Is the defect in pro-hormone processing in Type 2 diabetes mellitus restricted to the beta cell?
OBJECTIVE
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.
Bano
G
G
Division of Oncology, Gastroenterology, Endocrinology and Metabolism, St. George's Hospital Medical School, London, UK. gbano@sghms.ac.uk
Rodin
D A
DA
White
A
A
O'Rahilly
S
S
Nussey
S S
SS
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007194:India; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D011384:Proinsulin / Q000097:blood* / Q000378:metabolism*; D011498:Protein Precursors / Q000097:blood*; D011499:Protein Processing, Post-Translational; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D011498:Protein Precursors; C070703:proinsulin, des(31,32)-; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011384:Proinsulin; D006854:Hydrocortisone