,7 for the DESIR Study Group 2 * Recently, case-control studies demonstrated that a TCF7L2 (transcription factor 7-like 2 gene) noncoding variant (rs7903146 T at-risk allele) was strongly associated with an increased risk of type 2 diabetes. However, the predictive value of this marker in a nonselected general population remains unknown. In this study, our aim was to assess the contribution of this variant to the prevalence and incidence of hyperglycemia (type 2 diabetes and impaired fasting glucose) and insulin regulation in a 9-year prospective study of 4,976 middle-aged participants in the French DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) cohort. Our data support previous studies associating the T at-risk allele with a higher prevalence of hyperglycemia at baseline (P ‫؍‬ 0.049) and a higher incidence of hyperglycemia after 9 years of follow-up (P ‫؍‬ 0.014). The population-attributable risk to develop hyperglycemia due to the T at-risk allele was estimated to be 10.4% at the end of the prospective study. The most likely inheritance model was found to be additive (P ‫؍‬ 0.002) rather than deviating from linearity (P ‫؍‬ 0.098). An increase in the incidence of hyperglycemia was confirmed by survival analyses among C/C, C/T, and T/T carriers during the 9 years of follow-up (P ‫؍‬ 0.028 by log-rank test). Interestingly, in control individuals, there was weak evidence of association of the T at-risk allele with reduced fasting insulin levels and insulin secretion index (homeostasis model assessment of ␤-cell function) in control individuals. We conclude that the TCF7L2 T at-risk allele variation (rs7903146) predicts hyperglycemia incidence in a general French population, possibly through a deleterious effect on insulin secretion. Diabetes 55: 3189 -3192, 2006

Aims/hypothesis Among hepatic markers, gamma-glutamyltransferase (GGT) is the main predictor for development of type 2 diabetes, but there are no data to date on changes in GGT and type 2 diabetes incidence. Methods Data at baseline and at 3 years from the D.E.S.I.R. cohort were used, comprising 2,071 men and 2,130 women without baseline diabetes. Results Changes in GGT level were correlated with changes in markers of insulin resistance (fasting insulin, homeostasis model assessment of insulin resistance), as well as with the following elements of the metabolic syndrome: central obesity, and increased fasting glucose, triglycerides and blood pressure (systolic and diastolic). The 3-year increase in GGT was associated with incident type 2 diabetes in both sexes, after adjusting for age and baseline GGT. After further adjustment for baseline confounding factors, including alanine-aminotransferase, alcohol intake, obesity and fasting insulin, the odds ratios (95% CI) for an association between incident type 2 diabetes and unchanged or increased (as opposed to decreased) GGT levels were 2.54 (1.38-4.68) in men (p=0.003) and 2.78 (1.20-6.42) in women (p=0.02). These associations were slightly attenuated after adjusting for the 3-year change in BMI, alcohol consumption and fasting insulin, the odds ratios being 2.49 (1.28-4.86) in men and 2.53 (1.01-6.40) in women. This relationship was not dependent on intra-individual variability. Conclusions/interpretation An unchanged or increased GGT level over time, even when GGT is in the normal range, is correlated with increasing insulin resistance and is associated with a risk of incident type 2 diabetes in both sexes, independently of baseline GGT, which is itself a diabetes risk factor.

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Background: Bioavailable testosterone (BT) is measured [assayed BT (aBT)] or calculated (cBT) in the diagnosisResults: A slight decrease in TT, significant decreases in BT and 5-diol, no variation in DHT, and an increase in SHBG were observed with age. In young males (<39 years), the lower normal limits were between 2.30 and 2.72 nmol/L for aBT and 8.50 nmol/L for TT. For K s ‫؍‬ 1 ؋ 10 9 L/mol and K a ‫؍‬ 3.6 ؋ 10 4 L/mol, the lower cBT limit