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Model Assessment (model + assessment)

Distribution by Scientific Domains
Medical Sciences86%
Chemistry3%
Mathematics and Statistics2%
Life Sciences2%
Humanities and Social Sciences2%
Engineering2%
Distribution within Medical Sciences
Diabetes30%
General & Internal Medicine8%
Hepatology6%
Pediatrics5%
Pharmacology & Pharmaceutical Medicine4%
Nephrology2%
15 Other Subdomains43%

Kinds of Model Assessment

  • Homeostasi model assessment
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  • homeostasi model assessment
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  • homeostatic model assessment
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    Selected Abstracts

    Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptin

    DIABETES OBESITY & METABOLISM, Issue 10 2010
    R. Retnakaran
    Aim: Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. Methods: In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0,2 OADs were switched to 4,8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT (n = 21) were then randomized to metformin with either sitagliptin (n = 10) or placebo (n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUCCpep to AUCgluc over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUCCpep/gluc/HOMA-IR)] on 4-h meal tests. Results: During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUCCpep/gluc/HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). Conclusions: Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function. [source]

    Predictors of insulin sensitivity in Type 2 diabetes mellitus

    DIABETIC MEDICINE, Issue 7 2002
    E. Bonora
    Abstract Aims To identify the independent predictors of insulin sensitivity in Type 2 diabetes, and to establish whether isolated Type 2 diabetes (i.e. diabetes without overweight, dyslipidaemia and hypertension) is a condition of insulin resistance. Methods We examined 45 patients with non-insulin-treated Type 2 diabetes undergoing a 4-h euglycaemic hyperinsulinaemic clamp (20 mU/m2 per min) combined with 3H-3-D-glucose and 14C-U-glucose infusions and indirect calorimetry. We also examined 1366 patients with non-insulin-treated Type 2 diabetes randomly selected among those attending the Diabetes Clinic and in whom insulin resistance was estimated by Homeostasis Model Assessment (HOMA-IR). Results In the 45 patients undergoing glucose clamp studies, insulin-mediated total glucose disposal (TGD) was independently and negatively associated with systolic blood pressure (standardized , coefficient = ,0.407, P = 0.003), plasma triglycerides (,= ,0.355, P = 0.007), and HbA1c (,= ,0.350, P = 0.008). The overall variability of TGD explained by these variables was 53%. Overweight diabetic subjects with central fat distribution, hypertension, hypertriglyceridaemia and poor glycometabolic control had insulin-mediated TGD values markedly lower than their lean counterparts without hypertension, with normal triglycerides, and with good glycometabolic control (16 ± 5 vs. 31 ± 10 µmol/min per kg lean body mass, P < 0.01). Nevertheless, the latter still were markedly insulin-resistant when compared with sex- and age-matched non-diabetic control subjects (31 ± 10 vs. 54 ± 13 µmol/min per kg lean body mass, P < 0.01). In the 1366 Type 2 diabetic patients of the epidemiological study, HOMA-IR value was independently associated with HbA1c (, = 0.283, P < 0.0001), plasma triglycerides (, = 0.246, P < 0.0001), body mass index (, = 0.139, P < 0.001), waist girth (, = 0.124, P < 0.001) and hypertension (, = 0.066, P = 0.006). Conclusion Overweight, central fat distribution, dyslipidaemia, hypertension and poor glycometabolic control are strong independent predictors of insulin resistance in Type 2 diabetes. However, reduced insulin sensitivity can be found even when Type 2 diabetes is isolated and well controlled. Diabet. Med. 19, 535,542 (2002) [source]

    Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patients

    HEMODIALYSIS INTERNATIONAL, Issue 3 2009
    Essam KHEDR
    Abstract Insulin resistance is a characteristic feature of uremia. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Treatment with recombinant human erythropoietin (rHuEPO) was said to be associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin resistance in adult uremic hemodialysis (HD) patients including diabetic patients treated with or without rHuEPO. A total of 59 HD patients were studied, patients were divided into 2 groups of subjects: 30 HD patients on regular rHuEPO treatment (group A), and 29 HD patients not receiving rHuEPO (group B) diabetic patients were not excluded. Full medical history and clinical examination, hematological parameters, lipid profile, serum albumin, parathyroid horomone, Kt/V, fasting glucose, and insulin levels were measured in all subjects. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to compare insulin resistance. The results of this study showed that the mean insulin level of HD patients treated with rHuEPO (group A) (17.5 ± 10.6 ,U/mL) was significantly lower than patients without rHuEPO (group B) (28.8 ± 7.7 ,U/mL), (P<0.001). Homeostasis Model Assessment of Insulin Resistance levels in group A were significantly lower than in group B (3.8 ± 2.97, 7.98 ± 4.9, respectively, P<0.001). Insulin resistance reflected by HOMA-IR levels among diabetic patients in group A was significantly lower than among diabetic patients in group B (3.9 ± 3.2, 9.4 ± 7.2, respectively, P<0.001). Also, HOMA-IR levels among nondiabetic patients in group A were significantly lower than among nondiabetic patients in group B (3.7 ± 2.85, 6.9 ± 1.43, respectively, P<0.01). We found a statistically significant negative correlation between duration of erythropoietin treatment, fasting blood glucose, insulin levels, and insulin resistance (r=,0.62, ,0.71, and ,0.57, P<0.001). Patients treated with rHuEPO showed less insulin resistance compared with patients not treated with rHuEPO in diabetic and nondiabetic patients and, duration of erythropoietin treatment is negatively correlated with insulin levels and insulin resistance in HD patients. [source]

    Application of surrogate indicators of insulin sensitivity to critically ill cats

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2005
    D. L. Chan
    Hyperglycaemia associated with critical illness is a common finding in non-diabetic human patients and has important implications for nutritional support. The aetiology of the hyperglycaemia is multi-factorial but believed to involve alterations in hormones regulating glucose metabolism and the development of insulin resistance. We have previously demonstrated that hyperglycaemia in critically cats similarly involves alterations in circulating concentrations of insulin, glucagon, and cortisol. Namely, with critical illness cats had hypoinsulinaemia, hyperglucagonaemia, and hypercortisolaemia. However, direct determinations of insulin sensitivity in critically ill cats have remained untested due to the complexity of calculations and frequent blood sampling required. Such techniques have, therefore, been limited to experimental models. In the interest of studying insulin sensitivity in clinical cases, surrogate indicators of insulin sensitivity, e.g, Homeostasis Model Assessment (HOMA), and Quantitative Insulin Check Index (QUICKI), have been recently applied to cats and shown to correlate to more traditional insulin sensitivity testing. HOMA is calculated ([insulin]x[(glucose)/22.5]), while QUICKI is (1/ [log insulin + log glucose]). The goal of this study was to apply the HOMA and QUICKI indices to hyperglycaemic critically ill cats and compare them to those of euglycaemic critically ill cats and controls. Twenty-six critically ill, and 21 healthy control cats were evaluated. Groups were matched for age, weight, and body condition. Of the critically ill cats, 10 were euglycaemic, and 14 were hyperglycaemic (glucose > 180 mg/dL). As compared to euglycaemic critically ill cats, HOMA was found to be significantly greater in hyperglycaemic cats [median 5.30 (range 0.90 , 25.14) vs. [2.19 (0.69 , 7.33); p = 0.016], while QUICKI was significantly lower in hyperglycaemic cats [median 0.30 mg/dl (0.25 , 0.39 mg/dl) vs. [0.34 mg/dl (0.29 , 0.38 mg/dl); p = 0.039]. Higher HOMA and lower QUICKI indices are consistent with an insulin resistant state. However, HOMA and QUICKI were not significantly different between hyperglycaemic and control cats. While the application of these indices may prove useful in determining insulin sensitivity in critically ill cats, future studies are needed to resolve discrepancies demonstrate in the current study. [source]

    Calcium intake and its relationship with adiposity and insulin resistance in post-pubertal adolescents

    JOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 2 2008
    L. C. Dos Santos
    Abstract Background, Dietary calcium intake has been described as being a negative contributor to adiposity. In adolescents, this relationship is not well established. The objectives of the present study were to compare the calcium intake of normal-weight and obese adolescents and to evaluate its relationship with adiposity and insulin resistance. Methods, A cross-sectional analysis of 96 post-pubertal adolescents; 47 normal weight and 49 obese, mean age 16.6 (SD ± 1.3) years. Body composition was assessed by dual-energy X-ray absorptiometry. Dietary intake was evaluated using a 3-day dietary record. The biochemical evaluation comprised the measurements of serum lipids, lipoproteins, glucose and insulin. Insulin resistance was calculated using the Homeostasis Model Assessment of Insulin resistance (HOMA-IR). Results, The mean calcium intake, adjusted for energy, was lower in obese adolescents, 585.2 (±249.9) mg, than in normal weight adolescents, 692.1 (±199.5) mg. Only 4% of adolescents had an adequate intake of calcium. Calcium intake was inversely associated with body trunk fat, insulin and HOMA-IR in the obese group. The quartile analysis of calcium intake provided evidence that girls in the highest quartile had decreased adiposity and insulin resistance. Conclusions, This study showed a negative relationship between calcium intake and body fat and insulin resistance, mainly in obese girls, and demonstrates the importance of an increased dietary calcium intake. [source]

    The Role of the Flushing Response in the Relationship Between Alcohol Consumption and Insulin Resistance

    ALCOHOLISM, Issue 10 2010
    Jin-Gyu Jung
    Background:, Facial flushing responses to drinking, because of intolerance to alcohol, are observed in some people, especially Asians. This study examined the role of flushing responses in the relationship between alcohol consumption and insulin resistance (IR). Methods:, Participants in this cross-sectional analysis included 624 Korean men (80 nondrinkers, 306 nonflushing drinkers, and 238 flushing drinkers) who were free of cardiovascular disease and diabetes. Data on the flushing response to drinking and alcohol consumption were collected from medical records. IR was estimated using the Homeostasis Model Assessment (HOMAIR). On the basis of comparisons with nondrinkers, the risk of IR according to the quantity of alcohol consumed per week was analyzed among nonflushers and flushers. Results:, After adjusting for age, exercise status, smoking status, BMI, waist circumference, blood pressure, high-density lipoprotein cholesterol, and triglycerides using a logistic regression model, we found a low risk of IR among nonflushers who consumed ,4 drinks (1 drink = 14 g of alcohol) per week (OR = 0.3). In contrast, a higher risk of IR was associated with nonflushers who consumed >20 drinks per week (OR = 3.5). On the other hand, only a higher risk of IR was associated with flushers who consumed >12 drinks per week (>12 to 20 drinks: OR = 4.7; >20 drinks: OR = 3.5). Conclusions:, The amount of drinking associated with the development of IR in flushers was lower than in nonflushers. Additionally, no positive effect of moderate drinking on IR was observed in flushers. The findings support acetaldehyde-derived mechanisms in the development of alcohol-related IR. [source]

    Insulin Resistance, Serum Adipokines and Risk of Fibrosis Progression in Patients Transplanted for Hepatitis C

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
    B. J. Veldt
    In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10,3.91, p = 0.024), donor age (HR 1.33;CI 1.08,1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01,1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46,1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88,3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV. [source]

    Fibrinolytic risk factor clustering and insulin resistance in healthy male relatives of men with intermittent claudication,

    BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2006
    D. J. Parry
    Background: Raised fibrinolytic factors predict cardiovascular risk in healthy subjects. The aim of this study was to measure fibrinolytic factors and insulin resistance in healthy male first-degree relatives of men with intermittent claudication younger than 65 years. Methods: The study compared 165 healthy first-degree relatives with 165 age-, sex- and race-matched control subjects free from a personal or family history of premature cardiovascular disease. Primary outcome measures were plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA) and D-dimer levels. Insulin resistance was estimated by Homeostasis Model Assessment. Clinical and biochemical risk factors were measured and subjects genotyped for the PAI-1 4G/5G polymorphism. Results: First-degree relatives had significantly higher mean PAI-1 (10·23 versus 7·85 ng/ml; P = 0·024), tPA (9·98 versus 8·29 ng/ml; P < 0·001) and D-dimer levels (56·6 versus 46·1 ng/ml; P = 0·004). They also had significantly higher insulin resistance (1·85 versus 1·53; P < 0·001) and clustered multiple atherogenic risk factors. On multivariate analysis the association between both tPA and D-dimer levels and relative status was independent of other variables. Conclusion: Raised levels of PAI-1, tPA, D-dimer and estimated insulin resistance were present in the healthy male first-degree relatives of men with intermittent claudication. These data support the hypothesis of fibrinolytic risk factor clustering in this high-risk population. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

    Insulin resistance among Brazilian schoolchildren: association with risk factors for cardiovascular diseases

    ACTA PAEDIATRICA, Issue 10 2009
    MWL Strufaldi
    Abstract Aim:, Our purpose was to evaluate Insulin Resistance (IR) and its association with risk factors for cardiovascular diseases (CVDs) among 161 (6- to 10-year-old) schoolchildren. Methods:, This two-stage cross-sectional study evaluated: BMI, blood pressure, personal history (birth weight) and family history of CVDs. Children with at least one of the following criteria participated in the second stage: obesity, personal or family history. Insulin resistance was determined using Homeostasis Model Assessment (HOMA). Results:, The HOMA distribution in terciles showed mean values for the first, second and third tercile of 0.41, 0.79 and 2.11 respectively. The HOMA distribution in the third tercile demonstrated statistically significant associations with overweight/obesity (p = 0.007), hypertension (p = 0.008) and low HDL (p = 0.02). Analysis of mean birth weight in each tercile and between terciles did not present any positive correlation (p = 0.213). Conclusion:, Higher levels of HOMA (IR) were positively associated with risk factors for CVD among schoolchildren. [source]

    The changes in serum leptin, body fat mass and insulin resistance after renal transplantation

    CLINICAL TRANSPLANTATION, Issue 1 2003
    S Mehmet Kayacan
    Abstract:,Background:, In this prospective-controlled study, we aimed to investigate the effect of changes in insulin resistance and anthropometrical parameters on serum leptin levels (SLL) after renal transplantation (Tx). Patients and methods:, Thirty-four patients (M/F: 19/15, mean age: 29 ± 9 yr) and 30 age and sex-matched healthy controls (C) were included. Body weight, subscapular, suprailiac, periumbilical, biceps and triceps skinfold thicknesses, neck, wrist, hip and waist circumferences, as well as body mass index and body fat mass were measured as anthropometrical parameters. In order to measure the serum glucose, insulin and SLL, blood samples were obtained before and 1 wk, 1 and 6 months after Tx. Homeostasis Model Assessment (HOMA) values were calculated as an index of insulin resistance. Results:, Serum leptin levels (SLL) of the patients at pre-Tx were significantly higher than C (21.5 ± 3.5 vs. 7.8 ± 0.9 ng/mL, p = 0.002) and decreased at first week after Tx (from 21.5 ± 3.5 to 8.4 ± 1.5 ng/mL, p < 0.001). Thereafter, it gradually increased to 12.8 ± 2.1 ng/mL in the first month and to 14.4 ± 2.1 ng/mL in the sixth month after Tx. Serum leptin levels at sixth month were significantly higher than C (p = 0.005). Serum insulin and HOMA values changed similar to SLL after Tx. Correlations between SLL and HOMA persisted during the study period [pre-Tx (r: 0.40) and at first (r: 0.38) and sixth (r: 0.47) months]. In linear regression analysis, HOMA and fat mass were found as independent variables for predicting SLL at the sixth month after Tx. Conclusion:, Serum leptin levels dramatically decreased immediately after Tx and significantly correlated with serum insulin levels and HOMA during the entire study. Increase in SLL at sixth months was probably because of increase in fat mass, insulin resistance and steroid use in renal transplant recipients. [source]

    Effects of topiramate on weight and metabolism in children with epilepsy

    ACTA PAEDIATRICA, Issue 9 2009
    Hai-feng Li
    Abstract Aim:, To explore the mechanism of topiramate-induced weight loss in epilepsy children by monitoring metabolism indices. Methods: Children with epilepsy were treated with topiramate at their first clinical visit. Metabolism indices including body mass index (BMI) and its SD scores, leptin, adiponectin, leptin/adiponectin (L/A), lipid profile-insulin and Homeostasis Model Assessments (HOMA) index were collected before and after treatment. Results:, Topiramate treatment significantly reduced L/A (t = 2.156, p = 0.031), and markedly increased the serum level of adiponectin (t = 3.124, p = 0.002). Moreover, there were no relationships between the metabolism indices and dosages of topiramate (p > 0.05). Conclusion:, Our studies find that topiramate treatment in epilepsy children increases energy metabolism, resulting in weight loss. It has been demonstrated that adiponectin play a significant role in metabolic regulations. [source]

    Calculation of Posterior Probabilities for Bayesian Model Class Assessment and Averaging from Posterior Samples Based on Dynamic System Data

    COMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 5 2010
    Sai Hung Cheung
    Because of modeling uncertainty, a set of competing candidate model classes may be available to represent a system and it is then desirable to assess the plausibility of each model class based on system data. Bayesian model class assessment may then be used, which is based on the posterior probability of the different candidates for representing the system. If more than one model class has significant posterior probability, then Bayesian model class averaging provides a coherent mechanism to incorporate all of these model classes in making probabilistic predictions for the system response. This Bayesian model assessment and averaging requires calculation of the evidence for each model class based on the system data, which requires the evaluation of a multi-dimensional integral involving the product of the likelihood and prior defined by the model class. In this article, a general method for calculating the evidence is proposed based on using posterior samples from any Markov Chain Monte Carlo algorithm. The effectiveness of the proposed method is illustrated by Bayesian model updating and assessment using simulated earthquake data from a ten-story nonclassically damped building responding linearly and a four-story building responding inelastically. [source]

    Earlier triple therapy with pioglitazone in patients with type 2 diabetes

    DIABETES OBESITY & METABOLISM, Issue 9 2009
    G. Charpentier
    Aims: This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods: This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA1c) ,6.5%] or titrated up to 45 mg (if HbA1c >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA1c (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ,-cell function (HOMA-B) were calculated. Results: Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA1c and ,2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of <8.5% achieved the HbA1c target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA1c level was , 8.5%, 13% achieved the HbA1c target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions: In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA1c, FPG and surrogate measures of ,-cell function. Patients were more likely to reach target HbA1c levels (< 7.0%) with pioglitazone treatment if their baseline HbA1c levels were < 8.5%, highlighting the importance of early triple therapy. [source]

    Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy

    DIABETES OBESITY & METABOLISM, Issue 2 2009
    R. E. Pratley
    Aim:, To evaluate the efficacy and safety of alogliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy. Methods:, After a 2-week screening period, adult patients 18,80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide (open label) plus placebo (single blind). After the run-in period, patients were randomly assigned to double-blind treatment with alogliptin 12.5 mg (n = 203), alogliptin 25 mg (n = 198), or placebo (n = 99) for 26 weeks. The primary end-point was change from baseline to week 26 in glycosylated haemoglobin (HbA1c). Secondary end-points included clinical response rates and changes in fasting plasma glucose, ,-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment ,-cell function), body weight, and safety end-points [adverse events (AEs), clinical laboratory tests, vital signs and electrocardiographic readings]. Results:, The study population had a mean age of 57 years and a mean disease duration of 8 years; it was well balanced for gender (52% women) and was mainly white (71%). The mean baseline HbA1c was approximately 8.1% in each group. Significantly greater least squares (LS) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg (,0.38%) and 25 mg (,0.52%) vs. placebo (+0.01%; p < 0.001), and more patients in the alogliptin 25-mg group had HbA1c levels ,7.0% at week 26 (34.8%, p = 0.002) vs. placebo (18.2%). Proportionately more patients in the alogliptin 12.5 mg (47.3%) and 25 mg (50.5%) groups had an HbA1c reduction ,0.5% from baseline compared with patients in the placebo group (26.3%; p < 0.001). Minor improvements in individual markers of ,-cell function were seen with alogliptin, but no significant treatment group differences were noted relative to placebo. Minor LS mean changes in body weight were noted across groups (placebo, ,0.20 kg; alogliptin 12.5 mg, +0.60 kg; alogliptin 25 mg, +0.68 kg). AEs were reported for 63,64% of patients receiving alogliptin and 54% of patients receiving placebo. Few AEs were treatment limiting (2.0,2.5% across groups), and serious AEs (2.0,5.6%) were infrequent, similar across groups, and generally considered not related to treatment. The incidences of hypoglycaemia for placebo, alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1, 15.8 and 9.6% respectively. Conclusions:, In patients with type 2 diabetes inadequately controlled by glyburide monotherapy, the addition of alogliptin resulted in clinically significant reductions in HbA1c without increased incidence of hypoglycaemia. [source]

    Robust improvements in fasting and prandial measures of ,-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database

    DIABETES OBESITY & METABOLISM, Issue 10 2008
    R. E. Pratley
    Aim:, To assess the effects of 24-week treatment with vildagliptin on measures of ,-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). Methods:, Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of ,-cell function [homeostasis model assessment of ,-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test,derived) measures of ,-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). Results:, In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AM,) = 10.3 ± 1.5] and vs. placebo (between-treatment difference in AM, = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AM, = ,0.05 ± 0.01) and vs. placebo (between-treatment difference in AM, = ,0.09 ± 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test,derived parameters, and ISR/G (between-treatment difference in AM, = 9.8 ± 2.8 pmol/min/m2/mM, p < 0.001) and the insulinogenic index0,peak glucose (between-treatment difference in AM, = 0.24 ± 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. Conclusions:, Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test,derived measures of ,-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov. [source]

    Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patients

    DIABETES OBESITY & METABOLISM, Issue 6 2008
    A. Brunani
    Aim:, In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. Methods:, From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18,65 years and body mass index 35,50 kg/m2 and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. Results:, A significant weight loss and reduction of fat mass was demonstrated with metformin (,9.7 ± 1.8 kg and ,6.6 ± 1.1 kg) and also with rosiglitazone (,11.0 ± 1.9 kg and ,7.2 ± 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 ± 0.1 vs. 4.4 ± 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 ± 1.5 vs. 8.0 ± 0.,7 ,U/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 ± 8.8 vs. 109.9 ± 10.3, p < 0.005) with a concomitant decrease in ,-cell function as measured by HOMA of ,-cell function (163.2 ± 16.1 vs. 127.4 ± 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. Conclusion:, Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction. [source]

    Improvement of insulin sensitivity and ,-cell function by nateglinide and repaglinide in type 2 diabetic patients , a randomized controlled double-blind and double-dummy multicentre clinical trial

    DIABETES OBESITY & METABOLISM, Issue 4 2007
    J. Li
    Aim:, To evaluate the efficacy of nateglinide vs. repaglinide in blood glucose (BG) control and the effect on insulin resistance and ,-Cell function in patients with type 2 diabetes. Methods:, A randomized controlled double-blind and double-dummy multicentre clinical trial was conducted. A total of 230 Chinese patients with type 2 diabetes were enrolled in five clinical centres. The patients were divided randomly into group A [repaglinide 1.0 mg three times daily (t.i.d.), n = 115] or group B (nateglinide 90 mg t.i.d., n = 115). At baseline and end of the 12-week clinical trial, standard mixed meal tolerance tests were performed. Results:, A total of 223 patients (96.9%) completed the trial. There was no significant difference between repaglinide and nateglinide groups in the effects of reducing fasting blood glucose (FBG), 30-, 60- and 120-min BG during 12 weeks (p > 0.05). At week 12, no significant difference was shown between the two groups in BG or haemoglobin A1c (HbA1c) (p > 0.05). However, the effect on HbA1c in repaglinide group was stronger than that in nateglinide group (p < 0.05). After 12-week treatment, area under the curve (AUC) of BG decreased (p < 0.05), and AUC of insulin and C-peptide (CP) increased in both groups (p < 0.05). The effects of nateglinide on AUC of BG, insulin and CP were similar to that of repaglinide (p > 0.05). There was no significant difference between the two groups in AUC of BG, insulin or CP in week 12 (p > 0.05). Furthermore, homeostasis model assessment of insulin resistance (HOMA-IR) and ,-cell function indexes measured by HOMA-,, ,I30/,G30 and (,I30/,G30)/HOMA-IR were improved significantly in both groups during 12 weeks (p < 0.05). The effects of improving HOMA-IR and ,-cell function indexes in nateglinide group were comparable with that of repaglinide group (p > 0.05). Conclusions:, The efficacy of repaglinide and nateglinide in FBG, postprandial glucose excursion and early-phase insulin secretion is similar. But the effect of repaglinide 1.0 mg t.i.d. on HbA1c is stronger than that of nateglinide 90 mg t.i.d.. This trial had shown that nateglinide and repaglinide could comparably improve insulin sensitivity and ,-cell function. [source]

    Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal women

    DIABETES OBESITY & METABOLISM, Issue 3 2006
    A. D. Karelis
    Aim:, We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross-sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes. Methods:, Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3 ± 5.3 years; BMI: 32.8 ± 4.5 kg/m2) by using both the hyperinsulinaemic,euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the metabolic syndrome included visceral fat (>130 cm2), HDL-cholesterol (<1.29 mmol/l), fasting triglycerides (,1.7 mmol/l), blood pressure (,130/,85 mmHg) and fasting glucose (,6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0,1 vs. 2 vs. ,3 features of the metabolic syndrome. Results:, We found that insulin sensitivity decreased in a graded fashion (12.19 ± 3.2 vs. 11.80 ± 2.3 vs. 9.29 ± 2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95 ± 1.1 vs. 3.28 ± 1.3 vs. 4.65 ± 2.2), as the number of features of the metabolic syndrome increased from 0,1 to ,3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished. Conclusions:, These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship. [source]

    Incidence of insulin resistance in obese subjects in a rural Japanese population: The Tanno and Sobetsu study

    DIABETES OBESITY & METABOLISM, Issue 1 2005
    H. Ohnishi
    Objectives:, Although it is well known that obesity is closely related to insulin resistance, the incidence of the development of insulin resistance in people with obesity is not known. In this study, we investigated the incidence of insulin resistance in citizens of two rural communities in Japan. Subjects and methods:, The subjects were 102 men and 126 women over the age of 30 years selected from 1035 citizens who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, in 1991 and 1998. Those who were on medication for hypertension, diabetes, hyperlipidaemia, coronary heart disease and cerebral vessel disease were excluded. The simple index to determine insulin resistance [i.e. homeostasis model assessment (HOMA-R) , 1.73] was used, and subjects who were determined to be positive for insulin resistance according to this index in 1991 were also excluded in order to determine the incidence of insulin resistance in subjects who had no abnormalities other than obesity. The systolic blood pressure (SBP), diastolic blood pressure, body mass index (BMI), triglyceride level, high-density lipoprotein level, blood sugar level, serum insulin value and HOMA-R were measured in all subjects in 1991 and in 1998. Moreover, the subjects were divided into two groups according to BMI, a normal group consisting of subjects with BMI < 25 and an obesity group consisting of subjects with BMI , 25. We also compared the incidences of insulin resistance in normal and obesity groups of subjects who were newly determined to be positive for insulin resistance on the basis of data obtained from medical examinations conducted in 1998. Results:, The incidence of insulin resistance was significantly higher in the obesity group than in the normal group (25.0 vs. 4.5%). The results of logistic regression analysis showed that obesity was closely related to insulin resistance and that the relative risk of development of insulin resistance adjusted for age, sex, SBP, FPG and HDL was 3.193 (95% CI 1.085,9.401). Conclusions:, The incidence of insulin resistance was significantly higher in the obesity group than in the normal group in this study, suggesting that improvement in obesity is important for prevention of the occurrence of type 2 diabetes or atherosclerotic disease based on insulin resistance. [source]

    Elevated fasting plasma C-peptide occurs in non-diabetic individuals with fatty liver, irrespective of insulin resistance

    DIABETIC MEDICINE, Issue 9 2009
    G. Perseghin
    Abstract Aims Studies have pointed to insulin resistance as a pathogenic factor in fatty liver. Although pancreatic B-cell function is believed to be involved, its role is unclear. This study was undertaken to test whether fasting C-peptide, an index of fasting B-cell function, was related to intra-hepatic fat (IHF) content in non-diabetic humans. Methods We assessed, retrospectively, fasting plasma C-peptide concentration in 31 patients with fatty liver and 62 individuals without fatty liver. The IHF content was measured by proton magnetic resonance spectroscopy (1H-MRS), while insulin sensitivity was estimated based on fasting plasma glucose and insulin with the homestasis model assessment (HOMA) 2 method. Results Age, sex and body mass index (BMI) were not different between groups. Patients with fatty liver had higher fasting insulin (P < 0.01), C-peptide (P < 0.005) and lower insulin sensitivity (HOMA2-%S). Fasting insulin alone explained 14% of the IHF content variability (P < 0.001); inclusion of fasting C-peptide in multivariate regression explained up to 32% (P < 0.001). A subgroup analysis was performed by matching 1 : 1 for HOMA2-%S. These data were analysed by conditional logistic regression which showed that, when HOMA2-%S was matched between groups, fasting C-peptide remained the only significant predictor of fatty liver. Conclusions Non-diabetic individuals with fatty liver are characterized by increased fasting plasma C-peptide concentration, irrespective of their insulin resistant state. [source]

    J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes: an 8-year follow-up of relatively lean Japanese individuals

    DIABETIC MEDICINE, Issue 8 2009
    M. Sakurai
    Abstract Aims, This study investigated the relationship between waist circumference and the subsequent incidence of Type 2 diabetes and the association with insulin resistance and pancreatic B-cell function in relatively lean Japanese individuals. Methods, The study participants were 3992 employees (2533 men and 1459 women, aged 35,55 years) of a metal-products factory in Japan. The incidence of diabetes was determined in annual medical examinations during an 8-year follow-up. We calculated age- and sex-adjusted hazard ratios (HRs) according to the sex-specific quintile of waist circumference at baseline. Differences in baseline insulin resistance [homeostatis model assessment (HOMA)-IR] and pancreatic B-cell function (HOMA-B) were compared between participants who developed diabetes and those who did not. Results, During the follow-up, 218 participants developed diabetes. Age- and sex-adjusted HRs across the quintiles of waist circumference were 1.78, 1.00 (reference), 1.59, 3.11 and 3.30, respectively (P for trend, < 0.0001). The HR for the lowest quintile was significantly higher than that for the second quintile. Among participants with waist circumference of the lowest quintile, HOMA-B was lower in those who developed diabetes than in those who did not [33.1 (24.1,45.0) vs. 54.3 (37.9,74.6) median (interquartile range), P < 0.0001], but HOMA-IR did not differ between these groups. Conclusions, There was a J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes in relatively lean Japanese individuals; lower pancreatic B-cell function may also increase the risk of diabetes in very lean Japanese people. [source]

    Insulin resistance is an independent correlate of increased urine albumin excretion: a cross-sectional study in Iranian Type 2 diabetic patients

    DIABETIC MEDICINE, Issue 2 2009
    A. Esteghamati
    Abstract Aims, To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. Methods, Three hundred and sixty-one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005,2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE , 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Results, HOMA-IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA-IR were 11.81 ± 7.51 (mg/day) and 3.30 ± 2.21 in normoalbuminuric and 75.36 ± 55.57 (mg/day) and 4.98 ± 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA-IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA-IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7,6.2)]. Conclusions, In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA-IR is an independent predictor of UAE. [source]

    Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men

    DIABETIC MEDICINE, Issue 12 2007
    V. Rochira
    Abstract Aims The role of sex steroids in glucose and insulin metabolism in men remains unclear. To investigate the effects of sex steroids and oestrogen on insulin sensitivity in men, we studied two male adults with aromatase deficiency (subject 1 and subject 2). Methods The effects of transdermal oestradiol (tE2) treatment at different dosages on insulin sensitivity were studied before tE2 treatment (phase 1), and after 6 months (phase 2) and 12 months of tE2 treatment (phase 3) by means of homeostasis model assessment,insulin resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), insulin tolerance test (ITT), and oral glucose tolerance test (OGTT). The latter was performed only in subject 1, as subject 2 suffered from Type 2 diabetes. Results The restoration of normal serum oestradiol led to improved insulin sensitivity, as shown by changes in HOMA-IR and QUICKI. The ITT provided evidence of improved insulin sensitivity during tE2 treatment. Insulin secretion after OGTT was reduced during tE2 treatment in subject 1. After 12 months of tE2 treatment, insulin sensitivity was improved compared with in phases 1 and 2. Conclusions The study suggests a direct involvement of oestrogens in insulin sensitivity, and supports a possible role of oestradiol : testosterone ratio, which may be as influencial as the separate actions of each sex steroid on glucose homeostasis. [source]

    Effect of long-term treatment with rosiglitazone on arterial elasticity and metabolic parameters in patients with Type 2 diabetes mellitus: a 2-year follow-up study

    DIABETIC MEDICINE, Issue 11 2007
    M. Shargorodsky
    Abstract Aims, Thiazolidinediones may influence the atherogenic process by improving cardiovascular risk factors. The present study was designed to determine the long-term effect of rosiglitazone on arterial compliance and metabolic parameters in patients with Type 2 diabetes. Methods, In an open-label, prospective study, 65 diabetic patients received rosiglitazone orally (4,8 mg/day) for 6 months. After 6 months, the patients continued an open follow-up study and were divided into two groups: group 1 included patients continuing rosiglitazone for 2 years, group 2 included patients discontinuing rosiglitazone and receiving other oral glucose-lowering agents. Lipid profile, glycated haemoglobin (HbA1c), insulin, C-peptide, fibrinogen, high-sensitivity-CRP and homeostasis model assessment,insulin resistance were measured. Arterial elasticity was assessed using pulse wave contour analysis. Results, In patients treated with rosiglitazone for 2 years: the large artery elasticity index (LAEI) increased from 10.0 ± 4.6 to 13.9 ± 4.7 ml/mmHg × 100 after 2 years (P = 0.003). The small artery elasticity (SAEI) index increased significantly from 3.2 ± 1.2 to 5.1 ± 1.9 (P < 0.0001). In patients who discontinued rosiglitazone: LAEI did not change after 6 months, but decreased from 12.1 ± 5.4 to 8.9 ± 3.9 ml/mmHg × 10 (P < 0.0001) at the end of 2 years. SAEI increased during the first 6 months of treatment, from 3.9 ± 1.8 to 5.1 ± 1.5 ml/mmHg × 100 (P < 0.0001) and decreased after discontinuation of rosiglitazone (P = 0.042). Conclusions, Prolonged treatment with rosiglitazone improved arterial elasticity. However, significant deterioration in LAEI and SAEI was observed in patients who discontinued rosiglitazone. The beneficial vascular effect of rosiglitazone on arterial elasticity was independent of glycaemic control. [source]

    Reduced insulin secretion in normoglycaemic patients with ,-thalassaemia major

    DIABETIC MEDICINE, Issue 12 2006
    N. G. Angelopoulos
    Abstract Aims To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with ,-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload. Methods We measured fasting glucose, insulin and C-peptide levels in 24 patients with ,-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated. Results Fasting glucose levels in patients were increased compared with control subjects (5.5 ± 0.12 vs. 4.7 ± 0.13 mmol/l, mean ± sem, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SCHOMA) was lower in thalassaemic patients (SCHOMA 88.5 ± 11.11 vs. 184.3 ± 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SCHOMA was higher in the patients with NFG compared with those with IFG patients (110.6 ± 17.63 vs. 66.3 ± 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISIHOMA) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SCHOMA (r = 0.45, P = 0.02) and negatively with ISIHOMA (r = ,0.43, P = 0.03). Conclusions These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in ,-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent. [source]

    An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized study

    DIABETIC MEDICINE, Issue 6 2004
    T. M. Wallace
    Abstract Aims To investigate the effect of treatment with pioglitazone on beta-cell function and insulin sensitivity in Type 2 diabetes. Methods Thirty subjects with diet-controlled Type 2 diabetes were randomized to 3 months treatment with pioglitazone (n = 19) or placebo (n = 11). All subjects underwent basal sampling for homeostatic model assessment (HOMA), followed by an intravenous glucose tolerance test and hyperglycaemic clamp, followed by an euglycaemic hyperinsulinaemic clamp; at baseline and after treatment. Results All results are expressed as mean (sem). Pioglitazone increased basal insulin sensitivity by 24.7% (7.8) HOMA-%S vs. 2.1% (5.9) in the placebo group (P = 0.02). Stimulated insulin sensitivity, M/I, increased in the pioglitazone group compared with placebo: +15.1 (2.8) l kg,1 min,1 vs. +3.2 (2.9) l kg,1 min,1, respectively (P = 0.009). Pioglitazone increased adiponectin by 39.3 (6.3), ng/ml compared with a decrease of 0.8 (1.3) ng/ml with placebo (P = 0.00004). HOMA-%B increased with pioglitazone, +11.5% (4.8) vs. ,2.0% (4.8) with placebo (P = 0.049), but there was no change in stimulated beta-cell function as determined by hyperglycaemic clamps. There was a significant reduction in the proinsulin/insulin ratio in the pioglitazone group, ,0.057 (0.02) compared with placebo, +0.004 (0.02) (P = 0.03). There was a significant reduction in HbA1c of 0.6% (0.1) in the pioglitazone group compared with placebo (P = 0.003). There was no significant weight gain associated with pioglitazone therapy: +0.7 (sem 0.6) kg vs. +1.1 (sem 0.5) kg in placebo group (P = NS). Conclusions Basal beta-cell function and insulin sensitivity improved following pioglitazone therapy. The improvement in proinsulin to insulin ratio suggests that beta-cells are under less stress. [source]

    Heterogeneity of non-insulin-dependent diabetes expressed as variability in insulin sensitivity, ,-cell function and cardiovascular risk profile

    DIABETIC MEDICINE, Issue 1 2003
    K. I. Birkeland
    Abstract Aims The present study investigated the variability in insulin sensitivity and ,-cell function and their relationship to anti-glutamic acid decarboxylase (GAD) positivity and the metabolic syndrome in a group of patients with non-insulin-dependent diabetes mellitus (NIDDM). Methods Fifty-four subjects aged 59.5 ± 6.1 (mean ± sd) years with NIDDM for 7.9 ± 3.9 years referred to hospital due to poor glycaemic control, were investigated. Insulin sensitivity was determined by the euglycaemic hyperinsulinaemic glucose clamp technique as the glucose disposal rate relative to the insulin level obtained (GDRI), and also estimated with the homeostasis model assessment (HOMA-S). ,-cell function was measured by assaying the fasting and glucagon-stimulated C-peptide levels and with the HOMA-B. Results The insulin sensitivity varied 18-fold between subjects when estimated with the clamp and six-fold when estimated with HOMA-S, and was lower the more criteria for the metabolic syndrome present (P = 0.0001 by anova). The ,-cell function varied four-fold when measured as stimulated C-peptide, and eight-fold when estimated with the HOMA-B. The levels of fasting C-peptide and HOMA-B values tended to be lower in anti-GAD+ (n = 11) than in anti-GAD,subjects (P = 0.06 and P = 0.08, respectively). From previously published coronary risk charts, we estimated the 10-year risk of a coronary heart disease (CHD) event to be > 20% in 17 of 39 patients free from cardiovascular disease at the time of study, 16 of whom qualified for a diagnosis of the metabolic syndrome. Conclusions The wide variations in insulin sensitivity and ,-cell function found among subjects with NIDDM support the notion that the disorder is highly heterogeneous. Reduced insulin sensitivity was clearly related to the metabolic syndrome and an increased risk for CHD. [source]

    The prevalence of the mitochondrial DNA 16189 variant in non-diabetic Korean adults and its association with higher fasting glucose and body mass index

    DIABETIC MEDICINE, Issue 8 2002
    J. H. Kim
    Abstract Aims To evaluate the prevalence of the 16189 variant of mitochondrial DNA in Korean adults and its association with insulin resistance. Methods We investigated 160 non-diabetic subjects from a community-based diabetes survey conducted in Yonchon County, Korea in 1993. We extracted the DNA from peripheral blood and examined the 16189 variant by polymerase chain reaction and restrictive enzyme digestion. We compared body mass index (BMI), blood pressure, fasting plasma glucose, 2-h plasma glucose after 75 g glucose load, fasting insulin, cholesterol, and homeostasis model assessment of insulin resistance and ,-cell function between the subjects with 16189 variant and wild type. Results The prevalence of the 16189 variant in Korean adults was 28.8% (46 of 160). Subjects with the 16189 variant had higher fasting glucose and BMI than those with wild type, but fasting insulin, homeostasis model assessment of insulin resistance and ,-cell function, cholesterol, and blood pressure were not different between two groups. Conclusion Our results provide evidence for an association of a frequent mitochondrial polymorphism with higher fasting glucose and the risk factors of diabetes mellitus. [source]

    The assessment of insulin resistance in man

    DIABETIC MEDICINE, Issue 7 2002
    T. M. Wallace
    Abstract Background Insulin resistance exists when a normal concentration of insulin produces a less than normal biological response. The ability to measure insulin resistance is important in order to understand the aetiopathology of Type 2 diabetes, to examine the epidemiology and to assess the effects of intervention. Methods We assess and compare methods of measurement and have undertaken a literature review from 1966 to 2001. Results Quantitative estimates of insulin resistance can be obtained using model assessments, clamps or insulin infusion sensitivity tests. There is considerable variation in the complexity and labour intensity of the various methods. The most well-established methods are the euglycaemic clamp, minimal model assessment and homeostatic model assessment (HOMA). No single test is appropriate under all circumstances. Conclusions There are a number of well-established tests used to measure insulin resistance: the choice of method depends on the size and type of study to be undertaken. Although the so-called ,gold-standard' test, the euglycaemic clamp, is useful for intensive physiological studies on small numbers of subjects, a simpler tool such as HOMA is more appropriate for large epidemiological studies. It is important to be aware that most techniques measure stimulated insulin resistance whereas HOMA gives an estimate of basal insulin resistance. Caution should be exercised when making comparisons between studies due to variations in infusion protocols, sampling procedures and hormone assays used in different studies. [source]

    Age-related increase in haemoglobin A1c and fasting plasma glucose is accompanied by a decrease in , cell function without change in insulin sensitivity: evidence from a cross-sectional study of hospital personnel

    DIABETIC MEDICINE, Issue 3 2002
    A. P. Yates
    Abstract Aims To examine the influence of age on glucose homeostasis in a population of healthy, non-diabetic hospital personnel. Methods One hundred and twenty female and 71 male non-diabetic individuals (fasting plasma glucose < 7.0 mmol/l) were fasted overnight prior to blood sampling. Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and fasting plasma insulin (FPI) were measured using a BioRad Diamat automated HPLC, a Hitachi 747 analyser and a sensitive in-house radioimmunoassay, respectively. Mathematical modelling of the fasting glucose and insulin pairs (homeostasis model assessment (HOMA)) generated indices of pancreatic , cell function, HOMA-B and tissue insulin sensitivity HOMA-S. Results Spearman rank correlation analysis showed that in the whole group there was a significant negative correlation between age and HOMA-B (rs= ,0.218, P = 0.0022) and a significant positive correlation between age and both HbA1c (rs= 0.307, P = 0.0001) and FPG (rs= 0.26, P = 0.0003). There was no correlation between age and either FPI (rs= ,0.08, P = 0.266) or HOMA-S (rs= 0.024, P = 0.75). Analysis by gender showed the above associations to be present in the females (rs= ,0.243, P = 0.0076; rs= 0.304, P = 0.0007; rs= 0.32, P = 0.0004 for age vs. HOMA-B, HbA1c, and FPG, respectively). Again there was no correlation of age with FPI or insulin sensitivity. In the males there was a significant correlation of HbA1c with age (rs= 0.35, P = 0.002), but no significant correlation of age with any of the other parameters. Conclusions Glycaemic control deteriorates with age in healthy, non-diabetic individuals. Age-related rises in FPG and haemoglobin A1c result from a small but steady decline in pancreatic , cell function. Diabet. Med. 19, 254,258 (2002) [source]