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Disproportionately elevated proinsulin levels in type 2 diabetic patients treated with sulfonylurea
M Dworacka1, M Abramczyk, H Winiarska
1Department of Pharmacology, Poznan University of Medical Sciences, Poznan, Poland. mdworac@am.poznan.pl
Objective:
Hyperproinsulinemia in type 2 diabetic subjects has recently been accepted as an independent cardiovascular risk factor. Moreover, it has been confirmed that high proinsulin concentrations stimulate amylin secretion by pancreatic beta-cells and amyloid accumulation within pancreatic islets leading to impairment of pancreatic islets secretory function. The association between sulfonylureas administration and secretory function of pancreatic beta-cells, especially concerning insulin precursor peptides, is not sufficiently elucidated. Preliminary studies by our research group revealed that the fasting proinsulin serum concentration is significantly higher in type 2 diabetic patients treated with sulfonylureas than in a well-matched group treated with insulin only.
Methods:
A total of 101 subjects with type 2 diabetes were treated either with sulfonylureas (n = 32), with insulin (n = 40), with sulfonylureas + insulin (n = 17) or with diet alone (n = 12).
Results:
The basal secretory function in the four groups were comparable (C-peptide fasting serum level > 0.5 ng/l). An effect of fasting glycemia, long-term metabolic control (HbA1c), postprandial hyperglycemia (1,5-anhydro-D-glucitol), insulin resistance (HOMA(IR)score) and diabetes duration on the fasting proinsulin serum level in the subjects treated could be excluded.
Conclusion:
The disproportionately high proinsulin levels are due to sulfonylureas therapy. The effect is independent of fasting glycemia, long-term metabolic control, postprandial hyperglycemia, diabetes duration and peripheral insulin resistance.
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