Metabolic impact of a family history of Type 2 diabetes. Results from a European multicentre study (EGIR)

Background Insulin resistance was found in some but not in all previous stu dies of non-diabetic first degree relatives of Type 2 diabetic patients. Sm all study groups, ethnic differences and/or non-optimal techniques may expl ain the conflicting results. Aim To study the impact of a family history of Type 2 diabetes on insulin a ction in a large group of non-diabetic Europeans using the 'gold standard' euglycaemic hyperinsulinaemic clamp technique. Methods Non-diabetic subjects (n=235) with a positive family history of Typ e 2 diabetes (FH+) and 564 subjects with no family history of diabetes (FH- ) were recruited from The European Group of Insulin Resistance (EGIR) datab ase. This database includes measurements of insulin action using the insuli n clamp technique (1 mU/kg per min) in normal glucose-tolerant individuals from 20 different European centres. In a subset of subjects the measurement s were performed in combination with indirect calorimetry (n=80 vs. 213 wit h and without family history of Type 2 diabetes). Results The body mass index (BMI) was slightly higher in FH+ compared with FH- (26.7 +/-4.6 vs. 25.1 +/-4.7 kg/m(2); P<0.02). After correction for cov ariates according to differences between investigators and subject characte ristics including BMI (multiple regression analysis), insulin-stimulated gl ucose disposal was lower in FH+ compared with FH- (P<0.00001). Insulin-stim ulated glucose oxidation was slightly increased in FH+ compared with FH-, a nd insulin-stimulated non-oxidative glucose metabolism was consequently mar kedly reduced in FH+ compared with FH- (P<0.0005). Conclusion Insulin resistance is present in European non-diabetic relatives of Type 2 diabetic patients. The insulin resistance is independent of degr ee of obesity and is restricted solely to the pathway of non-oxidative gluc ose metabolism.