Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.

AIMS: To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). METHODS: Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. RESULTS: Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). CONCLUSIONS: Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.     

Daytime variations in glucose tolerance in people with impaired glucose tolerance

To determine whether glucose tolerance varies throughout the day in people with impaired glucose tolerance (IGT). We studied 15 healthy IGT, and 18 matched normal glucose tolerant (NGT) individuals. Blood samples were taken every 30-120 min during a 24h period in which all individuals had three mixed meals and nocturnal sleep. We measured glucose, free fatty acids, specific insulin, intact proinsulin, cortisol and growth hormone. Variable responses were considered as concentrations and areas under the curves. Comparison between the groups was by Student's t-test, Mann-Whitney, and analysis of variance. Higher total glucose response, inappropriate normal total insulin response, and unproportionally increased proinsulin total response were observed in the IGT group. Lower glucose tolerance occurred in IGT after dinner, as in the NGT, and after breakfast associated with increased insulin response after breakfast, and similar proinsulin response after all three meals. IGT had higher glucose response than NGT after breakfast and lunch, similar insulin responses, and increased proinsulin-insulin ratio after all three meals. Data from this study demonstrate that IGT individuals present lower glucose tolerance in the evening, as those with NGT, and in the morning, as reported in patients with type 2 diabetes.     

Association between circadian rhythm of blood pressure and glucose tolerance status in normotensive,non-diabetic subjects

AimsTo examine whether circadian rhythm of blood pressure (BP) is associated with glucose tolerance status in normotensive, non-diabetic subjects.MethodsA cross-sectional study recruited normotensive and non-diabetic subjects, aged 35–79 years. A 75 g oral glucose tolerance test (OGTT) and 24-h ambulatory blood pressure monitoring (24-h ABPM) were performed.ResultsAmong 31 impaired glucose tolerance (IGT) and 36 normal glucose tolerance (NGT) study subjects, the mean (±S.D.) diurnal–nocturnal differences of average systolic BP (SBP) were 7.1 ± 6.9 and 9.9 ± 6.2 mm Hg, respectively (p = 0.086). In a linear mixed-effects regression model, however, taking each measurement of BP as the outcome, nighttime reduction of SBP in the IGT group was 7.19 mm Hg, which was significantly smaller compared to a reduction of 9.80 mm Hg in the NGT group (p-value for IGT: nighttime interaction = 0.0014). The prevalence of non-dipping BP pattern was 77.4% in the IGT group which was significantly higher than 52.8% of the NGT group (p = 0.036). Logistic regression revealed a significant effect of IGT for predicting non-dipping pattern with an adjusted odds ratio of 3.71 (95% CI: 1.09, 12.66, p = 0.029).ConclusionsAmong normotensive, non-diabetic subjects, the decreased nocturnal BP reduction was associated with impaired glucose tolerance status.     

Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance

OBJECTIVE: This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, beta-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). METHODS: Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) < or = 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. RESULTS: After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4.25 +/- 0.22 vs 4.80 +/- 0.17 mmol/l, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (1.25 +/- 0.07 vs 1.43 +/- 0.06 mmol/l, P < 0.05), and low-density lipoprotein cholesterol (LDL-C) (2.70 +/- 0.15 vs 3.37 +/- 0.17 mmol/l, P < 0.05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic beta-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0.38 +/- 0.06 vs 0.54 +/- 0.09 x 10(-5) min(-1)/pmol, P < 0.05; 0.017 +/- 0.002 vs 0.021 +/- 0.001 min(-1), P < 0.05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0.05). CONCLUSION: Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on beta-cell secretory function.     

Platelet activation in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT), a prediabetic state, is associated with an increased risk of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk factor for atherothrombosis. This study was designed to answer the following questions: (i) Do MPV levels change in IGT? (ii) Is there any relation between MPV levels and 2 h plasma glucose levels after 75 g oral glucose tolerance test. We selected 48 subjects with IGT, and 48 healthy subjects with normal glucose tolerance matched for age, gender, and body mass index. MPV was significantly higher in IGT group than in control group (9.06 ± 1.5 fl vs. 8.28 ± 0.8 fl, p = 0.002). Also, MPV was positively correlated with 2 h plasma glucose concentration in IGT group (r = 0.39, p = 0.006). In conclusion, our results suggest that subjects with IGT tend to have increased platelet activation. Increased platelet activity could contribute to increasing the risk of cardiovascular disease in IGT.     

Platelet activation in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT), a prediabetic state, is associated with an increased risk of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk factor for atherothrombosis. This study was designed to answer the following questions: (i) Do MPV levels change in IGT? (ii) Is there any relation between MPV levels and 2 h plasma glucose levels after 75 g oral glucose tolerance test. We selected 48 subjects with IGT, and 48 healthy subjects with normal glucose tolerance matched for age, gender, and body mass index. MPV was significantly higher in IGT group than in control group (9.06 +/- 1.5 fl vs. 8.28 +/- 0.8 fl, p = 0.002). Also, MPV was positively correlated with 2 h plasma glucose concentration in IGT group (r = 0.39, p = 0.006). In conclusion, our results suggest that subjects with IGT tend to have increased platelet activation. Increased platelet activity could contribute to increasing the risk of cardiovascular disease in IGT.     

Association between insulin and blood pressure in a community population with normal glucose tolerance.

The purpose of this study was to examine the relationship between insulin and BP in patients with normal glucose tolerance. The associations between systolic and diastolic BP, age, body mass index, waist/hip ratio, fasting glucose, insulin, fructosamine, glycosylated haemoglobin, lipid profile, and glucose and insulin two hours after 75 g oral glucose were examined in 1,520 employees of a public utility company and non-medical staff of a district hospital. Patients with impaired glucose tolerance or diabetes mellitus (using WHO criteria) were excluded. In men (mean age 35.6 +/- 8.7 years, n = 769), both systolic and diastolic BP were positively associated with age, body mass index, waist/hip ratio, fasting and 2h glucose and insulin, triglycerides and apolipoprotein B, and were negatively associated with glucose/insulin ration, and high density lipoprotein and cholesterol and its subfractions. However, in multivariate analysis only body mass index, age, fasting glucose and insulin were independent predictors of systolic BP, while only body mass index and age predicted diastolic BP. In women, age, glycosylated haemoglobin, 2h glucose/insulin ratio, 2h glucose, fructosamine and triglycerides were predictors of systolic BP. Fasting or 2h insulin, and glucose/insulin ratios did not predict diastolic BP. The results are compatible with the hypothesis that systolic hypertension may reflect a hyper-insulinaemic state even in those with normal glucose tolerance, independent of age and obesity. The association between plasma lipids and blood pressure is probably mediated by insulin and obesity.     

Efficacy of acarbose in Chinese subjects with impaired glucose tolerance

This multicentre, double-blind, placebo-controlled study investigated the efficacy of acarbose in Chinese individuals with impaired glucose tolerance (determined using a 75 g oral glucose tolerance test). Subjects were randomised to either placebo or acarbose 50 mg t.i.d. for a period of 16 weeks. Primary efficacy variables were the maximum postprandial plasma glucose value (C(max)) and the serum insulin profile. Secondary efficacy parameters included postprandial glucose profile, maximum postprandial insulin concentration (C(max)), changes in lipid profile and blood pressure and HbA(1c) and body weight and conversion to Type 2 diabetes. In the intention-to-treat analysis, acarbose treatment resulted in significantly higher reductions in postprandial glucose and serum insulin concentrations compared to placebo. Triglyceride concentration was the only lipid parameter to be significantly reduced in acarbose subjects. Loss of body weight was also significantly greater for acarbose than placebo subjects. Some 19 individuals converted to Type 2 diabetes (seven acarbose, 12 placebo), but this difference was not significant. Acarbose is efficacious in improving the metabolic state of individuals with impaired glucose tolerance indicating a potential benefit for the delay or prevention of onset of Type 2 diabetes in Chinese subjects.     

Relationship between blood pressure and glucose tolerance in acromegaly

BACKGROUND: Hypertension represents a well-known risk factor for cardiovascular diseases. The pathogenesis of hypertension in acromegaly is commonly viewed as multifactorial, but the possible influence of metabolic disorders on blood pressure (BP) in affected patients is largely unknown. OBJECTIVE: The aim of the present study was to evaluate the impact of glucose metabolism abnormalities on BP values in a series of patients with active acromegaly. DESIGN: An open multicentre prospective study. PATIENTS: Sixty-eight patients with active disease, aged 47.5 +/- 11.7 years, have been studied. Thirty-nine had normal glucose tolerance (NGT), 16 impaired glucose tolerance (IGT) and 13 suffered from diabetes mellitus (DM). MEASUREMENTS: Mean clinical BP values were calculated as the mean of BP values obtained by sphygmomanometric measurement in three separate occasions and mean 24-h, diurnal and nocturnal systolic (SBP) and diastolic (DBP) values were obtained by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: Patient's age and the degree of glucose tolerance abnormalities were found to significantly and independently influence BP values. All clinical and ABPM SBP and DBP values significantly increased with age by linear regression (P < 0.02 for all BP values, 0.30 < or = R < or = 0.43), and the independent influence of this parameter on BP values was confirmed by mutivariate analysis. Similarly, the independent influence of glucose tolerance abnormalities on BP values was confirmed when introducing age as a covariable in a multivariate analysis, and patients with DM presented significantly higher clinical SBP and 24-h, diurnal and nocturnal SBP and DBP than patients with NGT (P < 0.02 for clinical SBP, P < 0.015 for all ABPM values, respectively). In addition, patients with DM showed significantly higher 24-h, diurnal and nocturnal DBP than those with IGT (P < 0.05 in all cases). In contrast, no significant difference was found between NGT and IGT patients. No significant influence of disease duration, BMI, GH, IGF-I, or fasting and 2-h post glucose load insulinaemia on BP values was observed. CONCLUSIONS: Abnormalities of glucose metabolism significantly contribute to increase systolic blood pressure and especially diastolic blood pressure in acromegalic patients. Careful control of blood pressure and of risk factors for developing systemic hypertension, with special reference to glucose tolerance, is mandatory to decrease cardiovascular morbidity and mortality in such patients.     

Haemostatic effects of simvastatin in subjects with impaired glucose tolerance

Background: Very little is known about extra‐lipid effects of statins in prediabetic subjects. Aim: Our study has assessed the effect of simvastatin on coagulation and fibrinolysis in patients with impaired glucose tolerance (IGT), comparing this effect with that exhibited by simvastatin in isolated hypercholesterolaemia. Methods: Lipid profile, fasting and 2‐h post‐glucose challenge plasma glucose levels, the homeostatic model assessment (HOMA) ratio, glycated haemoglobin, the prothrombin and partial thromboplastin time, plasma fibrinogen, plasminogen activator inhibitor‐1 (PAI‐1), von Willebrand factor (vWF), factor X levels and factor VII coagulant activity were assessed at baseline, and after 30 and 90 days of simvastatin treatment (20 mg daily) in 28 patients with IGT and 28 subjects with primary isolated hypercholesterolaemia. The control group included 26 age‐, sex‐ and weight‐matched dyslipidaemia‐free individuals with normal glucose tolerance. The experiments comply with the current law of Poland. Results: Compared to the control subjects, hypercholesterolaemic and IGT patients exhibited increased baseline plasma levels of fibrinogen, PAI‐1 and vWF, and increased factor VII activity, with no difference between the two groups of patients. All these haemostatic abnormalities were alleviated or normalized after simvastatin treatment, which was accompanied by a prolongation of the prothrombin and partial thromboplastin time. In both treatment groups simvastatin reduced total and low‐density lipoprotein (LDL)‐cholesterol, oxidized LDL and apoprotein B but did not affect glucose metabolism marker levels. Conclusions: Our study shows that haemostasis is disturbed to a similar degree in IGT and isolated hypercholesterolaemia. Simvastatin exhibits a multidirectional, lipid‐independent favourable action on coagulation and fibrinolysis in IGT patients, which may play a role in the prevention of initiation and progression of atherosclerosis in this prediabetic state.     

Long-term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance

AIMS: To assess the efficacy and long-term effects of glipizide treatment on glucose and insulin metabolism in individuals with impaired glucose tolerance (IGT). METHODS: Thirty-seven first-degree relatives of patients with type 2 diabetes fulfilling WHO criteria for IGT were randomized to treatment with either glipizide 2.5 mg once daily or matching placebo for 6 months. A 75 g, 2-h oral (OGTT) and 60 min intravenous glucose tolerance test (IVGTT) were performed at baseline and after 6 months. The subjects were followed up for another 12 months after discontinuation of treatment and a repeat OGTT was performed at 18 months. RESULTS: Thirty-three subjects fulfilled the study. Markers of insulin sensitivity - i.e. fasting insulin and HOMA(IR)-index - improved in the glipizide group (P = 0.04 and 0.02 respectively) as well as HDL cholesterol (P = 0.05) compared with placebo group after 6 months. At 18 months, both fasting and 2 h glucose concentrations were significantly lower in the glipizide group compared with the placebo group (P = 0.04 and 0.03 respectively). The prevalence of type 2 diabetes was 29.4% in the placebo group and 5.9% in the glipizide group at 18 months. This equals an 80% relative risk reduction in the active treatment group. CONCLUSIONS: Short-term treatment with glipizide improves glucose and insulin metabolism in subjects with IGT primarily by improving insulin sensitivity mediated by lowering glucose toxicity, thereby providing the beta cells rest. Larger studies are needed to establish whether these effects are sufficient to prevent progression to manifest type 2 diabetes and associated cardiovascular morbidity in subjects at increased risk of developing type 2 diabetes.     

Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance

Summary Recent evidence suggests that the post-prandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion ( 0–10 min insulin area ÷ 0–10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2–19.4] vs 9.1 [2.6–14.5] mU·mmol^–1; p<0.01). During the clamp, circulating insulin (93±8 [mean±SEM] and 81±10 mU·l^–1) and glucagon (54±4 and 44±6 ng·l^–1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78±0.27 vs 4.47±0.53 mg·kg^–1·min^–1; p<0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38±0.10 and 0.30±0.18 mg·kg^–1·min^–1). Therefore, the main defects in subjects with impaired glucose tolerance are decreased first phase insulin secretion and peripheral non-oxidative glucose disposal, but hepatic glucose output shows normal responsiveness to insulin.Abbreviations FPIS First phase insulin secretion - PG plasma glucose - NIDDM non-insulin-dependent diabetes mellitus - IGT impaired glucose tolerance - HGO hepatic glucose output - IVGTT intravenous glucose tolerance test - OGTT oral glucose tolerance test     

二甲双胍对原发性高血压伴糖耐量减低患者血压的影响

目的:观察二甲双胍单独或与苯那普利联合应用对原发性高血压(EH)患者的降压作用。方法:将120例伴糖耐量减低非糖尿病EH患者随机分为二甲双胍组(59例)和苯那普利组(61例),分别以二甲双胍500mg,3次/d和苯那普利10mg,1次/d治疗。治疗1个月后对收缩压≥140mmHg(1mmHg=0.133kPa)和(或)舒张压≥90mmHg者,给予上述2种药物联合治疗,剂量同上;达标者继续原治疗不变。总疗程为2个月。观察2组治疗前后血压和胰岛素敏感性变化。结果:①与治疗前比较,二甲双胍组和苯那普利组在治疗1个月后收缩压分别下降(12.5±6.4)mmHg和(14.9±6.5)mmHg,舒张压分别下降(8.5±6.2)mmHg和(9.9±3.8)mmHg;在治疗2个月后收缩压分别下降(16.9±5.0)mmHg和(19.9±6.4)mmHg,舒张压分别下降(13.1±5.3)mmHg和(14.3±1.2)mmHg,2组比较均差异无统计学意义(均P>0.05)。2组联合用药率均为56%。②与治疗前比较,空腹胰岛素、糖负荷1h胰岛素、糖负荷2h胰岛素、胰岛素曲线下面积在二甲双胍组于治疗1、2个月后明显下降(均P<0.01);在苯那普利组除糖负荷1h胰岛素于治疗1个月后开始下降外(P<0.05),其余于治疗2个月后明显下降(均P<0.01)。胰岛素敏感性指数在二甲双胍组于治疗1个月后明显高于苯那普利组(P<0.05),在治疗2个月后2组间比较差异无统计学意义(P>0.05)。结论:二甲双胍与苯那普利对伴糖耐量减低EH患者具有相似的降压效应和良好的协同作用。     

Impaired baroreflex sensitivity in subjects with impaired glucose tolerance,but not isolated impaired fasting glucose

Impaired baroreflex sensitivity (BRS) is associated with adverse cardiovascular outcomes. There are currently no studies on BRS changes in subjects with different glycemic statuses, including normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed diabetes (NDD). The aim of this study was to investigate the effects of NDD, IGT and isolated IFG on BRS, based on a community-based data. A total of 768 subjects were classified as NGT (n = 498), isolated IFG (n = 61), IGT (n = 126) and NDD (n = 83). Spontaneous BRS was determined by the spectral α coefficient method, i.e., the square root of the ratio between the power of the RR interval and the power of systolic blood pressure in the LF frequency region (0.04–0.15 Hz) after the subjects had rested in a supine position for 5 min. Valsalva ratio was calculated as the longest RR interval after release of the Valsalva maneuver, divided by the shortest RR interval during the maneuver. As compared with NGT subjects, NDD (p = 0.039) and IGT (p = 0.041) subjects had a reduced spontaneous BRS in multivariate analysis based on analysis of covariance. NDD subjects exhibited a lower Valsalva ratio than NGT subjects (p = 0.043). However, there were no significant differences in spontaneous BRS and Valsalva ratio between subjects with isolated IFG and NGT. In conclusion, NDD and IGT subjects had an impaired BRS as compared to NGT subjects. However, reduced BRS was not apparent in subjects with isolated IFG.     

糖耐量异常对原发性高血压患者血压变异性的影响

目的观察糖耐量异常对原发性高血压患者血压变异性的影响情况。方法入选正常血压及原发性高血压患者260例,按动态血压水平及是否合并糖耐量异常分为正常血压组（n=68）,正常血压合并糖耐量异常组（n=60）,原发性高血压组（n=70）,原发性高血压合并糖耐量异常组（n=62）。所有受试者进行24小时动态血压监测,观察各组血压变异性特点。结果原发性高血压合并糖耐量异常组24小时收缩压变异系数[（0.12±0.03）vs.（0.10±0.02）]、白天收缩压标准差[（15.37±2.66）vs.（13.34±2.27）]、变异系数[（0.12±0.02）vs.（0.10±0.02）]均高于原发性高血压组（P〈0.01）;正常血压合并糖耐量异常组与正常血压组各时间段血压标准差、变异系数差异无统计学意义（P〉0.05）。结论糖耐量异常影响原发性高血压人群血压变异性（以收缩压为主）,对正常血压人群无明显影响。     

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

AIMS: Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). METHODS: DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. RESULTS: There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). CONCLUSIONS: Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.