Dysfonction de la cellule bêta-pancréatique chez les descendants de patients diabétiques

Abstract

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/m²) 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/m², no significant differences between the groups for any characteristic) by performance of 75 g OGTT and 2-h hyperinsulinemic (40 mU/min/m²)-isoglycemic 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 the 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 patients with type 2 diabetes 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 that beta-cell dysfunction is considered to be a major defect determining the development of diabetes in diabetic offspring.