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To determine the effect of a 3-year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT).The study was a randomized controlled lifestyle intervention over 3 years. A total of 147 IGT subjects (75 male, 72 female) were randomized to the intervention (INT) group or control (CON) group; 106 subjects (52 INT, 54 CON) completed 3 years of intervention. Annually, glucose, insulin and free fatty acid (FFA) concentrations were determined fasting and after an oral glucose tolerance test. Measurements of body weight, serum lipids, blood pressure and maximal aerobic capacity were also performed.Analysis of those who completed the 3-year trial, showed that the lifestyle intervention improved body weight (INT -1.08 +/- 4.30 kg; CON +0.16 +/- 4.91 kg, P = 0.01), homeostatis model assessment index for insulin resistance and 2-h FFA. Two-hour glucose concentrations improved in the INT group, the difference being most pronounced after 1 year, with a return to baseline values after 3 years, from 8.59 +/- 1.55 to 8.55 +/- 0.34 mm; in contrast, 2-h glucose deteriorated in the CON group-from 8.46 +/- 1.84 to 9.35 +/- 2.50 mm (P = 0.02). In the INT group, diabetes incidence was reduced by 58% (P = 0.025).Our lifestyle intervention showed a sustained beneficial effect on 2-h glucose concentrations, insulin resistance and 2-h FFA, even after 3 years. Our lifestyle intervention is effective, but for implementation more information is needed about factors influencing adherence.

To evaluate the relation between common variants in the ATP-sensitive K+ channel genes and glucose intolerance.We conducted a meta-analysis of reported association studies in Caucasian populations for common variants in the ABCC8 (exons 16 and 18) and the KCNJ11 (E23K) gene and examined sources of heterogeneity in the results. The meta-analysis was based on 7768-10216 subjects (depending on the gene variant), and included two new population-based studies in the Netherlands with 725 cases and 742 controls.For the KCNJ11 variant, the summary odds ratio (OR) for glucose intolerance was 1.12 (1.01-1.23, P=0.03) for the EK genotype and 1.44 (1.17-1.78, P=0.0007) for the KK genotype, as compared with the EE genotype. For the ABCC8 exon 16 variant, the OR was 1.06 (0.94-1.19, P=0.34) for ct and 0.93 (0.71-1.20, P=0.56) for tt, as compared with the cc genotype. For ABCC8 exon 18, the OR was 1.20 (0.97-1.49, P=0.10) for CT/TT, as compared with the CC genotype. Studies of the ABCC8 variants that were published first or had smaller sample sizes (for the exon 18 variant) showed stronger associations, which may indicate publication bias. For the ABCC8 exon 18 and the KCNJ11 variant, associations were stronger for studies of clinical diabetes than newly detected glucose intolerance. The population attributable risk for clinical Type 2 diabetes was 6.2% for the KCNJ11 KK genotype and 10.1% for the KCNJ11 EK and KK genotype combined.The common KCNJ11 E23K gene variant, but not the ABCC8 exon 16 or exon 18 variant, was consistently associated with Type 2 diabetes.

The insulin receptor substrate-1 (IRS-1) gene is among the most frequently studied candidate genes for Type 2 diabetes, but findings have been inconsistent. This may have been due to generally small study sizes, or to interaction with body fatness as suggested by studies of insulin sensitivity. The aim of this study was to test the hypothesis that the IRS-1 Gly972Arg variant increases risk of Type 2 diabetes.We conducted two large population-based studies including a total of 725 cases and 742 control subjects, who were Caucasian Dutch men and women aged 40-70 years. We calculated odds ratios adjusted for body mass index, study centre, sex and age.Carriers of the Arg allele did not have a higher prevalence of newly detected (OR 0.49, 95% CI 0.24-1.01) or treated (OR 0.71, 0.37-1.35) Type 2 diabetes in the first study, or a higher prevalence of glucose intolerance (OR 1.07, 0.71-1.59) in the second study. The summary odds ratio was 0.86 (0.62-1.17) for carrying the Arg allele as compared with the Gly/Gly genotype. Associations did not differ appreciably by degree of obesity. Also, the Arg variant was not associated with detrimental values for body mass index, waist circumference, plasma HDL-and total cholesterol or hypertension.Our findings indicate that the IRS-1 Gly972Arg variant does not substantially increase risk of common Type 2 diabetes, or Type 2 diabetes in obese persons.