Is the defect in pro‐hormone processing in Type 2 diabetes mellitus restricted to the β cell?

AIMS: To investigate whether the defect in pro-hormone processing in people with Type 2 diabetes mellitus is restricted to the pancreatic beta cell or whether there is evidence of a more generalized abnormality. METHODS: Ten Indian subcontinent Asian women with diet-controlled Type 2 diabetes were compared with a control group of nine non-diabetic Asian women who were matched for body mass index. All subjects underwent a standard 75 g oral glucose tolerance test during which plasma glucose, insulin, proinsulin and 32,33 split proinsulin were measured. Subjects in both groups then underwent an intravenous corticotrophin-releasing hormone (CRH) test with 100 microg human CRH. Plasma cortisol, adrenocorticotrophic hormone (ACTH) and ACTH precursors were measured. RESULTS: Basal levels of insulin were lower in diabetic subjects (32.5 (12.5-52) pmol/l) than in the control group (42.2 (21.4-63.0) pmol/l); normalized geometric mean (95% confidence interval), P<0.05; as were the levels at 30 min (29.5 (3.7-55.3) pmol/l) and (34.4 (10.7-58.2) pmol/l), P<0.05. The levels at 60 min were (26.7 (6.4-47.0) pmol/l) in subjects with diabetes and (13.6 (-11.3-38.5) pmol/l) in controls, P<0.05 and at 90 min these were (43.4 (19.4-67.4) pmol/l) and (19.3 (-4.6-43.3) pmol/l), P<0.05, respectively, after the 75-g oral glucose load. The acute insulin response was markedly reduced in the subjects with diabetes (1.8 (0.60-3.1) pmol insulin/ mmol glucose), compared with the control group (31.4 (8.0-54) pmol/l insulin/mmol glucose), P<0.005. Intact proinsulin was much higher in the diabetic subjects (23.9 (10.1-37) pmol/1) than in the control group (7.2 (3.9-10) pmol/1), P<0.002, as was the percentage of proinsulin-like molecules (28 (14-42) and 12 (8-17)%), respectively, P<0.01. There were no differences between basal or stimulated levels of ACTH precursors, ACTH or cortisol between the diabetic subjects and the controls. CONCLUSIONS: The defect in insulin secretion in Indian subcontinent Asian women with Type 2 diabetes is similar to that described in other populations with an increased prevalence of Type 2 diabetes. The absence of any defect in the processing of cortisol precursors in the women with Type 2 diabetes suggests that they do not have a generalized defect of hormone processing.