Insulin secretion and sensitivity as determinants of HbA1c in type 2 diabetes.
BACKGROUND
Defects in insulin secretion and sensitivity, two major determinants of glycaemic control, can occur and progress or not in parallel. The present study was designed to compare the respective roles of both determinants on HbA1c, in type 2 diabetic patients, according to whether or not residual beta-cell function was stimulated with insulin secretagogues.


METHODS
Insulin secretion and insulin sensitivity were both estimated using the homeostasis model assessment (HOMA). HbA1c, insulin sensitivity (HOMA2%S) and insulin secretion (HOMA2%B) were determined in 289 noninsulin-using type 2 diabetic patients who were further divided into two groups according to treatment: metformin alone (group I, n = 57) or metformin and glyburide (group II, n = 232). The patients of both groups were further divided into three subsets in order to test the dependence of HbA1c on HOMA2%B and HOMA2%S.


RESULTS
In group I mean HbA1c were greater (8.4%) in patients with HOMA2%B < 50% than in the two subsets with HOMA2%B > or = 50%: 7.2 and 6.8% (P = 0.0013). In group II mean values of stimulated-insulin secretion (HOMA2%B) were lesser (40.7 and 30.1%) in the two subsets of patients with HbA1c > or = 8% than in patients with HbA1c < 8%: 55.1% (P < 0.0001). By contrast, we found no differences in both groups with HOMA2%S. A stepwise multiple regression showed that HOMA2%B contributed to HbA1c more than HOMA2%S both in groups I (33.5% vs. 23.4%) and II (22.7% vs. 8%).


CONCLUSIONS
Although the role of insulin sensitivity is not negligible, insulin secretion appears to be the major determinant of diabetic control in overt type 2 diabetic patients who are treated with metformin alone or with a two-drug therapy combining metformin and glyburide.
Monnier
L
L
Department of Metabolic Diseases, Lapeyronie Hospital, University Institute of Clinical Research, Montpellier, France. l-monnier@chu-montpellier.fr
Colette
C
C
Thuan
J-F
JF
Lapinski
H
H
D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis*; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D012044:Regression Analysis
D015415:Biomarkers; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin