Aims/hypothesis: The first-degree offspring of patients with type 2 diabetes are prone to develop type 2 diabetes, and have both insulin resistance and beta cell impairment. However, it is still unclear whether both pathophysiological features are inseparably combined and which is the outstanding determinant in the offspring.
Methods: Glucose metabolism, insulin sensitivity (calculated as M value divided by insulin [M/I]) and beta cell function were studied in the offspring of individuals with type 2 diabetes (n = 187; 57% females; age 43.8 +/- 8.1 years; BMI 26.8 +/- 4.5 kg/m(2)) and in individuals without a family history of type 2 diabetes (controls, n = 519, 55% females; age 43.4 +/- 8.2 years; BMI 26.4 +/- 3.7 kg/m(2), no significant differences between the groups for any characteristic) by performance of 75 g OGTT and 2 h hyperinsulinaemic (40 mU min(-1) m(-2))-isoglycaemic clamp tests. Beta cell function was evaluated by calculating insulinogenic index (IGI) from C-peptide AUC:glucose AUC ratios from the first hour of OGTT (IGI[60 min]) and from the total OGTT (IGI[120 min]).
Results: During the OGTT, the offspring of individuals with type 2 diabetes showed 4-14% higher plasma glucose from 30 to 120 min (p < 0.05) and 20-29% higher serum insulin from 90 to 120 min, but decreased IGI(60 min) and IGI(120 min) (p < 0.05). M/I was 11% lower in the offspring of affected individuals than in controls (p < 0.01). To study the offspring of patients with type 2 diabetes with insulin sensitivity similar to that of the control group, the offspring of affected patients were divided into M/I quartiles. Those in the third M/I quartile showed M/I values and major anthropometric characteristics similar to those of the controls, but insulin AUC and C-peptide AUC values were lower in the first hour and the total OGTT (p < 0.05). The third M/I quartile had lower IGI values at 60 min and 120 min: 11% and 14% lower, respectively (p < 0.02).
Conclusions/interpretation: The first-degree offspring of type 2 diabetic patients show insulin resistance and beta cell dysfunction in response to oral glucose challenge. Beta cell impairment exists in insulin-sensitive offspring of patients with type 2 diabetes, suggesting beta cell dysfunction to be a major defect determining diabetes development in diabetic offspring.