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

Abstract

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 ≥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 ≥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 ≥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. γ-Glutamyltransferase (GGT), either considered as a continuous variable or at levels ≥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 ≥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.

Evaluation of Serum Gamma Glutamyl Transferase Levels in Diabetic Patients With and Without Retinopathy

“…Relationship between GGT levels with BMI, BP, microalbuminuria, diabetic peripheral neuropathy, metabolic syndrome, and acute coronary syndromes has been shown previously (6,7,9,10,12,13,15,18).…”

“…Various studies showed that GGT levels may be a predictor of diabetes mellitus risk and its chronic complications (4,(6)(7)(8)(9)(10)15). Relationship between GGT levels with BMI, BP, microalbuminuria, diabetic peripheral neuropathy, metabolic syndrome, and acute coronary syndromes has been shown previously (6,7,9,10,12,13,15,18).…”

“…High GGT level causes excess fat accumulation in the liver, which reduces insulin sensitivity and contributes to hyperinsulinemia and metabolic syndrome (10,12).…”

“…It is also suggested that increased GGT levels is associated with metabolic syndrome and hepatic fat accumulation (6,(9)(10)(11). The association of GGT levels with BP, BMI, and acute coronary syndrome has been shown recently (4,10,12,13). Arkkila et al, in 2001, showed the association between GGT levels and DM complications including peripheral neuropathy and DR in DM Type 1 patients (14).…”

“…Some studies have revealed that higher GGT level is an earlier marker of diabetes development (6)(7)(8)(9). It is also suggested that increased GGT levels is associated with metabolic syndrome and hepatic fat accumulation (6,(9)(10)(11). The association of GGT levels with BP, BMI, and acute coronary syndrome has been shown recently (4,10,12,13).…”