Familiality of metabolic abnormalities is dependent upon age at onset and phenotype of the type 2 diabetic proband.

Summary, in English

To determine the impact of a family history of the common form of type 2 diabetes and the phenotype of the proband on anthropometric and metabolic variables in normoglycemic first degree relatives, we studied 2100 first degree relatives of patients with the common form of type 2 diabetes (FH+) and 388 subjects without a family history of diabetes (FH-). All subjects participated in an oral glucose tolerance test to allow measurement of insulin secretion (30min incremental insulin /glucose, I/G 30), and insulin sensitivity (HOMA insulin resistance). A subset participated in a euglycemic clamp (n=75) and an intravenous glucose tolerance test (n=300). To study the effect of a particular phenotype of the proband, insulin secretion and sensitivity were also compared between first degree relatives of diabetic probands with high and low waist to hip ratio (WHR) and probands with early and late onset of diabetes. FH+ subjects were more insulin resistant as seen from higher HOMA-IR index (P=0.007) and lower rate of insulin-stimulated glucose uptake (P=0.001) and had more features of the metabolic syndrome (P=0.02, P=0.0002) compared with FH- subjects. Insulin secretion adjusted for insulin resistance (disposition index, DI) was also lower in the FH+ vs FH- subjects (P=0.04). Relatives of diabetic probands with a high WHR had reduced insulin mediated glucose uptake compared with relatives of probands with a low WHR (P = 0.04). Relatives of diabetic patients with age at onset < 44 years had higher HOMA IR (P < 0.005) and lower DI (P < 0.005) than relatives of patients with age at onset >65 yrs (highest quartile). We conclude that early age at onset of type 2 diabetes and abdominal obesity have a significant influence on the metabolic phenotype in the non-diabetic firstdegree relative