Effect of rosiglitazone versus insulin on the pancreatic beta-cell function of subjects with type 2 diabetes.
OBJECTIVE
In a previous study, we found observational evidence of improvement in beta-cell function when rosiglitazone was added to a failing oral antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm our previous observations, we designed and performed a prospective, randomized, and controlled study.


METHODS
A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months. At baseline and at 6 months, the following were performed: measurement of fasting plasma glucose, fasting proinsulin, and insulin levels; frequently sampled intravenous glucose tolerance test; and glucagon stimulation test for C-peptide.


RESULTS
Nine subjects were randomized to the addition of 8 mg rosiglitazone, and eight subjects were randomized to the addition of one injection of insulin (premixed 70/30) before their evening meal. The treatment groups were well matched for age, duration of diabetes, and BMI. Most important, the HbA(1c) was well matched between groups before treatment (8.7 +/- 0.3 and 9.0 +/- 0.3%; NS) and at the end of the 6 months (7.8 +/- 0.5 and 7.8 +/- 0.3%; NS). After 6 months, at the end of the study, there was a significant improvement in acute insulin response to glucose in the rosiglitazone group (+15.3 microIU x ml(-1) x 10 min(-1); P < 0.001) that led to an increase in the disposition index from 0.18 at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study, the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36% (P = 0.03) but did not change significantly in the insulin treatment group.


CONCLUSIONS
Rosiglitazone, but not insulin, induced a recovery of pancreatic beta-cell function, as evidenced by the restoration of the first-phase insulin response to glucose, improvement in the disposition index, and a decrease in the proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral antihyperglycemic therapy failed. This improvement was independent of the correction of glucotoxicity.
Ovalle
Fernando
F
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
Bell
David S H
DS
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000503:physiopathology*; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood; D011446:Prospective Studies; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011384:Proinsulin