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

SUMMARY Aims  To investigate whether the defect in pro‐hormone processing in people with Type 2 diabetes mellitus is restricted to the pancreatic β 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 μg 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