Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of gamma-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR).

AIMS/HYPOTHESIS: Risk factors for incident type 2 diabetes, in particular, hepatic markers, have rarely been studied in leaner individuals. We aimed to identify the metabolic and hepatic markers associated with incident diabetes in men and women with a BMI of <27 kg/m(2) and to compare them with those in individuals with a BMI of >or=27 kg/m(2).

METHODS

Risk factors for 9 year incident diabetes were compared in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. Comparisons were made between the 2,947 participants with a BMI of <27 kg/m(2) and the 879 with a BMI of >or=27 kg/m(2).

RESULTS

There were 92 incident cases of diabetes in individuals with a BMI of <27 kg/m(2) and 111 in those with a BMI of >or=27 kg/m(2). Among those who were not markedly overweight, classical biological markers were associated with 9 year incident diabetes, glycaemia being the strongest predictor. gamma-Glutamyltransferase (GGT), either considered as a continuous variable or at levels >or=20 U/l, was associated with incident diabetes, with a stronger effect in the BMI <27 kg/m(2) group: OR 1.59 (95% CI 1.29-1.97, p < 0.001) in comparison with OR 1.07 (95% CI 0.82-1.38, p = 0.63) for those with a BMI of >or=27 kg/m(2) (results after adjustment for alcohol intake, alanine aminotransferase, waist circumference and the HOMA insulin resistance index).

CONCLUSIONS/INTERPRETATION: In individuals with a BMI of <27 kg/m(2), GGT was the strongest predictor of diabetes after fasting hyperglycaemia. This association with incident diabetes remained after adjustment for conventional markers of insulin resistance, suggesting potential interactions between GGT, enhanced hepatic neoglucogenesis and/or early alterations of insulin secretion.