Family history of diabetes impacts on interactions between minimal model estimates of insulin sensitivity and glucose effectiveness

Aims/hypothesis: Insulin resistance and glucose effectiveness (S G) are major determinants of glucose tolerance and independently predict the development of type 2 diabetes in individuals with a family history of disease. We examined the inter-relationship between insulin sensitivity (S_I) and S_G in offspring of two parents with type 2 diabetes and in individuals with no family history of diabetes. Methods: Fifty non-diabetic individuals, including 26 offspring of two type 2 diabetic parents (family history, FH+) and 24 with no family history of diabetes (FH-) similar in gender, age, ethnicity and body mass index (BMI) were studied. Each subject underwent a 100-g oral glucose tolerance test (OGTT) and insulin modified frequently sampled intravenous glucose tolerance, analysed using the Bergman's minimal model (MINMOD). Results: Thirteen subjects of the FH+ group and nine ofthe FH-group had impaired glucose tolerance (IGT). S I and S G were independent variables in the FH+ group, while they correlated highly with each other in the FH-group (r = 0.69, p = 0.0002). The relationship between S_I and S_G persisted when analysing the IGT and normal glucose tolerance subgroups separately, demonstrating that these associations were not because of differences in glycaemia. Consistently, S_G strongly correlated with additional measures of insulin resistance only in the FH-group, including fasting insulin (r = 0.56, p = 0.004), homeostasis model assessment of insulin resistance (r = 0.57 p = 0.003) and BMI (r = 0.66, p = 0.0004). Conclusions: These results demonstrate that familial factors impart important physiological differences in the inter-relationship between insulin-dependent and insulin-independent glucose disposal, which may be important in modulating risk for development of disease.