Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake.

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Mars, Monica; de Graaf, Cees; de Groot, Lisette C P G M; Kok, Frans J

2005-03-01

The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric compensation. The objective was to assess the effect of acute decreases in fasting leptin concentrations, induced by energy restriction, on subsequent energy intake compensation. We hypothesized that men with a large decrease in fasting leptin concentrations would have larger ad libitum energy intakes than would men with a small decrease in leptin. Thirty-four male unrestrained eaters [age: 23 +/- 3 y; body mass index (in kg/m(2)): 22.3 +/- 1.6] participated in a semicontrolled intervention study. Fasting serum leptin and insulin concentrations were measured before and 2 d after 62% energy restriction. Energy intake was measured on the 2 following days on which food was provided ad libitum. During energy restriction, fasting leptin and insulin concentrations decreased by 27.2% (95% CI: -34.4%, -19.9%) and 30.7% (95% CI: -41.0%, -20.4%), respectively. Subjects consumed 143 +/- 27% of their estimated energy requirements (18.3 +/- 2.9 MJ) on the first day and 124 +/- 20% (16.0 +/- 2.6 MJ) on the second day of ad libitum intake. No significant correlations were observed between decreases in fasting leptin or insulin concentrations and subsequent ad libitum energy intake; however, decreases in insulin were correlated with an increase in carbohydrate intake (r=-0.49, P < 0.01). Although fasting leptin concentrations decreased significantly during energy restriction and subjects showed compensatory behavior during subsequent ad libitum food intake, no association was observed between the decrease in fasting leptin concentrations and caloric compensation.

Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus.

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Smith, G D; Amos, T A; Mahler, R; Peters, T J

1987-01-01

Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin-dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin-dependent diabetes mellitus showed a significant improvement in their glucose tolerance, which paralleled the severity of their diabetes. This response seems to reflect decreased degradation of insulin rather than increased pancreatic output. These observations suggest that treatment with chloroquine or suitable analogues may be a new approach to the management of diabetes. PMID:3103729

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations

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Chen, Brian H.; Hivert, Marie-France; Peters, Marjolein J.; Pilling, Luke C.; Hogan, John D.; Pham, Lisa M.; Harries, Lorna W.; Fox, Caroline S.; Bandinelli, Stefania; Dehghan, Abbas; Hernandez, Dena G.; Hofman, Albert; Hong, Jaeyoung; Joehanes, Roby; Johnson, Andrew D.; Munson, Peter J.; Rybin, Denis V.; Singleton, Andrew B.; Uitterlinden, André G.; Ying, Saixia; Melzer, David; Levy, Daniel; van Meurs, Joyce B.J.; Ferrucci, Luigi; Florez, Jose C.; Dupuis, Josée

2016-01-01

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes–imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis. PMID:27625022

Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Tronier, B; Bülow, J B

1987-01-01

Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular...

The effect of feeding frequency on insulin and ghrelin responses in human subjects

DEFF Research Database (Denmark)

Solomon, Thomas; Chambers, Edward S; Jeukendrup, Asker E

2008-01-01

Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin...... and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2)years, body mass 75.7 (SEM 3.2) kg and BMI 23.8 (SEM 0.8) kg/m(2). Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency(two) meal ingestion (LOFREQ......(MEAL)); high-frequency (twelve) meal ingestion (HIFREQ(MEAL)). Meals were equi-energetic within trials,consisting of 64% carbohydrate, 23% fat and 13% protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between...

Fasting insulin, insulin resistance, and risk of cardiovascular or all-cause mortality in non-diabetic adults: a meta-analysis.

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Zhang, Xiaohong; Li, Jun; Zheng, Shuiping; Luo, Qiuyun; Zhou, Chunmei; Wang, Chaoyang

2017-10-31

Studies on elevated fasting insulin or insulin resistance (IR) and cardiovascular or all-cause mortality risk in non-diabetic individuals have yielded conflicting results. This meta-analysis aimed to evaluate the association of elevated fasting insulin levels or IR as defined by homeostasis model assessment of IR (HOMA-IR) with cardiovascular or all-cause mortality in non-diabetic adults. We searched for relevant studies in PubMed and Emabse databases until November 2016. Only prospective observational studies investigating the association of elevated fasting insulin levels or HOMA-IR with cardiovascular or all-cause mortality risk in non-diabetic adults were included. Risk ratio (RR) with its 95% confidence intervals (CIs) was pooled for the highest compared with the lowest category of fasting insulin levels or HOMA-IR. Seven articles involving 26976 non-diabetic adults were included. The pooled, adjusted RR of all-cause mortality comparing the highest with the lowest category was 1.13 (95% CI: 1.00-1.27; P =0.058) for fasting insulin levels and 1.34 (95% CI: 1.11-1.62; P =0.002) for HOMA-IR, respectively. When comparing the highest with the lowest category, the pooled adjusted RR of cardiovascular mortality was 2.11 (95% CI: 1.01-4.41; P =0.048) for HOMA-IR in two studies and 1.40 (95% CI: 0.49-3.96; P =0.526) for fasting insulin levels in one study. IR as measured by HOMA-IR but not fasting insulin appears to be independently associated with greater risk of cardiovascular or all-cause mortality in non-diabetic adults. However, the association of fasting insulin and HOMA-IR with cardiovascular mortality may be unreliable due to the small number of articles included. © 2017 The Author(s).

Circulating ApoJ is closely associated with insulin resistance in human subjects.

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Seo, Ji A; Kang, Min-Cheol; Ciaraldi, Theodore P; Kim, Sang Soo; Park, Kyong Soo; Choe, Charles; Hwang, Won Min; Lim, Dong Mee; Farr, Olivia; Mantzoros, Christos; Henry, Robert R; Kim, Young-Bum

2018-01-01

Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity. Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA. Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100±8.3 vs. 150.6±8.5AU, Pinsulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100±13.9 vs. 77±15.2AU, P=0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR. Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

In Nonobese Children, Fitness and BMI are Independent Predictors of Fasting Insulin.

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Watson, Andrew M; Eickhoff, Jens; Nemeth, Blaise A; Carrel, Aaron L

2015-05-01

Although fitness and obesity have been shown to be independent predictors of cardiometabolic disease risk in obese children, this interaction is not well defined in nonobese children. The purpose of this study was to define the relationships between peak aerobic capacity, body composition, and fasting insulin levels in nonobese middle school children. 148 middle school children (mean age 11.0 ± 2.1 years, 49% male) underwent determination of body mass index (BMI) z-score, fasting glucose, fasting insulin, body composition by DXA scan (lean body mass and body fat percentage), and peak oxygen uptake per kg of lean body mass (VO2peak). Univariate correlations and multivariate regression analysis were used to identify independent predictors of fasting insulin using age, sex, percent body fat, body mass index z-score, and VO2peak. fasting insulin was significantly related to VO2peak (r =-0.37, p fasting insulin, while age (p = .39), sex (p = .49), and percent body fat (p = .72) did not. Among nonobese middle school children, fasting insulin is independently related to aerobic fitness after accounting for age, sex, and body composition. Public health efforts to reduce cardiometabolic disease risk among all adolescents should include exercise programs to increase cardiovascular fitness.

Insulin resistance in obesity can be reliably identified from fasting plasma insulin

NARCIS (Netherlands)

ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

2015-01-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults

Directory of Open Access Journals (Sweden)

Laville Martine

2011-07-01

Full Text Available Abstract Background Accumulating data suggest a novel role for bile acids (BAs in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans. Findings Fasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D, and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects. Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA, chenodeoxycholic acid (CDCA and deoxycholic acid (DCA concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001, CA (β = 0.03, p = 0.09 and DCA concentrations (β = 0.07, p Conclusions Both plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.

Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

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Viscarra, Jose A; Rodriguez, Ruben; Vazquez-Medina, Jose Pablo; Lee, Andrew; Tift, Michael S; Tavoni, Stephen K; Crocker, Daniel E; Ortiz, Rudy M

2013-08-01

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation.

Ten-year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation.

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Pennings, Nicholas; Jaber, Johnny; Ahiawodzi, Peter

2018-05-01

Numerous studies have examined the relationship between endogenous insulin and weight change with mixed results. This study examined the relationship between fasting insulin levels, insulin resistance (IR), and 10-year weight change by glycaemic stage. Using data from the US National Health and Nutrition Examination Survey 2011-2014, 3840 participants were divided into 6 groups based on fasting glucose and fasting insulin levels. Fasting insulin concentrations were dichotomized into <25th percentile (normal) and ≥25th percentile (elevated). Ten-year weight change associated with fasting insulin was assessed by glycaemic stage. Average weight change over a 10-year period was higher in individuals with elevated insulin levels compared to the first quartile (1.40 lbs. vs 11.12 lbs, P < .0001). Across all groups, a 1 μU increase in fasting insulin levels resulted in a 0.52-pound increase in weight (P < .0001). Similarly, an increase in HOMA-IR was associated with increase in weight (1.32 lbs per IR unit, P < .0001). Marginal increases in weight were most pronounced in the normal insulin groups compared to elevated insulin groups and diminished as glycaemic stage progressed. Elevated fasting insulin level was positively associated with weight gain. The impact of fasting insulin and IR on weight gain preceded hyperglycaemia and diminished as glycaemic stage progressed. Copyright © 2018 John Wiley & Sons, Ltd.

Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol.

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Abbasi, Fahim; Reaven, Gerald M

2011-12-01

The objective was to compare relationships between insulin-mediated glucose uptake and surrogate estimates of insulin action, particularly those using fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. Insulin-mediated glucose uptake was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 455 nondiabetic subjects. Fasting TG, HDL-C, glucose, and insulin concentrations were measured; and calculations were made of the following: (1) plasma concentration ratio of TG/HDL-C, (2) TG × fasting glucose (TyG index), (3) homeostasis model assessment of insulin resistance, and (4) insulin area under the curve (insulin-AUC) during a glucose tolerance test. Insulin-AUC correlated most closely with SSPG (r ∼ 0.75, P index, homeostasis model assessment of insulin resistance, and fasting TG and insulin (r ∼ 0.60, P index correlated with SSPG concentration to a similar degree, and the relationships were comparable to estimates using fasting insulin. The strongest relationship was between SSPG and insulin-AUC. Copyright © 2011 Elsevier Inc. All rights reserved.

Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women.

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Farshchi, Hamid R; Taylor, Moira A; Macdonald, Ian A

2005-02-01

Breakfast consumption is recommended, despite inconclusive evidence of health benefits. The study's aim was to ascertain whether eating breakfast (EB) or omitting breakfast (OB) affects energy intake, energy expenditure, and circulating insulin, glucose, and lipid concentrations in healthy women. In a randomized crossover trial, 10 women [x+/-SD body mass index (BMI; in kg/m2): 23.2+/-1.4] underwent two 14-d EB or OB interventions separated by a 2-wk interval. In the EB period, subjects consumed breakfast cereal with 2%-fat milk before 0800 and a chocolate-covered cookie between 1030 and 1100. In the OB period, subjects consumed the cookie between 1030 and 1100 and the cereal and milk between 1200 and 1330. Subjects then consumed 4 additional meals with content similar to usual at predetermined times later in the day and recorded food intake on 3 d during each period. Fasting and posttest meal glucose, lipid, and insulin concentrations and resting energy expenditure were measured before and after each period. Reported energy intake was significantly lower in the EB period (P=0.001), and resting energy expenditure did not differ significantly between the 2 periods. OB was associated with significantly higher fasting total and LDL cholesterol than was EB (3.14 and 3.43 mmol/L and 1.55 and 1.82 mmol/L, respectively; P=0.001). The area under the curve of insulin response to the test meal was significantly lower after EB than after OB (P<0.01). OB impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained.

Fasting glucose, fasting insulin, and insulin resistance in the prediction of myocardial infarction and mortality at long-term follow-up

DEFF Research Database (Denmark)

Nielsen, M. L.; Pareek, M.; Leosdottir, M.

2015-01-01

Objective: To assess the additional prognostic value of fasting blood glucose (FBG), fasting plasma insulin (FPI), and homeostasis model assessment derived insulin resistance (HOMA-IR) for predicting incident myocardial infarction (MI) and all-cause mortality, independently of traditional...... measured at baseline. Subsequently, HOMA-IR was derived using the computerized HOMA calculator and ranked into quartiles due to the non-normal distribution and presumably non-linear biological effect of insulin resistance. Prognostic values of FBG, FPI, HOMA-IR, and traditional risk factors were tested.......1-48.3] years, whereas median [IQR] HOMA-IR was 0.9 [0.4-1.4]. Over a median follow-up time of 20 years, 1448 events occurred (11.3 per 1000 person-years). The simple prediction model, i.e. the model with traditional CV risk factors only, included age, gender, body mass index, systolic blood pressure, total...

Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.

Science.gov (United States)

Park, Sung Keun; Oh, Chang-Mo; Jung, Taegi; Choi, Young-Jun; Chung, Ju Youn; Ryoo, Jae-Hong

2017-04-01

This study was designed to investigate whether an elevated fasting insulin level predicts abdominal obesity. A cohort study was conducted with 13,707 non-obese Korean men. They were categorized into 4 groups according to the quartile of fasting insulin level, and followed up from 2005 to 2010. Incidence rates of obesity were compared among the 4 groups during follow-up, and a Cox proportional hazards model was used to calculate hazard ratios (HRs) for abdominal obesity according to fasting insulin level. The overall incidence rate of obesity was 16.2%, but the rate increased in proportion to the fasting insulin level (quartiles 1-4: 9.8%, 12.4%, 16.9%, 25.5%, Pobesity increased proportionally to baseline fasting insulin level in an unadjusted model. However, after adjustment for covariates, including baseline waist circumference (WC), only in the quartile 4 group was the statistical significance of the association maintained [quartile 2-4; abdominal obesity: 0.89 (0.76-1.02), 1.00 (0.86-1.14) and 1.24 (1.08-1.43), P for trend obesity was highest in the group with the highest fasting insulin levels, an overall proportional relationship between fasting insulin level and incident abdominal obesity was not found. Additionally, this association was largely accounted for by baseline WC. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary linolenic acid and fasting glucose and insulin: the National Heart, Lung, and Blood Institute Family Heart Study.

Science.gov (United States)

Djoussé, Luc; Hunt, Steven C; Tang, Weihong; Eckfeldt, John H; Province, Michael A; Ellison, R Curtis

2006-02-01

To assess whether dietary linolenic acid is associated with fasting insulin and glucose. In a cross-sectional design, we studied 3993 non-diabetic participants of the National Heart, Lung, and Blood Institute Family Heart Study 25 to 93 years of age. Linolenic acid was assessed through a food frequency questionnaire, and laboratory data were obtained after at least a 12-hour fast. We used generalized linear models to calculate adjusted means of insulin and glucose across quartiles of dietary linolenic acid. From the lowest to the highest sex-specific quartile of dietary linolenic acid, means +/- standard error for logarithmic transformed fasting insulin were 4.06 +/- 0.02 (reference), 4.09 +/- 0.02, 4.13 +/- 0.02, and 4.17 +/- 0.02 pM, respectively (trend, p continuous variable, the multivariable adjusted regression coefficient was 0.42 +/- 0.08. There was no association between dietary linolenic acid and fasting glucose (trend p = 0.82). Our data suggest that higher consumption of dietary linolenic acid is associated with higher plasma insulin, but not glucose levels, in non-diabetic subjects. Additional studies are needed to assess whether higher intake of linolenic acid results in an increased insulin secretion and improved glucose use in vivo.

Fasting serum insulin and the homeostasis model of insulin resistance (HOMA-IR) in the monitoring of lifestyle interventions in obese persons.

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Vogeser, Michael; König, Daniel; Frey, Ingrid; Predel, Hans-Georg; Parhofer, Klaus Georg; Berg, Aloys

2007-09-01

Lifestyle changes with increased physical activity and balanced energy intake are recognized as the principal interventions in obesity and insulin resistance. Only few prospective studies, however, have so far addressed the potential role of routine biochemical markers of insulin sensitivity in the monitoring of respective interventions. Fasting insulin and glucose was measured in 33 obese individuals undergoing a lifestyle modification program (MOBILIS) at baseline and after 1 year. The HOMA-IR index (homeostasis model of insulin resistance) was calculated as [fasting serum glucose*fasting serum insulin/22.5], with lower values indicating a higher degree of insulin sensitivity. While the median body mass index (BMI) and waist circumference decreased by 10% and 11%, respectively, the HOMA-IR index decreased in an over-proportional manner by 45% within 1 year (BMI baseline, median 35.7, interquartile range (IQR) 33.7-37.7; after 1 year, median 32.2, IQR 29.6-35.1. HOMA-IR baseline, median 2.9, IQR 1.5-4.6; after 1 year 1.6, IQR 0.9-2.7). In contrast to HOMA-IR and fasting serum insulin, no significant changes in fasting serum glucose were observed. Baseline and post-intervention HOMA-IR showed a high degree of inter-individual variation with eight individuals maintaining high HOMA-IR values despite weight loss after 1 year of intervention. Individual changes in the carbohydrate metabolism achieved by a lifestyle intervention program were displayed by fasting serum insulin concentrations and the HOMA-IR but not by fasting glucose measurement alone. Therefore, assessment of the HOMA-IR may help to individualize lifestyle interventions in obesity and to objectify improvements in insulin sensitivity after therapeutic lifestyle changes.

Decreased insulin response in dairy cows following a four-day fast to induce hepatic lipidosis.

Science.gov (United States)

Oikawa, S; Oetzel, G R

2006-08-01

Negative energy balance has been implicated in the development of fatty liver, insulin resistance, and impaired health in dairy cows. A 4-d fasting model previously was reported to increase liver triglycerides more than 2.5-fold. The purpose of the present study was to evaluate insulin response in this fasting model. Nonlactating, nonpregnant Holstein cows were fasted for 4 d (6 cows) or fed continuously as control cows (4 cows). Samples were collected 5 d before fasting, during fasting, and immediately after the 4-d fast, 8 d after the fast, and 16 d after the fast. Fasted cows had greater liver triglyceride content (49.4 vs. 16.2 mg/g, wet-weight basis) at the end of the fasting period compared with control cows. Fasted cows also had increased plasma nonesterified fatty acid (NEFA) concentrations (1.24 vs. 0.21 mmol/L) and increased plasma beta-hydroxybutyrate (BHBA) concentrations at the end of the fasting period. Liver triglyceride, plasma NEFA, and plasma BHBA in fasted cows returned to prefasting concentrations by the end of the experiment. Plasma glucose concentrations were not affected by fasting. Plasma insulin concentrations were decreased (6.3 vs. 14.1 microU/mL) and insulin-stimulated blood glucose reduction was decreased (24.9 vs. 48.6%) in the fasted cows compared with control cows at the end of the fast, indicating reduced insulin response. Insulin response was negatively correlated with plasma NEFA and liver triglycerides. Decreased insulin response may be an important complication of negative energy balance and hepatic lipidosis.

Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

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van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

2011-01-01

OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

Bromocriptine and insulin sensitivity in lean and obese subjects

Directory of Open Access Journals (Sweden)

L Bahler

2016-11-01

Full Text Available Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC 742 mmol/L * 120 min (695–818 vs 641 (504–750, P = 0.036, AUC for insulin did not change, P = 0.575. In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236–96,831 vs 36,448 (25,213–57,711, P = 0.012 and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614–988 vs 644 (568–829, P = 0.017 and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration.

Comparison of a carbohydrate-free diet vs. fasting on plasma glucose, insulin and glucagon in type 2 diabetes.

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Nuttall, Frank Q; Almokayyad, Rami M; Gannon, Mary C

2015-02-01

Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet. Improvement typically occurs soon after diet implementation. This rapid response could result from low fuel supply (calories), lower carbohydrate content of the weight-loss diet, and/or weight loss per se. To differentiate these effects, glucose, insulin, C-peptide and glucagon were determined during the last 24 h of a 3-day period without food (severe calorie restriction) and a calorie-sufficient, carbohydrate-free diet. Seven subjects with untreated type 2 diabetes were studied. A randomized-crossover design with a 4-week washout period between arms was used. Results from both the calorie-sufficient, carbohydrate-free diet and the 3-day fast were compared with the initial standard diet consisting of 55% carbohydrate, 15% protein and 30% fat. The overnight fasting glucose concentration decreased from 196 (standard diet) to 160 (carbohydrate-free diet) to 127 mg/dl (fasting). The 24 h glucose and insulin area responses decreased by 35% and 48% on day 3 of the carbohydrate-free diet, and by 49% and 69% after fasting. Overnight basal insulin and glucagon remained unchanged. Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations. Carbohydrate restriction per se could account for 71% of the reduction. Insulin could not entirely explain the glucose responses. In the absence of carbohydrate, the net insulin response was 28% of the standard diet. Glucagon did not contribute to the metabolic adaptations observed. Published by Elsevier Inc.

Therapeutic fasting in patients with metabolic syndrome and impaired insulin resistance.

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Stange, Rainer; Pflugbeil, Christine; Michalsen, Andreas; Uehleke, Bernhard

2013-01-01

In this study, we evaluated whether a short- to mid-term fasting therapy (7-18 days) might improve insulin resistance according to the homeostasis model assessment for insulin resistance (HOMA-IR), measured during mid-term (80 days) follow-up observation in patients with metabolic syndrome. In this open label observational study in inpatients, criteria of metabolic syndrome were defined. Before medically controlled Buchinger fasting, a wash-out period for hypoglycemic agents was conducted. Further evaluation was carried out on day 80. 25 patients (13 males, 12 females, mean age 61.3 years) were included in this study (mean fasting duration 11.5 days). Out of 16 inpatients with type 2 diabetes, 4 had been treated with metformin, 3 with insulin, and 1 with glimepiride before the intervention. After therapy, body mass index (BMI), fasting insulin, fasting glucose, and HOMA-IR were all significantly reduced. Compared to baseline, HOMA-IR decreased by 33% in all patients, by 38% in patients with type 2 diabetes, and by 23% in patients without diabetes. At day 80, BMI further improved, while other parameters showed complete (insulin) or partial (glucose, HOMA-IR) rebound. At this time, HOMA-IR values showed an only insignificant improvement in 15% of all patients, in 20% of patients with type 2 diabetes, and in 6% of patients without diabetes. There was no correlation between change in BMI and change in HOMA-IR (r(2) = 0.008, baseline minus day 80). No serious side effects were observed. Fasting as a safe and acceptable procedure may cause short- and mid-term improvement of increased insulin resistance (HOMA-IR). Patients with type 2 diabetes benefit more than those without diabetes. A possible clinical significance of this effect should be explored in larger and controlled clinical trials. © 2014 S. Karger GmbH, Freiburg.

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

Science.gov (United States)

Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

1988-11-12

To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

Diminished hepatic insulin removal in obesity

International Nuclear Information System (INIS)

Cano, I.; Salvador, J.; Rodriguez, R.; Arraiza, M.C.; Goena, M.; Barberia, J.J.; Moncada, E.

1986-01-01

Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out

Diminished hepatic insulin removal in obesity

Energy Technology Data Exchange (ETDEWEB)

Cano, I; Salvador, J; Rodriguez, R; Arraiza, M C; Goena, M; Barberia, J J; Moncada, E

1986-01-01

Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out.

Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up.

Science.gov (United States)

Aksungar, F B; Sarıkaya, M; Coskun, A; Serteser, M; Unsal, I

2017-01-01

Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance. Single-arm Interventional Human Study. 23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years). Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects' daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month. While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ± 146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the

Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes

DEFF Research Database (Denmark)

Fehse, Frauke; Trautmann, Michael; Holst, Jens Juul

2005-01-01

CONTEXT: First-phase insulin secretion (within 10 min after a sudden rise in plasma glucose) is reduced in type 2 diabetes mellitus (DM2). The incretin mimetic exenatide has glucoregulatory activities in DM2, including glucose-dependent enhancement of insulin secretion. OBJECTIVE: The objective...... of the study was to determine whether exenatide can restore a more normal pattern of insulin secretion in subjects with DM2. DESIGN: Fasted subjects received iv insulin infusion to reach plasma glucose 4.4-5.6 mmol/liter. Subjects received iv exenatide (DM2) or saline (DM2 and healthy volunteers), followed...... by iv glucose challenge. PATIENTS: Thirteen evaluable DM2 subjects were included in the study: 11 males, two females; age, 56 +/- 7 yr; body mass index, 31.7 +/- 2.4 kg/m2; hemoglobin A1c, 6.6 +/- 0.7% (mean +/- sd) treated with diet/exercise (n = 1), metformin (n = 10), or acarbose (n = 2). Controls...

[IMPACT OF DIETARY FATTY ACIDS ON LIPID PROFILE, INSULIN SENSITIVITY AND FUNCTIONALITY OF PANCREATIC β CELLS IN TYPE 2 DIABETIC SUBJECTS].

Science.gov (United States)

Sambra Vásquez, Verónica; Rojas Moncada, Pamela; Basfi-Fer, Karen; Valencia, Alejandra; Codoceo, Juana; Inostroza, Jorge; Carrasco, Fernando; Ruz Ortiz, Manuel

2015-09-01

the quality of fats could influence the metabolic control of patients with Type 2 Diabetes Mellitus (DM2). to determine the relationship between intake and quality of dietary fatty acids to lipid profile, metabolic control, functionality of pancreatic cells and insulin sensivity in subjects with DM2. we studied 54 subjects with DM2, anthropometric measurements were performed, body composition and dietary lipid intake, saturated fatty acids (SFA), trans, monounsaturated, polyunsaturated, omega 3, omega 6 and dietary cholesterol. Laboratory parameters related to their metabolic control were determined (fasting blood glucose, glycated hemoglobin, and lipid profile). The insulin secretion and insulin sensitivity was determined with the insulin-modified intravenous glucose tolerance test according to the Bergman's minimal model. 28 men and 26 women were studied (BMI of 29.5 ± 3.7 kg/m2; age 55.6 ± 6.8 y.), 48% had LDL-C 40 mg/dL and 7.4% of women c-HDL > 50 mg/dL. 32% consumed > 10% of AGS and > 300 mg/day of dietary cholesterol. The SFA intake and percentage of calories from fat (G%) were significantly associated with insulin resistance and fasting plasma glucose concentration. The G% predicted 84% variability on c-VLDL. in patients with DM2 a greater intake of fat and saturated fatty acids it associated with greater fasting glycemia and insulin resistance. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

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

Science.gov (United States)

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.

Postprandial Triglyceride Is Associated with Fasting Triglyceride and HOMA-IR in Korean Subjects with Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Seo Hee Lee

2011-08-01

Full Text Available BackgroundRecent studies indicate postprandial triglyceride (TG had a better association with cardiovascular events and metabolic syndrome than fasting TG. The authors of the present study investigated the metabolic and clinical relevance of postprandial TG.MethodsIn a cross-sectional retrospective study, the authors of the present study compared fasting and postprandial TG and analyzed the relationship between postprandial TG and various demographic and metabolic parameters in 639 Korean subjects with type 2 diabetes (T2D, group I, n=539 and impaired fasting glucose (IFG, group II, n=100 after ingestion of a standardized liquid meal (total 500 kcal, 17.5 g fat, 68.5 g carbohydrate, and 17.5 g protein.ResultsFasting and postprandial TG were significantly correlated (r=0.973, r=0.937, P<0.001 in group I and II, respectively. Of the variables, total cholesterol, waist circumference and body mass index were significantly correlated with fasting and postprandial TG in both groups. Only postprandial TG showed a significant correlation with glucose metabolic parameters (e.g., postprandial glucose, homeostatic model assessment of insulin resistance [HOMA-IR], and fasting C-peptide in subjects with T2D. Multiple regression analysis showed fasting TG and HOMA-IR could be predictable variables for postprandial TG in subjects with T2D.ConclusionPostprandial TG was very strongly correlated with fasting TG. The authors of the present study suggest insulin resistance may be more associated with postprandial TG than fasting TG in Korean T2D patients on a low-fat diet.

Insulin resistance in human subjects having impaired glucose regulation

International Nuclear Information System (INIS)

Khan, S.H.; Khan, F.A.; Ijaz, A.

2007-01-01

To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

Association of fasting glucagon and proinsulin concentrations with insulin resistance

DEFF Research Database (Denmark)

Ferrannini, E; Muscelli, E; Natali, A

2007-01-01

AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. METHODS: We measured IR [by a euglycaemic......, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin...

Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men.

Science.gov (United States)

Pincelli, A I; Brunani, A; Caumo, A; Scacchi, M; Pasqualinotto, L; Tibaldi, A; Dubini, A; Bonadonna, S; Cavagnini, F

2001-01-01

The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia.

Science.gov (United States)

Jackson, Kim G; Walden, Charlotte M; Murray, Peter; Smith, Adrian M; Minihane, Anne M; Lovegrove, Julie A; Williams, Christine M

2013-08-01

Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. MetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (Pcurve (AUC) and incremental AUC (P ≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (Pglucose to be an important predictor of the postprandial TAG and glucose response. Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods

DEFF Research Database (Denmark)

Kjems, L L; Vølund, A; Madsbad, Sten

2001-01-01

AIMS/HYPOTHESIS: We compared four methods to assess their accuracy in measuring insulin secretion during an intravenous glucose tolerance test in patients with Type II (non-insulin-dependent) diabetes mellitus and with varying beta-cell function and matched control subjects. METHODS: Eight control...... subjects and eight Type II diabetic patients underwent an intravenous glucose tolerance test with tolbutamide and an intravenous bolus injection of C-peptide to assess C-peptide kinetics. Insulin secretion rates were determined by the Eaton deconvolution (reference method), the Insulin SECretion method...... (ISEC) based on population kinetic parameters as well as one-compartment and two-compartment versions of the combined model of insulin and C-peptide kinetics. To allow a comparison of the accuracy of the four methods, fasting rates and amounts of insulin secreted during the first phase (0-10 min...

Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

International Nuclear Information System (INIS)

Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

1982-01-01

In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

The relationship between vitamin D status, physical activity and insulin resistance in overweight and obese subjects

Directory of Open Access Journals (Sweden)

Gülis Kavadar

2015-05-01

Full Text Available Type 2 diabetes mellitus (T2DM incidence has been increasing worldwide along with the rise of obesity and sedantery lifestyle. Decreased physical activity (PA and obesity have also been associated with the low vitamin D levels. We aimed to determine the association between PA, vitamin D status and insulin resistance in overweight and obese subjects. A total of 294 (186 female, 108 male overweight or obese subjects were included in this cross-sectional study. 25-hydroxy vitamin D (25(OHD, insulin, fasting plasma glucose (FPG and HbA1c levels were measured in blood samples. Body mass index (BMI, HOMA-index and total score of International Physical Activity Questionnaire-long form (IPAQ were calculated. Insulin resistant subjects were compared with the non-resistant group. The mean age of the participants was 45±12.25 and 41.39±10.32; 25(OHD levels were 8.91 ± 4.30 and 17.62 ± 10.47 ng/dL; BMIs were 31.29 ± 4.48  and 28.2 ± 3.16 kg/m², IPAQ total scores were 548.71±382.81 and 998±486.21 in the insulin resistant and nonresistant subjects, respectively. There was a statistically significant difference in terms of 25(OHD, FPG, insulin levels, IPAQ  total score and BMI between the two groups (p = 0.001, p = 0.001, p = 0.001, p = 0.001, p = 0.001.Significantly low 25(OHD levels, high BMI and low PA in insulin resistant subjects confirm the importance of active lifestyle and the maintenance of normal vitamin D levels in overweight and obese subjects in prevention of T2DM.

Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM

DEFF Research Database (Denmark)

Klein, H H; Vestergaard, H; Kotzke, G

1995-01-01

The role of skeletal muscle insulin receptor kinase in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) was investigated. Muscle biopsies from 13 patients with NIDDM and 10 control subjects at fasting serum insulin concentrations and approximately 1,000 pmol/l steady-state serum...... insulin during euglycemic hyperinsulinemic clamps were immediately frozen. The biopsies were then solubilized, and the receptors were immobilized to anti-insulin receptor antibody-coated microwells. Receptor kinase and binding activities were consecutively measured in these wells. The increase in serum...... and control groups, respectively). Moreover, by selecting only the receptors that bound to anti-phosphotyrosine antibody, we found similar hyperinsulinemia-induced increases of this receptor fraction and its kinase activity in both study groups. In vitro activation of the immobilized receptors with 2 mmol...

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

NARCIS (Netherlands)

Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa; Kabagambe, Edmond Kato; Hong, Jaeyoung; Ng, Maggie C. Y.; Hivert, Marie-France; Lu, Yingchang; An, Ping; Bentley, Amy R.; Drolet, Anne M.; Gaulton, Kyle J.; Guo, Xiuqing; Armstrong, Loren L.; Irvin, Marguerite R.; Li, Man; Lipovich, Leonard; Rybin, Denis V.; Taylor, Kent D.; Agyemang, Charles; Palmer, Nicholette D.; Cade, Brian E.; Chen, Wei-Min; Dauriz, Marco; Delaney, Joseph A. C.; Edwards, Todd L.; Evans, Daniel S.; Evans, Michele K.; Lange, Leslie A.; Leong, Aaron; Liu, Jingmin; Liu, Yongmei; Nayak, Uma; Patel, Sanjay R.; Porneala, Bianca C.; Rasmussen-Torvik, Laura J.; Snijder, Marieke B.; Stallings, Sarah C.; Tanaka, Toshiko; Yanek, Lisa R.; Zhao, Wei; Becker, Diane M.; Bielak, Lawrence F.; Biggs, Mary L.; Bottinger, Erwin P.; Bowden, Donald W.; Chen, Guanjie; Correa, Adolfo; Couper, David J.; Crawford, Dana C.; Cushman, Mary; Eicher, John D.; Fornage, Myriam; Franceschini, Nora; Fu, Yi-Ping; Goodarzi, Mark O.; Gottesman, Omri; Hara, Kazuo; Harris, Tamara B.; Jensen, Richard A.; Johnson, Andrew D.; Jhun, Min A.; Karter, Andrew J.; Keller, Margaux F.; Kho, Abel N.; Kizer, Jorge R.; Krauss, Ronald M.; Langefeld, Carl D.; Li, Xiaohui; Liang, Jingling; Liu, Simin; Lowe, William L.; Mosley, Thomas H.; North, Kari E.; Pacheco, Jennifer A.; Peyser, Patricia A.; Patrick, Alan L.; Rice, Kenneth M.; Selvin, Elizabeth; Sims, Mario; Smith, Jennifer A.; Tajuddin, Salman M.; Vaidya, Dhananjay; Wren, Mary P.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Julie T.; Zmuda, Joseph M.; Zonderman, Alan B.; Zwinderman, Aeilko H.; Adeyemo, Adebowale; Boerwinkle, Eric; Ferrucci, Luigi; Hayes, M. Geoffrey; Kardia, Sharon L. R.; Miljkovic, Iva; Pankow, James S.; Rotimi, Charles N.; Sale, Michele M.; Wagenknecht, Lynne E.; Arnett, Donna K.; Chen, Yii-Der Ida; Nalls, Michael A.; Province, Michael A.; Kao, W. H. Linda; Siscovick, David S.; Psaty, Bruce M.; Wilson, James G.; Loos, Ruth J. F.; Dupuis, Josée; Rich, Stephen S.; Florez, Jose C.; Rotter, Jerome I.; Morris, Andrew P.; Meigs, James B.

2016-01-01

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA)

A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

Science.gov (United States)

Tripathy, Devjit; Cobb, Jeff E; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Reaven, Peter D; Musi, Nicolas; Ferrannini, Ele; DeFronzo, Ralph A

2015-05-01

The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose M(Q) increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min(-1)·kgwbm(-1)) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose M(Q) correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose M(Q) outperformed both Matsuda and fasting insulin in predicting incident diabetes. In IGT subjects, Quantose M(Q) parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose M(Q) may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.

Peripheral blood transcriptomic signatures of fasting glucose and insulin concentrations

NARCIS (Netherlands)

B.H. Chen (Brian); M.-F. Hivert (Marie-France); M.J. Peters (Marjolein); L.C. Pilling (Luke); Hogan, J.D. (John D.); Pham, L.M. (Lisa M.); L.W. Harries (Lorna); C.S. Fox (Caroline); S. Bandinelli (Stefania); A. Dehghan (Abbas); D.G. Hernandez (Dena); A. Hofman (Albert); J. Hong (Jaeyoung); R. Joehanes (Roby); A.D. Johnson (Andrew); P.J. Munson (Peter); D. Rybin (Denis); A. Singleton (Andrew); A.G. Uitterlinden (André); S.-X. Ying (Sai-Xia); D. Melzer (David); D. Levy (Daniel); J.B.J. van Meurs (Joyce); L. Ferrucci (Luigi); J.C. Florez (Jose); J. Dupuis (Josée); J.B. Meigs (James); Kolaczyk, E.D. (Eric D.)

2016-01-01

textabstractGenome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting

The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity

DEFF Research Database (Denmark)

Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta

2016-01-01

Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy...... non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small...... effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates...

High serum fasting peptide YY (3-36) is associated with obesity-associated insulin resistance and type 2 diabetes.

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Ukkola, Olavi H; Puurunen, Veli-Pekka; Piira, Olli-Pekka; Niva, Jarkko T; Lepojärvi, E Samuli; Tulppo, Mikko P; Huikuri, Heikki V

2011-10-10

We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (pfasting glucose, impaired glucose tolerance and normal glucose tolerance (pfasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness. Copyright © 2011 Elsevier B.V. All rights reserved.

Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians12

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Fretts, Amanda M; Follis, Jack L; Nettleton, Jennifer A; Lemaitre, Rozenn N; Ngwa, Julius S; Wojczynski, Mary K; Kalafati, Ioanna Panagiota; Varga, Tibor V; Frazier-Wood, Alexis C; Houston, Denise K; Lahti, Jari; Ericson, Ulrika; van den Hooven, Edith H; Mikkilä, Vera; Kiefte-de Jong, Jessica C; Mozaffarian, Dariush; Rice, Kenneth; Renström, Frida; North, Kari E; McKeown, Nicola M; Feitosa, Mary F; Kanoni, Stavroula; Smith, Caren E; Garcia, Melissa E; Tiainen, Anna-Maija; Sonestedt, Emily; Manichaikul, Ani; van Rooij, Frank JA; Dimitriou, Maria; Raitakari, Olli; Pankow, James S; Djoussé, Luc; Province, Michael A; Hu, Frank B; Lai, Chao-Qiang; Keller, Margaux F; Perälä, Mia-Maria; Rotter, Jerome I; Hofman, Albert; Graff, Misa; Kähönen, Mika; Mukamal, Kenneth; Johansson, Ingegerd; Ordovas, Jose M; Liu, Yongmei; Männistö, Satu; Uitterlinden, André G; Deloukas, Panos; Seppälä, Ilkka; Psaty, Bruce M; Cupples, L Adrienne; Borecki, Ingrid B; Franks, Paul W; Arnett, Donna K; Nalls, Mike A; Eriksson, Johan G; Orho-Melander, Marju; Franco, Oscar H; Lehtimäki, Terho; Dedoussis, George V; Meigs, James B; Siscovick, David S

2015-01-01

Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049–ln-pmol/L (95% CI: 0.035, 0.063–ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic

The effect of Ramadan fasting on glycaemic control in insulin dependent diabetic patients: A literature review.

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Alabbood, Majid H; Ho, Kenneth W; Simons, Mary R

Ramadan fasting is one of the five pillars of Islam. People with diabetes are exempted from fasting according to Islamic rules. However, many people with diabetes wish to fast. Physicians are asked frequently by their patients about their ability to fast and the possible impact of fasting on their glycaemic control. Studies about the effect of Ramadan on people with insulin-treated diabetes are scarce. This review aims to provide clinicians with the best recommendations for their patients with insulin-treated diabetes who wish to fast. Four databases (Medline, EMBASE, Scopus and PubMed) were searched using the following MeSH terms and keywords: "insulin dependent diabetes mellitus", "type 1 diabetes mellitus", 'Ramadan' "and" "fasting". In addition, a hand search of key journals and reference lists was performed. Sixteen full text articles were selected for review and critical analysis. All of the included studies except one found improvement or no change in glycaemic control parameters during Ramadan fasting. The incidence of major complications were negligible. Minor hypoglycaemic events were reported in some studies but did not adversely affect fasting. Postprandial hyperglycaemia was a major concern in other studies. However, the incidence of severe hyperglycaemia and diabetic ketoacidosis were trivial. Ramadan fasting is feasible for insulin dependent diabetic patient who wish to fast. Clinicians should advise their patients about the importance of adequate glycaemic control before Ramadan and frequent glucose monitoring during fasting. Certain types of Insulin seem to be more beneficial than other. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

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Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

2017-07-01

Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (Pinsulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes.

Science.gov (United States)

D'Alessio, David A; Denney, Amanda M; Hermiller, Linda M; Prigeon, Ronald L; Martin, Julie M; Tharp, William G; Saylan, Monica Liqueros; He, Yanling; Dunning, Beth E; Foley, James E; Pratley, Richard E

2009-01-01

Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Consistent with this mechanism of action, DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma. However, DPP-4 inhibitors also reduce fasting blood glucose, an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state. The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function. We conducted a randomized, double-blind, placebo-controlled trial. The study was performed in General Clinical Research Centers at two University Hospitals. Forty-one subjects with T2DM were treated with metformin or diet, having good glycemic control with glycosylated hemoglobin values of 6.2-7.5%. Subjects were treated with vildagliptin (50 mg twice daily) or placebo for 3 months, followed by a 2-wk washout. Major Outcome Measure: We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout. There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months. Vildagliptin increased fasting GLP-1 levels in subjects taking metformin, but not those managed with diet, and raised active GIP levels slightly. DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose (50 and 100% respectively; P fasting conditions. This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity.

Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

Science.gov (United States)

Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

2011-01-01

OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

Effect of caloric restriction with or without n-3 polyunsaturated fatty acids on insulin sensitivity in obese subjects: A randomized placebo controlled trial.

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Razny, Urszula; Kiec-Wilk, Beata; Polus, Anna; Goralska, Joanna; Malczewska-Malec, Malgorzata; Wnek, Dominika; Zdzienicka, Anna; Gruca, Anna; Childs, Caroline E; Kapusta, Maria; Slowinska-Solnica, Krystyna; Calder, Philip C; Dembinska-Kiec, Aldona

2015-12-01

Caloric restriction and n-3 polyunsaturated fatty acid (PUFA) supplementation protect from some of the metabolic complications. The aim of this study was to assess the influence of a low calorie diet with or without n-3 PUFA supplementation on glucose dependent insulinotropic polypeptide (GIP) output and insulin sensitivity markers in obese subjects. Obese, non-diabetic subjects (BMI 30-40 kg/m(2)) and aged 25-65 yr. were put on low calorie diet (1200-1500 kcal/day) supplemented with either 1.8 g/day n-3 PUFA (DHA/EPA, 5:1) (n = 24) or placebo capsules (n = 24) for three months in a randomized placebo controlled trial. Insulin resistance markers and GIP levels were analysed from samples obtained at fasting and during an oral glucose tolerance test (OGTT). Caloric restriction with n-3 PUFA led to a decrease of insulin resistance index (HOMA-IR) and a significant reduction of insulin output as well as decreased GIP secretion during the OGTT. These effects were not seen with caloric restriction alone. Changes in GIP output were inversely associated with changes in red blood cell EPA content whereas fasting GIP level positively correlated with HOMA-IR index. Blood triglyceride level was lowered by caloric restriction with a greater effect when n-3 PUFA were included and correlated positively with fasting GIP level. Three months of caloric restriction with DHA + EPA supplementation exerts beneficial effects on insulin resistance, GIP and triglycerides. Combining caloric restriction and n-3 PUFA improves insulin sensitivity, which may be related to a decrease of GIP levels.

The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women

OpenAIRE

Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

2014-01-01

Background: Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. Methods: This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were m...

Effect of fructose consumption on insulin sensitivity in nondiabetic subjects: a systematic review and meta-analysis of diet-intervention trials.

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Ter Horst, Kasper W; Schene, Merle R; Holman, Rebecca; Romijn, Johannes A; Serlie, Mireille J

2016-12-01

High fructose consumption has been suggested to contribute to several features of metabolic syndrome including insulin resistance, but to our knowledge, no previous meta-analyses have investigated the effect of fructose on insulin sensitivity in nondiabetic subjects. We performed a systematic review and meta-analysis of controlled diet-intervention studies in nondiabetic subjects to determine the effect of fructose on insulin sensitivity. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials on the basis of predetermined eligibility criteria. Two investigators independently performed the study selection, quality assessment, and data extraction. Results were pooled with the use of the generic inverse-variance method with random effects weighting and were expressed as mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs. Twenty-nine articles that described 46 comparisons in 1005 normal-weight and overweight or obese participants met the eligibility criteria. An energy-matched (isocaloric) exchange of dietary carbohydrates by fructose promoted hepatic insulin resistance (SMD: 0.47; 95% CI: 0.03, 0.91; P = 0.04) but had no effect on fasting plasma insulin concentrations (MD: -0.79 pmol/L; 95% CI: -6.41, 4.84 pmol/L; P = 0.78), the homeostasis model assessment of insulin resistance (HOMA-IR) (MD: 0.13; 95% CI: -0.07, 0.34; P = 0.21), or glucose disposal rates under euglycemic hyperinsulinemic clamp conditions (SMD: 0.00; 95% CI: 20.41, 0.41; P = 1.00). Hypercaloric fructose (∼25% excess of energy compared with that of the weight-maintenance control diet) raised fasting plasma insulin concentrations (MD: 3.38 pmol/L; 95% CI: 0.03, 6.73 pmol/L; P fructose consumption, in isocaloric exchange or in hypercaloric supplementation, promotes the development of hepatic insulin resistance in nondiabetic adults without affecting peripheral or muscle insulin sensitivity. Larger and longer-term studies are needed to assess whether real

Gender differences in the associations between cortisol and insulin in healthy subjects

NARCIS (Netherlands)

Stolk, RP; Lamberts, SWJ; deJong, FH; Pols, HAP; Grobbee, DE

To investigate the role of cortisol in the etiology of insulin resistance in men and women, we examined 218 healthy non-hospitalized elderly, selected from the Rotterdam Study. Free cortisol was assessed by the ratio of fasting serum cortisol over corticosteroid-binding globulin (CBG), and insulin

Fatty Acids, Obesity and Insulin Resistance

Directory of Open Access Journals (Sweden)

Peter Arner

2015-04-01

Full Text Available Objective: Although elevated free fatty acid (FFA levels in obesity have been considered to be of importance for insulin resistance, a recent meta-analysis suggested normal FFA levels in obese subjects. We investigated fasting circulating FFA and glycerol levels in a large cohort of non-obese and obese subjects. Methods: Subjects recruited for a study on obesity genetics were investigated in the morning after an overnight fast (n = 3,888. Serum FFA (n = 3,306, plasma glycerol (n = 3,776, and insulin sensitivity index (HOMA-IR,n = 3,469 were determined. Obesity was defined as BMI ≥ 30 kg/m2 and insulin resistance as HOMA-IR ≥ 2.21. Results: In obese subjects, circulating FFA and glycerol levels were higher than in non-obese individuals (by 26% and 47%, respectively; both p Conclusion: Circulating FFA and glycerol levels are markedly elevated in obesity but only marginally influenced by insulin resistance and type 2 diabetes. Whether these differences persist during diurnal variations in circulating FFA/glycerol, remains to be established.

Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR).

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Abbasi, Fahim; Okeke, QueenDenise; Reaven, Gerald M

2014-04-01

Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = -0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = -0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40% of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.

Knockdown of angiopoietin-like 2 mimics the benefits of intermittent fasting on insulin responsiveness and weight loss.

Science.gov (United States)

Martel, Cécile; Pinçon, Anthony; Bélanger, Alexandre Maxime; Luo, Xiaoyan; Gillis, Marc-Antoine; de Montgolfier, Olivia; Thorin-Trescases, Nathalie; Thorin, Éric

2018-01-01

Angiopoietin-like 2 (ANGPTL2) is an inflammatory adipokine linking obesity to insulin resistance. Intermittent fasting, on the other hand, is a lifestyle intervention able to prevent obesity and diabetes but difficult to implement and maintain. Our objectives were to characterize a link between ANGPTL2 and intermittent fasting and to investigate whether the knockdown of ANGPTL2 reproduces the benefits of intermittent fasting on weight gain and insulin responsiveness in knockdown and wild-type littermates mice. Intermittent fasting, access to food ad libitum once every other day, was initiated at the age of three months and maintained for four months. Intermittent fasting decreased by 63% (p < 0.05) gene expression of angptl2 in adipose tissue of wild-type mice. As expected, intermittent fasting improved insulin sensitivity (p < 0.05) and limited weight gain (p < 0.05) in wild-type mice. Knockdown mice fed ad libitum, however, were comparable to wild-type mice following the intermittent fasting regimen: insulin sensitivity and weight gain were identical, while intermittent fasting had no additional impact on these parameters in knockdown mice. Energy intake was similar between both wild-type fed intermittent fasting and ANGPTL2 knockdown mice fed ad libitum, suggesting that intermittent fasting and knockdown of ANGPTL2 equally lower feeding efficiency. These results suggest that the reduction of ANGPTL2 could be a useful and promising strategy to prevent obesity and insulin resistance, although further investigation of the mechanisms linking ANGPTL2 and intermittent fasting is warranted. Impact statement Intermittent fasting is an efficient diet pattern to prevent weight gain and improve insulin sensitivity. It is, however, a difficult regimen to follow and compliance is expected to be very low. In this work, we demonstrate that knockdown of ANGPTL2 in mice fed ad libitum mimics the beneficial effects of intermittent fasting on weight gain and insulin

Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups

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Soñanez-Organis, José G.; Viscarra, Jose A.; Jaques, John T.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

2016-01-01

Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. PMID:26739649

Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis.

Science.gov (United States)

Pereira, Mark A; Kartashov, Alex I; Ebbeling, Cara B; Van Horn, Linda; Slattery, Martha L; Jacobs, David R; Ludwig, David S

Fast-food consumption has increased greatly in the USA during the past three decades. However, the effect of fast food on risk of obesity and type 2 diabetes has received little attention. We aimed to investigate the association between reported fast-food habits and changes in bodyweight and insulin resistance over a 15-year period in the USA. Participants for the CARDIA study included 3031 young (age 18-30 years in 1985-86) black and white adults who were followed up with repeated dietary assessment. We used multiple linear regression models to investigate the association of frequency of fast-food restaurant visits (fast-food frequency) at baseline and follow-up with 15-year changes in bodyweight and the homoeostasis model (HOMA) for insulin resistance. Fast-food frequency was lowest for white women (about 1.3 times per week) compared with the other ethnic-sex groups (about twice a week). After adjustment for lifestyle factors, baseline fast-food frequency was directly associated with changes in bodyweight in both black (p=0.0050) and white people (p=0.0013). Change in fast-food frequency over 15 years was directly associated with changes in bodyweight in white individuals (pfast-food restaurant use at baseline and follow-up (n=203), those with frequent (more than twice a week) visits to fast-food restaurants at baseline and follow-up (n=87) gained an extra 4.5 kg of bodyweight (p=0.0054) and had a two-fold greater increase in insulin resistance (p=0.0083). Fast-food consumption has strong positive associations with weight gain and insulin resistance, suggesting that fast food increases the risk of obesity and type 2 diabetes.

The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose

DEFF Research Database (Denmark)

Bock, Gerlies; Man, Chiara Dalla; Micheletto, Francesco

2010-01-01

Abstract Objective: Low Glucagon-like Peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain if these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin...... period, the mixed meal was repeated. Results: As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C....... Conclusions: DPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG....

Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

DEFF Research Database (Denmark)

Nellemann, B.; Vendelbo, M.H.; Nielsen, Thomas Svava

2014-01-01

Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

Effects of a fibre-enriched milk drink on insulin and glucose levels in healthy subjects

Directory of Open Access Journals (Sweden)

Pilvi Taru K

2009-10-01

Full Text Available Abstract Background The glycaemic response to foods is dependent on the quality and content of carbohydrates. Carbohydrates in the form of dietary fibre have favourable effects on insulin and glucose metabolism and may help to control energy intake. Dairy products have a relatively low carbohydrate content, and most of the carbohydrate is in the form of lactose which causes gastrointestinal symptoms in part of the population. In order to avoid these symptoms, dairy products can be replaced with lactose-free dairy products which are on the market in many parts of the world. However, the effects of lactose-free products on insulin and glucose metabolism have not been studied. Methods In the present study, we investigated the effects of 1 a lactose-free milk drink, 2 a novel fibre-enriched, fat- and lactose-free milk drink and 3 normal fat-free milk on serum glucose and insulin levels and satiety using a randomized block design. Following an overnight fast, 26 healthy volunteers ingested 200 ml of one of these drinks on three non-consecutive days. Insulin and glucose levels and subjective satiety ratings were measured before the ingestion of the milk product and 20, 40, 60, 120 and 180 minutes after ingestion. The responses were calculated as the area under the curve subtracted by the baseline value (AUC minus baseline. Results The insulin response was significantly lower for the fibre-enriched milk drink than it was for the other milk products (AUC, P = 0.007. There were no differences in the response for glucose or in the AUC for the subjective satiety ratings between the studied milk products. Conclusion The present results suggest that this novel milk drink could have positive effects on insulin response.

Insulin resistance, exercise capacity and body composition in subjects with two hypertensive parents

DEFF Research Database (Denmark)

Andersen, U B; Dige-Petersen, H; Ibsen, H

1999-01-01

OBJECTIVE: To study insulin resistance in subjects with strong genetic predisposition to essential hypertension, compared with non-disposed subjects. SUBJECTS: Thirty normotensive subjects aged 18-35 years whose parents both had essential hypertension, and 30 age- and sex matched subjects whose...... correlated to abdominal fat mass but not to insulin sensitivity. CONCLUSION: Subjects with a strong genetic predisposition to essential hypertension had increased diastolic blood pressure compared with subjects with normotensive parents, but they were not insulin resistant. This may be due to the subjects...... for the difference between the means; -0.5; -7.9), but the insulin sensitivity index was similar: 312 versus 362 I(2) min(-1) pmol(-1) kg(-1) (28; -129). The two groups were similar in terms of body composition, exercise capacity and composition of usual diet. Resting and 24-h diastolic blood pressures were...

Glycated Hemoglobin, Fasting Insulin and the Metabolic Syndrome in Males. Cross-Sectional Analyses of the Aragon Workers' Health Study Baseline.

Science.gov (United States)

Saravia, Gabriela; Civeira, Fernando; Hurtado-Roca, Yamilee; Andres, Eva; Leon, Montserrat; Pocovi, Miguel; Ordovas, Jose; Guallar, Eliseo; Fernandez-Ortiz, Antonio; Casasnovas, Jose Antonio; Laclaustra, Martin

2015-01-01

Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome. We used baseline data from 3200 non-diabetic male participants in the Aragon Workers' Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI). Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering. HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.

Blood homocysteine and fasting insulin levels are reduced and erythrocyte sedimentation rates increased with a glycophospholipid-vitamin formulation: a retrospective study in older subjects

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Rita R. Ellithorpe

2015-04-01

Full Text Available Background: Elevations in Homocyteine (Hcys levels in the blood have been correlated with increased risk for coronary heart disease and stroke, loss of cognition and memory, and other chronic medical conditions. Objective: A retrospective study was initiated to determine if Hcys levels and other blood markers were altered in subjects taking an oral functional food supplement containing a mixture of phosphoglycolipids (NT Factor® and vitamins. Methods: Thirty-five patients (28 females, 7 males, Av. Age=60.7±9.6 years who had used the functional food Advanced Physician’s FormulaTM with NTFactor® in tablet form each day were enrolled in a retrospective study on blood chemistry. This retrospective study followed a prospective study on the use of the same supplement to reduce fatigue in patients with chronic fatigue. Participants were patients with chronic fatigue syndrome (myalgic encephalomyelitis or other fatiguing illnesses. Subjects had blood drawn over a 6-month period, and routine blood testing was performed. In this laboratory study the results were analyzed for differences, and statistical analyses were performed. Results: All participants responded in the study and showed an average reduction of 31.8% in Hcys levels (from 10.85±0.42 to 7.40±0.42 µmol/L; t-test, p<0.001; Wilcoxon, p<0.001. Women responded better than men: women (from 11.06±0.50 to 8.67±0.82 µmol/L, 34.4% reduction, t-test, p< 0.001; Wilcoxon, p<0.001 versus men (from 10.80±0.51 to 7.01±0.47 µmol/L, 21.6% reduction, t-test, p< 0.0862. Differences were also found in fasting insulin levels (from 12.80±3.11 to 5.30±1.77 µIU/mL, 58.6% reduction, t-test, p<0.005 and erythrocyte sedimentation rate (ESR. ESR increased from 10.5±2.21 to 20.19±3.20 mm/hr (92.2% increase, t-test, p<0.0314; Wilcoxon, p<0.0154. Other tests were not significantly different after 6 months of supplement, there were no side effects from the test supplement, and none of the participants had

The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women.

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Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

2014-01-01

Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were measured five times on 0, 7th, 14th and 28th days of Ramadan and on the 14th day post-Ramadan. The data were analyzed by SPSS software (version 11.5) using repeated measures ANOVA to find whether any changes occurred in the variables of interest during the study, and Pearson correlation coefficient was used to examine the relations among the variables. A significant change in fasting blood sugar, neuropeptide Y and leptin was observed during the study (pRamadan and increased after Ramadan, with the lowest value at the end of Ramadan. Neuropeptide Y increased both during Ramadan and two weeks after Ramadan. Also, leptin decreased significantly two weeks after Ramadan compared to the end of Ramadan. No significant change was observed in insulin level during the study (p>0.05). The result of this study revealed the important role of leptin and neuropeptide Y in the long term regulation of energy balance in pregnant women with chronic diurnal fasting, and it further revealed that Ramadan fasting did not significantly change the serum insulin level.

Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

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Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

1998-08-01

We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

Thermogenesis induced by a high-carbohydrate meal in fasted lean and overweight young men: insulin, body fat, and sympathetic nervous system involvement.

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Marques-Lopes, Iva; Forga, Luis; Martínez, J Alfredo

2003-01-01

This dietary trial was designed to evaluate the effect of an experimental short-term fasting period followed by a high-carbohydrate meal on energy expenditure, thermogenesis, and sympathetic nervous system activity in normal (body mass index 27 kg/m(2)) men who were healthy, non-diabetic or with no other endocrine disease, non-smokers, not taking oral prescription medications, and with a stable body weight for the previous 3 mo. Fasting and fed energy expenditures and diet-induced thermogenesis were measured after a high-carbohydrate meal in seven overweight and six lean young male subjects by indirect calorimetry. Heart rate, urinary excretion of catecholamines, serum glucose, and insulin were also measured over the experimental fasting (7.5 h) and postprandial (4 h) periods. After carbohydrate intake, overweight men showed a significantly higher energy production (kJ/kg of fat-free mass) than did lean individuals, and the diet-induced thermogenesis (percentage of energy intake) was positively correlated with body fat (kg), percentage of body fat, fat-free mass (kg), and fasting pre-meal serum insulin levels. Postprandial cumulative energy expenditure was directly associated with postprandial insulin response and with mean postprandial heart rate values. No significant differences in urinary catecholamines were found between lean and overweight men at basal conditions or during the study period. Overweight individuals showed similar short-term sympathetic nervous system responses induced by an experimental fasting period. Although diet-induced thermogenesis after carbohydrate intake was not statistically different between lean and overweight men, the postprandial insulin response and body fat content seemed to be involved in sympathetic nervous system activity.

Insulin Secretion and Risk for Future Diabetes in Subjects with a Nonpositive Insulinogenic Index

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Daisuke Aono

2018-01-01

Full Text Available Aim. To characterize subjects with a nonpositive insulinogenic index and longitudinally observe changes in their glucose tolerance. Subjects and Methods. A historical cohort study was conducted using data from the medical checkups of public school workers. Indices of insulin secretion and insulin sensitivity derived from oral glucose tolerance test (OGTT and the incidences of diabetes and impaired glucose tolerance (IGT were compared among subgroups of subjects with different insulinogenic index (change in insulin/change in glucose over the first 30 min on the OGTT. Results. Of the 1464 nondiabetic subjects at baseline, 72 (4.9% subjects had a nonpositive insulinogenic index: 42 of those subjects had a nonpositive glucose response (ΔGlu0–30 ≤ 0 and 30 had a nonpositive insulin response (ΔIns0–30 ≤ 0. Compared with subjects who had normal glucose tolerance (NGT with insulinogenic index ≥ 0.4, subjects with a nonpositive glucose response had a higher first-phase Stumvoll and lower incidences of diabetes and IGT based on a log-rank test (p<0.05, whereas subjects with a nonpositive insulin response had lower indices of insulin secretion and a higher incidence of diabetes (p<0.05. Conclusions. These results demonstrate that in the first 30 min on the OGTT, subjects with a nonpositive insulinogenic index due to a nonpositive glucose response (ΔGlu0–30 ≤ 0 had a lower risk for future diabetes and that subjects with nonpositive insulin response (ΔIns0–30 ≤ 0 had a higher risk for future one.

Insulin Sensitivity Determines Effects of Insulin and Meal Ingestion on Systemic Vascular Resistance in Healthy Subjects.

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Woerdeman, Jorn; Meijer, Rick I; Eringa, Etto C; Hoekstra, Trynke; Smulders, Yvo M; Serné, Erik H

2016-01-01

In addition to insulin's metabolic actions, insulin can dilate arterioles which increase blood flow to metabolically active tissues. This effect is blunted in insulin-resistant subjects. Insulin's effect on SVR, determined by resistance arterioles, has, however, rarely been examined directly. We determined the effects of both hyperinsulinemia and a mixed meal on SVR and its relationship with insulin sensitivity. Thirty-seven lean and obese women underwent a hyperinsulinemic-euglycemic clamp, and 24 obese volunteers underwent a mixed-meal test. SVR was assessed using CPP before and during hyperinsulinemia as well as before and 60 and 120 minutes after a meal. SVR decreased significantly during hyperinsulinemia (-13%; p Insulin decreased SVR more strongly in insulin-sensitive individuals (standardized β: -0.44; p = 0.01). In addition, SVR at 60 minutes after meal ingestion was inversely related to the Matsuda index (β: -0.39; p = 0.04) and the change in postprandial SVR was directly related to postprandial glycemia (β: 0.53; p insulin resistance. This suggests that resistance to insulin-induced vasodilatation contributes to regulation of vascular resistance. © 2015 John Wiley & Sons Ltd.

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

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Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P

Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

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Bianchi, Cristina; Miccoli, Roberto; Trombetta, Maddalena; Giorgino, Francesco; Frontoni, Simona; Faloia, Emanuela; Marchesini, Giulio; Dolci, Maria A; Cavalot, Franco; Cavallo, Gisella; Leonetti, Frida; Bonadonna, Riccardo C; Del Prato, Stefano

2013-05-01

In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis. The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL. The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well. A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function. Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.

Insulin resistance, insulin response, and obesity as indicators of metabolic risk

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Ferrannini, Ele; Balkau, Beverley; Coppack, Simon W

2007-01-01

CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been...... evaluated. OBJECTIVE: The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at 21 research centers in Europe. SUBJECTS: The study included a cohort of 1308......-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P

Application of insulin-like growth factor-I and insulin release test in diabetes mellitus

International Nuclear Information System (INIS)

Chen Dong; Ma Yongxiu; Duan Wenruo

2003-01-01

The purpose of this study was to determine the role of insulin-like growth factor-I (IGF-I) and insulin release test (IRT) in understanding the extent of damage to ability of reducing blood sugar in different types of diabetes mellitus (DM) and in selection of treatment plan and adjustment of using drugs. OGTT, IRT and determination of IGF-I level of 67 normal subjects and 217 DM patients were performed. The result was analyzed comparatively. The level of IGF-I was negatively correlated with the level of fasting blood sugar, and positively correlated with the level of fasting insulin. Our conclusions are: There are two ways of reducing blood sugar: one is by insulin, and the other is by IGF-I. IRT can reflect the former better, and IGF-I the latter. The combination of these two is of significant value in diagnosis and treatment of DM

Insulin resistance in Nigerians with essential hypertension | Akande ...

African Journals Online (AJOL)

Homeostasis model assessment (HOMA) was used to determine insulin resistance (IR). Results: The hypertensive subjects had significantly higher fasting insulin and HOMA-IR compared with normotensives (p =0.02 and 0.04) respectively. There were significant correlations between HOMA-IR, BMI, waist and hip ...

Insulin resistance in non-obese subjects is associated with activation of the JNK pathway and impaired insulin signaling in skeletal muscle.

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Umesh B Masharani

2011-05-01

Full Text Available The pathogenesis of insulin resistance in the absence of obesity is unknown. In obesity, multiple stress kinases have been identified that impair the insulin signaling pathway via serine phosphorylation of key second messenger proteins. These stress kinases are activated through various mechanisms related to lipid oversupply locally in insulin target tissues and in various adipose depots.To explore whether specific stress kinases that have been implicated in the insulin resistance of obesity are potentially contributing to insulin resistance in non-obese individuals, twenty healthy, non-obese, normoglycemic subjects identified as insulin sensitive or resistant were studied. Vastus lateralis muscle biopsies obtained during euglycemic, hyperinsulinemic clamp were evaluated for insulin signaling and for activation of stress kinase pathways. Total and regional adipose stores and intramyocellular lipids (IMCL were assessed by DXA, MRI and (1H-MRS. In muscle of resistant subjects, phosphorylation of JNK was increased (1.36±0.23 vs. 0.78±0.10 OD units, P<0.05, while there was no evidence for activation of p38 MAPK or IKKβ. IRS-1 serine phosphorylation was increased (1.30±0.09 vs. 0.22±0.03 OD units, P<0.005 while insulin-stimulated tyrosine phosphorylation decreased (10.97±0.95 vs. 0.89±0.50 OD units, P<0.005. IMCL levels were twice as high in insulin resistant subjects (3.26±0.48 vs. 1.58±0.35% H(2O peak, P<0.05, who also displayed increased total fat and abdominal fat when compared to insulin sensitive controls.This is the first report demonstrating that insulin resistance in non-obese, normoglycemic subjects is associated with activation of the JNK pathway related to increased IMCL and higher total body and abdominal adipose stores. While JNK activation is consistent with a primary impact of muscle lipid accumulation on metabolic stress, further work is necessary to determine the relative contributions of the various mediators of impaired

Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance.

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Connelly, Margery A; Wolak-Dinsmore, Justyna; Dullaart, Robin P F

2017-05-01

Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the extent to which the association of BCAA with insulin resistance is attributable to altered leptin and adiponectin levels in individuals with varying degrees of glucose tolerance. BCAA were measured by nuclear magnetic resonance, whereas leptin and adiponectin were measured by immunoassay, in subjects with normal fasting glucose (n = 30), impaired fasting glucose (n = 25), and T2DM (n = 15). Insulin resistance was estimated by homeostasis model assessment (HOMAir). BCAA were higher in men than in women (P BCAA were correlated with HOMAir (r = 0.46; P  0.05). Multivariable linear regression analysis, adjusting for age, sex, T2DM, and body mass index (BMI), demonstrated that BCAA were positively associated with HOMAir (β = 0.242, P = 0.023). When BCAA, leptin, and adiponectin were included together, the positive relationship of HOMAir with BCAA (β = 0.275, P = 0.012) remained significant. Insulin resistance was associated with BCAA. This association remained after adjusting for age, sex, T2DM, BMI, as well as leptin and adiponectin. It is unlikely that the relationship of insulin resistance with BCAA is to a major extent attributable to effects of leptin and adiponectin.

Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes

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Hulman, Adam; Simmons, Rebecca K; Brunner, Eric J

2017-01-01

AIMS/HYPOTHESIS: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South...... Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. METHODS: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose...... (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during...

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

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Nettleton, Jennifer A; McKeown, Nicola M; Kanoni, Stavroula; Lemaitre, Rozenn N; Hivert, Marie-France; Ngwa, Julius; van Rooij, Frank J A; Sonestedt, Emily; Wojczynski, Mary K; Ye, Zheng; Tanaka, Tosh; Garcia, Melissa; Anderson, Jennifer S; Follis, Jack L; Djousse, Luc; Mukamal, Kenneth; Papoutsakis, Constantina; Mozaffarian, Dariush; Zillikens, M Carola; Bandinelli, Stefania; Bennett, Amanda J; Borecki, Ingrid B; Feitosa, Mary F; Ferrucci, Luigi; Forouhi, Nita G; Groves, Christopher J; Hallmans, Goran; Harris, Tamara; Hofman, Albert; Houston, Denise K; Hu, Frank B; Johansson, Ingegerd; Kritchevsky, Stephen B; Langenberg, Claudia; Launer, Lenore; Liu, Yongmei; Loos, Ruth J; Nalls, Michael; Orho-Melander, Marju; Renstrom, Frida; Rice, Kenneth; Riserus, Ulf; Rolandsson, Olov; Rotter, Jerome I; Saylor, Georgia; Sijbrands, Eric J G; Sjogren, Per; Smith, Albert; Steingrímsdóttir, Laufey; Uitterlinden, André G; Wareham, Nicholas J; Prokopenko, Inga; Pankow, James S; van Duijn, Cornelia M; Florez, Jose C; Witteman, Jacqueline C M; Dupuis, Josée; Dedoussis, George V; Ordovas, Jose M; Ingelsson, Erik; Cupples, L Adrienne; Siscovick, David S; Franks, Paul W; Meigs, James B

2010-12-01

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Delayed clearance of triglyceride-rich lipoproteins in young, healthy obese subjects.

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Larsen, M A; Goll, R; Lekahl, S; Moen, O S; Florholmen, J

2015-12-01

Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age- and sex-matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA-IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. © 2015 World Obesity.

High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling.

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Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

2011-04-13

The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days. Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test. High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet. Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet

Effect of insulin degludec versus insulin glargine on glycemic control and daily fasting blood glucose variability in insulin-naïve Japanese patients with type 2 diabetes: I'D GOT trial.

Science.gov (United States)

Aso, Yoshimasa; Suzuki, Kunihiro; Chiba, Yasuko; Sato, Minoru; Fujita, Nobuya; Takada, Yoshihisa; Murano, Shunichi; Kuroda, Hisamoto

2017-08-01

Insulin degludec (IDeg) is an ultra-long-acting insulin that has a smooth time/action profile over more than 42h. The present study compared the effects of IDeg and insulin glargine (IGlar) on HbA1c reduction and on within-subject day-to-day variability of fasting blood glucose (FBG) in insulin-naïve patients with type 2 diabetes. Eligible patients were randomly allocated at a 3:1 ratio to receive once-daily IDeg (n=31) or IGlar (n=12). Both basal insulins were administered before breakfast and titrated to achieve a target FBG <110mg/dl. The primary endpoints were the change in HbA1c from baseline to 24weeks of treatment, as well as the standard deviation (SD) and coefficient of variation (CV) of FBG from 8 to 12weeks and from 20 to 24weeks. Secondary endpoints included the QOL evaluated by the Diabetes Therapy-Related QOL questionnaire. After 24weeks, HbA1c was decreased by 1.6% in the IDeg group and 1.7% in the IGlar at the same insulin dosage. At 24weeks, FBG was significantly lower in the IDeg group than in the IGlar group and the CV of FBG was significantly smaller in the IDeg group. The frequency of total and severe hypoglycemic episodes did not differ between the groups. In the IDeg group, QOL showed significant improvement regarding anxiety and dissatisfaction with treatment. Treatment with IDeg or IGlar achieved similar improvement in glycemic control in insulin-naïve patients with type 2 diabetes. The day-to-day variation of FBG was smaller in patients receiving IDeg. Copyright © 2017. Published by Elsevier B.V.

Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

DEFF Research Database (Denmark)

Vestergaard, H; Andersen, P H; Lund, S

1994-01-01

The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle...... glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin...... were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis of muscle biopsies from...

Relationship between postprandial changes in cardiac left ventricular function, glucose and insulin concentrations, gastric emptying, and satiety in healthy subjects

Directory of Open Access Journals (Sweden)

Björgell Ola

2011-03-01

Full Text Available Abstract Background The digestion of food is known to alter the hemodynamics of the body significantly. The purpose of this study was to study the postprandial changes in stroke volume (SV, cardiac output (CO and left ventricular (LV longitudinal systolic and diastolic functions measured with tissue Doppler imaging, in relation to gastric emptying rate (GER, satiety, and glucose and insulin concentrations in healthy subjects. Methods Twenty-three healthy subjects were included in this study. The fasting and postprandial changes at 30 min and 110 min in CO, heart rate (HR and blood pressure were measured. Moreover, tissue Doppler imaging systolic (S', early (E' and late (A' mitral annular diastolic velocities were measured in the septal (s and lateral (l walls. Glucose and insulin concentrations, and satiety were measured before and 15, 30, 45, 60, 90, and 120 min after the start of the meal. The GER was calculated as the percentage change in the antral cross-sectional area 15-90 min after ingestion of the meal. Results This study show that both CO, systolic longitudinal ventricular velocity of the septum (S's and lateral wall (S'l, the early diastolic longitudinal ventricular velocity of the lateral wall (E'l, the late diastolic longitudinal ventricular velocity of the septum (A's and lateral wall (A'l increase significantly, and were concomitant with increased satiety, antral area, glucose and insulin levels. The CO, HR and SV at 30 min were significantly higher, and the diastolic blood pressure was significantly lower, than the fasting. The satiety was correlated to HR and diastolic blood pressure. The insulin level was correlated to HR. Conclusions This study shows that postprandial CO, HR, SV and LV longitudinal systolic and diastolic functions increase concomitantly with increased satiety, antral area, and glucose and insulin levels. Therefore, patients should not eat prior to, or during, cardiac evaluation as the effects of a meal may

Effect of cigarette smoking on insulin resistance risk.

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Haj Mouhamed, D; Ezzaher, A; Neffati, F; Douki, W; Gaha, L; Najjar, M F

2016-02-01

Smoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics. This study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6±16.0 and 38.5±21.9 years. All subjects are not diabetic. Fasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR=[fasting insulin (mU/L)×fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance. Compared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine. Our results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers. Copyright © 2015. Published by Elsevier SAS.

Status of serum adiponectin related to insulin resistance in prediabetics

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Ahsan, S.; Ahmed, S.D.H.; Nauman, K

2014-01-01

Obejctive: To find the status of serum adiponectin in individuals progressing towards Type 2 diabetes mellitus and compare it with normal glucose tolerant subjects to determine the stage where alteration of adiponectin occurred. Methods: The cross-sectional study was carried out at the Department of Biochemistry, Jinnah Postgraduate Medical Centre, Karachi, during January to August 2008. Subjects were invited through various diabetes screening camps. A total of 608 subjects >30 years of age without prior history of diabetes were screened through fasting plasma glucose and 2-hour oral glucose tolerance test. Forty randomly selected pre-diabetic subjects and 40 age and gender-matched subjects were included in the study. Anthropometric measurements were done. Serum insulin and adiponectin were estimated by enzyme-linked immunosorbent assay. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance mathematically. Result: Mean fasting and two-hour plasma glucose, body mass index, waist, hip circumference and blood pressure were significantly raised in pre-diabetics compared to those with normal glucose tolerance. Adiponectin was significantly decreased, while insulin and HOMA-IR were raised significantly in the pre-diabetics. Adiponectin showed significant negative correlation with body mass index (r=-0.31, p=0.005), fasting plasma glucose (r=-0.24, p= 0.032), 2-hour plasma glucose (r=-0.42, p<0.0001)), insulin (r-0.43, p<0.0001) and HOMA-IR (r= -0.43, p<0.0001) and remained significant after adjustment of body mass index, gender and insulin level in pre-diabetics. Conclusion: Adiponectin estimation may help in earlier identification of impending diabetes. However, casual link between adiponectin and pre-diabetes remained unexplored due to the study design and small sample size that warrants longitudinal large-scale studies. (author)

Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance

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Rask, E; Olsson, T; Söderberg, S

2004-01-01

of glucose, insulin, C-peptide, GLP-1, and GIP. Insulin secretion (TIS) and insulin sensitivity (OGIS) were assessed using models describing the relationship between glucose, insulin and C-peptide data. These models allowed estimation also of the hepatic extraction of insulin. The age (54.2 +/- 9.7 [mean......Subjects with impaired glucose tolerance (IGT) are usually overweight and exhibit insulin resistance with a defective compensation of insulin secretion. In this study, we sought to establish the interrelation between insulin secretion and insulin sensitivity after oral glucose in non-obese subjects...... over the whole 180-minute period was higher in IGT (26.2 +/- 2.4 v 20.0 +/- 2.0 nmol/L; P =.035). Hepatic insulin extraction correlated linearly with OGIS (r = 0.71; P

Fasting plasma insulin and the default mode network in women at risk for Alzheimer's disease.

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Kenna, Heather; Hoeft, Fumiko; Kelley, Ryan; Wroolie, Tonita; DeMuth, Bevin; Reiss, Allan; Rasgon, Natalie

2013-03-01

Brain imaging studies in Alzheimer's disease research have demonstrated structural and functional perturbations in the hippocampus and default mode network (DMN). Additional evidence suggests risk for pathological brain aging in association with insulin resistance (IR). This study piloted investigation of associations of IR with DMN-hippocampal functional connectivity among postmenopausal women at risk for Alzheimer's disease. Twenty middle-aged women underwent resting state functional magnetic resonance imaging. Subjects were dichotomized relative to fasting plasma insulin levels (i.e., > 8 μIU/mL [n = 10] and < 8 μIU/mL [n = 10]), and functional connectivity analysis contrasted their respective blood oxygen level-dependent signal correlation between DMN and hippocampal regions. Higher-insulin women had significantly reduced positive associations between the medial prefrontal cortex and bilateral parahippocampal regions extending to the right hippocampus, and conversely, between the left and right hippocampus and medial prefrontal cortex. Neuropsychological data (all within normal ranges) also showed significant differences with respect to executive functioning and global intelligence. The results provide further evidence of deleterious effects of IR on the hippocampus and cognition. Further imaging studies of the IR-related perturbations in DMN-hippocampal functional connectivity are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Obesity modifies the association between serum 25-hydroxyvitamin D and insulin resistance in Korean general population without increased fasting glucose levels.

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Lee, Sung Woo; Kim, Myounghee; Kim, Ho; Han, Seung Seok; Lee, Hajeong; Lee, Jung Pyo; Kim, Dong Ki; Lim, Chun Soo; Kim, Yon Su; Park, Ae Kyung; Joo, Kwon Wook

2014-10-01

The inverse relationship between 25-hydroxyvitamin D [25(OH)D] status and insulin resistance (IR) has been reported, but many interventional studies failed to reduce IR with 25(OH)D supplementation. In addition, there has been a paucity of literature on the interaction between 25(OH)D status and IR according to the degree of obesity in Asian subjects. We therefore evaluated the association between 25(OH)D status and IR according to the degree of obesity. Data from the Korea National Health and Nutrition Examination Survey in 2008-2010 were analyzed. The study subjects comprised 10,629 participants aged ≥20 years with fasting glucoseobesity in an adult Korean population without increased fasting glucose levels. We suggest that proper supplementation of vitamin D might be beneficial in obese Korean adults.

Possible metabolic impact of Ramadan fasting in healthy men.

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Vardarli, Mustafa Cumhur; Hammes, Hans-Peter; Vardarli, İrfan

2014-01-01

Insulin sensitivity and β-cell function during Ramadan fasting in healthy male subjects have not been investigated so far. We assessed the changes of these and other metabolic parameters to judge the potential metabolic benefits of Ramadan fasting. Twenty-four healthy males of Turkish origin living in Germany, with normal glucose tolerance, participated in this study during Ramadan of 2009; 19 who completed fasting were analyzed. Blood was drawn at sunset after a period of fasting lasting approximately 15 h on days 0, 16, and 30 of Ramadan, as well as 7 and 28 days later. Insulin sensitivity (Homeostasis Model Assessment, HOMA), β-cell function, and other parameters were assessed. Ramadan fasting was associated with a significant reduction (-) or increment (+) for the following variables: insulin sensitivity (-20%; P = 0.04), β-cell function (+10%; P = 0.049), high-density lipoprotein cholesterol (-23%; P = 0.0003), low-density lipoprotein cholesterol (+14%; P = 0.007), nonesterified fatty acids (-62%; P Ramadan fasting is associated with transiently impaired insulin sensitivity, compensated for by an increased β-cell function. However, the pattern of insulin resistance-mediating adipocytokines suggests a potentially beneficial metabolic effect of Ramadan fasting.

A Study of the Insulin and the C-Peptide Responses to Oral Glucose Load in Nondiabetic and Diabetic Subjects

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Lee, Myung Chul; Choi, Sung Jae; Kim, Eung Jin; Koh, Chang Soon; Min, Hun Ki [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1977-03-15

The present study was undertaken to evaluate the significance of the insulin and the C-peptide response to oral glucose loads in normal and diabetic subjects and to establish the effects of the obesity. In this study, the authors have measured plasma insulin and C-peptide by means of radioimmunoassay in 10 nonobese normal, 5 obese normal, 13 nonobese moderate diabetic patients, 9 obese moderate diabetic patients and 9 severe diabetic patients. The results obtained were as follows; 1) In 10 nonobese normal subjects, the plasma insulin level at fasting state and at 30, 60, 90, and 120 min after oral glucose loads were 15.7+-3.4, 48.3+-9.8, 40.4+-6.7, 37.4+-6.5 and 26.0+-4.2 uU/ml (Mean+-S.E.) and C-peptide were 1.9+-0.3, 3.9+-0.6, 6.3+-0.6, 5.7+-0.5 and 4.0+-0.5 ng/ml. The change of C-peptide was found to go almost parallel with that of insulin and the insulin value reaches to the highest level at 30 min whereas C-peptide reaches to its peak at 60 min.. 2) The plasma insulin level in 5 obese normal subjects were 38.9+-12.3, 59.5+-12.3, 59.2+-17.1, 56.1+-20.0 and 48.4+-17.2 uU/ml and the C-peptide were 5.5+-0.4, 6.8+-0.5, 7.9+-0.8, 7.9+-0.8 and 7.8+-2.0 ng/ml. The insulin response appeared to be greater than nonobese normal subjects. 3) In 13 nonobese moderate diabetic patients, the plasma insulin levels were 27.1+-4.9, 44.1+-6.0, 37.3+-6.6, 35.5+-8.1 and 34.7+-10.7 uU/ml and the C-peptide levels were 2.7+-0.4, 4.9+-0.7, 6.5+-0.5, 7.0+-0.3 and 6.7+-1.0 ng/ml. There was little significance compared to nonobese normal groups but delayed pattern is noted. 4) In 9 obese moderated diabetic patients, the plasma insulin levels were 22.1+-7.9, 80.0+-19.3, 108.0+-27.0, 62.0+-17.6 and 55.5+-10.l uU/ml and the C-peptide levels were 5.2+-0.4, 8.0+-1.0, 10.4+-1.6, 10.4+-1.7 and 10.1+-1.0 ng/ml and its response was also greater than that of nonobese moderate diabetic patients. 5) The plasma insulin concentrations in 9 severe diabetic subjects were 8.0+-3.8, 12.1+-3.5, 16.8+-4.6, 19

Association between HOMA-IR, fasting insulin and fasting glucose with coronary heart disease mortality in nondiabetic men: a 20-year observational study.

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Kurl, Sudhir; Zaccardi, Francesco; Onaemo, Vivian N; Jae, Sae Young; Kauhanen, Jussi; Ronkainen, Kimmo; Laukkanen, Jari A

2015-02-01

Whether glucose and insulin are differently associated with the risk of coronary heart disease (CHD) mortality is unclear. We aimed to estimate the association between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR), fasting serum insulin (FI) and fasting plasma glucose (FPG) with incident CHD mortality in a prospective study including middle-aged nondiabetic Finnish men. During an average follow-up of 20 years, 273 (11 %) CHD deaths occurred. In a multivariable Cox regression analysis adjusted for age, body mass index, systolic blood pressure, serum LDL-cholesterol, cigarette smoking, history of CHD, alcohol consumption, blood leukocytes and plasma fibrinogen, the hazard ratios (HRs) for CHD mortality comparing top versus bottom quartiles were as follows: 1.69 (95 % CI: 1.15-2.48; p = 0.008) for HOMA-IR; 1.59 (1.09-2.32; p = 0.016) for FI; and 1.26 (0.90-1.76; p = 0.173) for FPG. These findings suggest that IR and FI, but not FPG, are independent risk factors for CHD mortality. Further studies could help clarify these results in terms of screening and risk stratification, causality of the associations, and therapeutical implications.

Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects.

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Reyna, Sara M; Ghosh, Sangeeta; Tantiwong, Puntip; Meka, C S Reddy; Eagan, Phyllis; Jenkinson, Christopher P; Cersosimo, Eugenio; Defronzo, Ralph A; Coletta, Dawn K; Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.

Clustering effects on postprandial insulin secretion and sensitivity in response to meals with different fatty acid compositions.

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Bermudez, Beatriz; Ortega-Gomez, Almudena; Varela, Lourdes M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

2014-07-25

Dietary fatty acids play a role in glucose homeostasis. The aim of this study was to assess the individual relationship between dietary saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids with postprandial β-cell function and insulin sensitivity in subjects with normal and high fasting triglycerides. We assessed postprandial β-cell function (by the insulinogenic index and the ratio of the insulin to glucose areas under the time-concentration curve) and insulin sensitivity (by the oral glucose and the minimal model insulin sensitivity indices) over four nonconsecutive, randomly assigned, high-fat meals containing a panel of SFA (palmitic and stearic acids), MUFA (palmitoleic and oleic acids) and PUFA (linoleic and α-linolenic acids) in 14 subjects with normal and in 14 subjects with high fasting triglycerides. The proportions of each fatty acid in the meals and the values for surrogate measures of postprandial β-cell function and insulin sensitivity were subjected to a Pearson correlation and hierarchical cluster analysis, which revealed two classes of dietary fatty acids for regulating postprandial glucose homeostasis. We successfully discriminated the adverse effects of SFA palmitic acid from the beneficial effects of MUFA oleic acid on postprandial β-cell function (r ≥ 0.84 for SFA palmitic acid and r ≥ -0.71 for MUFA oleic acid; P < 0.05) and insulin sensitivity (r ≥ -0.92 for SFA palmitic acid and r ≥ 0.89 for MUFA oleic acid; P < 0.001) both in subjects with normal and high fasting triglycerides. In conclusion, dietary MUFA oleic acid, in contrast to SFA palmitic acid, favours the tuning towards better postprandial glycaemic control in subjects with normal and high fasting triglycerides.

Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period—The Da Qing Children Cohort Study

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Chen, Yan Yan; Wang, Jin Ping; Jiang, Ya Yun; Li, Hui; Hu, Ying Hua; Lee, Kok Onn; Li, Guang Wei

2015-01-01

Background The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance. Objective To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood. Methods 424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later. Results Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight). Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001) in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001) in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index) at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglycerides at 10 years of age. Conclusions Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin. PMID:26047327

Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period-The Da Qing Children Cohort Study.

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Yan Yan Chen

Full Text Available The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance.To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood.424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later.Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight. Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001 in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001 in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR and triglycerides at 10 years of age.Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin.

Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects

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Sara M. Reyna

2013-01-01

Full Text Available Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD. Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC were obtained for determination of Toll-like receptor (TLR 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

Short-term exercise training improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells from insulin-resistant subjects.

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Reyna, Sara M; Tantiwong, Puntip; Cersosimo, Eugenio; Defronzo, Ralph A; Sriwijitkamol, Apiradee; Musi, Nicolas

2013-01-01

Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC) were obtained for determination of Toll-like receptor (TLR) 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

Effects of Ramadan fasting on glucose homeostasis and adiponectin levels in healthy adult males.

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Gnanou, Justin V; Caszo, Brinnell A; Khalil, Khalifah M; Abdullah, Shahidah L; Knight, Victor F; Bidin, Mohd Z

2015-01-01

Adiponectin is a hormone secreted by adipocytes during the fasting phase of the fast-fed cycle. Ramadan fasting involves prolonged fasting for up to twelve hours and thus could lead to increased secretion of adiponectin by adipocytes. However, studies on the role of adiponectin on glucose and body weight homeostasis during Ramadan fasting is still a matter of controversy. Thus the specific aim of this study was to assess the effect of fasting during Ramadan on the adiponectin levels, body weight and glucose homeostasis in healthy male Malaysian subjects. Twenty healthy male (19-23 years) Muslim subjects were followed up during the fasting month of Ramadan. Anthropometry and blood samples were taken one week before and during the fourth week of fasting. Plasma glucose, insulin and adiponectin were estimated and insulin sensitivity indices were estimated using the Homeostasis Model Assessment. Subjects experienced a significant decrease in body weight (2.4 %, p Ramadan fasting in young healthy individuals has a positive impact on the maintenance of glucose homeostasis. It also shows that adiponectin levels dropped along with significant loss in weight. We feel caloric restriction during the Ramadan fasting is in itself sufficient to improve insulin sensitivity in healthy individuals.

Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity.

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Dunn, Julia P; Kessler, Robert M; Feurer, Irene D; Volkow, Nora D; Patterson, Bruce W; Ansari, Mohammad S; Li, Rui; Marks-Shulman, Pamela; Abumrad, Naji N

2012-05-01

Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S(I)) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [(18)F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S(I) was determined by modified oral glucose tolerance test. Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S(I) was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

DEFF Research Database (Denmark)

Laakso, M; Zilinskaite, J; Hansen, T

2008-01-01

AIMS/HYPOTHESIS: We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. METHODS: Non-diabetic offspring (n=874; mean age 40+/-10.4 years; BMI 26.6+/-4.9 kg/m(2)) of type 2 diabetic...

A Study of the Insulin and the C-Peptide Responses to Oral Glucose Load in Nondiabetic and Diabetic Subjects

International Nuclear Information System (INIS)

Lee, Myung Chul; Choi, Sung Jae; Kim, Eung Jin; Koh, Chang Soon; Min, Hun Ki

1977-01-01

The present study was undertaken to evaluate the significance of the insulin and the C-peptide response to oral glucose loads in normal and diabetic subjects and to establish the effects of the obesity. In this study, the authors have measured plasma insulin and C-peptide by means of radioimmunoassay in 10 nonobese normal, 5 obese normal, 13 nonobese moderate diabetic patients, 9 obese moderate diabetic patients and 9 severe diabetic patients. The results obtained were as follows; 1) In 10 nonobese normal subjects, the plasma insulin level at fasting state and at 30, 60, 90, and 120 min after oral glucose loads were 15.7±3.4, 48.3±9.8, 40.4±6.7, 37.4±6.5 and 26.0±4.2 uU/ml (Mean±S.E.) and C-peptide were 1.9±0.3, 3.9±0.6, 6.3±0.6, 5.7±0.5 and 4.0±0.5 ng/ml. The change of C-peptide was found to go almost parallel with that of insulin and the insulin value reaches to the highest level at 30 min whereas C-peptide reaches to its peak at 60 min.. 2) The plasma insulin level in 5 obese normal subjects were 38.9±12.3, 59.5±12.3, 59.2±17.1, 56.1±20.0 and 48.4±17.2 uU/ml and the C-peptide were 5.5±0.4, 6.8±0.5, 7.9±0.8, 7.9±0.8 and 7.8±2.0 ng/ml. The insulin response appeared to be greater than nonobese normal subjects. 3) In 13 nonobese moderate diabetic patients, the plasma insulin levels were 27.1±4.9, 44.1±6.0, 37.3±6.6, 35.5±8.1 and 34.7±10.7 uU/ml and the C-peptide levels were 2.7±0.4, 4.9±0.7, 6.5±0.5, 7.0±0.3 and 6.7±1.0 ng/ml. There was little significance compared to nonobese normal groups but delayed pattern is noted. 4) In 9 obese moderated diabetic patients, the plasma insulin levels were 22.1±7.9, 80.0±19.3, 108.0±27.0, 62.0±17.6 and 55.5±10.l uU/ml and the C-peptide levels were 5.2±0.4, 8.0±1.0, 10.4±1.6, 10.4±1.7 and 10.1±1.0 ng/ml and its response was also greater than that of nonobese moderate diabetic patients. 5) The plasma insulin concentrations in 9 severe diabetic subjects were 8.0±3.8, 12.1±3.5, 16.8±4.6, 19

Comparative effects of several simple carbohydrates on erythrocyte insulin receptors in obese subjects.

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Rizkalla, S W; Baigts, F; Fumeron, F; Rabillon, B; Bayn, P; Ktorza, A; Spielmann, D; Apfelbaum, M

1986-09-01

The effects of simple carbohydrates on erythrocyte insulin receptors, plasma insulin and plasma glucose were studied during four hypocaloric, hyperproteic, diets. One diet contained no carbohydrate; the other three contained 36 g of either glucose, galactose or fructose. These diets were given for a 14-day period to groups of moderately obese subjects. The hypocaloric carbohydrate-free diet produced a decrease in plasma insulin and glucose concentrations concomitant with an increase in the number of insulin receptors. A similar increase in insulin receptor number was found when the diet was supplemented with glucose or galactose, but not with fructose. The presence of fructose in the diet prevented any increase in insulin receptor number.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

DEFF Research Database (Denmark)

Manning, Alisa K; Hivert, Marie-France; Scott, Robert A

2012-01-01

pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci...... associated with fasting insulin at P triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci...

Impact of ENPP1 K121Q on change of insulin resistance after web-based intervention in Korean men with diabetes and impaired fasting glucose.

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Kang, Ji Yeon; Sung, Sook Hee; Lee, Yeon Ju; Choi, Tae In; Choi, Seung Jin

2014-10-01

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We hypothesized that the difference in genotype may be one of the factors that affect the outcome of intervention. We genotyped 448 men with fasting glucose≥5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ) (13 CG and 64 IG). The web-based intervention based on a lifestyle modification was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated significantly decreased levels of fasting serum insulin (FSI) as compared to CG and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased, and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of covariance, K121Q did significantly influence the change of HbA1c in CG after appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR change (adjusted β=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q did not influence the change in IR. However, individuals with T2DM carrying the K121 variant are very responsive to the effect of BMI reduction on HOMA-IR.

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

DEFF Research Database (Denmark)

Madsbad, Sten

2002-01-01

To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

Metabolic and clinical effects of Ramadan fasting in patients with type II diabetes

International Nuclear Information System (INIS)

Yarahmadi, S.; Larijani, B.; Bastanhagh, M.H.; Pajouhi, M.; Bardar, J. R.; Zahedi, F.; Zendehdel, K.; Akrami, S.M.

2003-01-01

Objective: To evaluate the effects of fasting on anthropometric indices and carbohydrate and lipid metabolism in patients with type II diabetes. Results: Daily cholesterol intake increased in all subjects (p 0.01). Blood pressure, fasting blood glucose and serum fructosamine did not change during the study. Plasma insulin (p < 0.05), C-peptide (p < 0.01) and insulin resistance (p < 0.01) decreased only in men. Total and LDL cholesterol increased significantly in all subjects during the study. Conclusion: Ramadan fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in patients with type II diabetes given appropriate dietary education and rescheduling of oral hypoglycaemic medication. Lipid profile is unfavorably altered due to changes in both diet and biochemical response to starvation. (author)

Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects

DEFF Research Database (Denmark)

Jacobsen, Siv Hesse; Olesen, S C; Dirksen, C

2012-01-01

measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin......, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance. RESULTS: Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated...... postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after...

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

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Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

2013-11-15

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects.

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Wickenberg, Jennie; Ingemansson, Sandra Lindstedt; Hlebowicz, Joanna

2010-10-12

Previous animal studies have shown that Curcuma (C.) longa lowers plasma glucose. C. longa may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of C. longa on postprandial plasma glucose, insulin levels and glycemic index (GI) in healthy subjects. Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with capsules containing a placebo or C. longa. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively. The ingestion of 6 g C. longa had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (P = 0.03) and 60 min (P = 0.041) after the OGTT including C. longa. The insulin AUCs were also significantly higher after the ingestion of C. longa, 15 (P = 0.048), 30 (P = 0.035), 90 (P = 0.03), and 120 (P = 0.02) minutes after the OGTT. The ingestion of 6 g C. longa increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that C. longa may have an effect on insulin secretion.

[Primary study on characteristics of insulin secretion rate, metabolic clearance rate and sensitivity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees].

Science.gov (United States)

Ran, J; Cheng, H; Li, F

2000-01-01

To investigate the characteristics of insulin secretion rate (ISR), metabolic clearance rate (MCR-I) and sensitivity and to explore their relationship with obesity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees (MDP). Fifteen subjects with normal glucose tolerance and 11 non-insulin-dependent diabetic patients from MDP were included in the study. Frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. Glucose, insulin (INS) and connecting-peptide (C-P) concentrations were measured. A computer procedure devised by our laboratory was used to calculate the value of ISR at each time point, then MCR-I was acquired. Insulin sensitivity index (SI) was calculated according to minimal model technique about glucose in FSIVGTT. The ISR curve in control group was biphasic, while in non-insulin. In non-insulin-dependent diabetic group, areas under the curves of C-P (AUCC) and ISR level (AUCS) measured during 0 approximately 16 min were 7.9 nmol.min(-1).L(-1) +/- 2.8 nmol.min(-1).L(-1), and 6.1 nmol +/- 2.2 nmol, respectively, which were significantly lower than those in control group 17.7 nmol.min(-1).L(-1) +/- 4.92 nmol.min(-1).L(-1) and 12.3 nmol +/- 3.9 nmol (P < 0.01). The two parameters were slightly higher than those in control group 155 nmol.min(-1).L(-1) +/- 44 nmol.min(-1).L(-1) vs 101 nmol.min(-1).L(-1) +/- 30 nmol.min(-1).L(-1) and 76 nmol +/- 26 nmol vs 54 nmol +/- 20.0 nmol (P < 0.05)measured during 16 approximately 180 min. There was no significant difference, between the two groups about the amount of insulin secretion during 3 hours (82 nmol +/- 28nmol vs 68 nmol +/- 21 nmol, P = 0.2). In control group, there were significant positive correlation, between AUCS, waist-hip ratio (WHR), and body surface area, (BSA) and significant negative correlation between MCR-I, SI and WHR, BSA (P < 0.01), and also between MCR-I and SI. In non-insulin-dependent diabetic group, AUCS were significantly correlated with body mass

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...

Homeostatic Model Assessment-Insulin Resistance (HOMA-IR 2) in Mild Subclinical Hypothyroid Subjects.

Science.gov (United States)

Sengupta, Shreejita; Jaseem, T; Ambalavanan, Jayachidambaram; Hegde, Anupama

2018-04-01

Despite various studies with conflicting results, the effect of thyroid hormones on lipids and insulin levels in dysthyroidism is of great interest. This case control study was aimed to perceive the existence of IR and dyslipidemia in mild subclinical hypothyroid subjects (TSH ≤ 9.9 µIU/ml) as compared to their age and gender matched euthyroid controls. Basic demographic information like height, weight was recorded. Serum samples of all the subjects were assayed for thyroid profile, lipid profile, blood glucose, HbA1C and insulin. BMI and insulin resistance was calculated. Compared to controls patients with mild subclinical hypothyroidism demonstrated hyperinsulinemia and dyslipidemia observed by the higher LDL cholesterol. A significantly positive correlation was observed for HOMA-IR with TSH and LDL cholesterol. Hence, even in the mild subclinical hypothyroid state assessment of thyroid function should be combined with estimation of plasma glucose, insulin and serum lipids to monitor and prevent its associated effects.

The effect of nano-curcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: a randomized clinical trial

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Hamid Reza Rahimi

2016-08-01

Full Text Available Objective: Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both or insulin resistance. Curcumin inhibits NF-κB signaling pathway. The aim of this study is evaluation of the effect of Nano-curcumin on HbA1C, fast blood glucose and lipid profile in diabetic patients. Materials and Methods: Seventy type-2 diabetic patients (fasting blood glucose (FBG ≥ 126 mg/dL or 2-hr postprandial blood glucose ≥200 mg/dl randomly receivedeither Curcumin (as nano-micelle 80 mg/day or placebo for 3 months in a double blind randomized clinical trial. Fasting blood glucose, HbA1C, and lipids profile were checked before and after the intervention. Data analyses, including parametric and nonparametric tests were done using the SPSS 11.5 software. A p value < 0.05 was regarded as statistically significant. (RCT registration code: IRCT2013081114330N1 Results: Mean age, BMI, FBG, total cholesterol (TC, triglyceride (TG, LDL, HDL, HbA1c , and  sex and had no significant difference at the baseline between the groups. In Nano-curcumin group, a significant decrease was found in HbA1C, FBG, TG, and BMI comparing results of each subject before and after the treatment (p

Effects of Curcuma longa (turmeric on postprandial plasma glucose and insulin in healthy subjects

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Ingemansson Sandra

2010-10-01

Full Text Available Abstract Background Previous animal studies have shown that Curcuma (C. longa lowers plasma glucose. C. longa may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of C. longa on postprandial plasma glucose, insulin levels and glycemic index (GI in healthy subjects. Methods Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT was administered together with capsules containing a placebo or C. longa. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively. Results The ingestion of 6 g C. longa had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (P = 0.03 and 60 min (P = 0.041 after the OGTT including C. longa. The insulin AUCs were also significantly higher after the ingestion of C. longa, 15 (P = 0.048, 30 (P = 0.035, 90 (P = 0.03, and 120 (P = 0.02 minutes after the OGTT. Conclusions The ingestion of 6 g C. longa increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that C. longa may have an effect on insulin secretion. Trial registration number NCT01029327

Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

Science.gov (United States)

Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

2017-10-01

Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

Relationship of serum resistin with insulin resistance and obesity

International Nuclear Information System (INIS)

Zaidi, S.I.Z.

2015-01-01

Background: Adipokines have been implicated in the modulation of insulin sensitivity and glucose tolerance and have thus gained importance in the study of Type 2 diabetes mellitus (T2DM). Resistin, a unique signalling molecule, is being proposed as a significant factor in the pathogenesis of obesity-related insulin resistance. However, its relevance to human diabetes mellitus remains uncertain and controversial. This study was therefore planned to compare and correlate the potential role of resistin in obese patients with T2DM and obese non-diabetic controls and also to evaluate the correlation between resistin and marker of obesity and glycaemic parameters. Method: Fasting serum resistin, glucose and insulin were measured in forty obese diabetics (mean±SD BMI 35±5 kg/m2) and forty obese non-diabetics (mean±SD BMI 33±3 kg/m2). Insulin resistance was assessed using the HOMA-IR formula derived from fasting insulin and glucose levels. Results: Serum resistin levels (38±8 ng/ml) were significantly higher in type 2 diabetic patients as compared with the controls. Fasting blood glucose (164±46 mg/dl), serum insulin (37±7 μU/ml) and insulin resistance (19±8), were considerably higher among the studied diabetics than in the controls. Pearson's correlation analysis revealed positive correlation between serum resistin and BMI (p=0.001) and HOMA-IR (p=0.561) in diabetic subjects. Similarly, a correlation also existed between serum resistin and BMI (p=0.016) and HOMA-IR (p=0.307) in control obese subjects. However, it was highly significant in diabetics as compared to non-diabetic controls. Conclusion: A significant BMI-dependent association exists between resistin and insulin resistance in patients with T2DM. It appears that resistin may play a role in the pathogenesis of obesity and insulin resistance and that both of these may contribute to the development of T2DM. (author)

Fasting and post-prandial adipose tissue lipoprotein lipase and hormone-sensitive lipase in obesity and type 2 diabetes.

Science.gov (United States)

Costabile, G; Annuzzi, G; Di Marino, L; De Natale, C; Giacco, R; Bozzetto, L; Cipriano, P; Santangelo, C; Masella, R; Rivellese, A A

2011-05-01

Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone- sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups - obese with Type 2 diabetes and obese without diabetes - and in non-diabetic normal-weight controls. Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (pobese subjects compared to controls in both fasting condition and 6 h after the meal (pfasting and 6 h after meal measurements in either LPL or HSL activities and gene expressions. Lipolytic activities in AT are differently altered in obesity and Type 2 diabetes being HSL alteration associated with both insulin-resistant conditions and LPL with diabetes per se. These abnormalities are similarly observed in the fasting condition and after a fat-rich meal.

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

Science.gov (United States)

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.

Triglyceride glucose index, a marker of insulin resistance, is associated with coronary artery stenosis in asymptomatic subjects with type 2 diabetes.

Science.gov (United States)

Lee, Eun Young; Yang, Hae Kyung; Lee, Joonyub; Kang, Borami; Yang, Yeoree; Lee, Seung-Hwan; Ko, Seung-Hyun; Ahn, Yu-Bae; Cha, Bong Yun; Yoon, Kun-Ho; Cho, Jae Hyoung

2016-09-15

Insulin resistance is one of the most important contributing factors to cardiovascular disease. This study aimed to investigate the association between coronary artery stenosis (CAS) and triglyceride glucose index (TyG index), a simple insulin resistance marker, in asymptomatic subjects with type 2 diabetes. We recruited asymptomatic adults with type 2 diabetes but without previous history of coronary heart disease (n = 888). Significant CAS was defined as maximum intraluminal stenosis ≥70 % by coronary CT angiography. TyG index was calculated as log [fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2]. Mean age was 63.8 ± 9.5 and 58.9 % of the subjects were men. We analyzed the participants according to the tertile of TyG index. The TyG index was correlated with HOMA-IR (r = 0.397, P index were younger but showed worse clinical and metabolic parameters. The prevalence of CAS was higher in subjects with higher tertile of TyG compared with those with lower tertile of TyG (14 % vs. 7.8 %, P = 0.022). On multiple regression analysis, the highest tertile of TyG index was an independent risk factor for CAS after adjustment for other confounders (odds ratio, 3.19 [95 % CI, 1.371-7.424]). Subgroup analysis showed that TyG index showed more significant association with CAS in patients with risk factors such as old age, longer duration of diabetes, poor glycemic control, no statin use, and male gender. Higher TyG index is associated with increased risk of CAS in asymptomatic subjects with type 2 diabetes, particularly when they have risk factors for cardiovascular disease. This study was retrospectively registered in ClinicalTrials. gov with the registration number of NCT02070926 in Feb 23, 2014.

Efficacy of insulin lispro in improving glycemic control in gestational diabetes

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M C Deepaklal

2014-01-01

Full Text Available Aim: To assess the safety and efficacy of insulin lispro in improving glycemic control in patients with gestational diabetes. Materials and Methods: A retrospective observational study was conducted at a single center on 201 gestational women with diabetes. Subjects who received insulin lispro performed blood glucose self-monitoring and recorded the readings in the fasting state and 1 h after each meal. At each contact (in person or telephonic contact, the insulin dose was adjusted based on the readings measured. A total of 53 subjects also recorded glucose levels post-partum. Pregnancy and post-delivery glucose level and insulin requirements of these 53 patients were compared. Results: Analysis of glucose levels both fasting and post-prandial glucose levels revealed that after using insulin lispro, the number of episodes of post-prandial hyperglycemia (1 h plasma glucose >120 mg/dL was minimal and so was the incidence of hypoglycemia. Hypoglycemia was defined as a blood sugar value of. There was neither any congenital abnormality except for a poorly formed pinna in the right ear of one baby nor any post-partum complications of note. Conclusion: Insulin lispro is an effective and safe treatment option in gestational diabetes.

Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

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Silke A Herzberg-Schäfer

Full Text Available BACKGROUND: To date, fasting state- and different oral glucose tolerance test (OGTT-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05. The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset were summed up resulting in a final ranking. This approach revealed area under the curve (AUC(Insulin(0-30/AUC(Glucose(0-30 as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30/AUC(Glucose(0-30, corrected insulin response (CIR, AUC(C-Peptide(0-30/AUC(Glucose(0-30, AUC(C-Peptide(0-120/AUC(Glucose(0-120, two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI(2 and IGI(1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05. AUC(C-Peptide(0-120/AUC(Glucose(0-120 was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last. CONCLUSIONS/SIGNIFICANCE: With AUC(Insulin(0

Beneficial effects on fasting insulin and postprandial responses through 7-day intake of New Zealand blackcurrant powder

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Mark Elisabeth Theodorus Willems

2017-07-01

Full Text Available Background: Blood glucose and insulin are elevated after intake of carbohydrate, with levels returning to normal in about 2-3 hours after ingestion. We examined the effects of daily New Zealand blackcurrant intake over 7 days on fasting glucose and insulin levels and the responses of glucose and insulin during an oral glucose tolerance test (i.e. OGTT. Methods: Seventeen healthy participants (9 males, 8 females, age: 24±8 years, body mass: 75.4±16.4 kg, height 172±11 cm, body mass index: 25.3±3.3 consumed 6 g·day-1 New Zealand blackcurrant (NZBC powder for 7 days. Every 6 g of the serving contained 138.6 mg anthocyanins, 49 mg vitamin C, and 5.2 g of carbohydrates with total phenolic content 271.6 mg. A cross-over design was used. Participants completed one OGTT before starting the supplementation (day 0 and another OGTT after 7 days of the supplementation (day 7. For the OGTT, participants were seated and consumed 75 g of glucose dissolved in 250 mL water. Finger prick capillary samples were taken before and every 30 minutes for a total of 120 minutes after consuming the glucose drink. Following duplicate glucose analysis, blood samples were centrifuged and then plasma was separated and frozen (-20°C for triplicate insulin analysis using a human 96-well insulin enzyme-linked immunosorbent assay (IBL international, Hamburg, Germany. Results: NZBC had no effect on fasting glucose (control: 4.46±0.45; NZBC: 4.41±0.44 mmol·L1, P=0.657, although there was a trend for fasting insulin to be 14.3% lower (control: 66.5±28.2; NZBC: 57.0±29.5 pmol·L-1 (P=0.091. HOMA-IR was not different between the control and NZBC (1.81±0.73 vs 1.58±0.83 (P=0.126. With NZBC during the OGTT, plasma glucose at 60 min was 8.1% lower (control: 6.68±1.13; NZBC: 6.14±1.41 mmol·L-1; P=0.016, insulin at 30 min was 18.4% lower (control: 337.1±228.3; NZBC: 275.0±136.4 pmol·L-1; P= 0.021, and insulin at 60 min was 39.2% lower (control: 297.8±154.3; NZBC: 181.2�

Baseline Levels, and Changes Over Time in Body Mass Index and Fasting Insulin, and Their Relationship to Change in Metabolic Trait Clustering

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Sullivan, Lisa M.; Fox, Caroline S.; Wilson, Peter W.F.; Nathan, David M.; Vasan, Ramachandran S.; D'Agostino, Ralph B.; Meigs, James B.

2014-01-01

Abstract Background: Multiple abnormal metabolic traits are found together or “cluster” within individuals more often than is predicted by chance. The individual and combined role of adiposity and insulin resistance (IR) on metabolic trait clustering is uncertain. We tested the hypothesis that change in trait clustering is a function of both baseline level and change in these measures. Methods: In 2616 nondiabetic Framingham Offspring Study participants, body mass index (BMI) and fasting insulin were related to a within-person 7-year change in a trait score of 0–4 Adult Treatment Panel III metabolic syndrome traits (hypertension, high triglycerides, low high-density lipoprotein cholesterol, hyperglycemia). Results: At baseline assessment, mean trait score was 1.4 traits, and 7-year mean (SEM) change in trait score was +0.25 (0.02) traits, Pfasting insulin were similarly related to trait score change. In models adjusted for age–sex–baseline cluster score, 7-year change in trait score was significantly related to both a 1-quintile difference in baseline BMI (0.07 traits) and fasting insulin (0.18 traits), and to both a 1-quintile 7-year increase in BMI (0.21 traits) and fasting insulin (0.18 traits). Conclusions: Change in metabolic trait clustering was significantly associated with baseline levels and changes in both BMI and fasting insulin, highlighting the importance of both obesity and IR in the clustering of metabolic traits. PMID:25007010

Insulin sensitivity and clustering of coronary heart disease risk factors in young adults. The Northern Ireland Young Hearts Study

DEFF Research Database (Denmark)

Andersen, Lars Bo; Boreham, Colin A.G.; Young, Ian S.

2006-01-01

risk factor. Subjects with clustered risk were defined as those displaying four or more risk factors. Blood glucose and insulin were measured in the fasting state and 2 h after ingestion of a 75 g glucose load. Results. Fasting insulin and the homeostasis model assessment insulin resistance score (HOMA......) were strong, graded predictors of clustered risk. The odds ratio (OR) for having clustered risk was 10.8 (95% CI: 3.6-32.4) for the upper quartile of fasting insulin compared to the lowest quartile, and the corresponding OR for HOMA was 23.2 (95% CI: 5.3-101.6). Conclusion. HOMA score predicts...

Linking lifestyle factors and insulin resistance, based on fasting plasma insulin and HOMA-IR in middle-aged Japanese men: a cross-sectional study.

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Otake, Toshie; Fukumoto, Jin; Abe, Masao; Takemura, Shigeki; Mihn, Pham Ngoc; Mizoue, Tetsuya; Kiyohara, Chikako

2014-09-01

Insulin resistance (IR) is regarded as one of the earliest features of many metabolic diseases, and major efforts are aimed at improving insulin function to confront this issue. The aim of this study was to investigate the relationship of body mass index (BMI), cigarette smoking, alcohol intake, physical activity, green tea and coffee consumption to IR. We performed a cross-sectional study of 1542 male self defense officials. IR was defined as the highest quartile of the fasting plasma insulin (≥ 50 pmol/L) or the homeostasis model assessment-estimated IR (HOMA-IR ≥ 1.81). An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between IR and influential factors. Stratified analysis by obesity status (BMI IR was significantly positively related to BMI and glucose tolerance, negatively related to alcohol use. Independent of obesity status, significant trends were observed between IR and alcohol use. Drinking 30 mL or more of ethanol per day reduced IR by less than 40%. Strong physical activity was associated with decreased risk of IR based on fasting plasma insulin only in the obese. Coffee consumption was inversely associated with the risk of IR based on HOMA-IR in the non-obese group. Higher coffee consumption may be protective against IR among only the non-obese. Further studies are warranted to examine the effect modification of the obesity status on the coffee-IR association.

Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects

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Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

2017-01-01

Background Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Methods Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Results Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05), and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4–5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). Conclusion This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images. PMID:28715453

Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects.

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Kenji Ishibashi

Full Text Available Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images.Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR was calculated.Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05, and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4-5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002, and no correlation with plasma insulin levels (r = 0.156, p = 0.12 or HOMA-IR (r = 0.096, p = 0.24.This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images.

G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans

DEFF Research Database (Denmark)

Sparsø, Thomas; Bonnefond, Amélie; Andersson, Ehm

2009-01-01

independent effect on FPG with isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), type 2 diabetes, and measures of insulin release and peripheral and hepatic insulin sensitivity. RESEARCH DESIGN AND METHODS: We examined European-descent participants in the Inter99 study...... (n = 5,553), in a sample of young healthy Danes (n = 372), in Danish twins (n = 77 elderly and n = 97 young), in additional Danish type 2 diabetic patients (n = 1,626) and control subjects (n = 505), in the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study (n = 4...

Tolerance of centrifuge-simulated suborbital spaceflight in subjects with implanted insulin pumps.

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Levin, Dana R; Blue, Rebecca S; Castleberry, Tarah L; Vanderploeg, James M

2015-04-01

With commercial spaceflight comes the possibility of spaceflight participants (SFPs) with significant medical conditions. Those with previously untested medical conditions, such as diabetes mellitus (DM) and the use of indwelling medical devices, represent a unique challenge. It is unclear how SFPs with such devices will react to the stresses of spaceflight. This case report describes two subjects with Type I DM using insulin pumps who underwent simulated dynamic phases of spaceflight via centrifuge G force exposure. Two Type I diabetic subjects with indwelling Humalog insulin pumps, a 23-yr-old man averaging 50 u of Humalog daily and a 27-yr-old man averaging 60 u of Humalog daily, underwent seven centrifuge runs over 48 h. Day 1 consisted of two +Gz runs (peak = +3.5 Gz, run 2) and two +Gx runs (peak = +6.0 Gx, run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +Gx and +Gz). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular evaluation, and questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Neither subject experienced adverse clinical responses to the centrifuge exposure. Both maintained blood glucose levels between 110-206 mg · dl(-1). Potential risks to SFPs with insulin pump dependent DM include hypo/hyperglycemia, pump damage, neurovestibular dysfunction, skin breakdown, and abnormal stress responses. A search of prior literature did not reveal any previous studies of individuals with DM on insulin pumps exposed to prolonged accelerations. These cases suggest that individuals with conditions dependent on continuous medication delivery might tolerate the accelerations anticipated for commercial spaceflight.

Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

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Mimi Z Chen

Full Text Available Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB, and compared this to lean volunteers.The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2 patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2. Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50 and maximal (GDR100 GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001. Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004 but not GDR100 (P=0.3. These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001. Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA, and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA, and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively.Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

Circulating omentin-1 levels and its association with insulin resistance in newly diagnosed impaired glucose tolerant subjects

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L Hossain

2016-01-01

Full Text Available Adipose tissue derived a novel adipokine; omentin -1, w hich has recently been characterized as a potent insulin-sensitizing agent, but its pathophysiologic role in the development of insulin resistance among the impaired glucose tolerance (IGT su bjects remains largely unknow n. The present study has been undertaken to explore the relationship of serum omentin -1 w ith insulin resistance in new ly diagnosed IGT subjects of Bangladeshi population. Fifty-five subjects w ith IGT and 50 (age, sex and body m ass index (BMI matched healthy control subjects w ere recruited in this study. Serum insulin and omentin-1 w ere measured by the ELISA technique. Insulin resistance (IR w as calculated by homeostasis model assessment (HOMA. HOMA-IR w as significantly higher (p < 0.001 as w ell as log transformed omentin-1 w as significantly low er (p = 0.031 in IGT subjects compared to the control. Pearson′s correlation analysis show ed a significant negative correlation of log omentin -1 w ith HOMA-IR (r = -0.290, p = 0.008 in all subjects. Multiple linear regression analysis show ed a significant negative association of HOMA-IR w ith log omentin-1 (β = -0.285, p = 0.017 in IGT subjects after adjusting the effects of potential confounders of glycated hemoglobin (HbA1c and triglyceride (TG. Binary logistic regression analysis show ed that log omentin-1 [odds ratio (OR = 0.631, p = 0.038] and HOMA-IR (OR = 1.998, p = 0.029 w ere found to be significant determinants of IGT after adjusting the effect of HbA1c and TG. Serum concentration of omentin-1 is decreased in the state of insulin resistance of IGT subjects and this reduction seemed to be mediated by adiposity and hyperglycemia among these subjects.

Different susceptibility to insulin resistance and fatty liver depending on the combination of TNF-α C-857T and adiponectin G+276T gene polymorphisms in Japanese subjects with type 2 diabetes

International Nuclear Information System (INIS)

Ohara, Mio; Maesawa, Chihaya; Takebe, Noriko

2012-01-01

The C-857T promoter polymorphism of tumor necrosis factor (TNF)-α gene is associated with obese type 2 diabetes, while the adiponectin G+276T gene polymorphism in intron 2 may influence the fat accumulation in the liver. In this study, we examined effects of these polymorphisms on clinical markers of insulin resistance and fatty liver (a liver/spleen CT ratio <0.9). These polymorphisms were determined in 342 Japanese subjects with type 2 diabetes. The liver/spleen CT ratio was lower in the subjects with the adiponectin +276G/G genotype than that in the subjects with the +276T allele (P<0.05), indicating that fat accumulation in the liver is associated with the +276G/G genotype. Multiple comparisons among the 4 combinations of each polymorphism of the TNF-α and adiponectin genes revealed a significant difference in the liver/spleen CT ratio (P<0.05) among the 4 groups, indicating that the gene combinations influence the degree of fat accumulation in the liver. The subjects carrying the TNF-α-857T allele (C/T or T/T genotype) and the adiponectin +276G/G genotype had greater risks for fatty liver and insulin resistance that was evaluated by higher levels of fasting insulin and homeostasis model assessment of insulin resistance, as compared with the other groups. Therefore, Japanese subjects with the TNF-α-857T allele and the adiponectin +276G/G genotype may be more susceptible to insulin resistance and fatty liver. The present study provides the evidence for the interaction between TNF-α and adiponectin genes in the insulin resistance and fatty liver in Japanese subjects with type 2 diabetes. (author)

Effects of a meal rich in 1,3-diacylglycerol on postprandial cardiovascular risk factors and the glucose-dependent insulinotropic polypeptide in subjects with high fasting triacylglycerol concentrations.

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Shoji, Kentaro; Mizuno, Tomohito; Shiiba, Daisuke; Kawagoe, Tadanobu; Mitsui, Yuuki

2012-03-14

It was previously reported that compared to triacylglycerol (TAG) oil, diacylglycerol (DAG) oil improves postprandial lipid response. However, the effects of DAG oil on postprandial hyperglycemia and incretin response have not yet been determined. In this study, the effects of DAG oil on both postprandial hyperlipidemia and hyperglycemia and the response to the glucose-dependent insulinotropic polypeptide (GIP) were studied. This randomized, double-blind, crossover study analyzed data for 41 individuals with high fasting triacylglycerol concentrations. The subjects ingested test meals (30.3 g of protein, 18.6 g of fat, and 50.1 g of carbohydrate) containing 10 g of DAG oil (DAG meal) or TAG oil (TAG meal) after fasting for at least 12 h. Blood samples were collected prior to and 0.5, 2, 3, 4, and 6 h after ingestion of the test meal. Postprandial TAG concentrations were significantly lower after the DAG meal compared with the TAG meal. Postprandial TAG, insulin, and GIP concentrations were significantly lower after the DAG meal compared with the TAG meal in 26 subjects with fasting serum TAG levels between 1.36 and 2.83 mmol/L. DAG-oil-based meals, as a replacement for TAG oil, may provide cardiovascular benefits in high-risk individuals by limiting lipid and insulin excursions.

Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?

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Anthony, Karen; Reed, Laurence J; Dunn, Joel T; Bingham, Emma; Hopkins, David; Marsden, Paul K; Amiel, Stephanie A

2006-11-01

The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.

Effect of gender on lipid-induced insulin resistance in obese subjects

DEFF Research Database (Denmark)

Vistisen, Bodil; Hellgren, Lars; Vadset, T.

2008-01-01

Objective: In obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during...... a hyperinsulinemic-euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates Such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor...... the clamp was similar in females and males (46+/-10 and 60+/-4%,, respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (P...

Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

DEFF Research Database (Denmark)

Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

2002-01-01

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure...... rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion...... = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole...

Regular meal frequency creates more appropriate insulin sensitivity and lipid profiles compared with irregular meal frequency in healthy lean women.

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Farshchi, H R; Taylor, M A; Macdonald, I A

2004-07-01

To investigate the impact of irregular meal frequency on circulating lipids, insulin, glucose and uric acid concentrations which are known cardiovascular risk factors. A randomised crossover dietary intervention study. Nottingham, UK--Healthy free-living women. A total of nine lean healthy women aged 18-42 y recruited via advertisement. A randomised crossover trial with two phases of 14 days each. In Phase 1, subjects consumed their normal diet on either 6 occasions per day (regular) or by following a variable meal frequency (3-9 meals/day, irregular). In Phase 2, subjects followed the alternative meal pattern to that followed in Phase 1, after a 2-week (wash-out) period. Subjects were asked to come to the laboratory after an overnight fast at the start and end of each phase. Blood samples were taken for measurement of circulating glucose, lipids, insulin and uric acid concentrations before and for 3 h after consumption of a high-carbohydrate test meal. Fasting glucose and insulin values were not affected by meal frequency, but peak insulin and AUC of insulin responses to the test meal were higher after the irregular compared to the regular eating patterns (P meal frequency was associated with higher fasting total (P meal frequency appears to produce a degree of insulin resistance and higher fasting lipid profiles, which may indicate a deleterious effect on these cardiovascular risk factors. : The Ministry of Health and Medical Education, IR Iran.

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

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Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

1991-07-01

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

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Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

1996-08-01

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

Assessment of insulin resistance and impaired glucose tolerance in lean women with polycystic ovary syndrome.

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Stovall, Dale William; Bailey, Amelia Purser; Pastore, Lisa M

2011-01-01

To analyze insulin resistance (IR) and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance (IGT) in lean nondiabetic women with polycystic ovary syndrome (PCOS). This was a cross-sectional analysis of treatment-naive women with PCOS who enrolled in a university-based clinical trial. Nondiabetic women with PCOS based on the Eunice Kennedy Shriven National Institute of Child Health and Human Development (NICHD) definition, aged 18-43 years and weighing ≤113 kg, were evaluated. Glucose and insulin levels were assessed at times 0, 30, 60, 90, and 120 minutes after a 75-g glucose load. Lean was defined as body mass index (BMI) women was studied. The prevalence of IR was 0% among lean women vs. 21% among nonlean subjects based on fasting insulin I(0) and 40%-68% based on two different homeostatic model assessment (HOMA) cutoff points (p women with IR had a BMI ≥ 28. Controlling for age and race, BMI explained over 57% of the variation in insulin fasting (I(o)), glucose fasting/Io (G(o)/I(o)), the qualitative insulin sensitivity check index (QUICKI), and HOMA and was a highly significant predictor of these outcomes (p lean PCOS women had IGT based on a 2-hour OGTT, and no lean subjects had IGT based on their fasting blood glucose. Diabetes mellitus, IGT, and IR are far less common in young lean women with PCOS compared with obese women with PCOS. These data imply that it is unnecessary to routinely perform either IR testing or 2-hour OGTT in lean women with PCOS; however, greater subject accumulation is needed to determine if OGTT is necessary in lean women with PCOS. BMI is highly predictive of both insulin and glucose levels in women with PCOS.

Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth.

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Tirabanchasak, Sirapassorn; Siripunthana, Sukumarn; Supornsilchai, Vichit; Wacharasindhu, Suttipong; Sahakitrungruang, Taninee

2015-09-01

Subjects with impaired glucose tolerance (IGT) are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. The predictors of IGT in obese youth are not well described. We studied 115 obese Thai children who underwent an oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were calculated for assessment of β-cell function. Hemoglobin A1c (HbA1c), lipid profile, and clinical parameters were also used to determine predictors of IGT. We found that three patients had T2DM and 30 subjects had IGT. IGT patients had significantly higher fasting glucose (FG), 1-h postload glucose, 2-h postload insulin, and lower whole-body insulin sensitivity indices than in normal glucose tolerance subjects whereas other indices were comparable. By ROC curve analyses, 1-h postload glucose was the best predictor of IGT, but FG or HbA1c represented a poor diagnostic tool for prediabetes screening. Subjects with 1-h OGTT glucose > 155 mg/dL had significantly lower high-density lipoprotein levels, lower insulin sensitivity, and more insulin resistance than those with 1-h postload glucose of ≤ 155 mg/dL. Abnormal glucose tolerance is highly prevalent in obese Thai youth. Several fasting indices and HbA1c fail to predict IGT. An 1-h OGTT glucose of > 155 mg/dL appears to be more associated with adverse insulin dynamics and metabolic profile than 2-h postload glucose.

Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

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Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; Defronzo, Ralph A; Dubé, John J; Musi, Nicolas

2013-06-01

Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IBα protein (an indication of decreased IB kinase-nuclear factor B signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs.

High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation.

LENUS (Irish Health Repository)

O'Malley, G

2010-06-01

A high but normal fasting plasma glucose level in adults is a risk factor for future development of type 2 diabetes mellitus and cardiovascular disease. We investigated whether normal fasting plasma glucose levels (<5.60 mmol\\/l) are associated with decreases in insulin sensitivity and beta cell function, as well as an adverse cardiovascular profile in obese youth.

Circulating complement-C1q TNF-related protein 1 levels are increased in patients with type 2 diabetes and are associated with insulin sensitivity in Chinese subjects.

Directory of Open Access Journals (Sweden)

Xuebo Pan

Full Text Available BACKGROUND: Complement-C1q TNF-related protein 1 (CTRP1, a member of the CTRP superfamily, possesses anti-inflammatory and anti-diabetic effects in mice. However, the clinical relevance of CTRP1 has been seldom explored. The current study aimed to investigate the association of circulating CTRP1 and type 2 diabetes mellitus (T2DM in a Chinese population. DESIGN AND METHODS: Serum CTRP1 and adiponectin levels of 96 T2DM patients and 85 healthy subjects were determined by ELISA, and their associations with adiposity, glucose and lipid profiles were studied. In a subgroup of this study, the 75-g oral glucose tolerance test (OGTT was performed in 20 healthy and 20 T2DM subjects to evaluate the relationship among serum levels of CTRP1 and adiponectin, insulin secretion and insulin sensitivity. RESULTS: Serum CTRP1 levels were significantly increased in patients with T2DM, compared with healthy controls (p<0.001. Similar to adiponectin, serum levels of CTRP1 were significantly correlated to several parameters involved in glucose metabolism and insulin resistance, and independently associated with fasting glucose levels (p<0.05 after BMI and gender adjustments. Furthermore, CTRP1 levels were positively correlated to insulin secretion, while negatively to insulin sensitivity, as measured by OGTT. CONCLUSION: CTRP1 is a novel adipokine associated with T2DM in humans. The paradoxical increase of serum CTRP1 levels in T2DM subjects may be due to a compensatory response to the adverse glucose and lipid metabolism, which warrants further investigation.

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

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Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence12

Science.gov (United States)

2016-01-01

Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects. PMID:27422504

[Normal plasma insulin and HOMA values among Chilean children and adolescents].

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Barja, Salesa; Arnaiz, Pilar; Domínguez, Angélica; Villarroel, Luis; Cassis, Berta; Castillo, Oscar; Salomó, Gianina; Farías, Marcelo; Goycoolea, Manuela; Quiroga, Teresa; Mardones, Francisco

2011-11-01

Plasma insulin and HOMA (homeostasis model assessment) index, used to determine insulin resistance, do not have local standard values for children and adolescents in Chile. To establish the normal reference intervals for insulin and HOMA in children and adolescents aged 10-15 years, according to sex and puberal maturation. A cross-sectional study of 2,153 children and adolescents from Puente Alto County was performed, during 2009 and 2010. Anthropometry and self-report of puberal maturation were assessed. Fasting glucose (hexoquinase) and insulin blood levels (chemiluminiscence), were determined and HOMA index was calculated. Percentile distributions of these variables were calculated. The reference group included only subjects with normal body mass index and fasting blood glucose (n = 1,192). Girls had higher insulin and HOMA values than boys (12.5 ± 6.0 and 9.1 ± 4.9 μϋ/mL (p HOMA mean values than subjects with Tanner III and IV (9.0 ± 4.3 and 12.5 ± 6.2μϋ/ml (p HOMA distributions according to sex and maturation, was selected as the upper cut-off point to identify individuals with insulin resistance. HOMA cutoff point for Tanner I and II boys was 3.2, for Tanner I and II girls was 4.1, for Tanner III and IV boys was 4.2 and for Tanner III and IV girls was 5.0.

Performance of a glucose meter with a built-in automated bolus calculator versus manual bolus calculation in insulin-using subjects.

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Sussman, Allen; Taylor, Elizabeth J; Patel, Mona; Ward, Jeanne; Alva, Shridhara; Lawrence, Andrew; Ng, Ronald

2012-03-01

Patients consider multiple parameters in adjusting prandial insulin doses for optimal glycemic control. Difficulties in calculations can lead to incorrect doses or induce patients to administer fixed doses, rely on empirical estimates, or skip boluses. A multicenter study was conducted with 205 diabetes subjects who were on multiple daily injections of rapid/ short-acting insulin. Using the formula provided, the subjects manually calculated two prandial insulin doses based on one high and one normal glucose test result, respectively. They also determined the two doses using the FreeStyle InsuLinx Blood Glucose Monitoring System, which has a built-in, automated bolus calculator. After dose determinations, the subjects completed opinion surveys. Of the 409 insulin doses manually calculated by the subjects, 256 (63%) were incorrect. Only 23 (6%) of the same 409 dose determinations were incorrect using the meter, and these errors were due to either confirmed or potential deviations from the study instructions by the subjects when determining dose with meter. In the survey, 83% of the subjects expressed more confidence in the meter-calculated doses than the manually calculated doses. Furthermore, 87% of the subjects preferred to use the meter than manual calculation to determine prandial insulin doses. Insulin-using patients made errors in more than half of the manually calculated insulin doses. Use of the automated bolus calculator in the FreeStyle InsuLinx meter minimized errors in dose determination. The patients also expressed confidence and preference for using the meter. This may increase adherence and help optimize the use of mealtime insulin. © 2012 Diabetes Technology Society.

Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.

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Lu, Jianghua; E, Lezi; Wang, Wenfang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Phil; Choi, In Young; Brooks, William M; Burns, Jeffrey M; Aires, Daniel; Swerdlow, Russell H

2011-04-01

Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Effect of starvation on human muscle protein metabolism and its response to insulin

International Nuclear Information System (INIS)

Fryburg, D.A.; Barrett, E.J.; Louard, R.J.; Gelfand, R.A.

1990-01-01

To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using [3H]phenylalanine (Phe) and [14C]leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans (1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and (2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action

Effect of starvation on human muscle protein metabolism and its response to insulin

Energy Technology Data Exchange (ETDEWEB)

Fryburg, D.A.; Barrett, E.J.; Louard, R.J.; Gelfand, R.A. (Yale Univ. School of Medicine, New Haven, CT (USA))

1990-10-01

To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using (3H)phenylalanine (Phe) and (14C)leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans (1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and (2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action.

Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

Directory of Open Access Journals (Sweden)

Maria Adelaide Marini

Full Text Available Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl at 1 h during an oral glucose tolerance test (OGTT can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high. The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low. To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001 and insulin clearance (P = 0.006 after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02 in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects.

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Hagen, Imke; Schulte, Dominik M; Müller, Nike; Martinsen, Jessica; Türk, Kathrin; Hedderich, Jürgen; Schreiber, Stefan; Laudes, Matthias

2015-06-01

Obesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD). 22 severe obese subjects (Median Body Mass Index (BMI): 44.5kg/m(2)) were included in a dietary intervention study of 6month, consisting of a very low calorie formula diet phase (VLCD: 800kcal/d) for 12 weeks and a following 12 week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR). Mean body weight reduction by VLCD accounted to 21.7kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (rS=-0.642, p=0.001) and HOMA (rS=-0.419, p=0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p=0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p=0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (rS=-0.650, p=0.022) during intervention. Anti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence.

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Harvie, Michelle N; Howell, Tony

2016-07-01

Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects. © 2016 American Society for Nutrition.

Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women.

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Moazzami, Ali A; Shrestha, Aahana; Morrison, David A; Poutanen, Kaisa; Mykkänen, Hannu

2014-06-01

Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P insulin. Women with higher fasting concentrations of leucine and isoleucine and lower fasting concentrations of sphingomyelins and phosphatidylcholines had higher insulin responses despite similar glucose concentration after all kinds of bread (cross-validated ANOVA, P = 0.048). High blood concentration of branched-chain amino acids, i.e., leucine and isoleucine, has been associated with the increased risk of diabetes, which suggests that additional consideration should be given to bread proteins in understanding the beneficial health effects of different kinds of breads. The present study suggests that the fasting metabolic profile can be used to characterize the postprandial insulin demand in individuals with normal glucose metabolism that can be used for establishing strategies for the stratification of individuals in personalized nutrition. © 2014 American Society for Nutrition.

Fasting Lipoprotein Lipase Protein Levels Can Predict a Postmeal Increment of Triglyceride Levels in Fasting Normohypertriglyceridemic Subjects.

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Tsuzaki, Kokoro; Kotani, Kazuhiko; Yamada, Kazunori; Sakane, Naoki

2016-09-01

Although a postprandial increment in triglyceride (TG) levels is considered to be a risk factor for atherogenesis, tests (e.g., fat load) to assess postprandial changes in TG levels cannot be easily applied to clinical practice. Therefore, fasting markers that predict postprandial TG states are needed to be developed. One current candidate is lipoprotein lipase (LPL) protein, a molecule that hydrides TGs. This study investigated whether fasting LPL levels could predict postprandial TG levels. A total of 17 subjects (11 men, 6 women, mean age 52 ± 11 years) with normotriglyceridemia during fasting underwent the meal test. Several fasting parameters, including LPL, were measured for the area under the curve of postprandial TGs (AUC-TG). The subjects' mean fasting TG level was 1.30 mmol/l, and their mean LPL level was 41.6 ng/ml. The subjects' TG levels increased after loading (they peaked after two postprandial hours). Stepwise multiple regression analysis demonstrated that fasting TG levels were a predictor of the AUC-TG. In addition, fasting LPL mass levels were found to be a predictor of the AUC-TG (β = 0.65, P fasting TG levels. Fasting LPL levels may be useful to predict postprandial TG increment in this population. © 2015 Wiley Periodicals, Inc.

Korean Red Ginseng Improves Glucose Control in Subjects with Impaired Fasting Glucose, Impaired Glucose Tolerance, or Newly Diagnosed Type 2 Diabetes Mellitus

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Bang, Hyangju; Kwak, Jung Hyun; Ahn, Hyeon Yeong; Shin, Dong Yeob; Lee, Jong Ho

2014-01-01

This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5 g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2...

Insulin analogs with improved pharmacokinetic profiles.

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Brange; Vølund

1999-02-01

The aim of insulin replacement therapy is to normalize blood glucose in order to reduce the complications of diabetes. The pharmacokinetics of the traditional insulin preparations, however, do not match the profiles of physiological insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties. Fast-acting analogs are based on the idea that an insulin with less tendency to self-association than human insulin would be more readily absorbed into the systemic circulation. Protracted-acting analogs have been created to mimic the slow, steady rate of insulin secretion in the fasting state. The present paper provides a historical review of the efforts to change the physicochemical and pharmacological properties of insulin in order to improve insulin therapy. The available clinical studies of the new insulins are surveyed and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs.

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

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Zhu, Qibo; Zhou, Huang; Zhang, Aipin; Gao, Rufei; Yang, Shumin; Zhao, Changhong; Wang, Yue; Hu, Jinbo; Goswami, Richa; Gong, Lilin; Li, Qifu

2016-01-01

Lipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS. In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level. The study was performed in a clinical research center. Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, plean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP. Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

DEFF Research Database (Denmark)

Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga

2010-01-01

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up...... to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA......2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell...

A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals

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Dorian S Houser

2013-11-01

Full Text Available Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris, which fasts from food and water for periods of up to three months. During this time, ~90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM. All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures

A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

Science.gov (United States)

Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

2013-11-01

Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.

Acanthosis nigricans: a flag for insulin resistance

African Journals Online (AJOL)

2013-11-04

Nov 4, 2013 ... Outcome measures: OGTT, fasting serum insulin and HOMA IR were the outcome measures studied. Results: This cross-sectional study revealed that 94 subjects with acanthosis nigricans (31.34%) had IR. Grades III and IV, and textures II and III, were more predictive of IR. Acanthosis nigricans grading was ...

Clinical study on insulin receptors of mononuclear cells in diabetes

Energy Technology Data Exchange (ETDEWEB)

Dalimunthe, D [Hiroshima Univ. (Japan). School of Medicine

1980-12-01

/sup 125/I-insulin binding activity to mononuclear cells was studied in 75 noninsulin-dependent diabetic subjects and 31 normal subjects and the following results were obtained. 1. /sup 125/I-insulin binding is directly proportional to the mononuclear cell concentrations. There is a linear increase of specific /sup 125/I-insulin binding. 2. The binding of /sup 125/I-insulin to mononuclear cells is displaced by the increasing concentration of native insulin. 3. The /sup 125/I-insulin degradation in the incubation medium after incubation of mononuclear cells for 24 hours at 4/sup 0/C was almost 5% in this study. 4. The insulin binding activity in diabetic subjects was lower than that in normal subjects (P < 0.001) without any significant difference in affinity constant. 5. The relationship of binding activity to age of diabetics (r = 0.06, N.S), relative body weitht (r = 0.06, N.S) and duration of diabetes from onset was not significant. 6. In untreated noninsulin-dependent diabetics the insulin binding activity was inversely correlated to fasting blood glucose level (r = 0.78, P < 0.001) and slightly inversely correlated to serum insulin level (r = 0.47, P < 0.01). A slight inverse correlation was also observed in serum triglyceride level (r = 0.53, P < 0.01) and in total cholesterol level (r = 0.29, P < 0.05). 7. No significant difference between the binding activity was observed by grade of diabetic retinopathy. 8. After treatment with diet and/or sulfonylurea, the diabetics exhibited a significant increase in insulin binding activity (P < 0.005) but no significant difference in plasma insulin level, body weight and plasma lipid levels was observed.

Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity.

Science.gov (United States)

Knop, Filip K; Aaboe, K; Vilsbøll, T; Vølund, A; Holst, J J; Krarup, T; Madsbad, S

2012-06-01

People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β-cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses. Four hour 50-g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35-41) kg/m(2)]; (ii) Eight obese subjects with NGT [BMI: 33 (35-38) kg/m(2)]; (iii) Eight lean patients with T2DM [BMI: 24 (22-25) kg/m(2)]; and (iv) Eight lean healthy subjects [BMI: 23 (20-25) kg/m(2)]. The incretin effect was significantly (p obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects. Our findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin-resistant state have NGT. © 2011 Blackwell Publishing Ltd.

A study on the altered glycemic and lipid parameters and prevalence of insulin resistance in nonalcoholic fatty liver disease

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Sangeetha Suresh

2018-01-01

Full Text Available Introduction: Nonalcoholic fatty liver disease (NAFLD is a hepatic disorder that develops in the absence of alcohol intake. Obesity and diabetes are considered risk factors for the development of fatty liver; however, whether fatty liver is the cause or consequence of these conditions is not yet clear. Insulin resistance (IR is found to be a common risk factor for the development of diabetes, obesity and fatty liver. Aims and Objectives: The aim and objective of this study is to determine the prevalence of undetected diabetes, dyslipidemia, and IR in subjects with NAFLD. Materials and Methods: In apparently healthy 100 subjects, with ultrasound diagnosis of fatty liver, fasting and postprandial blood sugar levels, fasting insulin levels, and fasting lipid profile were checked. IR value was estimated using homeostatic model assessment-IR formula. Appropriate statistical methods were adopted to analyze the data. Results: A total of 66 subjects out of the 100 had IR. It was noted that IR significantly correlated with raised fasting blood sugar and fasting plasma insulin values. There was no significant correlation between IR and lipid profile values. Conclusion: The chance of developing NAFLD was high if the subjects are having IR, or vice versa. There was an increased prevalence of prediabetes and diabetes in the subjects with NAFLD. Waist circumference, rather than body mass index, was found to be a strong predictor of central adiposity and IR.

D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

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Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V.

1990-01-01

We used D-[U-11C]glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-[U-11C]-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia [arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects]. Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects

Fasting and Systemic Insulin Signaling Regulate Phosphorylation of Brain Proteins That Modulate Cell Morphology and Link to Neurological Disorders*

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Li, Min; Quan, Chao; Toth, Rachel; Campbell, David G.; MacKintosh, Carol; Wang, Hong Yu; Chen, Shuai

2015-01-01

Diabetes is strongly associated with cognitive decline, but the molecular reasons are unknown. We found that fasting and peripheral insulin promote phosphorylation and dephosphorylation, respectively, of specific residues on brain proteins including cytoskeletal regulators such as slit-robo GTPase-activating protein 3 (srGAP3) and microtubule affinity-regulating protein kinases (MARKs), in which deficiency or dysregulation is linked to neurological disorders. Fasting activates protein kinase A (PKA) but not PKB/Akt signaling in the brain, and PKA can phosphorylate the purified srGAP3. The phosphorylation of srGAP3 and MARKs were increased when PKA signaling was activated in primary neurons. Knockdown of PKA decreased the phosphorylation of srGAP3. Furthermore, WAVE1, a protein kinase A-anchoring protein, formed a complex with srGAP3 and PKA in the brain of fasted mice to facilitate the phosphorylation of srGAP3 by PKA. Although brain cells have insulin receptors, our findings are inconsistent with the down-regulation of phosphorylation of target proteins being mediated by insulin signaling within the brain. Rather, our findings infer that systemic insulin, through a yet unknown mechanism, inhibits PKA or protein kinase(s) with similar specificity and/or activates an unknown phosphatase in the brain. Ser858 of srGAP3 was identified as a key regulatory residue in which phosphorylation by PKA enhanced the GAP activity of srGAP3 toward its substrate, Rac1, in cells, thereby inhibiting the action of this GTPase in cytoskeletal regulation. Our findings reveal novel mechanisms linking peripheral insulin sensitivity with cytoskeletal remodeling in neurons, which may help to explain the association of diabetes with neurological disorders such as Alzheimer disease. PMID:26499801

Observations on the insulin-secretion function in the offsprings of patients with type II diabetes

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Xu Shujie; Tian Xiaoping; Wu Yan

2004-01-01

Objective: To investigate the disturbance of insulin-secretion function in the offsprings of patients with type II diabetes. Methods: Blood sugar (with oxidase method) and insulin (with RIA) levels were measured after overnight fasting and repeatedly measured 2h after 75g glucose per oral in the following subjects: 1) Group A, 23 non-obese offsprings of type II diabetics 2) group B, 18 obese offsprings (BMI ≥25kg/m 2 ) and 3) 27 controls. Homeostatic model assessment-insulin resistance (HOMA-IR) and β-cell function index (HCI) were calculated from the data (glucose and insulin levels) obtained. Results: For Group A subjects, the fasting blood sugar (FPG) levels were significantly higher and HBCI significantly lower than those in te controls (both P<0.05). For Group B obese subjects, in addition to the above two parameters (with HBCI P<0.01), 2h PG levels as well as HOMA-IR were also significantly higher (both P<0.05). Conclusion: Present study showed that in the offsprings of diabetics, HBCI was already lowered before definite impaired glucose tolerance (IGT) could be demonstrated, especially in the obese ones. (authors)

Observations on the insulin-secretion function in the offsprings of patients with type II diabetes

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Shujie, Xu; Xiaoping, Tian; Yan, Wu [The First People' s Hospital of Lianyungang (China)

2004-10-01

Objective: To investigate the disturbance of insulin-secretion function in the offsprings of patients with type II diabetes. Methods: Blood sugar (with oxidase method) and insulin (with RIA) levels were measured after overnight fasting and repeatedly measured 2h after 75g glucose per oral in the following subjects: 1) Group A, 23 non-obese offsprings of type II diabetics 2) group B, 18 obese offsprings (BMI {>=}25kg/m{sup 2} ) and 3) 27 controls. Homeostatic model assessment-insulin resistance (HOMA-IR) and {beta}-cell function index (HCI) were calculated from the data (glucose and insulin levels) obtained. Results: For Group A subjects, the fasting blood sugar (FPG) levels were significantly higher and HBCI significantly lower than those in te controls (both P<0.05). For Group B obese subjects, in addition to the above two parameters (with HBCI P<0.01), 2h PG levels as well as HOMA-IR were also significantly higher (both P<0.05). Conclusion: Present study showed that in the offsprings of diabetics, HBCI was already lowered before definite impaired glucose tolerance (IGT) could be demonstrated, especially in the obese ones. (authors)

The Effect of Metformin and Standard Therapy Versus Standard Therapy Alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial

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2009-01-01

histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA - IR scores, serum...BMI through diet and exercise significantly improved HOMA - IR scores, serum aminotransferases and liver histology. 15. SUBJECT TERMS 16. SECURITY...insulin resistance (or HOMA - IR ) score was calculated using the formula: fasting insulin (mIU/ml) fasting glu- cose (mg/dl)/405 [Matthews et al. 1985

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.

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.

Different Criteria for the Definition of Insulin Resistance and Its Relation with Dyslipidemia in Overweight and Obese Children and Adolescents

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de Mello, Elza Daniel

2018-01-01

Purpose to compare cut off points corrected for age and gender (COOP) with fixed cut off points (FCOP) for fasting plasma insulin and Homeostatic model assessment-insulin resistance (HOMA-IR) for the diagnosis of IR in obese children and adolescents and their correlation with dyslipidemia. Methods A multicenter, cross-sectional study including 383 subjects aged 7 to 18 years, evaluating fasting blood glucose, plasma insulin, and lipid profile. Subjects with high insulin levels and/or HOMA-IR were considered as having IR, based on two defining criteria: FCOP or CCOP. The frequency of metabolic abnormalities, the presence of IR, and the presence of dyslipidemia in relation to FCOP or CCOP were analyzed using Fisher and Mann-Whitney exact tests. Results Using HOMA-IR, IR was diagnosed in 155 (40.5%) and 215 (56.1%) patients and, using fasting insulin, 150 (39.2%) and 221 (57.7%), respectively applying FCOP and CCOP. The use of CCOP resulted in lower insulin and HOMA-IR values than FCOP. Dyslipidemia was not related to FCOP or CCOP. Blood glucose remained within normal limits in all patients with IR. There was no difference in the frequency of IR identified by plasma insulin or HOMA-IR, both for FCOP and CCOP. Conclusion The CCOP of plasma insulin or of HOMA-IR detected more cases of IR as compared to the FCOP, but were not associated with the frequency of dyslipidemia. As blood glucose has almost no fluctuation in this age group, even in the presence of IR, fasting plasma insulin detected the same cases of IR that would be detected by HOMA-IR. PMID:29383306

Association of insulin resistance with obesity in children

International Nuclear Information System (INIS)

Siddiqui, S.A.; Bashir, S.; Shabbir, I.; Sherwani, M.K.; Aasim, M.

2011-01-01

Background: Insulin resistance is the primary metabolic disorder associated with obesity. Little is known about its role as a determinant of the metabolic syndrome in obese children. Objectives: To assess the association of insulin resistance with metabolic syndrome in obese and non obese children. Study type and settings: Cross sectional analytical study conducted among children of ten Municipal Corporation high schools of Data Ganj Buksh Town Lahore. Subjects and Methods: A total of 46 obese and 49 non obese children with consent were recruited for the study. Fasting blood glucose, serum insulin, high density lipoprotein in cholesterol, triglycerides, cholesterol, non HDL-cholesterol LDL-cholesterol were measured using standard methods. Data were analyzed by using statistical software SPSS-Version 15. Results: A total of 95 children 49 obese and 46 non obese were recruited for the study. A significant association of serum triglyceride(p<0.001), high density lipoprotein cholesterol(p<0.001), fasting blood glucose(p<0.001), and insulin levels (p<0.001) , was seen between the two groups. For each component of metabolic syndrome, when insulin resistance increased so did odds ratios for cardio metabolic risk factors. Conclusions: Insulin resistance was seen in 34.7% children. Metabolic syndrome was found in 31.6% children reflecting that obese children are at high risk for metabolic syndrome and have low HDL-cholesterol and high triglycerides levels. (author)

Effects of Roux-en-Y gastric bypass on fasting and postprandial inflammation-related parameters in obese subjects with normal glucose tolerance and in obese subjects with type 2 diabetes

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Bovbjerg, Kirsten Katrine Lindegaard; Jorgensen, Nils Bruun; Just, Rasmus

2015-01-01

after surgery. Interleukin (IL)-6, leptin, adiponectin, IL-8, transforming growth factor beta (TGF-beta), and the incretin hormone glucagon-like peptide-1 (GLP-1) were measured in the fasting state and during a liquid meal. Insulin resistance was evaluated by HOMA-IR. Results: Weight loss did not differ...... between the two groups. Before surgery, HbA1c was higher and HOMA-IR lower in T2D patients, however, converged to the values of NGT subjects one year after surgery. Circulating cytokine concentrations did not differ between the two groups at any time point. One week after surgery, circulating IL-6 and IL...

Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects

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Soronen Jarkko

2012-04-01

Full Text Available Abstract Background To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. Methods Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 hours of intravenously maintained euglycemic hyperinsulinemia from 9 insulin-resistant and 11 insulin-sensitive females. Gene expression was measured using Affymetrix HG U133 Plus 2 microarrays and qRT-PCR. Microarray data and pathway analyses were performed with Chipster v1.4.2 and by using in-house developed nonparametric pathway analysis software. Results The most prominent difference in gene expression of the insulin-resistant group during hyperinsulinemia was reduced transcription of nuclear genes involved in mitochondrial respiration (mitochondrial respiratory chain, GO:0001934. Inflammatory pathways with complement components (inflammatory response, GO:0006954 and cytokines (chemotaxis, GO:0042330 were strongly up-regulated in insulin-resistant as compared to insulin-sensitive subjects both before and during hyperinsulinemia. Furthermore, differences were observed in genes contributing to fatty acid, cholesterol and triglyceride metabolism (FATP2, ELOVL6, PNPLA3, SREBF1 and in genes involved in regulating lipolysis (ANGPTL4 between the insulin-resistant and -sensitive subjects especially during hyperinsulinemia. Conclusions The major finding of this study was lower expression of mitochondrial respiratory pathway and defective induction of lipid metabolism pathways by insulin in insulin-resistant subjects. Moreover, the study reveals several novel genes whose aberrant regulation is associated with the obese insulin-resistant phenotype.

A clinical study on insulin receptors of mononuclear cells in diabetes

International Nuclear Information System (INIS)

Dalimunthe, D.

1980-01-01

125 I-insulin binding activity to mononuclear cells was studied in 75 noninsulin-dependent diabetic subjects and 31 normal subjects and the following results were obtained. 1. 125 I-insulin binding is directly proportional to the mononuclear cell concentrations. There is a linear increase of specific 125 I-insulin binding. 2. The binding of 125 I-insulin to mononuclear cells is displaced by the increasing concentration of native insulin. 3. The 125 I-insulin degradation in the incubation medium after incubation of mononuclear cells for 24 hours at 4 0 C was almost 5% in this study. 4. The insulin binding activity in diabetic subjects was lower than that in normal subjects (P < 0.001) without any significant difference in affinity constant. 5. The relationship of binding activity to age of diabetics (r = 0.06, N.S), relative body weitht (r = 0.06, N.S) and duration of diabetes from onset was not significant. 6. In untreated noninsulin-dependent diabetics the insulin binding activity was inversely correlated to fasting blood glucose level (r = 0.78, P < 0.001) and slightly inversely correlated to serum insulin level (r = 0.47, P < 0.01). A slight inverse correlation was also observed in serum triglyceride level (r = 0.53, P < 0.01) and in total cholesterol level (r = 0.29, P < 0.05). 7. No significant difference between the binding activity was observed by grade of diabetic retinopathy. 8. After treatment with diet and/or sulfonylurea, the diabetics exhibited a significant increase in insulin binding activity (P < 0.005) but no significant difference in plasma insulin level, body weight and plasma lipid levels was observed. (author)

Fasting gall bladder volume and lithogenicity in relation to glucose tolerance, total and intra-abdominal fat masses in obese non-diabetic subjects

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Hendel, H W; Højgaard, L; Andersen, T

1998-01-01

OBJECTIVE: To investigate whether total body fat mass or fat distribution and associated metabolic disturbances in glucose and lipid metabolism influence the well known gallstone pathogenetic factors in obese subjects in order to explain why some obese subjects develop gallstones and some do not...... with a specific radioimmunoassay. Insulin sensitivity was measured by the Minimal Model and glucose tolerance by an oral glucose tolerance test (OGTT). Serum lipid concentrations were measured by standard methods. RESULTS: The gallbladder volume in the fasting state increased with increasing intra-abdominal fat...... mass (P=0.006) and was increased in subjects with impaired glucose tolerance (41 vs 27 ml, P=0.001). The lithogenic index was > 1 in all subjects and correlated with total fat mass (P=0.04). CONCLUSION: Gallstone pathogenesis in obesity seems to be influenced by the total body fat mass and its regional...

The Association of Fasting Glucose, Insulin, and C-Peptide, with 19-Year Incidence of Coronary Heart Disease in Older Japanese-American Men; the Honolulu Heart Program

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Nazneem Wahab

2018-04-01

Full Text Available The role of fasting glucose, insulin levels, and C-peptide in coronary heart disease (CHD in non-diabetic individuals remains uncertain. We examined the association between fasting glucose, insulin and C-peptide with the long-term incidence of CHD in Japanese-American men. In 1980–1982, from a random sample of the Honolulu Heart Program men (n = 1378, aged 61–81 years, data on several CHD and metabolic risk factors were obtained to examine the relation of fasting glucose, insulin and C-peptide to 19-year CHD incidence. Age-adjusted incidence of CHD increased with increasing quintiles of glucose, insulin and C-peptide. Age-adjusted CHD rates in the glucose quintiles were 11.9, 11.6, 14.4, 18.1 and 24.1 per 1000 person-years (trend p < 0.001. In individual Cox models (lowest quintiles of glucose, insulin and C-peptide as reference the relative risks (95% confidence interval of CHD incidence for the glucose quintiles adjusting for age, smoking, hypertension, cholesterol, physical activity, and body mass index, were 0.9 (0.6–1.4, 1.2 (0.8–1.8, 1.4 (0.9–2.2, and 1.7 (1.1–2.6, respectively (trend p = 0.004. Insulin and C-peptide were not significantly associated with CHD on multivariate analysis. Fasting glucose remained the only significant predictor of increased CHD risk (p = 0.003 in a model combining all 3 metabolic variables. In this cohort, only fasting glucose independently predicts long-term incidence of CHD. Age-adjusted insulin and C-peptide levels were associated with CHD incidence, but after adjustment for other risk factors, do not independently predict CHD.

Metabolic and Inflammatory Changes with Orlistat and Sibutramine Treatment in Obese Malaysian Subjects.

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Al-Tahami, Belqes Abdullah Mohammad; Al-Safi Ismail, Ab Aziz; Sanip, Zulkefli; Yusoff, Zurkurnai; Shihabudin, Tg Muzaffar Tm; Singh, Taran Singh Pall; Rasool, Aida Hanum Ghulam

2017-01-01

Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker. Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment. Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention. Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.

Fasting and Systemic Insulin Signaling Regulate Phosphorylation of Brain Proteins That Modulate Cell Morphology and Link to Neurological Disorders.

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Li, Min; Quan, Chao; Toth, Rachel; Campbell, David G; MacKintosh, Carol; Wang, Hong Yu; Chen, Shuai

2015-12-11

Diabetes is strongly associated with cognitive decline, but the molecular reasons are unknown. We found that fasting and peripheral insulin promote phosphorylation and dephosphorylation, respectively, of specific residues on brain proteins including cytoskeletal regulators such as slit-robo GTPase-activating protein 3 (srGAP3) and microtubule affinity-regulating protein kinases (MARKs), in which deficiency or dysregulation is linked to neurological disorders. Fasting activates protein kinase A (PKA) but not PKB/Akt signaling in the brain, and PKA can phosphorylate the purified srGAP3. The phosphorylation of srGAP3 and MARKs were increased when PKA signaling was activated in primary neurons. Knockdown of PKA decreased the phosphorylation of srGAP3. Furthermore, WAVE1, a protein kinase A-anchoring protein, formed a complex with srGAP3 and PKA in the brain of fasted mice to facilitate the phosphorylation of srGAP3 by PKA. Although brain cells have insulin receptors, our findings are inconsistent with the down-regulation of phosphorylation of target proteins being mediated by insulin signaling within the brain. Rather, our findings infer that systemic insulin, through a yet unknown mechanism, inhibits PKA or protein kinase(s) with similar specificity and/or activates an unknown phosphatase in the brain. Ser(858) of srGAP3 was identified as a key regulatory residue in which phosphorylation by PKA enhanced the GAP activity of srGAP3 toward its substrate, Rac1, in cells, thereby inhibiting the action of this GTPase in cytoskeletal regulation. Our findings reveal novel mechanisms linking peripheral insulin sensitivity with cytoskeletal remodeling in neurons, which may help to explain the association of diabetes with neurological disorders such as Alzheimer disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets.

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Park, Sunmin; Yoo, Kyung Min; Hyun, Joo Suk; Kang, Suna

2017-02-01

Intermittent fasting (IMF) is a relatively new dietary approach to weight management, although the efficacy and adverse effects have not been full elucidated and the optimal diets for IMF are unknown. We tested the hypothesis that a one-meal-per-day intermittent fasting with high fat (HF) or protein (HP) diets can modify energy, lipid, and glucose metabolism in normal young male Sprague-Dawley rats with diet-induced obesity or overweight. Male rats aged 5 weeks received either HF (40% fat) or HP (26% protein) diets ad libitum (AL) or for 3 h at the beginning of the dark cycle (IMF) for 5 weeks. Epidydimal fat pads and fat deposits in the leg and abdomen were lower with HP and IMF. Energy expenditure at the beginning of the dark cycle, especially from fat oxidation, was higher with IMF than AL, possibly due to greater activity levels. Brown fat content was higher with IMF. Serum ghrelin levels were higher in HP-IMF than other groups, and accordingly, cumulative food intake was also higher in HP-IMF than HF-IMF. HF-IMF exhibited higher area under the curve (AUC) of serum glucose at the first part (0-40 min) during oral glucose tolerance test, whereas AUC of serum insulin levels in both parts were higher in IMF and HF. During intraperitoneal insulin tolerance test, serum glucose levels were higher with IMF than AL. Consistently, hepatic insulin signaling (GLUT2, pAkt) was attenuated and PEPCK expression was higher with IMF and HF than other groups, and HOMA-IR revealed significantly impaired attenuated insulin sensitivity in the IMF groups. However, surprisingly, hepatic and skeletal muscle glycogen storage was higher in IMF groups than AL. The higher glycogen storage in the IMF groups was associated with the lower expression of glycogen phosphorylase than the AL groups. In conclusion, IMF especially with HF increased insulin resistance, possibly by attenuating hepatic insulin signaling, and lowered glycogen phosphorylase expression despite decreased fat mass in young

Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity

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Li Chun-jun

2012-11-01

Full Text Available Abstract Objective To assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose. Methods A 12-week, randomized, parallel-group study was carried out. A total of 84 patients completed the trial who had been randomly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment. Insulin dose was reduced by 0-30% upon the initiation of liraglutide. Insulin doses were subsequently adjusted to optimized glycemic control. Glycosylated hemoglobin (HbA1c values, blood glucose, total daily insulin dose, body weight, waist circumference, and the number of hypoglycemic events and adverse events were evaluated. Results At the end of study, the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different (1.9% vs. 1.77%, p>0.05. However, the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0% with no weight gain and no hypoglycemia, was significantly higher in the liraglutide-added group than in the insulin-increasing group (67% vs. 19%, p2, p Conclusions Addition of liraglutide to abdominally obese, insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage, but with a lower daily dose of insulin and fewer hypoglycemic events. Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference. Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity.

Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [3-3H]glucose studies in healthy subjects

International Nuclear Information System (INIS)

Schmitz, O.; Arnfred, J.; Hother Nielsen, O.; Beck-Nielsen, H.; Oerskov, H.

1986-01-01

To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45mU/kg · min or in identical amounts in pulses of 1 1 / 2 to 2 1 / 4 min followed by intervals of 10 1 / 2 to 9 3 / 4 min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270-294 min: 8.7±0.7 vs 6.8±0.9 ml/kg · min, P 3 H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion. (author)

Blood pressure, serum lipids, fasting insulin, and adrenal hormones in 12-year-old children born with maternal preeclampsia.

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Tenhola, Sirpa; Rahiala, Eero; Martikainen, Anneli; Halonen, Pirjo; Voutilainen, Raimo

2003-03-01

Women with prior preeclamptic pregnancies have an increased risk for metabolic syndrome and cardiovascular diseases. Maternal preeclampsia has been associated with elevated blood pressure (BP) in offspring during childhood. The aim of our study was to determine whether elevated BP pressure and metabolic changes, such as dyslipidemia, insulin resistance, and increased adrenal hormonal activity, are found in 12-yr-old children of preeclamptic mothers. Sixty children born after preeclamptic pregnancy (PRE) and 60 matched control subjects born after normotensive pregnancy (non-PRE) were studied at the age of 12 yr. The case-control pairs were matched for sex, gestational age (+/-1 wk), and size at birth. We measured BP and concentrations of blood glucose, serum fasting insulin, total and high density lipoprotein cholesterol, triglycerides, cortisol, dehydroepiandrosterone sulfate, and plasma epinephrine (E) and norepinephrine (NE). Low density lipoprotein cholesterol was calculated according to the Friedewald-Fredrickson formula. The PRE children had significantly higher mean systolic (116.4 vs. 113.2 mm Hg; P = 0.021) and diastolic (73.9 vs. 70.3 mm Hg; P = 0.022) BP than the non-PRE children, even when adjusted by current weight and height. At 12 yr of age, systolic BP values correlated inversely with birth weight (r = -0.459; P < 0.001) and length SD scores (r = -0.429; P = 0.001) in the PRE children. The mean concentrations of serum total, low density lipoprotein, and high density lipoprotein cholesterol; triglycerides; fasting insulin; blood glucose; serum cortisol; and dehydroepiandrosterone sulfate did not differ between the PRE and non-PRE groups. However, the mean plasma E concentration was higher in the PRE than in the non-PRE children (0.32 vs. 0.28 nmol/liter; P = 0.042), whereas the mean NE concentration did not differ between these two groups. In conclusion, 12-yr-old children born with maternal preeclampsia had elevated systolic and diastolic BPs and

Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

DEFF Research Database (Denmark)

Juul, A; Scheike, Thomas Harder; Pedersen, A T

1997-01-01

Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH......-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

Variability of HOMA and QUICKI insulin sensitivity indices.

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Žarković, Miloš; Ćirić, Jasmina; Beleslin, Biljana; Stojković, Mirjana; Savić, Slavica; Stojanović, Miloš; Lalić, Tijana

2017-07-01

Assessment of insulin sensitivity based on a single measurement of insulin and glucose, is both easy to understand and simple to perform. The tests most often used are HOMA and QUICKI. The aim of this study was to assess the biological variability of estimates of insulin sensitivity using HOMA and QUICKI indices. After a 12-h fast, blood was sampled for insulin and glucose determination. Sampling lasted for 90 min with an intersample interval of 2 min. A total of 56 subjects were included in the study, and in nine subjects sampling was done before and after weight reduction, so total number of analyzed series was 65. To compute the reference value of the insulin sensitivity index, averages of all 46 insulin and glucose samples were used. We also computed point estimates (single value estimates) of the insulin sensitivity index based on the different number of insulin/glucose samples (1-45 consecutive samples). To compute the variability of point estimates a bootstrapping procedure was used using 1000 resamples for each series and for each number of samples used to average insulin and glucose. Using a single insulin/glucose sample HOMA variability was 26.18 ± 4.31%, and QUICKI variability was 3.30 ± 0.54%. For 10 samples variability was 11.99 ± 2.22% and 1.62 ± 0.31% respectively. Biological variability of insulin sensitivity indices is significant, and it can be reduced by increasing the number of samples. Oscillations of insulin concentration in plasma are the major cause of variability of insulin sensitivity indices.

Skin Tags and Acanthosis Nigricans in Patients with Hepatitis C Infection in Relation to Insulin Resistance and Insulin Like Growth Factor-1 Levels

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El Safoury, Omar Soliman; Shaker, Olfat G; Fawzy, May Mohsen

2012-01-01

Background: Skin tags (ST) are papillomas commonly found in the neck, axillae of middle-aged and elderly people Aim: Insulin and insulin-like growth factor (IGF-1) levels are affected by hepatitis C virus (HCV) infection and both of them may be implicated in the etiopathogenesis of ST and acanthosis nigricans (AN) through their proliferative and differentiating properties. So, the aim of this work was to evaluate the impact of HCV infection on ST and AN through the estimation of insulin resistance and IGF-1. Materials and Methods: Participants were arranged into four groups: (ST +ve / HCV +ve) 23 subjects, (ST+ / HCV -ve) 19 subjects, (HCV -ve / ST-ve) 20 subjects and (ST-ve /HCV +ve) 22 subjects. Age, ST size, color, number, AN, fasting glucose, fasting insulin, insulin resistance, IGF-1, HCV-antibodies (Ab) were recorded. Results: The mean number of ST in Group 1 was half the number of ST in Group 2 (11.0±9.3 / 22.3±14.0) (P=0.005). The difference in insulin resistance between the same groups was non-significant (13.1±10.6 / 9.0±5.5) (P=0.441) while the difference in IGF-1 was statistically significant (218.6±46.2 /285.4±32.8) (P=0.002). The multivariate logistic regression for the variables revealed that insulin resistance is the only factor affecting the occurrence of ST (OR=1.096, P=0.023). Multivariate regression analysis for the variables showed that HCV was borderline but not a significant factor affecting the number of ST (Beta=-0.409, P=0.053). The number of patients with AN was doubled in Group 2 in comparison to Group 1 but this was non significant 3(13%) / 6(32%) (P=0.2800). Conclusion: HCV is associated with a significant decrease in the ST number and in the serum level of IGF-1 together with an obvious decrease in the occurrence of AN. Our results may point to the entrant effect of insulin resistance and IGF-1 in ST and AN development. The current study suggests the evaluation of IGF-1-lowering agents in the control of ST and AN especially in

The Relationship among Smoking, Plasma Adiponectin, Leptin, Inflammatory Markers and Insulin Resistance

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.Et

2012-01-01

We aimed to study how smoking influences the relationship between fat mass ,soluble tumor necrosis factor-α, (TNF?) receptors 1 and 2 (sTNFR1 and sTNFR2),highly sensitive C-reactive protein(hs-CRP), adiponectin, leptin and insulin resistance.A total of 60 healthy men (age: 27-53 years, body mass index (BMI): 20-35 kg/m 2 ), 30 of whom were never-smokers and 30 smokers, matched for age, BMI and waist-to-hip ratio were included in this study. Those were subdivided into insulin resistant (IR) and insulin sensitive (IS) subgroups. Measures included circulating soluble fractions of the tumor necrosis factor α (TNF α) receptors (sTNFR1 and sTNFR2) and their relationship to fat mass, fasting plasma adiponectin, leptin, hs- CRP and insulin sensitivity index.Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass, insulin and leptin, smokers showed significantly increased circulating sTNFR2 levels (3.7±0.8 vs. 2.9 ±0.8 ng/ml, π=0.03). Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (π = 0.046 and 0.001, respectively). No difference was detected in average hs- CRP concentrations between smokers and nonsmokers (π = 0.18) and between IR and IS subjects (π = 0.13).Both fat mass and smoking are related to increased activity of the TNFα axis. Plasma adiponectin concentrations are lower in smokers and IR subjects. These two mechanisms could be associated with increased cardiovascular risk in smokers

The Relationship among Smoking, Plasma Adiponectin, Leptin, Inflammatory Markers and Insulin Resistance

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.Et.

2011-01-01

The study aimed to investigate how smoking influences the relationship between fat mass, soluble tumor necrosis factor-α , (TNFα ) receptors 1 and 2 (sTNFR1 and sTNFR2), highly sensitive C-reactive protein (hs-CRP), adiponectin, leptin and insulin resistance. A total of 60 healthy men (age: 27-53 years, body mass index (BMI): 20-35 kg/m2), 30 of whom were never-smokers and 30 smokers, matched for age, BMI and waist-to-hip ratio were included in this study. Those were subdivided into insulin resistant (IR) and insulin sensitive (IS) subgroups. Measures included circulating soluble fractions of the tumor necrosis factor α (TNFα ) receptors (sTNFR1 and sTNFR2) and their relationship to fat mass, fasting plasma adiponectin, leptin, hs-CRP and insulin sensitivity index. Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass, insulin and leptin, smokers showed significantly increased circulating sTNFR2 levels (3.7±0.8 vs. 2.9±0.8 ng/ml, P=0.03). Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (P = 0.046 and 0.001, respectively). No difference was detected in average hs- CRP concentrations between smokers and nonsmokers (P = 0.18) and between IR and IS subjects (P = 0.13).Both fat mass and smoking are related to increased activity of the TNFα axis. Plasma adiponectin concentrations are lower in smokers and IR subjects. These two mechanisms could be associated with increased cardiovascular risk in smokers

Influence of Fasting Status and Sample Preparation on Metabolic Biomarker Measurements in Postmenopausal Women.

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Murphy, Neil; Falk, Roni T; Messinger, Diana B; Pollak, Michael; Xue, Xiaonan; Lin, Juan; Sgueglia, Robin; Strickler, Howard D; Gaudet, Mia M; Gunter, Marc J

2016-01-01

Epidemiologic data linking metabolic markers-such as insulin, insulin-like growth factors (IGFs)-and adipose tissue-derived factors with cancer are inconsistent. Between-study differences in blood collection protocols, in particular participant's fasting status, may influence measurements. We investigated the impact of fasting status and blood sample processing time on components of the insulin/IGF axis and in adipokines in a controlled feeding study of 45 healthy postmenopausal-women aged 50-75 years. Fasting blood samples were drawn (T0), after which subjects ate a standardized breakfast; subsequent blood draws were made at 1 hour (T1), 3 hours (T3), and 6 hours (T6) after breakfast. Serum samples were assayed for insulin, C-peptide, total- and free-IGF-I, IGF-binding protein [BP]-1 and -3, total and high molecular weight (HMW)-adiponectin, retinol binding protein-4, plasminogen activator inhibitor (PAI)-1, and resistin. Insulin and C-peptide levels followed similar postprandial trajectories; intra-class correlation coefficients [ICC] for insulin = 0.75, (95%CI:0.64-0.97) and C-peptide (ICC = 0.66, 95%CI:0.54-0.77) were similarly correlated in fasting (Spearman correlation, r = 0.78, 95%CI:0.64-0.88) and postprandial states (T1, r = 0.77 (95%CI: 0.62-0.87); T3,r = 0.78 (95%CI: 0.63-0.87); T6,r = 0.77 (95%CI: 0.61-0.87)). Free-IGF-I and IGFBP-1 levels were also affected by fasting status, whereas total-IGF-I and IGFBP-3 levels remained unchanged. Levels of adipokines were largely insensitive to fasting status and blood sample processing delays. Several components of the insulin/IGF axis were significantly impacted by fasting state and in particular, C-peptide levels were substantially altered postprandially and in a similar manner to insulin.

Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

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Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

2014-01-17

Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

Use of the oral sugar test in ponies when performed with or without prior fasting.

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Knowles, E J; Harris, P A; Elliott, J; Menzies-Gow, N J

2017-07-01

It is recommended that the oral sugar test (OST) for insulin dysregulation (ID) be performed after an overnight fast, but fasting is impractical in ponies kept solely at pasture. There are few data on OST repeatability and reliability in ponies. To report 1) whether OST results obtained in the morning after an overnight fast or without fasting in the afternoon (FASTING/FED) can be used interchangeably, 2) time of highest insulin concentration T max [insulin], repeatability and reliability of insulin response to the OST when FASTING or FED and 3) dichotomous agreement (ID/normal) within a small sample when FASTING or FED. Method comparison study. Oral sugar tests were performed on four occasions in 10 adult native British ponies, twice FASTING and twice FED. Insulin concentrations were measured by radioimmunoassay at 0-120 min (T 0,30,60,75,90,120 ). Differences between FASTING and FED results were assessed using mixed effects models. Indices of repeatability and reliability were calculated; dichotomous agreement was reported using kappa statistics. Serum [insulin] was significantly (P≤0.05) higher at T 60 -T 90 with prior fasting (estimated differences [95% confidence intervals]): T 60 : 23.5 μiu/ml (8.7-38.4 μiu/ml), T 75 : 27.1 μiu/ml (12.3-41.8 μiu/ml), T 90 : 15.1 (0.36-29.9 μiu/ml). Most frequently, T max [ins] occurred at T 30 . At any single time point, within-subject coefficients of variation were: FASTING: 40% and FED: 31%. The 95% limits for repeatability were FASTING: 29-340%, FED: 41-240%. Test reliabilities were FASTING: 0.70 and FED: 0.67. For dichotomous interpretation similar results (kappa = 0.7) were obtained using cut-offs of [Insulin] >60 μiu/ml at T 60 or T 90 for FASTING and [Insulin] >51 μiu/ml at T 30 or T 60 for FED samples. Oral sugar tests were performed on a small number of animals on one pasture during one season (spring). Clinicians should beware of interpreting changes in absolute OST results owing to poor repeatability. When

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes

DEFF Research Database (Denmark)

Lund, Søren S; Tarnow, Lise; Frandsen, Merete

2008-01-01

metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels. CONCLUSIONS: In non-obese T2DM patients, metformin reduced postprandial levels...... of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients......OBJECTIVE: Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (Hb...

Fasting plasma glucose levels and coronary artery calcification in subjects with impaired fasting glucose.

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Eun, Young-Mi; Kang, Sung-Goo; Song, Sang-Wook

2016-01-01

Prediabetes is associated with an increased risk of cardiovascular disease (CVD). While the association of impaired glucose tolerance with CVD has been shown in many studies, the relationship between impaired fasting glucose (IFG) and CVD remains unclear. The purpose of this study was to compare the coronary artery calcium (CAC) scores of participants with normal fasting glucose versus those with IFG, according to fasting plasma glucose (FPG) levels, and to assess whether differences in CAC scores were independent of important confounders. Retrospective study. Health Promotion Center of the University Hospital (Gyeonggi-do, South Korea), during the period 2010-2014. Participants were enrolled from the general population who visited for a medical check-up. CAC was assessed in asymptomatic individuals by multidetector computed tomography. Anthropometric parameters and metabolic profiles were also recorded. Subjects were divided into four fasting glucose groups. Participants with a history of CVD or diabetes mellitus were excluded. Correlation between FPG and CAC scores, CAC score categories, and association between CAC score and FPG categories. Of 1112 participants, 346 (34.2%) had a CAC score > 0. FPG values in the IFG patients were positively but weakly correlated with CAC scores (r=0.099, P=.001). The incidence of CAC differed according to FPG level (P =110 mg/dL had a significantly higher risk of CAC than did subjects with normal fasting glucose (110.

In vivo kinetics of 123I-labelled insulin: studies in normal subjects and patients with diabetes mellitus

International Nuclear Information System (INIS)

Sinclair, A.J.; Signore, A.; Bomanji, J.; Britton, K.E.; Pozzilli, P.; Gale, E.A.M.

1987-01-01

Radioactive tracer techniques using 131 I- and 125 I-insulin have been applied to study insulin metabolism. A simple method to label human insulin with 123 I to a high specific activity is described. We have used this radiotracer to study insulin kinetics in vivo in normal subjects and in two groups of diabetic patients. The rate of decline in plasma radioactivity was shown to be significantly reduced in patients with diabetes. There were no significant differences in the time -activity profiles of liver and kidneys between the groups studied. This technique may provide insight into the mechanism of some forms of insulin resistance. (author)

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

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Qibo Zhu

Full Text Available Lipopolysaccharide-binding protein (LBP is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS. The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR in PCOS.In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP. Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level.The study was performed in a clinical research center.Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, p<0.001, and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001. Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI, fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c, free testosterone, high sensitive C reactive protein (hs-CRP and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c and sex hormone binding globulin (SHBG. Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP.Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

Differences in cardiovascular risk profile based on relationship between post-load plasma glucose and fasting plasma levels.

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Succurro, Elena; Marini, Maria Adelaide; Grembiale, Alessandro; Lugarà, Marina; Andreozzi, Francesco; Sciacqua, Angela; Hribal, Marta Letizia; Lauro, Renato; Perticone, Francesco; Sesti, Giorgio

2009-05-01

It has been shown that subjects with normal glucose tolerance (NGT), whose plasma glucose (PG) levels do not return to their fasting PG level within 2 h during an oral glucose tolerance test (OGTT) (Group I), have a significantly higher risk to develop type 2 diabetes than NGT subjects whose 2-h glucose returns to, or drops below, the fasting level (Group I). However, it is still unsettled whether individuals in Group II have a more atherogenic profile than Group I subjects. To address this issue, we examined 266 non-diabetic offspring of type 2 diabetic patients, recruited in the context of EUGENE2 cross-sectional study. All subjects underwent an euglycaemic-hyperinsulinemic clamp to assess glucose tolerance and insulin sensitivity. Furthermore, cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. Individuals in Group II exhibited significantly higher waist circumference, blood pressure, triglycerides, 2-h post-load PG, hsC-reactive protein, interleukin-6, insulin-like growth factor-1 (IGF-1), IMT, and lower insulin sensitivity than subjects in Group I. Subjects with NGT, whose PG concentration does not return to their fasting PG level within 2 h during OGTT, have an atherogenic profile, suggesting that performing OGTT with measurement of PG every 30 min may be useful to assess the risk for cardiovascular disease in glucose-tolerant subjects.

Hydrocortisone and insulin effect on oxidative phosphorylation in mitochondria of liver and spleen th rats exposed to fast neutrons

International Nuclear Information System (INIS)

Sutkovoj, D.A.; Alferov, A.N.; Letov, V.N.

1979-01-01

Total-body exposure of rats to fast neutrons (100 rad) elicits an increase in the content of 11-oxycorticosteroids in blood plasma and an appreciable decrease in the respiratory and phosphorylation activity of liver and spleen mitochondria. Administration of hydrocortisone (50 mg/kg) and particularly insulin (2 units/kg) intensifies energy generation in the liver. In the spleen, a beneficial effect was only produced by insulin. Glucocorticoid considerably aggravates the postradiation impairment of oxidative phosphorylation

IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

DEFF Research Database (Denmark)

Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik

2006-01-01

Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied...... by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal...... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas transplant recipients

DEFF Research Database (Denmark)

Bouzakri, Karim; Karlsson, Håkan K R; Vestergaard, Henrik

2006-01-01

Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied...... by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal...... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

Reference intervals for glucose, beta-cell polypeptides and counterregulatory factors during prolonged fasting

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Højlund, Kurt; Wildner-Christensen, M; Eshøj, O

2001-01-01

To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P ... of counterregulatory factors increased during the fast [P fasting (P ... decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

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Halden, Thea A S; Egeland, Erlend J; Åsberg, Anders

2016-01-01

OBJECTIVE: Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon...... h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp. RESULTS: Fasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups...... to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations...

Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey.

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Park, R J; Moon, J D

2015-05-01

The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance. We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50 years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes. Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes. Lower transferrin saturations were associated with an increased risk of impaired fasting glucose and insulin resistance among general South Korean population. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Limitations of insulin resistance assessment in polycystic ovary syndrome

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Lewandowski, Krzysztof C; Płusajska, Justyna; Horzelski, Wojciech; Bieniek, Ewa; Lewiński, Andrzej

2018-01-01

Background Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable. Subjects and methods In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices). Results There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = −0.999, HOMA-IR/McAuley index, r = −0.849 and between all OGTT-derived IR indices (e.g. r = −0.876, for IRI/Matsuda, r = −0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P IR indices derived from fasting vs OGTT-derived variables, ranging from r = −0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = −0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations. Conclusions Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution. PMID:29436386

Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies1234

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Hruby, Adela; Ngwa, Julius S.; Renström, Frida; Wojczynski, Mary K.; Ganna, Andrea; Hallmans, Göran; Houston, Denise K.; Jacques, Paul F.; Kanoni, Stavroula; Lehtimäki, Terho; Lemaitre, Rozenn N.; Manichaikul, Ani; North, Kari E.; Ntalla, Ioanna; Sonestedt, Emily; Tanaka, Toshiko; van Rooij, Frank J. A.; Bandinelli, Stefania; Djoussé, Luc; Grigoriou, Efi; Johansson, Ingegerd; Lohman, Kurt K.; Pankow, James S.; Raitakari, Olli T.; Riserus, Ulf; Yannakoulia, Mary; Zillikens, M. Carola; Hassanali, Neelam; Liu, Yongmei; Mozaffarian, Dariush; Papoutsakis, Constantina; Syvänen, Ann-Christine; Uitterlinden, André G.; Viikari, Jorma; Groves, Christopher J.; Hofman, Albert; Lind, Lars; McCarthy, Mark I.; Mikkilä, Vera; Mukamal, Kenneth; Franco, Oscar H.; Borecki, Ingrid B.; Cupples, L. Adrienne; Dedoussis, George V.; Ferrucci, Luigi; Hu, Frank B.; Ingelsson, Erik; Kähönen, Mika; Kao, W. H. Linda; Kritchevsky, Stephen B.; Orho-Melander, Marju; Prokopenko, Inga; Rotter, Jerome I.; Siscovick, David S.; Witteman, Jacqueline C. M.; Franks, Paul W.; Meigs, James B.; McKeown, Nicola M.; Nettleton, Jennifer A.

2013-01-01

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = −0.009 mmol/L (95% CI: −0.013, −0.005), P magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. PMID:23343670

Is insulin the most effective injectable antihyperglycaemic therapy?

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Buse, J B; Peters, A; Russell-Jones, D; Furber, S; Donsmark, M; Han, J; MacConell, L; Maggs, D; Diamant, M

2015-02-01

The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high. However, randomized studies comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once-weekly [OW; DURATION-3 (Diabetes therapy Utilization: Researching changes in A1c, weight, and other factors Through Intervention with exenatide ONce-Weekly)] and liraglutide once-daily [OD; LEAD-5 (Liraglutide Effect and Action in Diabetes)] with insulin glargine documented greater HbA1c reduction with GLP-1RAs, from baseline HbA1c ∼8.3% (67 mmol/mol). This post hoc analysis of DURATION-3 and LEAD-5 examined changes in HbA1c, fasting glucose and weight with exenatide OW or liraglutide and glargine, by baseline HbA1c quartile. Descriptive statistics were provided for change in HbA1c, fasting glucose, weight, and insulin dose, and subjects (%) achieving HbA1c <7.0%, by baseline HbA1c quartile. Inferential statistical analysis on the effect of baseline HbA1c quartile was performed for change in HbA1c. An analysis of covariance (ANCOVA) model was used to evaluate similarity in change in HbA1c across HbA1c quartiles. At 26 weeks, in both studies, HbA1c reduction, and proportion of subjects reaching HbA1c <7.0%, were similar or numerically greater with the GLP-1RAs than glargine for all baseline HbA1c quartiles. Fasting glucose reduction was similar or numerically greater with glargine. Weight decreased with both GLP-1RAs across all quartiles; subjects taking glargine gained weight, more at higher baseline HbA1c. Adverse events were uncommon although gastrointestinal events occurred more frequently with GLP-1RAs. HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c. This suggests that liraglutide and exenatide OW may be appropriate

Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects

DEFF Research Database (Denmark)

Rasmussen, M H; Hvidberg, A; Juul, A

1995-01-01

levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), as well as insulin in obese subjects before and after a massive weight loss. We studied 18 obese subjects (age, 26 +/- 1 yr; body mass index, 40.9 +/- 1.1 kg/m2); 18 normal age-, and sex-matched control subjects; and 9...... using anthropometric measurements and dual energy x-ray absorptiometry scanning (DXA). In the obese subjects, 24-h spontaneous GH release profiles and the GH responses to insulin-induced hypoglycemia and L-arginine as well as basal IGF-I levels and the IGF-I/IGFBP-3 molar ratio were decreased, whereas...

Relationship between neck circumference, insulin resistance and arterial stiffness in overweight and obese subjects.

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Fantin, Francesco; Comellato, Gabriele; Rossi, Andrea P; Grison, Elisa; Zoico, Elena; Mazzali, Gloria; Zamboni, Mauro

2017-09-01

Background Only a few studies have investigated the relationship between neck circumference and cardiometabolic risk. The aim of this study was to assess the relationships between neck circumference, waist circumference, metabolic variables and arterial stiffness in a group of overweight and obese subjects evaluating a possible independent role of neck circumference in determining arterial stiffness. Methods and results We studied 95 subjects (53 women) with an age range of 20-77 years and body mass index range from 25.69 to 47.04 kg/m 2 . In each subject we evaluated body mass index, waist, hip and neck circumference, systolic and diastolic blood pressure, insulin, fasting glucose, cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWVcf) and carotid-radial pulse wave velocity (PWVcr). Both PWVcf and PWVcr were higher in subjects with high values of neck circumference compared with subjects with normal values of neck circumference. Subjects with high values of neck circumference and abdominal obesity presented higher values of mean arterial pressure, PWVcr and homeostasis model assessment (HOMA) index and lower values of high-density lipoprotein than subjects with only abdominal obesity. Two models of stepwise multiple regression were performed in order to evaluate the combined effect of independent variables on arterial stiffness. In the first model PWVcf was considered a dependent variable, and age, gender, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, waist circumference, neck circumference, HOMA index and the use of anti-hypertensive medications were considered independent variables. Age, systolic blood pressure, triglycerides and waist circumference were significant predictors of PWVcf, explaining 65% of its variance. In the second model, in which PWVcr was considered a dependent variable, neck circumference

Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects

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Frid, Anders H; Nilsson, Mikael; Holst, Jens Juul

2005-01-01

glycemic index (GI) with whey proteins may increase insulin secretion and improve blood glucose control in type 2 diabetic subjects. DESIGN: Fourteen diet-treated subjects with type 2 diabetes were served a high-GI breakfast (white bread) and subsequent high-GI lunch (mashed potatoes with meatballs...... insulin release and reduces postprandial blood glucose excursion after a lunch meal consisting of mashed potatoes and meatballs in type 2 diabetic subjects....

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

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Manning, Alisa K.; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L.; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F.; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U.; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E.; Navarro, Pau; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J.; Tanaka, Toshiko; van Duijn, Cornelia M.; An, Ping; de Andrade, Mariza; Andrews, Jeanette S.; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S.; Beilby, John P.; Bellis, Claire; Bergman, Richard N.; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Borecki, Ingrid B.; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S.; Clarke, Robert; Collins, Francis S.; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G.; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L.; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B.; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo Riitta; Jhun, Min A.; Johnson, Paul C.D.; Jukema, J Wouter; Jula, Antti; Kao, W.H.; Kaprio, Jaakko; Kardia, Sharon L. R.; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J.; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J. F.; Luan, Jian’an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K. E.; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Miljkovic, Iva; Narisu, Narisu; O’Connell, Jeff; Ong, Ken K.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Pankow, James S.; Peden, John F.; Pedersen, Nancy L.; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P.; Province, Michael A.; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I.; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B.; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R.; Sijbrands, Eric J.G.; Siscovick, David S.; Smit, Johannes H.; Small, Kerrin S.; Smith, Nicholas L.; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V.; Swift, Amy J.; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G.; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F.; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H.; Willems, Sara M.; Willemsen, Gonneke; Wilson, James F.; Witteman, Jacqueline C.M.; Wright, Alan F.; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J.; McCarthy, Mark I.; Barroso, Ines; Watanabe, Richard M.; Florez, Jose C.; Dupuis, Josée; Meigs, James B.; Langenberg, Claudia

2013-01-01

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction, but contributed little to our understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways may be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and genetic variants. We applied a novel joint meta-analytical approach to test associations with fasting insulin (FI) and glucose (FG) on a genome-wide scale. We present six previously unknown FI loci at P<5×10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496non-diabetic individuals. Risk variants were associated with higher triglyceride and lower HDL cholesterol levels, suggestive of a role for these FI loci in insulin resistance pathways. The localization of these additional loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. PMID:22581228

The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men

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Slivkoff-Clark Karin M

2012-02-01

Full Text Available Abstract Background Visceral obesity and insulin resistance are associated with a postprandial accumulation of atherogenic chylomicron remnants that is difficult to modulate with lipid-lowering therapies. Dietary fish oil and exercise are cardioprotective interventions that can significantly modify the metabolism of TAG-rich lipoproteins. In this study, we investigated whether chronic exercise and fish oil act in combination to affect chylomicron metabolism in obese men with moderate insulin resistance. Methods The single blind study tested the effect of fish oil, exercise and the combined treatments on fasting and postprandial chylomicron metabolism. Twenty nine men with metabolic syndrome were randomly assigned to take fish oil or placebo for four weeks, before undertaking an additional 12 week walking program. At baseline and at the end of each treatment, subjects were tested for concentrations of fasting apo B48, plasma lipids and insulin. Postprandial apo B48 and TAG kinetics were also determined following ingestion of a fat enriched meal. Results Combining fish oil and exercise resulted in a significant reduction in the fasting apo B48 concentration, concomitant with attenuation of fasting TAG concentrations and the postprandial TAGIAUC response (p Conclusion Fish oil was shown to independently improve plasma TAG homeostasis but did not resolve hyper-chylomicronaemia. Instead, combining fish oil with chronic exercise reduced the plasma concentration of pro-atherogenic chylomicron remnants; in addition it reduced the fasting and postprandial TAG response in viscerally obese insulin resistant subjects.

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a levels in human subjects with rheumatoid diseases.

Directory of Open Access Journals (Sweden)

Olaf Schultz

2010-12-01

Full Text Available Interleukin-6 (IL-6 is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab.11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a (Lp (a were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a levels significantly decreased.Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a serum levels, which might reduce the cardiovascular risk of human subjects.

Safety and feasibility of fasting in combination with platinum-based chemotherapy.

Science.gov (United States)

Dorff, Tanya B; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I

2016-06-10

Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. NCT00936364 , registered propectively on July 9, 2009.

Safety and feasibility of fasting in combination with platinum-based chemotherapy

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Dorff, Tanya B.; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I.

2016-01-01

Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. Clinicaltrials.gov: NCT00936364, registered propectively on July 9, 2009. The online version of this article (doi:10.1186/s12885-016-2370-6) contains supplementary material, which is available to authorized users

Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action

DEFF Research Database (Denmark)

Faerch, K; Vaag, A; Holst, Jens Juul

2008-01-01

.892) compared with NGT. Hepatic insulin sensitivity was normal in i-IFG and i-IGT individuals (p > or = 0.179). Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and consequently the disposition index (DI; insulin secretion x insulin sensitivity) during IVGTT (DI(IVGTT))) was reduced......AIMS/HYPOTHESIS: The impact of strategies for prevention of type 2 diabetes in isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose tolerance (i-IGT) may differ depending on the underlying pathophysiology. We examined insulin secretion during OGTTs and IVGTTs, hepatic...

Altered insulin distribution and metabolism in type I diabetics assessed by [123I]insulin scanning

International Nuclear Information System (INIS)

Hachiya, H.L.; Treves, S.T.; Kahn, C.R.; Sodoyez, J.C.; Sodoyez-Goffaux, F.

1987-01-01

Scintigraphic scanning with [ 123 I]insulin provides a direct and quantitative assessment of insulin uptake and disappearance at specific organ sites. Using this technique, the biodistribution and metabolism of insulin were studied in type 1 diabetic patients and normal subjects. The major organ of [ 123 I]insulin uptake in both diabetic and normal subjects was the liver. After iv injection in normal subjects, the uptake of [ 123 I]insulin by the liver was rapid, with peak activity at 7 min. Activity declined rapidly thereafter, consistent with rapid insulin degradation and clearance. Rapid uptake of [ 123 I]insulin also occurred in the kidneys, although the uptake of insulin by the kidneys was about 80% of that by liver. In type 1 diabetic patients, uptake of [ 123 I]insulin in these organ sites was lower than that in normal subjects; peak insulin uptakes in liver and kidneys were 21% and 40% lower than those in normal subjects, respectively. The kinetics of insulin clearance from the liver was comparable in diabetic and normal subjects, whereas clearance from the kidneys was decreased in diabetics. The plasma clearance of [ 123 I]insulin was decreased in diabetic patients, as was insulin degradation, assessed by trichloroacetic acid precipitability. Thirty minutes after injection, 70.9 +/- 3.8% (+/- SEM) of [ 123 I]insulin in the plasma of diabetics was trichloroacetic acid precipitable vs. only 53.9 +/- 4.0% in normal subjects. A positive correlation was present between the organ uptake of [123I]insulin in the liver or kidneys and insulin degradation (r = 0.74; P less than 0.001)

The Effect of Ramadan Fasting on Biochemical Parameters in Healthy Thai Subjects.

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Ongsara, Sara; Boonpol, Sakulrat; Prompalad, Nussaree; Jeenduang, Nutjaree

2017-09-01

Although, the effect of Ramadan fasting on the risks for Cardiovascular Disease (CVD) has been reported in several studies, the results were inconsistent. In addition, the effect of Ramadan fasting on biochemical parameters in Thai subjects has not been evaluated. The aim of this study was to investigate the effect of Ramadan fasting on anthropometry, blood pressure, Fasting Blood Glucose (FBG), lipid profiles, and body composition in healthy Thai subjects. A total of 65 healthy subjects (21 men and 44 women) aged between 19-24 years were randomly recruited. Anthropometry, blood pressure, FBG, Total Cholesterol (TC), Triglyceride (TG), High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol (LDL-C), and body composition were measured before Ramadan, end of Ramadan and after one month of Ramadan. There were no changes in anthropometry, blood pressure, lipid profiles and body composition in both genders before Ramadan, end of Ramadan and after one month of Ramadan. Nevertheless, FBG levels were significantly increased after one month of Ramadan compared with baseline (5.09±0.50 versus 4.83±0.38 mmol/L, p=0.016, respectively) in women. The Ramadan fasting did not affect the lipid, anthropometric and body composition in healthy Thai subjects. However, the increased FBG levels after one month of Ramadan were observed in women. To improve the favourable biochemical parameters after Ramadan fasting, the lifestyle modifications such as, increased intake of healthy diets and increased physical activity should be recommended.

Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

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Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

2013-08-01

Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

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.

Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study.

Science.gov (United States)

Backeström, Anna; Eriksson, Sture; Nilsson, Lars-Göran; Olsson, Tommy; Rolandsson, Olov

2015-01-01

Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

Supervised exercise training counterbalances the adverse effects of insulin therapy in overweight/obese subjects with type 2 diabetes.

Science.gov (United States)

Balducci, Stefano; Zanuso, Silvano; Cardelli, Patrizia; Salerno, Gerardo; Fallucca, Sara; Nicolucci, Antonio; Pugliese, Giuseppe

2012-01-01

To examine the effect of supervised exercise on traditional and nontraditional cardiovascular risk factors in sedentary, overweight/obese insulin-treated subjects with type 2 diabetes from the Italian Diabetes Exercise Study (IDES). The study randomized 73 insulin-treated patients to twice weekly supervised aerobic and resistance training plus structured exercise counseling (EXE) or to counseling alone (CON) for 12 months. Clinical and laboratory parameters were assessed at baseline and at the end of the study. The volume of physical activity was significantly higher in the EXE versus the CON group. Values for hemoglobin A(1c), BMI, waist circumference, high-sensitivity C-reactive protein, blood pressure, LDL cholesterol, and the coronary heart disease risk score were significantly reduced only in the EXE group. No major adverse events were observed. In insulin-treated subjects with type 2 diabetes, supervised exercise is safe and effective in improving glycemic control and markers of adiposity and inflammation, thus counterbalancing the adverse effects of insulin on these parameters.

Plasma resistin, adiponectin and leptin levels in relation to insulin resistance

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.E.T.

2010-01-01

Adipose tissue regulates insulin sensitivity via the circulating adipo cytokines, adiponectin, resistin and leptin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 20 lean subjects with mean body mass index (BMI) of 24, and, 36 nondiabetic obese individuals with mean BMI 34. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 30.4±6.5 vs. 14.4±2.9 mg/l, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P < 0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly reduced in obese compared with lean subjects, P < 0.005 and higher in women, P< 0.001. Adiponectin levels showed significant correlation with HOMA-R and this correlation remained significant after adjustment for gender and BMI. Leptin levels were significantly higher in obese subjects and women and correlated with resistin, but, didn't correlate with HOMA-R. In this small group of patients we demonstrated that insulin resistance correlated most strongly and reciprocally with adiponectin levels. Significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for leptin, the correlation with insulin resistance did not achieve statistical significance

No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin Sensitivity during the Early Postnatal Period

Directory of Open Access Journals (Sweden)

Tong-yan Han

2010-01-01

Full Text Available Objective. To investigate the relationship between weight catch-up growth and insulin sensitivity in small for gestational age (SGA infants. Methods. Forty-four singleton SGA subjects met the inclusion criteria and finished-3-month followup. Body weight, length, fasting glucose, and fasting insulin (FI levels were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and homeostasis model assessment (HOMA. Results. According to the change of weight Z-score, forty-four subjects were divided into two groups: noncatch-up growth (NCUG and catch-up growth (CUG. By 3 months of age, the body weight, body length and BMI of NCUG group were significantly lower than those of CUG group. The FI and HOMA were significantly higher in NCUG group. The change of weight Z-score during 3 months was inversely related to the HOMA at 3 months. Conclusion. Our data exemplified that no weight catch-up growth during the first 3 months was associated with impaired insulin sensitivity in SGA infants.

Temporal Relationship Between Hyperuricemia and Insulin Resistance and Its Impact on Future Risk of Hypertension.

Science.gov (United States)

Han, Tianshu; Lan, Li; Qu, Rongge; Xu, Qian; Jiang, Ruyue; Na, Lixin; Sun, Changhao

2017-10-01

Although hyperuricemia and insulin resistance significantly correlated, their temporal sequence and how the sequence influence on future risk of hypertension are largely unknown. This study assessed temporal relationship between uric acid and insulin resistance and its impact on future risk of hypertension by examining a longitudinal cohort including 8543 subjects aged 20 to 74 years from China, with an average follow-up of 5.3 years. Measurements of fasting uric acid, as well as fasting and 2-hour serum glucose and insulin, were obtained at baseline and follow-up. Indicators of hepatic and peripheral insulin resistance were calculated. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between uric acid and insulin resistance and its impact on follow-up hypertension. After adjusting for covariates, the cross-lagged path coefficients ( β 1 values) from baseline uric acid to follow-up insulin resistance indices were significantly greater than path coefficients ( β 2 values) from baseline insulin resistance indices to follow-up uric acid ( β 1 =0.110 versus β 2 =0.017; P hypertensive group were significantly greater than that in the normotensive group ( P hypertension, and the mediation effect of peripheral insulin resistance was significantly greater than that of hepatic insulin resistance (31.3% versus 13.2%; P hypertension than hepatic insulin resistance does. © 2017 American Heart Association, Inc.

Fasting and postprandial levels of a novel anorexigenic peptide nesfatin in childhood obesity.

Science.gov (United States)

Anık, Ahmet; Çatlı, Gönül; Abacı, Ayhan; Küme, Tuncay; Bober, Ece

2014-07-01

Nesfatin-1, a recently discovered anorexigenic peptide, is expressed in several tissues, including pancreatic islet cells and central nervous system. However, its pathophysiological role in the development of obesity and insulin resistance remains unknown. To investigate the possible involvement of nesfatin-1 in the pathogenesis of childhood obesity, we examined the relationship between fasting and postprandial nesfatin-1 concentrations and metabolic/antropometric parameters in obese children. The study included obese children with a body mass index >95th percentile. Fasting serum glucose, insulin, lipid profile, fasting and postprandial (120th min) nesfatin-1 levels were measured to evaluate the metabolic parameters. Different cutoff values for prepubertal and pubertal stages were used to determine the status of insulin resistance (HOMA-IR) (prepubertal >2.5, pubertal >4). The percentage of body fat was measured using bioelectric impedance analysis. Seventy-one obese children were included in this study. There was no statistically significant difference between fasting and postprandial nesfatin-1 levels in obese subjects (0.70 ± 0.15 and 0.69 ± 0.14 ng/mL, p>0.05, respectively). Insulin resistance was observed in 58% (41/71) of the cases. There was no significant difference in either fasting or postprandial serum nesfatin-1 levels between the insulin-resistant and non-resistant groups (p>0.05). There was no correlation between fasting and postprandial serum nesfatin-1 levels and anthropometric and metabolic parameters in insulin-resistant and non-resistant groups. In this study, there was no significant increase in the postprandial level of nesfatin-1. This observation suggested that oral glucose load in obese children may not be sufficient for nesfatin-1 response and that nesfatin-1 may not have an effect as a short-term regulator of food intake.

Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice.

Science.gov (United States)

Mitchell, James R; Verweij, Mariëlle; Brand, Karl; van de Ven, Marieke; Goemaere, Natascha; van den Engel, Sandra; Chu, Timothy; Forrer, Flavio; Müller, Cristina; de Jong, Marion; van IJcken, Wilfred; IJzermans, Jan N M; Hoeijmakers, Jan H J; de Bruin, Ron W F

2010-02-01

Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2-4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water-only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short-term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin-like growth factor-1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short-term DR or fasting revealed a significant enrichment of signature genes of long-term DR. These data demonstrate that brief periods of reduced food intake, including short-term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals.

Evaluation of chronic kidney disease patients for insulin resistance in tertiary care hospital

International Nuclear Information System (INIS)

Tahir, S.; Hayat, A.; Khan, S.A.; Ahmad, T.M.; Majeed, N.

2018-01-01

Objective: To evaluate the patients of chronic kidney disease for insulin resistance. Study Design: Cross sectional observational study. Place and Duration of Study: The study was conducted in the chemical pathology department of Army Medical College/Military Hospital Rawalpindi, from Nov 2016 to Apr 2017. Material and Methods: Fifty patients were recruited for this study with deranged renal functions and/or having any structural renal abnormality for more than 3 months. These patients did not have any history of diabetes and dialysis. Fifty ages matched healthy individuals were included as controls. Renal function tests, lipid profile, complete blood count, fasting plasma glucose and serum insulin levels were performed in all subjects. Insulin resistance was calculated by using homeostatic model for assessment of insulin resistance (HOMA-IR). Results of this study were analyzed on SPSS version 23. Results: Fasting insulin levels were much higher in the patient with chronic kidney disease as compared to controls (p-value=0.001). HOMA-IR in cases was also significantly higher. Statistical comparison of lipid profile showed significant difference of only triglycerides level. Conclusion: HOMA-IR is markedly raised in the patients of chronic kidney disease. This indicates a significant association of chronic kidney disease with insulin resistance. (author)

The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

DEFF Research Database (Denmark)

Bentzen, J; Poulsen, P; Vaag, A

2002-01-01

on parameters associated with the insulin resistance syndrome in Danish twins. METHODS: The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55-74 years. RESULTS: The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin......, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T-allele was associated with higher levels......AIMS: The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism...

Insulin aspart in diabetic pregnancy

DEFF Research Database (Denmark)

Mathiesen, Elisabeth R

2008-01-01

in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

DEFF Research Database (Denmark)

Hansen, Tue Haldor; Vestergaard, Henrik; Jørgensen, Torben

2015-01-01

,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did.......024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate......Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present...

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

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...

Spectrum of lipid and lipoprotein indices in human subjects with insulin resistance syndrome

International Nuclear Information System (INIS)

Khan, S.H.; Khan, F.A.; Mohammad, A.S.

2008-01-01

Insulin resistance syndrome or metabolic syndrome is one of the major metabolic threats our recently urbanized society is going to face in near future. The management of this syndrome requires a very effective biochemical marker for screening. The objective of this cross sectional study were to compare various lipid and lipoprotein indices in human subjects with insulin resistance syndrome This study was carried out between April 2004 to January 2006 at the department of chemical pathology and endocrinology, Armed Forces Institute of Pathology, Rawalpindi. A total of forty-seven subjects with metabolic syndrome were selected as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III) from a target population diagnosed to have impaired glucose regulation at AFIP. Forty-seven age and sex-matched healthy controls were also included in the study. Insulin resistance was calculated by the method of HOMA-IR, using the formula of Mathew's et al. The various lipid and lipoproteins, their ratios and log-transformed versions were evaluated for differences between subjects with metabolic syndrome and controls. Finally the diagnostic performances of these candidate lipid markers were evaluated. Results between subjects with metabolic syndrome and controls were found to be significant for serum triglyceride (p<0.05), HDL-C (p<0.05), triglyceride/HDLC (p<0.01), Log triglyceride/HDL-C (p<0.01), total cholesterol/HDL-C (p<0.01), LDL-C/HDL-C (p<0.01). However there was weak correlation between these lipid based markers and HOMA-IR ((serum triglyceride: r= 0.225), (HDL-C: r= -0.235), (triglyceride/HDL-C: r= 0.333), (total cholesterol/HDL-C: r= 0.239)). The AUCs for the diagnosis of metabolic syndrome remained highest for HOMA-IR (0.727 (95%CI: 0.642-0.812)), followed by triglyceride/HDL-C (0.669 (95%CI: 0.572-0.766)) and LDLC/ HDL-C (0.639 (95%CI: 0.537-0.742)). The differences for lipids and lipoproteins between subjects with metabolic

Specific insulin and proinsulin secretion in glucokinase-deficient individuals

Directory of Open Access Journals (Sweden)

V.C. Pardini

1999-04-01

Full Text Available Glucokinase (GCK is an enzyme that regulates insulin secretion, keeping glucose levels within a narrow range. Mutations in the glucokinase gene cause a rare form of diabetes called maturity-onset diabetes of the young (MODY. An early onset (less than 25 years, autosomal dominant inheritance and low insulin secretion stimulated by glucose characterize MODY patients. Specific insulin and proinsulin were measured in serum by immunofluorimetric assays (IFMA during a 75-g oral glucose tolerance test (OGTT. Two kindreds (SA and LZ were studied and compared to non-diabetic unrelated individuals (control group 1 matched for age and body mass index (BMI. In one kindred, some of these subjects were also obese (BMI >26 kg/m2, and other family members also presented with obesity and/or late-onset NIDDM. The MODY patients were also compared to a group of five of their first-degree relatives with obesity and/or late-onset NIDDM. The proinsulin profile was different in members of the two MODY kindreds. Fasting proinsulin and the proinsulin/insulin ratio were similar in MODY members of kindred LZ and subjects from control group 1, but were significantly lower than in MODY members of kindred SA (P<0.02 and P<0.01, for proinsulin and proinsulin/insulin ratio, respectively. Moreover, MODY members of family SA had higher levels of proinsulin and proinsulin/insulin ratio, although not significantly different, when compared to their first-degree relatives and to subjects from control group 2. In conclusion, we observed variable degrees of proinsulin levels and proinsulin/insulin ratio in MODY members of two different kindreds. The higher values of these parameters found in MODY and non-MODY members of kindred SA is probably related to the obesity and late-onset NIDDM background present in this family.

Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus

International Nuclear Information System (INIS)

Bolinder, J.; Ostman, J.; Arner, P.

1982-01-01

The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono- 125 I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis

Total body fat, pro-inflammatory cytokines and insulin resistance in Indian subjects

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Yajnik, C S [Diabetes Unit, KEM Hospital Research Centre, Pune (India); Yudkin, J S [Whittington Hospital, University College of London, London (United Kingdom); Shetty, P S [London School of Hygiene and Tropical Medicine, London (United Kingdom); Kurpad, A [St. John' s Medical College, Bangalore (India)

1999-07-01

There is a growing epidemic of insulin resistance syndrome (IRS) in Indians. We postulate that increased susceptibility of the urban Indians to insulin resistance is a result of a tendency to increased fat deposition from the time of intrauterine life (thrifty phenotype), exaggerated in the urban environment by a positive energy balance. The pro-inflammatory cytokines secreted by the inflammatory cells as well by the adipose tissue could aggravate insulin resistance and endothelial damage and therefore, increase the susceptibility to type 2 diabetes and coronary heart disease (CHD) independent of the previously proposed glucose fatty acid cycle mechanism. In a preliminary study, we propose to make detailed measurements of the proposed mechanisms in a selected population from 3 geographical locations in and near the city of Pune, India and also validate simple 'epidemiologic' measurements of body composition with 'reference' measurements. One hundred men (30 to 50y) each from the three geographical locations (rural, urban slum-dwellers and urban middle class in Pune) will be studied for: (i) Body composition: Anthropometric and bioimpedance measurement of total body fat (to be calibrated against deuterated water in 30 subjects from each location), and muscle mass by anthropometry and urinary creatinine excretion; (ii) Body fat distribution by subscapular- triceps ratio, waist-hip ratio; (iii) Metabolic: Glucose tolerance and insulin resistance variables (insulin, lipids, NEFA) and leptin; (iv) Endothelial markers: e-Selectin and von Willebrand Factor (vWF); (v) Inflammatory markers and pro-inflammatory cytokines: C-reactive protein (CRP), Interleukin-6 (IL-6) and tumour necrosis factor (TNF- {alpha}); (vi) Energy Balance: Assessment of nutritional intake (calories, carbohydrates, proteins and fats, n3 and n6 fatty acids) and physical activity by a questionnaire. Insulin resistance variables, endothelial markers, cytokines and obesity parameters will be compared in

Total body fat, pro-inflammatory cytokines and insulin resistance in Indian subjects

International Nuclear Information System (INIS)

Yajnik, C.S.; Yudkin, J.S.; Shetty, P.S.; Kurpad, A.

1999-01-01

There is a growing epidemic of insulin resistance syndrome (IRS) in Indians. We postulate that increased susceptibility of the urban Indians to insulin resistance is a result of a tendency to increased fat deposition from the time of intrauterine life (thrifty phenotype), exaggerated in the urban environment by a positive energy balance. The pro-inflammatory cytokines secreted by the inflammatory cells as well by the adipose tissue could aggravate insulin resistance and endothelial damage and therefore, increase the susceptibility to type 2 diabetes and coronary heart disease (CHD) independent of the previously proposed glucose fatty acid cycle mechanism. In a preliminary study, we propose to make detailed measurements of the proposed mechanisms in a selected population from 3 geographical locations in and near the city of Pune, India and also validate simple 'epidemiologic' measurements of body composition with 'reference' measurements. One hundred men (30 to 50y) each from the three geographical locations (rural, urban slum-dwellers and urban middle class in Pune) will be studied for: (i) Body composition: Anthropometric and bioimpedance measurement of total body fat (to be calibrated against deuterated water in 30 subjects from each location), and muscle mass by anthropometry and urinary creatinine excretion; (ii) Body fat distribution by subscapular- triceps ratio, waist-hip ratio; (iii) Metabolic: Glucose tolerance and insulin resistance variables (insulin, lipids, NEFA) and leptin; (iv) Endothelial markers: e-Selectin and von Willebrand Factor (vWF); (v) Inflammatory markers and pro-inflammatory cytokines: C-reactive protein (CRP), Interleukin-6 (IL-6) and tumour necrosis factor (TNF- α); (vi) Energy Balance: Assessment of nutritional intake (calories, carbohydrates, proteins and fats, n3 and n6 fatty acids) and physical activity by a questionnaire. Insulin resistance variables, endothelial markers, cytokines and obesity parameters will be compared in the 3

Serum cortisol level and its correlation to serum insulin and fasting blood sugar levels in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Chen Jianzhong; Zhang Jun

2004-01-01

Objective: To investigate the change of serum cortisol levels and its correlation to blood sugar and serum insulin levels in patients with type 2 diabetes mellitus. Methods: Blood sugar with oxidase method and serum cortisol insulin levels with RIA (8 AM fasting specimen) were measured in 26 patients with type 2 diabetes mellitus and 30 controls. Results: The serum cortisol levels in the diabetic patients were significantly higher than those in the controls (P<0.01). The cortisol levels were positively correlated to the blood sugar levels (r=0.32, p<0.01), but not correlated to insulin levels. Conclusion: There were cortisol secretion disturbances in patients with type 2 diabetes

Beneficial metabolic effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in healthy obese women.

Science.gov (United States)

Farshchi, Hamid R; Taylor, Moira A; Macdonald, Ian A

2005-01-01

Although a regular meal pattern is recommended for obese people, its effects on energy metabolism have not been examined. We investigated whether a regular meal frequency affects energy intake (EI), energy expenditure, or circulating insulin, glucose, and lipid concentrations in healthy obese women. Ten women [x +/- SD body mass index (in kg/m(2)): 37.1 +/- 4.8] participated in a randomized crossover trial. In phase 1 (14 d), the subjects consumed their normal diet on 6 occasions/d (regular meal pattern) or followed a variable meal frequency (3-9 meals/d, irregular meal pattern). In phase 2 (14 d), the subjects followed the alternative pattern. At the start and end of each phase, a test meal was fed, and blood glucose, lipid, and insulin concentrations were determined before and for 3 h after (glucose and insulin only) the test meal. Subjects recorded their food intake on 3 d during each phase. The thermogenic response to the test meal was ascertained by indirect calorimetry. Regular eating was associated with lower EI (P thermogenesis (P meal pattern, but peak insulin concentrations and area under the curve of insulin responses to the test meal were lower after the regular than after the irregular meal pattern (P thermogenesis.

A low-frequency inactivating AKT2 variant enriched in the Finnish population is associated with fasting insulin levels and type 2 diabetes risk

Science.gov (United States)

Grarup, Niels; Rivas, Manuel A; Mahajan, Anubha; Locke, Adam E; Cingolani, Pablo; Pers, Tune H; Viñuela, Ana; Brown, Andrew A; Wu, Ying; Flannick, Jason; Fuchsberger, Christian; Gamazon, Eric R; Gaulton, Kyle J; Im, Hae Kyung; Teslovich, Tanya M; Blackwell, Thomas W; Bork-Jensen, Jette; Burtt, Noël P; Chen, Yuhui; Green, Todd; Hartl, Christopher; Kang, Hyun Min; Kumar, Ashish; Ladenvall, Claes; Ma, Clement; Moutsianas, Loukas; Pearson, Richard D; Perry, John R B; Rayner, N William; Robertson, Neil R; Scott, Laura J; van de Bunt, Martijn; Eriksson, Johan G; Jula, Antti; Koskinen, Seppo; Lehtimäki, Terho; Palotie, Aarno; Raitakari, Olli T; Jacobs, Suzanne BR; Wessel, Jennifer; Chu, Audrey Y; Scott, Robert A; Goodarzi, Mark O; Blancher, Christine; Buck, Gemma; Buck, David; Chines, Peter S; Gabriel, Stacey; Gjesing, Anette P; Groves, Christopher J; Hollensted, Mette; Huyghe, Jeroen R; Jackson, Anne U; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S; Stringham, Heather M; Trakalo, Joseph; Banks, Eric; Carey, Jason; Carneiro, Mauricio O; DePristo, Mark; Farjoun, Yossi; Fennell, Timothy; Goldstein, Jacqueline I; Grant, George; de Angelis, Martin Hrabé; Maguire, Jared; Neale, Benjamin M; Poplin, Ryan; Purcell, Shaun; Schwarzmayr, Thomas; Shakir, Khalid; Smith, Joshua D; Strom, Tim M; Wieland, Thomas; Lindstrom, Jaana; Brandslund, Ivan; Christensen, Cramer; Surdulescu, Gabriela L; Lakka, Timo A; Doney, Alex S F; Nilsson, Peter; Wareham, Nicholas J; Langenberg, Claudia; Varga, Tibor V; Franks, Paul W; Rolandsson, Olov; Rosengren, Anders H; Farook, Vidya S; Thameem, Farook; Puppala, Sobha; Kumar, Satish; Lehman, Donna M; Jenkinson, Christopher P; Curran, Joanne E; Hale, Daniel Esten; Fowler, Sharon P; Arya, Rector; DeFronzo, Ralph A; Abboud, Hanna E; Syvänen, Ann-Christine; Hicks, Pamela J; Palmer, Nicholette D; Ng, Maggie C Y; Bowden, Donald W; Freedman, Barry I; Esko, Tõnu; Mägi, Reedik; Milani, Lili; Mihailov, Evelin; Metspalu, Andres; Narisu, Narisu; Kinnunen, Leena; Bonnycastle, Lori L; Swift, Amy; Pasko, Dorota; Wood, Andrew R; Fadista, João; Pollin, Toni I; Barzilai, Nir; Atzmon, Gil; Glaser, Benjamin; Thorand, Barbara; Strauch, Konstantin; Peters, Annette; Roden, Michael; Müller-Nurasyid, Martina; Liang, Liming; Kriebel, Jennifer; Illig, Thomas; Grallert, Harald; Gieger, Christian; Meisinger, Christa; Lannfelt, Lars; Musani, Solomon K; Griswold, Michael; Taylor, Herman A; Wilson, Gregory; Correa, Adolfo; Oksa, Heikki; Scott, William R; Afzal, Uzma; Tan, Sian-Tsung; Loh, Marie; Chambers, John C; Sehmi, Jobanpreet; Kooner, Jaspal Singh; Lehne, Benjamin; Cho, Yoon Shin; Lee, Jong-Young; Han, Bok-Ghee; Käräjämäki, Annemari; Qi, Qibin; Qi, Lu; Huang, Jinyan; Hu, Frank B; Melander, Olle; Orho-Melander, Marju; Below, Jennifer E; Aguilar, David; Wong, Tien Yin; Liu, Jianjun; Khor, Chiea-Chuen; Chia, Kee Seng; Lim, Wei Yen; Cheng, Ching-Yu; Chan, Edmund; Tai, E Shyong; Aung, Tin; Linneberg, Allan; Isomaa, Bo; Meitinger, Thomas; Tuomi, Tiinamaija; Hakaste, Liisa; Kravic, Jasmina; Jørgensen, Marit E; Lauritzen, Torsten; Deloukas, Panos; Stirrups, Kathleen E; Owen, Katharine R; Farmer, Andrew J; Frayling, Timothy M; O'Rahilly, Stephen P; Walker, Mark; Levy, Jonathan C; Hodgkiss, Dylan; Hattersley, Andrew T; Kuulasmaa, Teemu; Stančáková, Alena; Barroso, Inês; Bharadwaj, Dwaipayan; Chan, Juliana; Chandak, Giriraj R; Daly, Mark J; Donnelly, Peter J; Ebrahim, Shah B; Elliott, Paul; Fingerlin, Tasha; Froguel, Philippe; Hu, Cheng; Jia, Weiping; Ma, Ronald C W; McVean, Gilean; Park, Taesung; Prabhakaran, Dorairaj; Sandhu, Manjinder; Scott, James; Sladek, Rob; Tandon, Nikhil; Teo, Yik Ying; Zeggini, Eleftheria; Watanabe, Richard M; Koistinen, Heikki A; Kesaniemi, Y Antero; Uusitupa, Matti; Spector, Timothy D; Salomaa, Veikko; Rauramaa, Rainer; Palmer, Colin N A; Prokopenko, Inga; Morris, Andrew D; Bergman, Richard N; Collins, Francis S; Lind, Lars; Ingelsson, Erik; Tuomilehto, Jaakko; Karpe, Fredrik; Groop, Leif; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf; Kuusisto, Johanna; Abecasis, Gonçalo; Bell, Graeme I; Blangero, John; Cox, Nancy J; Duggirala, Ravindranath; Seielstad, Mark; Wilson, James G; Dupuis, Josee; Ripatti, Samuli; Hanis, Craig L; Florez, Jose C; Mohlke, Karen L; Meigs, James B; Laakso, Markku; Morris, Andrew P; Boehnke, Michael; Altshuler, David; McCarthy, Mark I; Gloyn, Anna L; Lindgren, Cecilia M

2017-01-01

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting insulin, a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in fasting plasma insulin (FI) levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-hour insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio=1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2. PMID:28341696

Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

DEFF Research Database (Denmark)

Akintola, Abimbola A; van den Berg, Annette; van Buchem, Mark A

2015-01-01

[fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR......-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p 65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose......, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction

Validation of insulin resistance indexes in a stable renal transplant population

NARCIS (Netherlands)

Oterdoom, Leendert H.; de Vries, Aiko P. J.; van Son, Willem J.; Homan van der Heide, Jaap J.; Ploeg, Rutger J.; Gansevoort, Ron T.; de Jong, Paul E.; Gans, Rijk O. B.; Bakker, Stephan J. L.

2005-01-01

The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and

Validation of insulin resistance indexes in a stable renal transplant population

NARCIS (Netherlands)

Oterdoom, LH; De Vries, APJ; Van Son, WJ; Van Der Heide, JJH; Ploeg, RJ; Gansevoort, RT; De Jong, PE; Gans, ROB; Bakker, SJL

2005-01-01

OBJECTIVE - The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. RESEARCH DESIGN AND METHODS - Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin

Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease.

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Pirgon, Özgür; Bilgin, Hüseyin; Çekmez, Ferhat; Kurku, Hüseyin; Dündar, Bumin Nuri

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8 ± 2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7 ± 2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance.

Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

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Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

2014-08-01

Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

Analog insulin detemir for patients with type 1 and type 2 diabetes: a review

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Gregory E Peterson

2009-05-01

Full Text Available Gregory E PetersonDepartment of Internal Medicine, Des Moines University, USAObjective: To review insulin detemir for clinical use to better manage patients with type 1 and type 2 diabetes.Methods: A MEDLINE search, in English, from June 30, 2006 to December 1, 2008, using the terms “insulin analogs,” “insulin detemir” and “long-acting insulin analog.”Results: Insulin detemir improves glycemic control, based on HbA1C reduction and fasting glucose levels, without increasing the risk of hypoglycemia and weight gain. Insulin detemir has lower glycemic variability, with less intra-subject variability in blood glucose levels in patients with type 1 and type 2 diabetes, without increasing the risk of hypoglycemia. When added to oral anti-diabetes agents (OADs in type 2 diabetes, insulin detemir demonstrates superiority to other basal insulin options.Conclusion: Insulin detemir appears to provide better glycemic control with a lower risk of hypoglycemia and less weight gain in the treatment of patients with type 1 and type 2 diabetes.Keywords: type 1 diabetes, type 2 diabetes, insulin analogs, insulin detemir

alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population.

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Walter E Gall

2010-05-01

Full Text Available Insulin resistance is a risk factor for type 2 diabetes and cardiovascular disease progression. Current diagnostic tests, such as glycemic indicators, have limitations in the early detection of insulin resistant individuals. We searched for novel biomarkers identifying these at-risk subjects.Using mass spectrometry, non-targeted biochemical profiling was conducted in a cohort of 399 nondiabetic subjects representing a broad spectrum of insulin sensitivity and glucose tolerance (based on the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing, respectively.Random forest statistical analysis selected alpha-hydroxybutyrate (alpha-HB as the top-ranked biochemical for separating insulin resistant (lower third of the clamp-derived M(FFM = 33 [12] micromol x min(-1 x kg(FFM (-1, median [interquartile range], n = 140 from insulin sensitive subjects (M(FFM = 66 [23] micromol x min(-1 x kg(FFM (-1 with a 76% accuracy. By targeted isotope dilution assay, plasma alpha-HB concentrations were reciprocally related to M(FFM; and by partition analysis, an alpha-HB value of 5 microg/ml was found to best separate insulin resistant from insulin sensitive subjects. alpha-HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of, and in an additive fashion to, insulin resistance. These associations were also independent of sex, age and BMI. Other metabolites from this global analysis that significantly correlated to insulin sensitivity included certain organic acid, amino acid, lysophospholipid, acylcarnitine and fatty acid species. Several metabolites are intermediates related to alpha-HB metabolism and biosynthesis.alpha-hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation. The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress.

Cortisol, obesity, and the metabolic syndrome: a cross-sectional study of obese subjects and review of the literature.

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Abraham, S B; Rubino, D; Sinaii, N; Ramsey, S; Nieman, L K

2013-01-01

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome (MS). To evaluate these relationships, a cross-sectional study of 369 overweight and obese subjects and 60 healthy volunteers was performed and reviewed the previous literature. Overweight and obese subjects had at least two other features of Cushing's syndrome. They underwent measurements representing cortisol dynamics (24 h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol, and weight from 60 healthy volunteers were analyzed. No subject had Cushing's syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P cortisol levels were weak to moderately correlated with fasting insulin (rs = -0.31, P = 0.01) and HOMA-IR (rs = -0.31, P = 0.01) in men and systolic (rs = 0.18, P = 0.02) and diastolic BP (rs = 0.20, P = 0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA-IR, and systolic BP (adjusted for BMI and gender; P cortisol and metabolic parameters. Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or MS. Copyright © 2013 The Obesity Society.

Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects

NARCIS (Netherlands)

ter Maaten, JC; Bakker, SJL; Serne, EH; Moshage, HJ; Gans, ROB

2000-01-01

Background Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

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Nicole M. Templeman

2017-07-01

Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

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Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

2017-07-11

The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin resistant phenotypes

DEFF Research Database (Denmark)

Malin, Steven K; Haus, Jacob M; Solomon, Thomas

2013-01-01

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance, however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilizati...

Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

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Everman, Sarah; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

2015-01-01

Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U) during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5) to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5). In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U) in association with the above BCAA infusion (N = 4) or under the same conditions without BCAA infusion (N = 3). Plasma glucose turnover was measured prior to and during insulin infusion. Insulin infusion completely suppressed the endogenous glucose production (EGP) across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05). Insulin infusion stimulated whole-body glucose disposal rate (GDR) across all groups. However, the increase (%) in GDR was not different [median (1st quartile - 3rd quartile)] between Control and BCAA in either the 40U ([199 (167-278) vs. 186 (94-308)] or 80 U ([491 (414-548) vs. 478 (409-857)] experiments (P > 0.05). Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P BCAA in either of the experiments (P > 0.05). Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

Directory of Open Access Journals (Sweden)

Sarah Everman

Full Text Available Plasma branched-chain amino acids (BCAA are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5 to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5. In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U in association with the above BCAA infusion (N = 4 or under the same conditions without BCAA infusion (N = 3. Plasma glucose turnover was measured prior to and during insulin infusion.Insulin infusion completely suppressed the endogenous glucose production (EGP across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05. Insulin infusion stimulated whole-body glucose disposal rate (GDR across all groups. However, the increase (% in GDR was not different [median (1st quartile - 3rd quartile] between Control and BCAA in either the 40U ([199 (167-278 vs. 186 (94-308] or 80 U ([491 (414-548 vs. 478 (409-857] experiments (P > 0.05. Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P 0.05.Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

AHSG tag single nucleotide polymorphisms associate with type 2 diabetes and dyslipidemia: studies of metabolic traits in 7,683 white Danish subjects

DEFF Research Database (Denmark)

Andersen, Gitte; Burgdorf, Kristoffer Sølvsten; Sparsø, Thomas

2008-01-01

been largely successful. We related seven frequent AHSG tag single nucleotide polymorphisms to a range of metabolic traits, including type 2 diabetes, obesity, and dyslipidemia. RESEARCH DESIGN AND METHODS: The polymorphisms were genotyped in 7,683 white Danish subjects using Taqman allelic...... with dyslipidemia (P = 0.003 and P(corr) = 0.009). Thr248Met (rs4917) tended to associate with lower fasting and post-oral glucose tolerance test serum insulin release (P = 0.02, P(corr) = 0.1 for fasting and P = 0.04, P(corr) = 0.2 for area under the insulin curve) and improved insulin sensitivity estimated...

METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes.

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Bello-Chavolla, Omar Yaxmehen; Almeda-Valdes, Paloma; Gomez-Velasco, Donaji; Viveros-Ruiz, Tannia; Cruz-Bautista, Ivette; Romo-Romo, Alonso; Sánchez-Lázaro, Daniel; Meza-Oviedo, Dushan; Vargas-Vázquez, Arsenio; Campos, Olimpia Arellano; Sevilla-González, Magdalena Del Rocío; Martagón, Alexandro J; Hernández, Liliana Muñoz; Mehta, Roopa; Caballeros-Barragán, César Rodolfo; Aguilar-Salinas, Carlos A

2018-05-01

We developed a novel non-insulin-based fasting score to evaluate insulin sensitivity validated against the euglycemic-hyperinsulinemic clamp (EHC). We also evaluated its correlation with ectopic fact accumulation and its capacity to predict incident type 2 diabetes mellitus (T2D). The discovery sample was composed by 125 subjects (57 without and 68 with T2D) that underwent an EHC. We defined METS-IR as Ln((2*G 0 )+TG 0 )*BMI)/(Ln(HDL-c)) (G 0 : fasting glucose, TG 0 : fasting triglycerides, BMI: body mass index, HDL-c: high-density lipoprotein cholesterol), and compared its diagnostic performance against the M-value adjusted by fat-free mass (MFFM) obtained by an EHC. METS-IR was validated in a sample with EHC data, a sample with modified frequently sampled intravenous glucose tolerance test (FSIVGTT) data and a large cohort against HOMA-IR. We evaluated the correlation of the score with intrahepatic and intrapancreatic fat measured using magnetic resonance spectroscopy. Subsequently, we evaluated its ability to predict incident T2D cases in a prospective validation cohort of 6144 subjects. METS-IR demonstrated the better correlation with the MFFM ( ρ  = -0.622, P  index obtained from the FSIVGTT (AUC: 0.67, 95% CI: 0.53-0.81). METS-IR significantly correlated with intravisceral, intrahepatic and intrapancreatic fat and fasting insulin levels ( P  50.39) had the highest adjusted risk to develop T2D (HR: 3.91, 95% CI: 2.25-6.81). Furthermore, subjects with incident T2D had higher baseline METS-IR compared to healthy controls (50.2 ± 10.2 vs 44.7 ± 9.2, P  < 0.001). METS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity. © 2018 European Society of Endocrinology.

Association of paraoxonase-1 gene polymorphisms with insulin resistance in South Indian population.

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Gomathi, Panneerselvam; Iyer, Anandi Chandramouli; Murugan, Ponniah Senthil; Sasikumar, Sundaresan; Raj, Nancy Bright Arul Joseph; Ganesan, Divya; Nallaperumal, Sivagnanam; Murugan, Maruthamuthu; Selvam, Govindan Sadasivam

2018-04-15

Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P  R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population. Copyright © 2018 Elsevier B.V. All rights reserved.

Insulin resistance in young adults born small for gestational age (SGA).

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Putzker, Stephanie; Bechtold-Dalla Pozza, Susanne; Kugler, Karl; Schwarz, Hans P; Bonfig, Walter

2014-03-01

This work aimed to assess glucose metabolism and insulin sensitivity in young adults born small for gestational age (SGA) as well as to measure the body composition and adipocytokines of these subjects. A total of 108 out of 342 SGA-born participants were invited for reexamination from the former Bavarian Longitudinal Study (BLS), in which 7505 risk-newborns of the years 1985 to 1986 were prospectively followed. Of these, 76 (34 female/42 male) participants at the age of 19.7±0.5 years were enrolled. Clinical examination and oral glucose tolerance testing (oGTT) was performed with assessment of insulin resistance indices, HbA1c, body mass index (BMI), adipocytokines, and body composition by bioimpedance analysis (BIA). A total of 25 out of 76 (32.9%) patients had abnormal fasting and/or glucose-stimulated insulin levels. Glucose values measured during oGTT showed no abnormalities, except one participant who had impaired glucose tolerance. Homeostasis model assessment insulin resistance index (HOMA-IR) was 1.92±4.2, and insulin sensitivity index by Matsuda (ISI(Matsuda)) showed mean values of 7.85±4.49. HOMA-IR>2.5 was found in 8 patients (10.5%), and 20 patients (26.3%) had an ISI(Matsuda)range for both genders and correlated significantly with BMI (r=0.465, p0.001), but not with adiponectin. Insulin resistance correlated with change in weight-for-height Z-score during the first 3 months of age, indicating that weight gain during that early phase might be a risk factor for the development of insulin resistance in children born SGA. A high percentage of insulin-resistant subjects were reconfirmed in a large German cohort of young adults born SGA. Therefore, regular screening for disturbances in glucose metabolism is recommended in these subjects.

Reduced viscosity Barley β-Glucan versus placebo: a randomized controlled trial of the effects on insulin sensitivity for individuals at risk for diabetes mellitus

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Schmelzer Wade

2011-08-01

Full Text Available Abstract Background Prior studies suggest soluble fibers may favorably affect glucose/insulin metabolism. Methods This prospective, randomized, placebo controlled, double blind, parallel group trial evaluated 50 generally healthy subjects without prior diagnosis of diabetes mellitus (44 completers, who were administered beverages containing placebo (control, lower dose (3 g/d, or higher dose (6 g/d reduced viscosity barley β-glucan (BBG extract. Subjects (68% women mean age 56 years, Body Mass Index (BMI 32 kg/m2 and baseline fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining Therapeutic Lifestyle Changes (TLC diet and consumed three 11 oz study beverages daily with meals for 12 weeks. The four primary study endpoint measures were plasma glucose and insulin [each fasting and post-Oral Glucose Tolerance Testing (OGTT]. Results Compared to placebo, administration of 3 g/d BBG over 12 weeks significantly reduced glucose incremental Area Under the Curve (iAUC measures during OGTT and 6 g/d BBG over 12 weeks significantly reduced fasting insulin as well as the related homeostasis model assessment of insulin resistance (HOMA-IR. Beverages were generally well tolerated with no serious adverse experiences and no significant differences between groups for adverse experiences. Per protocol instruction, subjects maintained body weight. Conclusions These findings suggest 6 g/d BBG consumed in a beverage over 12 weeks may improve insulin sensitivity among hyperglycemic individuals with no prior diagnosis of diabetes mellitus, and who experience no change in body weight. Trial Registration ClinicalTrials.gov Identifier: NCT01375803.

The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.

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Guerrero-Romero, Fernando; Simental-Mendía, Luis E; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Ramos-Zavala, María G; Hernández-González, Sandra O; Jacques-Camarena, Omar; Rodríguez-Morán, Martha

2010-07-01

To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. We performed a euglycemic-hyperinsulinemic clamp test. Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

The survey of abnormal glucose tolerance and insulin resistace and incidence of diabetes type 2 in poly cystic ovary syndrome patients in Shiraz

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marziye Akbarzadeh

2009-03-01

Full Text Available Background: Polycystic ovarian syndrome is one of the most commen hyper androgenic disorders affecting women, its prevalence being estimated at 5% – 10%. Our goal was to survey abnormal glucose tolerance, insulin resistance and incidence of diabetes type 2 in patients with polycystic ovary syndrome. Materials and methods: This investigation is a descriptive – analytic study which is done to survey abnormal glucose tolerance, insulin resistance and incidene of diabetes type 2 in polycystic ovary syndrome (PCOS. This study included 150 patients with the diagnosis of PCOS. These patients were chosen by target based sampling. Among the subjects, laboratory tests were performed for 125 patients. Questionnaire, fasting blood suger test, fasting insulin and glucose tolerance test by 75gr glucose, were used as data gathering tools. The results of the blood suger test were interpreted using the WHO 1999 criteria. Results: The results of oral and glucose tolerance test showed 14. 4 percent of the patients had impaired fasting glucose and 4 percent of the patients had diabetes type 2 (FBS>126mg/dl. Insulin resistance was seen in 9. 8 percent of the patients. 7. 2 percent of the patients had impaired blood suger after two hours (140-199 mg/dl and 0. 8 persent of patients had diabetes type 2 (200>mg/dl. Conclusion: level of fasting blood suger and insulin and ratio of fasting blood suger to fasting insulin were good markers for diagnosis of insulin resistance. American diabetic association recommended for the care of young women with PCOS, screening for impaired glucose tolerance and diabetes type2.

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

Subject-driven titration of biphasic insulin aspart 30 twice daily is non-inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open-label, parallel-group, multicenter trial.

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Yang, Wenying; Zhu, Lvyun; Meng, Bangzhu; Liu, Yu; Wang, Wenhui; Ye, Shandong; Sun, Li; Miao, Heng; Guo, Lian; Wang, Zhanjian; Lv, Xiaofeng; Li, Quanmin; Ji, Qiuhe; Zhao, Weigang; Yang, Gangyi

2016-01-01

The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID). In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group. Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

Correlation between the Plasma Insulin and Glucose Concentration in Normal Korean Adults

Energy Technology Data Exchange (ETDEWEB)

Lee, Jang Kyu; Sung, Ho Kyung; Kim, Jin Eui [Radiological Research Institute, Seoul (Korea, Republic of)

1971-09-15

The correlation between the plasma insulin, and glucose concentration was studied in healthy Korean adults consisting of 20 males and 22 females of 16 to 38 years of age. The blood samples of above subjects were obtained through cubital vein at arbitrary times during their usual working hours. Plasma insulin was assayed by means of double antibody system of radioimmunoassay technics, and blood glucose was determined by means of Van Slyke-Folch method. Results were as follows : 1. There were no differences in the blood sugar levels in relation to the plasma insulin concentration either by sex or age. 2. In the case, when the plasma insulin concentration was within 50 mmuU/ml, the correlation between the insulin, and glucose concentration existed, the ratio of which was expressed as; Plasma glucose concentration (mg/dl)=91.9 + 0.08 X Insulin concentration r=0.62. 3. Insulinogenic index was 12.4%, which was somewhat higher than other reports. 4. It is suggested that the correlation between plasma insulin and glucose concentration could be determined at arbitrary times instead of fasting times.

Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

Science.gov (United States)

Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

1995-05-01

A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects.

Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

Science.gov (United States)

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.

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

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Chih-Ting Su

2016-11-01

Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome.

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Pablo Perez-Martinez

Full Text Available Glucokinase Regulatory Protein (GCKR plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS risk.To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP and n-3 PUFA in MetS subjects.Homeostasis model assessment of insulin resistance (HOMA-IR, HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019, C-peptide (P = 0.004, HOMA-IR (P = 0.008 and CRP (P = 0.032 as compared with subjects carrying the minor T-allele (Leu446. In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.ClinicalTrials.gov NCT00429195.

Characterisation of insulin analogues therapeutically available to patients

KAUST Repository

Adams, Gary G.

2018-03-29

The structure and function of clinical dosage insulin and its analogues were assessed. This included \\'native insulins\\' (human recombinant, bovine, porcine), \\'fast-acting analogues\\' (aspart, glulisine, lispro) and \\'slow-acting analogues\\' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

Serum acylated ghrelin is negatively correlated with the insulin resistance in the CODING study.

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Peyvand Amini

Full Text Available Ghrelin is a 28-amino acid orexigenic peptide synthesized mainly in the stomach. Acute administration of ghrelin has been found to decrease insulin secretion. However, little data is available regarding whether ghrelin contributes to the long-term regulation of insulin resistance at the population level. The aim of this study is to investigate the association between circulating ghrelin and insulin resistance in a large population based study.A total of 2082 CODING study (Complex Diseases in the Newfoundland population: Environment and Genetics subjects were assessed. Subjects were of at least third generation Newfoundland descent, between the ages of 20 and 79 years, and had no serious metabolic, cardiovascular, or endocrine diseases. Ghrelin was measured with an Enzyme Immunoassay method. Insulin and fasting glucose were measured by Immulite 2500 autoanalyzer and Lx20 clinical chemistry analyzer, respectively. Homeostatic Model Assessment of β cell function (HOMA-β and Insulin Resistance (HOMA-IR and Quantitative Insulin-sensitivity Check Index (QUICKI were used for measurement of insulin resistance.Partial correlation analyses showed a significant negative correlation between circulating ghrelin and insulin level and insulin resistance in the entire cohort and also in men and women separately. The aforementioned correlation was independent of age, percentage of trunk fat and HDL-cholesterol. According to menopausal status, only pre-menopausal women revealed negative correlations.Our results suggest that except for postmenopausal women, high circulating ghrelin level is associated with lower insulin resistance in the general population.

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.

Some metabolic and anthropometric variables in obes children by measuring serum insulin, and leptin

International Nuclear Information System (INIS)

Nour Eldin, A.M.

2004-01-01

The present study aimed to assess serum leptin level in obese children to study its correlation with some metabolic variables as serum insulin and serum glucose. The study was conducted on 30 obese children of age from 9-14 years with body mass index (BMI) > 27.8 Kg/m 2 . All children were subjected to history taking, clinical examination, anthropometric measurements and laboratory investigations including fasting serum leptin, insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml) compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric measurements and laboratory investigations including fasting serum insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml)compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric variables was positively correlated with BMI r s = 0.68, (p s = 0.59.(p<0.01). It is concluded that serum leptin is increased in obesity and its concentration effects the size of the body. Moreover, the relation of leptin and insulin suggests a positive role of leptin in insulin resistance, which are common metabolic disorders associated with obesity

Characterization of the chicken muscle insulin receptor

International Nuclear Information System (INIS)

Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

1987-01-01

Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

Supervised Exercise Training Counterbalances the Adverse Effects of Insulin Therapy in Overweight/Obese Subjects With Type 2 Diabetes

OpenAIRE

Balducci, Stefano; Zanuso, Silvano; Cardelli, Patrizia; Salerno, Gerardo; Fallucca, Sara; Nicolucci, Antonio; Pugliese, Giuseppe

2011-01-01

OBJECTIVE To examine the effect of supervised exercise on traditional and nontraditional cardiovascular risk factors in sedentary, overweight/obese insulin-treated subjects with type 2 diabetes from the Italian Diabetes Exercise Study (IDES). RESEARCH DESIGN AND METHODS The study randomized 73 insulin-treated patients to twice weekly supervised aerobic and resistance training plus structured exercise counseling (EXE) or to counseling alone (CON) for 12 months. Clinical and laboratory paramete...

Effect of metformin compared with hypocaloric diet on serum C-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome.

Science.gov (United States)

Esfahanian, Fatemeh; Zamani, Mohammad Mahdi; Heshmat, Ramin; Moini nia, Fatemeh

2013-04-01

The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein (CRP) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome (PCOS). Forty women with body mass index ≥ 27 and PCOS were randomly allocated to receive either Metformin or hypocaloric diet and were assessed before and after a treatment period of 12 weeks. High-sensitivity CRP (hs-CRP) and markers of insulin resistance (IR), homeostasis model assessment-IR, quantitative insulin-sensitivity check index and fasting glucose to insulin ratio were evaluated in each patient. A total of 10 subjects did not complete the trial (three patients in the Metformin group and seven patients in the diet group) and a total of 30 subjects completed the trial (17 subjects in the Metformin group and 13 subjects in the diet group). Serum concentration of hs-CRP significantly decreased in both the Metformin (5.29 ± 2.50 vs 3.81 ± 1.99, P = 0.008) and diet groups (6.08 ± 2.14 vs 4.27 ± 1.60, P = 0.004). There were no significant differences in mean hs-CRP decrement between the two groups. Decrease in hs-CRP levels was significantly correlated with waist circumference in the diet group (r = 0.8, P hypocaloric diet with 5-10% weight reduction on markers of insulin resistance (homeostasis model assessment-IR, fasting glucose to insulin ratio, quantitative insulin-sensitivity check index) was better than Metformin therapy (P = 0.001). Although weight reduction has equal efficacy with Metformin in decreasing serum hs-CRP levels, it was significantly more effective in improving insulin resistance in obese and overweight PCOS women. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Radioimmunoassay of insulin by the double antibody method. Evaluation of the technique in practice

International Nuclear Information System (INIS)

Wojckikowski, C.; Zakoslki, W.

1974-01-01

The aim of this study was to develop a simplified procedure for the radioimmunoassay of insulin by the double antibody method. Anti-insulin serum was obtained by immunizing guinea pigs with porcine insulin suspended in Freund's incomplete adjuvant supplemented with Hemophilus pertussis vaccine. After two injections, sera from four guinea pigs diluted 1:10,000 bound more than 70% of the 125 I-insulin added. Under the conditions of the method, the insulin binding reagent bound 43%+-5% (n=94) of added 125 I-insulin. Accuracy of the method in simultaneous series for insulin concentrations of 27 μU/ml and 49 μU/ml was +-5% and +-7% respectively; and in a nonsimultaneous series of determinations for insulin concentrations of 21 μU/ml and 77 μU/ml, +-11% and +-8%. Recovery of insulin added to human plasma was 104%. Concentrations of insulin in the plasma of healthy fasting subjects ranged from 5-22 μU/ml (m=13+-5 μU/ml; n=21). The results were in complete agreement with results obtained by the use of the Amersham radioimmunoassay insulin kit. (author)

Radioimmunoassay of insulin by the double antibody method. Evaluation of the technique in practice

Energy Technology Data Exchange (ETDEWEB)

Wojckikowski, C; Zakoslki, W [Akademia Medyczna, Gdansk (Poland)

1974-01-01

The aim of this study was to develop a simplified procedure for the radioimmunoassay of insulin by the double antibody method. Anti-insulin serum was obtained by immunizing guinea pigs with porcine insulin suspended in Freund's incomplete adjuvant supplemented with Hemophilus pertussis vaccine. After two injections, sera from four guinea pigs diluted 1:10,000 bound more than 70% of the /sup 125/I-insulin added. Under the conditions of the method, the insulin binding reagent bound 43%+-5% (n=94) of added /sup 125/I-insulin. Accuracy of the method in simultaneous series for insulin concentrations of 27 ..mu..U/ml and 49 ..mu..U/ml was +-5% and +-7% respectively; and in a nonsimultaneous series of determinations for insulin concentrations of 21 ..mu..U/ml and 77 ..mu..U/ml, +-11% and +-8%. Recovery of insulin added to human plasma was 104%. Concentrations of insulin in the plasma of healthy fasting subjects ranged from 5-22 ..mu..U/ml (m=13+-5 ..mu..U/ml; n=21). The results were in complete agreement with results obtained by the use of the Amersham radioimmunoassay insulin kit.

Central insulin administration improves odor-cued reactivation of spatial memory in young men.

Science.gov (United States)

Brünner, Yvonne F; Kofoet, Anja; Benedict, Christian; Freiherr, Jessica

2015-01-01

Insulin receptors are ubiquitously found in the human brain, comprising the olfactory bulb, essential for odor processing, and the hippocampus, important for spatial memory processing. The present study aimed at examining if intranasal insulin, which is known to transiently increase brain insulin levels in humans, would improve odor-cued reactivation of spatial memory in young men. We applied a double-blind, placebo-controlled, counterbalanced within-subject design. The study was conducted at the research unit of a university hospital. Interventions/Participants/Main Outcome Measures: Following intranasal administration of either insulin (40 I.U.) or placebo, male subjects (n = 18) were exposed to eight odors. During each odor exposure, a green-colored field was presented on a 17-in. computer screen. During immediate recall (comprising 3 runs), the participants were re-exposed to each odor cue, and were asked to select the corresponding field (with visual feedback after each response). The delayed recall was scheduled ∼10 min later (without feedback). To test if insulin's putative effect on odor-place memory would be domain-specific, participants also performed a separate place and odor recognition task. Intranasal insulin improved the delayed but not immediate odor-cued recall of spatial memory. This effect was independent of odor type and in the absence of systemic side effects (eg, fasting plasma glucose levels remained unaltered). Place and odor recognition were unaffected by the insulin treatment. These findings suggest that acute intranasal insulin improves odor-cued reactivation of spatial memory in young men.

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)

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus

NARCIS (Netherlands)

Schindhelm, RK; Diamant, M; Bakker, SJL; van Dijk, RAJM; Scheffer, PG; Teerlink, T; Kostense, PJ; Heine, RJ

Background Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus

NARCIS (Netherlands)

Schindhelm, R.K.; Diamant, M.; Bakker, S.J.L.; van Dijk, R.A.; Scheffer, P.G.; Teerlink, T.; Kostense, P.J.; Heine, R.J.

2005-01-01

Background: Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer

Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects

International Nuclear Information System (INIS)

Wolfe, R.R.; Peters, E.J.; Klein, S.; Holland, O.B.; Rosenblatt, J.; Gary, H. Jr.

1987-01-01

In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion were determined. The rate of appearance (R/sub a/) of free fatty acids (FFA) and glycerol were quantified by infusion of [1- 13 C]palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H 2 18 O dilution. In normal volunteers, the basal R/sub a/ FFA and R/sub a/ glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting

Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts

Science.gov (United States)

Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether...

Clinical significance of changes of serum true insulin and proinsulin levels in relations of patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Tian Xiaoping; Huang Huijian; Huang Haibo; Wu Yan; He Haoming

2004-01-01

Objective: To explore the degree of insulin resistance and β-cell secretory function impairment in close (1st degree) relations of patients with type 2 diabetes (DMII). Methods: Serum true insulin (TI), pro-insulin (PI), immunoreactive insulin (IRI) levels at fasting and after oral 75g glucose loading were determined in: 1) patients with DM 2, n=65 2)relations of DM 2 patients with impaired glucose tolerance (IGT), n=34 3) relations of DM 2 patients with normal glucose tolerance (NGT), n=66 and 4) controls, n=48. HOMA-IR and HOMA-β cell secretory indices were calculated from the data. Results: Fasting serum PI levels were significantly higher in DM 2 patients, relations with IGT and NGT than those in the controls (t=2.38, t=2.16, t=1.95, P 1 C percentages were significantly higher in DM 2 patients and IGT, NGT groups than those in controls (t=3.67, t=2.45, t=1.97, P 1 C percentage, fasting TI and IRI levels. Conclusion: Insulin resistance was already obvious in those relations of DM 2 patients with normal glucose tolerance and β-cell secretory function impairment was also present. Early intervention in these subjects might be beneficial. (authors)

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

Science.gov (United States)

Liang, Hanyu; Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J; Musi, Nicolas

2018-01-01

The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

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)

Metformin and insulin receptors

International Nuclear Information System (INIS)

Vigneri, R.; Gullo, D.; Pezzino, V.

1984-01-01

The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting.

Science.gov (United States)

Heemstra, Karen A; Soeters, Maarten R; Fliers, Eric; Serlie, Mireille J; Burggraaf, Jacobus; van Doorn, Martijn B; van der Klaauw, Agatha A; Romijn, Johannes A; Smit, Johannes W; Corssmit, Eleonora P; Visser, Theo J

2009-06-01

The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in systemic as well as local T3 production. We determined D2 activity and D2 mRNA expression in human skeletal muscle biopsies under control conditions and during hypothyroidism, fasting, and hyperinsulinemia. This was a prospective study. The study was conducted at a university hospital. We studied 11 thyroidectomized patients with differentiated thyroid carcinoma (DTC) on and after 4 wk off T4( replacement and six healthy lean subjects in the fasting state and during hyperinsulinemia after both 14 and 62 h of fasting. D2 activity and D2 mRNA levels were measured in skeletal muscle samples. No differences were observed in muscle D2 mRNA levels in DTC patients on and off T4 replacement therapy. In healthy subjects, muscle D2 mRNA levels were lower after 62 h compared to 14 h of fasting. Insulin increased mRNA expression after 62 h, but not after 14 h of fasting. Skeletal muscle D2 activities were very low and not influenced by hypothyroidism and fasting. Human skeletal muscle D2 mRNA expression is modulated by fasting and insulin, but not by hypothyroidism. The lack of a clear effect of D2 mRNA modulation on the observed low D2 activities questions the physiological relevance of D2 activity in human skeletal muscle.

Effects of acute exercise on pancreatic endocrine function in subjects with type 2 diabetes

DEFF Research Database (Denmark)

Knudsen, Sine H; Karstoft, Kristian; Winding, Kamilla

2015-01-01

We determined the effects of exercise on pancreatic endocrine responses to metabolic stimuli in type 2 diabetic (T2D) subjects and examined the influence of the diabetic status. Fourteen subjects underwent a hyperglycaemic clamp with GLP-1 infusion and arginine injection, the morning after a one.......05-P arginine (P = 0.08). The same trends were seen for low HbA1c subjects. Furthermore, exercise increased GLP-1- and arginine-stimulated insulin secretion (P diabetic......-hour walk or no exercise. Subjects were stratified by high and low quantiles of fasting plasma glucose (FPG) and HbA1c as well as current use/non-use of anti-diabetic medication. In the entire cohort, exercise did not alter insulin secretion, while glucagon levels were increased in all clamp phases (P 

Circulating Levels of Irisin in Hypopituitary and Normal Subjects.

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Lara Pena-Bello

Full Text Available The recently identified myokine irisin conveys some of the benefits of exercise. Hypopituitarism with adult growth hormone deficiency (HP is a situation characterized by decreased GH secretion and an altered body composition.Our aim was to study the skeletal muscle hormone irisin in HP, and compare the results with a similar group of normal subjects.Seventeen HP patients and fifty-one normal subjects of similar age and sex were studied. The diagnosis of GH deficiency was confirmed by the presence of pituitary disease and a peak GH secretion below 3 μg/L after an insulin tolerance test. The patients were adequately treated for all pituitary hormone deficits, except for GH. Fasting serum irisin was measured with an enzyme immunoassay, and HOMA-IR, QUICKI and HOMA-β were calculated.Fasting irisin levels (ng/ml were similar in normal [208.42 (168.44-249.23] and HP patients [195.13 (178.44-241.44]. In the control group there were moderate significant positive correlations between irisin and BMI, waist circumference, leptin, fasting insulin, HOMA-IR, HOMA-β, triglycerides, and cholesterol. In the control group there were moderate significant negative correlations between irisin and IGF-I and QUICKI. In the hypopituitary group there were moderate significant positive correlations between irisin and body fat and HOMA-β.We found similar irisin levels in GH deficiency hypopituitary patients when compared with normal subjects. The correlation between irisin and adiposity related factors suggests that that in the case of this clinical model, irisin is regulated by adiposity and not by GH.

Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats

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Xin-Yu Huang

2016-01-01

Full Text Available To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6, Zusanli (ST36, and Sanyinjiao (SP6; in contrast, acupuncture to Shenshu (BL23 was administered perpendicularly. For Neiguan (PC6 and Zusanli (ST36, needles were connected to an electroacupuncture (EA apparatus. Fasting blood glucose (FPG was measured by glucose oxidase method. Plasma fasting insulin (FINS and serum C peptide (C-P were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR, which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

Intranasal insulin therapy: the clinical realities

DEFF Research Database (Denmark)

Hilsted, J; Madsbad, Sten; Hvidberg, A

1995-01-01

To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose

Czech Academy of Sciences Publication Activity Database

Wohl, P.; Krušinová, E.; Hill, M.; Kratochvílová, S.; Zídková, K.; Kopecký, J.; Neškudla, T.; Pravenec, Michal; Klementová, M.; Vrbíková, J.; Wohl, P.; Mlejnek, Petr; Pelikánová, T.

2010-01-01

Roč. 163, č. 4 (2010), s. 573-583 ISSN 0804-4643 R&D Projects: GA MZd(CZ) NR9359; GA MZd(CZ) NS10528 Institutional research plan: CEZ:AV0Z50110509 Keywords : telmisartan * insulin resistance * adipokines Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.482, year: 2010

Lack of relationship between plasma insulin and glucogen levels and angiographically-documented coronary atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Mookherjee, S; Potts, J L; Hill, N E; Warner, R; Raheja, K L; Patel, D G; Vardan, S; Smulyan, H [Upstate Medical Center, Syracuse, NY (USA)

1983-10-01

In 120 consecutive patients undergoing diagnostic coronary arteriography, fasting blood glucose, plasma insulin, glucagon, serum cholesterol and triglyceride concentrations were measured. The insulin-glucose ratio and insulin-glucagon ratio were calculated. Forty-five patients had normal coronary arteries, 19 had single vessel coronary artery disease and 56 patients had multiple vessel disease. Fasting blood glucose was >120 mg/100 ml in 37 patients (group A) and included 9 of the 10 known diabetics, 3 of whom were being treated with insulin. Seventy-seven patients included in group B had fasting blood glucose concentration <120 mg/100 ml. Patients with multiple vessel coronary disease in either group had higher blood glucose and cholesterol concentrations than those with normal coronary arteries or glucagon levels nor increased insulin-glucose or insulin-glucagon ratios. With comparable extent of coronary artery disease patients in group A had higher plasma insulin levels and insulin-glucagon ratios than those in group B, but no correlation exists between the presence of extent of coronary atherosclerosis and these variables in either group. Thus, neither fasting plasma insulin level nor insulin-glucagon ratio predicts the status of underlying coronary atherosclerosis in either diabetes or nondiabetes.

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

International Nuclear Information System (INIS)

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 whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects.

Science.gov (United States)

Frid, Anders H; Nilsson, Mikael; Holst, Jens Juul; Björck, Inger M E

2005-07-01

Whey proteins have insulinotropic effects and reduce the postprandial glycemia in healthy subjects. The mechanism is not known, but insulinogenic amino acids and the incretin hormones seem to be involved. The aim was to evaluate whether supplementation of meals with a high glycemic index (GI) with whey proteins may increase insulin secretion and improve blood glucose control in type 2 diabetic subjects. Fourteen diet-treated subjects with type 2 diabetes were served a high-GI breakfast (white bread) and subsequent high-GI lunch (mashed potatoes with meatballs). The breakfast and lunch meals were supplemented with whey on one day; whey was exchanged for lean ham and lactose on another day. Venous blood samples were drawn before and during 4 h after breakfast and 3 h after lunch for the measurement of blood glucose, serum insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1). The insulin responses were higher after both breakfast (31%) and lunch (57%) when whey was included in the meal than when whey was not included. After lunch, the blood glucose response was significantly reduced [-21%; 120 min area under the curve (AUC)] after whey ingestion. Postprandial GIP responses were higher after whey ingestion, whereas no differences were found in GLP-1 between the reference and test meals. It can be concluded that the addition of whey to meals with rapidly digested and absorbed carbohydrates stimulates insulin release and reduces postprandial blood glucose excursion after a lunch meal consisting of mashed potatoes and meatballs in type 2 diabetic subjects.

In Vivo Experimental Study of Noninvasive Insulin Microinjection through Hollow Si Microneedle Array

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Drago Resnik

2018-01-01

Full Text Available An experimental study of in vivo insulin delivery through microinjection by using hollow silicon microneedle array is presented. A case study was carried out on a healthy human subject in vivo to determine the influence of delivery parameters on drug transfer efficiency. As a microinjection device, a hollow microneedle array (13 × 13 mm2 having 100 microneedles (220 µm high, 130 µm-outer diameter and 50 µm-inner diameter was designed and fabricated using classical microfabrication techniques. The efficiency of the delivery process was first characterized using methylene blue and a saline solution. Based on these results, the transfer efficiency was found to be predominantly limited by the inability of viable epidermis to absorb and allow higher drug transport toward the capillary-rich region. Two types of fast-acting insulin were used to provide evidence of efficient delivery by hollow MNA to a human subject. By performing blood analyses, infusion of more-concentrated insulin (200 IU/mL, international units (IU exhibited similar blood glucose level drop (5–7% compared to insulin of standard concentration (100 IU/mL, however, significant increase of serum insulin (40–50% with respect to the preinfusion values was determined. This was additionally confirmed by a distinctive increase of insulin to C-peptide ratio as compared to preinfusion ratio. Moreover, we noticed that this route of administration mimics a multiple dose regimen, able to get a “steady state” for insulin plasma concentration.

Rapid changes in plasma androgens during insulin withdrawal in male type 1 (insulin-dependent) diabetics

DEFF Research Database (Denmark)

Madsbad, S; Gluud, C; Bennett, Patrick

1986-01-01

Plasma concentrations of testosterone, androstenedione and dihydrotestosterone were measured in 15 Type 1 (insulin-dependent) diabetics with (n = 8) and without (n = 7) B-cell function during 12 h of insulin withdrawal and compared with those of 8 normal subjects. Before insulin withdrawal......, testosterone and dihydrotestosterone concentrations were lower in the diabetics after 4 h of insulin withdrawal and remained so throughout the study. The concentrations of androstenedione were not significantly different between diabetics and normal subjects except after 4 h of insulin withdrawal. Despite...

Pancreatic beta-cell function is a stronger predictor of changes in glycemic control after an aerobic exercise intervention than insulin sensitivity

DEFF Research Database (Denmark)

Solomon, Thomas; Malin, Steven K; Karstoft, Kristian

2013-01-01

glucose-stimulated insulin secretion (GSIS), and disposition index (DI) were measured following 12-16-weeks of aerobic exercise training. Regression analyses were used to identify relationships between variables.ResultsFollowing training, 86% of subjects increased VO2max and lost weight. HbA1c, fasting......ContextUnderstanding inter-subject variability in glycemic control following exercise training will help individualize treatment.ObjectiveTo determine whether this variability is related to training-induced changes in insulin sensitivity or pancreatic beta-cell function.Design, Setting....... Training increased first- and second-phase DI in 83% and 74% of subjects. Training-induced changes in glycemic control were related to changes in GSIS (P...

Unprecedented high insulin secretion in a healthy human subject after intravenous glucagon-like peptide-1

DEFF Research Database (Denmark)

Knop, Filip K; Lund, Asger; Madsbad, Sten

2014-01-01

BACKGROUND: The gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are released in response to ingestion of nutrients. Both hormones are highly insulinotropic in strictly glucose-dependent fashions and glucagon-like peptide-1 is often referred...... to as one of the most insulinotropic substances known. CASE PRESENTATION: Plasma insulin and C-peptide concentrations were measured in a healthy Caucasian male (age: 53 years; body mass index: 28.6 kg/m2; fasting plasma glucose: 5.7 mM; 2 h plasma glucose value following 75 g-oral glucose tolerance test: 3...

Professional continuous glucose monitoring for the identification of type 1 diabetes mellitus among subjects with insulin therapy.

Science.gov (United States)

Chen, Yin-Chun; Huang, Yu-Yao; Li, Hung-Yuan; Liu, Shih-Wei; Hsieh, Sheng-Hwu; Lin, Chia-Hung

2015-01-01

The identification of type 1 diabetes in diabetic subjects receiving insulin therapy is sometimes difficult. The purpose of this study is to evaluate whether results of professional continuous glucose monitoring can improve the identification of type 1 diabetes.From 2007 to 2012, 119 adults receiving at least twice-daily insulin therapy and professional continuous glucose monitoring were recruited. Type 1 diabetes was diagnosed by endocrinologists according to American Diabetes Association standards, including a very low C-peptide level (diabetic ketoacidosis. Continuous glucose monitoring was applied for 3 days.Among 119 subjects, 86 were diagnosed with type 1 diabetes. Subjects with type 1 diabetes were younger (33.8 vs 52.3 years old, P 1), had lower body mass index (BMI, 21.95 vs 24.42, P = 0.003), lower serum creatinine (61.77  vs 84.65 μmol/L, P = 0.001), and higher estimated glomerular filtration rate (108.71 vs 76.48 mg/mL/min/1.73m2, P 1) than subjects with type 2 diabetes. Predictive scores for identification of type 1 diabetes were constructed, including age, BMI, average mean amplitude of glucose excursion in days 2 and 3, and the area under the curve of nocturnal hyperglycemic and hypoglycemic states. The area under the receiver operating characteristic curve was 0.90. With the cutoff of 0.58, the sensitivity was 86.7% and the specificity was 80.8%. The good performance was validated by the leave-one-out method (sensitivity 83.3%, specificity 73.1%).Professional continuous glucose monitoring is a useful tool that improves identification of type 1 diabetes among diabetic patients receiving insulin therapy.

Effects of supervised structured aerobic exercise training program on fasting blood glucose level, plasma insulin level, glycemic control, and insulin resistance in type 2 diabetes mellitus.

Science.gov (United States)

Shakil-Ur-Rehman, Syed; Karimi, Hossein; Gillani, Syed Amir

2017-01-01

To determine the effects of supervised structured aerobic exercise training (SSAET) program on fasting blood glucose level (FBGL), plasma insulin level (PIL), glycemic control (GC), and insulin resistance (IR) in type 2 diabetes mellitus (T2DM). Riphah Rehabilitation and Research Centre (RRRC) was the clinical setting for this randomized controlled trial, located at Pakistan Railways General Hospital (PRGH), Rawalpindi, Pakistan. Study duration was 18 months from January 1, 2015 to June 30, 2016. Patients of both genders ranging 40-70 years of age with at least one year of history of T2DM were considered eligible according to WHO criteria, while patients with other chronic diseases, history of smoking, regular exercise and diet plan were excluded. Cohorts of 195 patients were screened out of whom 120 fulfilled the inclusion criteria. Amongst them 102 agreed to participate and were assigned to experimental (n=51) and control (n=51) groups. Experimental group underwent SSAET program, routine medication and dietary plan, whereas the control group received routine medication and dietary plan, while both group received treatment for 25 weeks. The blood samples were taken at baseline and on the completion of 25 weeks. The investigation of fasting blood glucose level, plasma insulin level, and glycemic control was conducted to calculate IR. Patients with T2DM in experimental group (n=51) treated with SSAET program, routine medication and dietary plan significantly improved FBGL (pre-mean= 276.41±25.31, post-mean=250.07±28.23), PIL (pre-mean=13.66±5.31, post-mean=8.91±3.83), GC (pre-mean=8.31±1.79, post-mean 7.28±1.43), and IR (pre-mean=64.95±27.26, post-mean 37.97±15.58), as compared with patients in control group treated with routine medication and dietary plan in whom deteriorations were noted in FBGL (pre-mean=268.19±22.48, post-mean=281.41±31.30), PIL(pre-mean=14.14±5.48, post-mean=14.85±5.27) GC (pre-mean=8.15±1.74, post-mean=8.20±1.44, and IR (pre

Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

Science.gov (United States)

Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

2014-08-05

The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between insulin resistance and plasma endothelin in hypertension patients

International Nuclear Information System (INIS)

Duan Yongqiang; Wang Zuobing; Yu Hui; Cao Wei; Wang Jing; Li Xiaoqin

2011-01-01

To explore the relationship between plasma endothelin and hypertension insulin resistance, and the improvement of insulin resistance in hypertension patients treated with captopril and l-amlodipine, 25 patients with primary hypertension and impaired glucose tolerance were selected and treated by captopril and l-amlodipine. Systolic pressure, diastolic pressure, fasting blood glucose, insulin and insulin antibody were measured before and after treatment and compared with healthy controls. The results showed that the plasma ET-1 level in hypertension group was significantly higher than that of healthy controls (P<0.01), and he plasma ET-1 level was positively correlated with FPG, FINS, Anti-INS, HOMA-IR. The systolic pressure, diastolic pressure, fasting blood glucose, insulin, insulin antibody and insulin resistance index in hypertension patients were decreased significantly after treatment (P<0.05). There is a good correlation between endothelin and insulin resistance index in hypertension patients. Captopril and l-amlodipine had obvious improvement effect on insulin resistance in hypertension patients. (authors)

Poor zinc status is associated with increased risk of insulin resistance in Spanish children.

Science.gov (United States)

Ortega, R M; Rodríguez-Rodríguez, E; Aparicio, A; Jiménez, A I; López-Sobaler, A M; González-Rodríguez, L G; Andrés, P

2012-02-01

Zn plays a key role in the synthesis and action of insulin. The aim of the present work was to determine whether a poorer Zn status was associated with insulin resistance in a group of 357 Spanish schoolchildren. Zn intake was determined by using a 3 d food record (i.e. Sunday to Tuesday). The body weight, height and waist and hip circumferences of all subjects were recorded and fasting plasma glucose, insulin and Zn concentrations were determined. Insulin resistance was determined using the homoeostasis model assessment (HOMA) marker. Children (11·5 %) with Zn deficiency (serum Zn concentration 3·16 made a significantly smaller contribution to the coverage of those recommended (59·7 (sd 14·7) %) than observed in children with lower HOMA values (73·6 (sd 18·2) %; P health and nutritional status of these children, and thus contribute to diminish problems of insulin resistance.

FoxO6 Integrates Insulin Signaling With Gluconeogenesis in the Liver

Science.gov (United States)

Kim, Dae Hyun; Perdomo, German; Zhang, Ting; Slusher, Sandra; Lee, Sojin; Phillips, Brett E.; Fan, Yong; Giannoukakis, Nick; Gramignoli, Roberto; Strom, Stephen; Ringquist, Steven; Dong, H. Henry

2011-01-01

OBJECTIVE Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied the ability of forkhead box O6 (FoxO6) to mediate insulin action on hepatic gluconeogenesis and its contribution to glucose metabolism. RESEARCH DESIGN AND METHODS We characterized FoxO6 in glucose metabolism in cultured hepatocytes and in rodent models of dietary obesity, insulin resistance, or insulin-deficient diabetes. We determined the effect of FoxO6 on hepatic gluconeogenesis in genetically modified mice with FoxO6 gain- versus loss-of-function and in diabetic db/db mice with selective FoxO6 ablation in the liver. RESULTS FoxO6 integrates insulin signaling to hepatic gluconeogenesis. In mice, elevated FoxO6 activity in the liver augments gluconeogenesis, raising fasting blood glucose levels, and hepatic FoxO6 depletion suppresses gluconeogenesis, resulting in fasting hypoglycemia. FoxO6 stimulates gluconeogenesis, which is counteracted by insulin. Insulin inhibits FoxO6 activity via a distinct mechanism by inducing its phosphorylation and disabling its transcriptional activity, without altering its subcellular distribution in hepatocytes. FoxO6 becomes deregulated in the insulin-resistant liver, accounting for its unbridled activity in promoting gluconeogenesis and correlating with the pathogenesis of fasting hyperglycemia in diabetes. These metabolic abnormalities, along with fasting hyperglycemia, are reversible by selective inhibition of hepatic FoxO6 activity in diabetic mice. CONCLUSIONS Our data uncover a FoxO6-dependent pathway by which the liver orchestrates insulin regulation of gluconeogenesis, providing the proof-of-concept that selective FoxO6 inhibition is beneficial for curbing excessive hepatic glucose production and improving glycemic control in diabetes. PMID:21940782

Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

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Ellen B. Fung

2015-06-01

Full Text Available Up to 20% of adult patients with Thalassemia major (Thal live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05 and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048. Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL, showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL and insulin to glucose ratios at 120 min post glucose dose (p = 0.05. Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

Science.gov (United States)

Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Houten, Sander M.

2014-01-01

Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = −0.36, P fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. PMID:24432996

GLUT-4 content in plasma membrane of muscle from patients with non-insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Lund, S; Vestergaard, H; Andersen, P H

1993-01-01

The abundance of GLUT-4 protein in both total crude membrane and plasma membrane fractions of vastus lateralis muscle from 13 obese non-insulin-dependent diabetes mellitus (NIDDM) patients and 14 healthy subjects were examined in the fasting state and after supraphysiological hyperinsulinemia....... In the basal state the immunoreactive mass of GLUT-4 protein both in the crude membrane preparation and in the plasma membrane fraction was similar in NIDDM patients and control subjects. Moreover, in vivo insulin exposure neither for 30 min nor for 4 h had any impact on the content of GLUT-4 protein in plasma...... membranes. With the use of the same methodology, antibody, and achieving the same degree of plasma membrane purification and recovery, we found, however, that intraperitoneal administration of insulin to 7-wk-old rats within 30 min increased the content of GLUT-4 protein more than twofold (P

Studies on insulin receptor, 2

International Nuclear Information System (INIS)

Sakai, Yukio

1979-01-01

The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125 I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125 I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

Normalization of fasting glycaemia by intravenous GLP-1 ([7-36 amide] or [7-37]) in type 2 diabetic patients

DEFF Research Database (Denmark)

Nauck, M A; Weber, I; Bach, I

1998-01-01

(glucose-oxidase), insulin and C-peptide (ELISA) was measured during infusion and for 4 h thereafter. Indirect calorimetry was performed. Fasting hyperglycaemia was 11.7+/-0.9 [7-36 amide] and 11.3+/-0.9 mmol l(-1) [7-37]. GLP-1 infusions stimulated insulin secretion approximately 3-fold (insulin peak 168......Intravenous GLP-1 [7-36 amide] can normalize fasting hyperglycaemia in Type 2 diabetic patients. Whether GLP-1 [7-37] has similar effects and how quickly plasma glucose concentrations revert to hyperglycaemia after stopping GLP-1 is not known. Therefore, 8 patients with Type 2 diabetes (5 female, 3...... male; 65+/-6 years; BMI 34.3+/-7.9 kg m(-2); HbA1c 9.6+/-1.2%; treatment with diet alone (n=2), sulphonylurea (n=5), metformin (n=1)) were examined twice in randomized order. GLP-1 [7-36 amide] or [7-37] (1 pmol kg(-1)min(-1) were infused intravenously over 4 h in fasted subjects. Plasma glucose...

Body Fat Distribution, Serum Leptin, And Insulin Resistance In Obese Subjects With Obstructive Sleep Apnoea

OpenAIRE

Hassan ZA*,Attia MF**, Ahmed AH**;Hassan HA***,

2006-01-01

Obstructive sleep apnoea (OS A) is strongly associated with obesity and is characterized by endocrine and metabolic changes. The aim of the present study is to clarify whether there is interrelationship between body fat, serum leptin, glucose-insulin metabolism and OSA. Subjects and measurements: we studied 23 obese subjects with OSA (13 males,& 10 females; age mean 36 ± 4.4 years; BMI: 31.7 ± 3.6 kg/m2; WHR: 1.2 ± .25 in males and 0.81+.5 in females ;Apnoea Index "AI"( 9.2 ±6.1) event/hour o...

Food fried in extra-virgin olive oil improves postprandial insulin response in obese, insulin-resistant women.

Science.gov (United States)

Farnetti, Sara; Malandrino, Noemi; Luciani, Davide; Gasbarrini, Giovanni; Capristo, Esmeralda

2011-03-01

The benefits of low glycemic load (GL) diets on clinical outcome in several metabolic and cardiovascular diseases have extensively been demonstrated. The GL of a meal can be affected by modulating the bioavailability of carbohydrates or by changing food preparation. We investigated the effect on plasma glucose and insulin response in lean and obese women of adding raw or fried extra-virgin olive oil to a carbohydrate-containing meal. After an overnight fast, 12 obese insulin-resistant women (body mass index [BMI], 32.8 ± 2.2 kg/m(2)) and five lean subjects (BMI, 22.2 ± 1.2 kg/m(2)) were randomly assigned to receive two different meals (designated A and B). Meal A was composed of 60 g of pasta made from wheat flour and 150 g of grilled courgettes with 25 g of uncooked oil. Meal B included 15 g of oil in the 150 g of deep-fried courgettes and 10 g of oil in the 60 g of stir-fried pasta. Both meals included 150 g of apple. Blood samples were collected at baseline and every 30 minutes over a 3-hour post-meal period and were tested for levels of glucose, insulin, C-peptide, and triglycerides. The area under the curve (AUC) values were calculated. In obese women the AUCs for C-peptide were significantly higher after meal A than after meal B at 120 minutes (W [Wilcoxon sign rank test] = 27.5, P = .0020), 150 minutes (W = 26.5, P = .0039), and 180 minutes (W = 26.5, P = .0039). No differences were found in lean subjects. This study demonstrated that in obese, insulin-resistant women, food fried in extra-virgin olive oil significantly reduced both insulin and C-peptide responses after a meal.

The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects.

Science.gov (United States)

Claessens, M; Calame, W; Siemensma, A D; van Baak, M A; Saris, W H M

2009-01-01

To study the effect of four protein hydrolysates from vegetable (pea, gluten, rice and soy) and two protein hydrolysates from animal origin (whey and egg) on glucagon and insulin responses. Eight healthy normal-weight male subjects participated in this study. The study employed a repeated-measures design with Latin square randomization and single-blind trials. Protein hydrolysates used in this study (pea, rice, soy, gluten, whey and egg protein hydrolysate) consisted of 0.2 g hydrolysate per kg body weight (bw) and 0.2 g maltodextrin per kg bw and were compared to maltodextrin alone. Postprandial plasma glucose, glucagon, insulin and amino acids were determined over 2 h. All protein hydrolysates induced an enhanced insulin secretion compared to maltodextrin alone and a correspondingly low plasma glucose response. A significant difference was observed in area under the curve (AUC) for plasma glucagon between protein hydrolysates and the maltodextrin control drink (Pprotein hydrolysate induced the lowest glucagon response. High amino-acid-induced glucagon response does not necessarily go together with low insulin response. Protein hydrolysate source affects AUC for glucagon more profoundly than for insulin, although the protein load used in this study seemed to be at lower level for significant physiological effects.

Insulin and C peptide response, and antibody levels in hepatitis C related chronic liver disease

International Nuclear Information System (INIS)

Abbas, Z.; Tariq, N.; Iqbal, M.; Shah, M.A.

2002-01-01

Objective: Patients with cirrhosis due to hepatitis C (HC) have an increased prevalence of diabetes mellitus. The pathogenic mechanism by which HC predisposes to DM is not clear. The objective of this study was to determine the insulin and C-peptide response to 75 gram oral glucose load and measure anti phospholipid antibody levels in patients with chronic liver disease due to HC. Design: a prospective study. Place and duration of study: This study was conducted at the department of medicine, Jinnah postgraduate medical centre over period of three months. Subjects and methods: An analytical case control study was carried out on 37 patients (m-18,f=19); none of these patients had received interferon. They were divided into four groups: (a) HC cirrhosis with DM (n=9 ), (b) HC cirrhosis without DM (n=11), (c) hepatitis B (HB) cirrhosis without DM (n=7), (d) chronic hepatitis C without DM (n=10). Group C and D were taken as controls. Fasting blood samples were taken and repeated after 2 hours of 75 gram oral glucose load (2 h PG). Result: mean ages of group A,B,C and D were (yr +- SD) 51.3 +- 7.6,48.9 +- 2.4, 33.7 +-10.8 and 31.7 +- 8.8 respectively. There was no statistically significant difference in the age, Pugh score and body mass index of HC cirrhotic patients with and without DM. Patients of group A had higher fasting and 2 h PG glucose levels (P=0.003 and 0.000) and higher fasting insulin level (p=0.045). However, increments in insulin and c peptide levels 2 h PG were much less (p=0.048 and 0.003). HB cirrhotics without diabetes (group C behaved just like HC cirrhotic without diabetes (group B). Patients of group D had normal glucose tolerance and insulin and C peptide levels. All four groups had normal anti phospholipid antibody levels. Conclusion: Patients with cirrhosis due to HC nd HB show evidence of glucose intolerance in spite of hyperinsulinaemia probably due to insulin resistance. HC cirrhotics with diabetes have fasting hyperglycemia in spite of

Tracking Weight Change, Insulin Resistance, Stress, and Aerobic Fitness over 4 Years of College

Science.gov (United States)

Hopper, Mari K.; Moninger, Shana Lynn

2017-01-01

Objective: To determine if weight gain is accompanied by development of insulin resistance (IR) during 4 years in college. Participants: Two cohorts of college students were enrolled in fall semesters 2009 and 2010 and tracked for 4 years. Methods: Following a 12-hour fast, subjects reported for measurement of body mass index (BMI), perceived…

Peripheral Insulin Doesn’t Alter Appetite of Broiler Chicks

Directory of Open Access Journals (Sweden)

Lei Liu

2016-09-01

Full Text Available An experiment was conducted to investigate the effect of peripheral insulin treatment on appetite in chicks. Six-d-age chicks with ad libitum feeding or fasting for 3 h before injection received a subcutaneous injection of 0, 1, 3, 5, 10, or 20 IU of insulin or vehicle (saline. The results showed peripheral insulin treatment (1 to 20 IU did not alter significantly the feed intake in chicks under either ad libitum feeding or fasting conditions within 4 h (p>0.05. Compared with the control, plasma glucose concentration was significantly decreased after insulin treatment of 3, 5, 10, and 20 IU for 4 h in chicks with ad libitum feeding (p0.05. All results suggest peripheral administration of insulin has no effect on appetite in chicks.