Pathogenic mechanism of type 2 diabetes in Ghanaians--the importance of beta cell secretion, insulin sensitivity and glucose effectiveness

Objective. To assess insulin sensitivity and beta cell secretion in indigenous Ghanaian subjects with a spectrum of glucose intolerance. Research and methods. We evaluated beta cell secretion, insulin sensitivity (Si) and glucose effectiveness (Sg) in three groups: group 1, 15 healthy control subjects without family history of type 2 diabetes; group 2, 11 healthy non-diabetic first-degree relatives of Ghanaian patients with type 2 diabetes; and group 3, 10 patients with type 2 diabetes living in Accra, Ghana, West Africa. A standard oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance (FSIGT) test were performed for each subject. Si and Sg were measured using Bergman's minimal model method. Results. The mean body mass index (BMI) and lean body mass were not different among the three groups. However, the waist-to-hip circumference ratio, total body fat as well as triceps and biceps skinfolds were significantly greater in group 3 (diabetic patients) than in group 2 (relatives) and group 1 (healthy controls). Mean fasting and postprandial serum glucose levels were not significantly different between the relatives and healthy controls during oral glucose challenge. The mean fasting and postprandial serum glucose levels were significantly higher in the group 3 diabetic patients than in the non-diabetic groups. Mean fasting serum insulin and C-peptide levels tended to be higher in group 3 than in groups 1 and 2. However, mean serum insulin and C-peptide responses after oral glucose load were significantly greater in group 2 than in the group 1 healthy controls. The insulin responses in the two non-diabetic groups after oral glucose challenge were significantly greater than in the diabetic patients. During the FSIGT, the mean serum glucose responses were similar in the two non-diabetic groups (groups 1 and 2). The serum glucose responses were significantly greater in group 3 than in the non-diabetic groups. Mean total and acute first and second phases of insulin and C-peptide responses were greater in group 2 than group 1. However, acute phases of insulin secretion were severely blunted in group 3 when compared with groups 1 and 2 during FSIGT in our Ghanaians. We found that the mean Si was slightly lower in group 2 (1.72 ± 0.32) than in the healthy controls in group 1 (1.9 ± 0.55, P = NS). Mean Si was remarkably lower in the diabetic patients in group 3 (1.30 ± 0.35 x 10-4/min (μU/ml)) when compared with the relatives and healthy controls, but the differences were not statistically significant. Mean glucose effectiveness at basal insulin level (Sg) was not significantly different among the relatives in group 2 (2.38 ± 0.50), the healthy controls in group 1 (2.66 ± 0.38) and the diabetic patients in group 3 (2.27 ± 0.49 x 10-2/min). Conclusions. We conclude that (i) the pathogenetic mechanisms of type 2 diabetes in indigenous Ghanaians are characterised by severe beta cell dysfunction and moderate reduction in Si. Although the healthy relatives manifest insulin resistance with compensatory hyperinsulinaemia, our study suggests that the conversion of such subjects to type 2 diabetes is determined by deterioration in beta cell function and perhaps Si but not tissue Sg in Ghanaians. Prospective studies are needed to examine the sequential changes that lead to the development of type 2 diabetes in indigenous Ghanaians.

Source: UG