Impairment of insulin action in non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients

Abstract

Aims: To investigate first-phase insulin release and peripheral insulin sensitivity of non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients.

Methods: 12 euglycemic first-degree relatives of type 2 diabetic patients (ERDM), 12 newly diagnosed type 2 diabetic patients (DM-2) and 12 healthy individuals (control) participated in the study. All subjects were non-obese (BMI< 25 kg/m(2)). Intravenous glucose tolerance test and euglycemic hyperinsulinemic clamp test were performed to evaluate first-phase insulin release and quantify insulin sensitivity, respectively.

Results: the first-phase insulin release did not differ between the ERDM and control subjects (p=0.532), while the acute insulin response was absent in the DM-2 patients (p=0.001). Peripheral glucose deposit rate (GDR) was significantly lower in the ERDM (10.6 ± 2.1mg/kg·min, p=0.000) and DM-2 (9.6 ± 1.1mg/kg·min, p=0.000) groups than that in the control group (13.2 ± 1.2mg/kg·min). There was no statistical difference in GDR between the ERDM and DM-2 groups (p=0.110). Fasting FFA levels of the ERDM (p=0.007) and DM-2 (p=0.000) subjects were significantly higher than those of the controls.

Conclusions: non-obese, first-degree relatives of type 2 diabetic patients with normal glucose tolerance (NGT) exhibit remarkable impairment of insulin sensitivity and increased FFA levels. Insulin resistance is independent of obesity and blood glucose level. Progression from NGT to type 2 diabetes may mainly be attributed to deterioration of early insulin secretion.