impaired insulin secretion in pregnant women with gestational diabetes mellitus (GDM. Materials and methods. A total of 100 healthy pregnant women and 185 patients with GDM were available for examination. 80 patients developedGDM during current pregnancy, in 105 it was diagnosed 4-19 years ago. 25 of the 105 GDM patients had a history of type 2 DM. The following parameterswere measured: beta-cell secretory activity (proinsulin, ITI, C-peptide, total cholesterol (CH, HDL and LDL CH, triglycerides, HbA1c,fasting glycemia. Molecular-genetic DNA testing using PCR included studies of KCNJ 11, TCF7L2, PPARG2, ADIPOQ, ADIPOR1, ADIPOR2gene polymorphism. These genes were chosen based on the published data associating them with disturbed insulin secretion and sensitivity in DM2patient. Results. Pregnant women with GDM and obesity showed elevated IRI and leptin levels compared with controls. This rise was accompanied bymarked insulin resistance in 75% of these patients. In 50% of the healthy women proinsulin and insulin secretion decreased. Obesity in pregnantpatients was associated with significant elevation of proinsulin, IRI, and C-peptyide levels and GDM with Lys/Lys genotype of polymorphous markerGlu23k of KCNJ11 gene, pro and ala allele of polymorphous marker A219T of ADIPOR2 gene. These associations suggest specific genetic featuresof GDM related to impaired insulin secretion and sensitivity. Conclusion. Studies of common genetic nature of GDM and DM2 permit to identify risk groups at the preclinical stage, plan prevention and treatmentof these disorders.

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

Science.gov (United States)

Petrak, Frank; Herpertz, Stephan; Stridde, Elmar; Pfützner, Andreas

2013-08-01

"Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but

Hypertension resistant to antihypertensive agents commonly occurs with the progression of diabetic nephropathy in Japanese patients with type 2 diabetes mellitus: a prospective observational study

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Ito Hiroyuki

2012-06-01

Full Text Available Abstract Background We investigated 1 the frequency of hypertension in patients with type 2 diabetes graded by the new classification of chronic kidney disease (CKD reported by the Kidney Disease: Improving Global Outcomes (KDIGO and 2 the number of antihypertensive agents needed to achieve treatment goals using a prospective observational study. Methods A population of 2018 patients with type 2 diabetes mellitus was recruited for the study. The CKD stage was classified according to the eGFR and the urinary albumin excretion levels. Results Hypertension was found in 1420 (70% of the patients, and the proportion of subjects showing a blood pressure  Conclusions Hypertension resistant to antihypertensive agents was common in the patients with type 2 diabetes mellitus and increased with the progression of CKD. Although powerful combination therapy using antihypertensive agents is considered necessary for the strict control of blood pressure, this became difficult in individuals who were in advanced stages as graded based on the eGFR and the urinary albumin excretion levels.

Alcohol Consumption in Diabetic Patients with Nonalcoholic Fatty Liver Disease

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Preya J. Patel

2017-01-01

Full Text Available Aim. To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD. Methods. A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day, and moderate drinkers (any period with intake >20 g/day. Result. Compared with lifetime nondrinkers, light and moderate drinkers were more likely to be male (p=0.008 and to be Caucasian (p=0.007 and to have a history of cigarette smoking (p=0.000, obstructive sleep apnea (p=0.003, and self-reported depression (p=0.003. Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control (p=0.041 and fibrate medication to lower blood triglyceride levels (p=0.044. Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67–4.82; p=0.247 and moderate drinkers had 0.91 (95% CI: 0.27–3.10; p=0.881 times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index. Conclusions. In diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation.

The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertriglyceridemia

NARCIS (Netherlands)

Stalenhoef, A. F.; de Graaf, J.; Wittekoek, M. E.; Bredie, S. J.; Demacker, P. N.; Kastelein, J. J.

2000-01-01

We evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil (1200 mg/day) versus Omacor (4 g/day), a drug containing the n-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on lipid and

Overproduction of a kinetic subclass of VLDL-apoB, and direct catabolism of VLDL-apoB in human endogenous hypertriglyceridemia: an analytical model solution of tracer data

International Nuclear Information System (INIS)

Eaton, R.P.; Allen, R.C.; Schade, D.S.

1983-01-01

To investigate the participation of the major apoprotein involved in triglyceride transport in the pathogenesis of endogenous hypertriglyceridemia, five kinetic studies of apoprotein B were conducted in volunteer normolipidemic subjects and six studies in four patients with endogenous hypertriglyceridemia. The transport of apoprotein B within four kinetic subclasses of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was studied by injection of [ 75 Se]selenomethionine. A 24-fold increase in the entry of newly synthesized apoprotein B at the initial kinetic subclass of the four-compartment VLDL delipidation sequence characterized the hypertriglyceridemic studies relative to normal subjects. Moreover, approximately 75 mg/kg per day of VLDL-B turnover reflected direct catabolism independent of conversion to IDL and/or to LDL, in contrast to the 8 mg/kg per day observed in controls. IDL-B was derived from VLDL-B in both normal and hypertriglyceridemic subjects, and was responsible for greater than 70% of all LDL-B synthesis. LDL-B pool size and turnover were indistinguishable in hypertriglyceridemic subjects from that observed in normal subjects. These studies suggest that two kinetic phenomena may characterize the pathophysiology of endogenous hypertriglyceridemia: a) over-production of apoB within a kinetic subclass of VLDL and b) preferential catabolism of hypertriglyceridemic VLDL without prior conversion to IDL/LDL

Insulin resistance and maximal oxygen uptake

DEFF Research Database (Denmark)

Seibaek, Marie; Vestergaard, Henrik; Burchardt, Hans

2003-01-01

BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown. HYPOTHESIS: This study was undertaken to determine the relationship between insulin resistance, maximal oxygen uptake......, and the presence of either diabetes or ischemic heart disease. METHODS: The study population comprised 33 patients with and without diabetes and ischemic heart disease. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was measured during a bicycle exercise test. RESULTS......: There was a strong correlation between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p = 0.001), and maximal oxygen uptake was the only factor of importance for determining insulin sensitivity in a model, which also included the presence of diabetes and ischemic heart disease. CONCLUSION...

Changes of serum leptin and their relationships with insulin resistance in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity

International Nuclear Information System (INIS)

Zhang Lei; Changzhou Wujin People's Hospital of Jiangsu Province, Changzhou; Shi Linlin; Lu Dan; Zhang Lei; Wang Qing; Yao Wenhua

2005-01-01

Objective: To study the changes of serum leptin in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity in order to explore the relationship of leptin and insulin resistance and the role of leptin in the occurrence of type 2 diabetes mellitus. Methods: 60 cases of simple obesity, 60 cases of type 2 diabetes mellitus and 30 cases of normal control were included according to the diagnostic criteria of obesity and type 2 diabetes mellitus. the levels of fasting serum leptin, fasting serum insulin, fasting glucose, fasting blood lipid were measured in all cases. The body mass index (BMI) and insulin action index were calculated. Results: The level of BMI, serum leptin, serum insulin, blood lipid were significantly higher in patients with simple obesity and with type 2 diabetes mellitus complicated with obesity than in normal control cases, while (IAI) was significantly lower. The levels of free serum leptin, serum insulin, free glucose, and blood lipid were significantly higher in patients with type 2 diabetes mellitus complicated with obesity than in patients with simple obesity, while IAI was significantly lower. The level of serum leptin was positively correlated with BMI (r=0.48, P<0.55) and fasting serum leptin (r=0.55, P<0.05) and negatively correlated with IAI (r=-0.47, P<0.05) in patients with type 2 diabetes complicated with obesity. Conclusion: The overexpression of serum leptin may play an important role in the occurrence of the insulin resistance and type 2 diabetes mellitus in obesity patients. (authors)

Exercise and its role in gestational diabetes mellitus

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Chen Wang

2016-12-01

Full Text Available Gestational diabetes mellitus (GDM refers to diabetes diagnosed in the second or third trimester of pregnancy that is not clearly either type 1 or type 2 diabetes. GDM is a common medical complication in pregnancy that has been rapidly increasing worldwide. GDM is associated with both short- and long-term health issues for both mothers and offspring. Consistent with type 2 diabetes, peripheral insulin resistance contributes to the hyperglycemia associated with GDM. Accordingly, it is important to identify strategies to reduce the insulin resistance associated with GDM. To date, observational studies have shown that exercise can be a non-invasive therapeutic option for preventing and managing GDM that can be readily applied to the antenatal population. However, the relevant mechanisms for these outcomes are yet to be fully elucidated. The present review aimed to explain the potential mechanisms of exercise from the perspective of reducing the insulin resistance, which is the root cause of GDM. Exercise recommendations and opinions of exercise during pregnancy are briefly summarized. Keywords: Exercise, Gestational diabetes mellitus, Insulin resistance, Pregnancy

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

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Valdivielso Pedro

2010-04-01

Full Text Available Abstract Background Hypertriglyceridemia (HTG is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years was genotyped for the LPL-HindIII (rs320, S447X (rs328, D9N (rs1801177 and N291S (rs268 polymorphisms, the APOA5-S19W (rs3135506 and -1131T/C (rs662799 variants, and the APOE polymorphism (rs429358; rs7412 using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L, including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p p p p p p p = 0.042 and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p p Conclusion Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ε4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

Data in support of fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice

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Du-Qiang Luo

2015-09-01

Full Text Available This data article contains data related to the research article entitled “Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice” in the Toxicology and Applied Pharmacology [1]. Fumosorinone (FU is a new inhibitor of protein phosphatase 1B inhibitor, which was isolated from insect pathogenic fungi Isaria fumosorosea. FU was found to inhibit PTP1B activity in our previous study [2]. PTP1B is the physiological antagonist of the insulin signalling pathway. Inhibition of PTP 1B may increase insulin sensitivity [3]. PTP1B has been considered promising as an insulin-sensitive drug target for the prevention and the treatment of insulin-based diseases [4]. We determined the effect of FU on the glucose consumption of IR HepG2 cells. FU caused significant enhancement in glucose consumption by insulin-resistant HepG2 cells compared with control cells.

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.

Effects of one year treatment of sibutramine on insulin resistance parameters in type 2 diabetic patients.

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Derosa, Giuseppe; Maffioli, Pamela; Ferrari, Ilaria; Palumbo, Ilaria; Randazzo, Sabrina; D'Angelo, Angela; Cicero, Arrigo F G

2010-01-01

Comparison of the effects of one year treatment with sibutramine compared to placebo on insulin resistance parameters, body weight, glycemic control, and lipid profile, in type 2 diabetic patients. Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: homeostasis model assessment insulin resistance index (HOMA-IR), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP), body weight, body mass index (BMI), glycated hemoglobin (HbA(₁c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglycerides (T(g)). A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups, and a faster improvement of HbA(₁c), FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. Sibutramine gave a faster improvement of insulin resistance parameters and glycemic control compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight.

Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

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Qiuwei Wang

Full Text Available OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function were calculated in maternal and cord blood respectively. RESULTS: Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively. Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019, in the pregnant women with GDM. CONCLUSIONS: Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

Alcoholism and Diabetes Mellitus

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Soo-Jeong Kim

2012-04-01

Full Text Available Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM, which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.