Disproportionately elevated proinsulin levels in type 2 diabetic patients treated with sulfonylurea.
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.


CONCLUSIONS
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.
Dworacka
M
M
Department of Pharmacology, Poznan University of Medical Sciences, Poznan, Poland. mdworac@am.poznan.pl
Abramczyk
M
M
Winiarska
H
H
Kuczynski
S
S
Borowska
M
M
Szczawinska
K
K
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D031204:Caloric Restriction; D003847:Deoxyglucose / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D015999:Multivariate Analysis; D018579:Patient Selection; D011384:Proinsulin / Q000097:blood* / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
D001786:Blood Glucose; D002096:C-Peptide; D003847:Deoxyglucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D011384:Proinsulin; D013453:Sulfonylurea Compounds; C006584:1,5-anhydroglucitol