Proinsulin levels in patients with pancreatic diabetes are associated with functional changes in insulin secretion rather than pancreatic beta-cell area.
BACKGROUND
Hyperproinsulinaemia has been reported in patients with type 2 diabetes. It is unclear whether this is due to an intrinsic defect in β-cell function or secondary to the increased demand on the β-cells. We investigated whether hyperproinsulinaemia is also present in patients with secondary diabetes, and whether proinsulin levels are associated with impaired β-cell area or function.


METHODS
Thirty-three patients with and without diabetes secondary to pancreatic diseases were studied prior to pancreatic surgery. Intact and total proinsulin levels were compared with the pancreatic β-cell area and measures of insulin secretion and action.


RESULTS
Fasting concentrations of total and intact proinsulin were similar in patients with normal, impaired (including two cases of impaired fasting glucose) and diabetic glucose tolerance (P=0.58 and P=0.98 respectively). There were no differences in the total proinsulin/insulin or intact proinsulin/insulin ratio between the groups (P=0.23 and P=0.71 respectively). There was a weak inverse association between the total proinsulin/insulin ratio and pancreatic β-cell area (r(2)=0.14, P=0.032), whereas the intact proinsulin/insulin ratio and the intact and total proinsulin levels were unrelated to β-cell area. However, a strong inverse relationship between homeostasis model assessment index of β-cell function and both the total and the intact proinsulin/insulin ratio was found (r(2)=0.55 and r(2)=0.48 respectively). The association of insulin resistance (IR) with intact proinsulin was much weaker than the correlation with fasting insulin.


CONCLUSIONS
Hyperproinsulinaemia is associated with defects in insulin secretion rather than a reduction in β-cell area. The weak association between intact proinsulin and IR argues against the usefulness of this parameter in clinical practice.
Breuer
Thomas G K
TG
Department of Medicine I, St Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, Bochum, Germany.
Menge
Bjoern A
BA
Banasch
Matthias
M
Uhl
Waldemar
W
Tannapfel
Andrea
A
Schmidt
Wolfgang E
WE
Nauck
Michael A
MA
Meier
Juris J
JJ
D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D010182:Pancreatic Diseases / Q000097:blood / Q000378:metabolism / Q000473:pathology; D011384:Proinsulin / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin