Impact of rosiglitazone on beta-cell function, insulin resistance, and adiponectin concentrations: results from a double-blind oral combination study with glimepiride.
Addition of rosiglitazone to sulfonylurea has been shown to improve glycemic control in patients with type 2 diabetes previously treated with sulfonylurea monotherapy alone. This investigation was performed to assess the specific impact of rosiglitazone on insulin resistance, beta-cell function, cardiovascular risk markers, and adiponectin secretion in this treatment concept. One hundred two patients from a double-blind, 3-arm comparator trial (group 0, glimepiride + placebo, n = 30; group 4, glimepiride + 4 mg rosiglitazone, n = 31; group 8, glimepiride + 8 mg rosiglitazone, n = 41; 48 women, 54 men; age [mean +/- SD], 62.8 +/- 9.1 years; body mass index, 28.7 +/- 4.5 kg/m2; diabetes duration, 6.4 +/- 4.8 years; HbA1c, 8.1% +/- 1.5%) were analyzed after 0 and 16 weeks of treatment. Observation parameters were HbA1c, glucose, homeostasis model assessment for insulin resistance score, insulin, intact proinsulin, and adiponectin. Insulin resistance was defined by elevated intact proinsulin values or homeostasis model assessment for insulin resistance score of more than 2. All parameters were comparable in the 3 groups at baseline. Substantial and significant dose-dependent improvements were observed after addition of rosiglitazone for fasting glucose (group 0, -9 +/- 48 mg/dL; group 4, -38 +/- 47 mg/dL; group 8, -46 +/- 53 mg/dL), HbA1c (-0.1% +/- 0.7%, -1.1% +/- 1.2%, -1.3% +/- 1.2%), insulin (1.4 +/- 6.2, -1.2 +/- 5.3, -3.7 +/- 9.9 microU/mL), intact proinsulin (1.6 +/- 7.1, -2.0 +/- 4.6, -3.1 +/- 6.1 pmol/L), and high-sensitivity C-reactive protein (0.2 +/- 2.6, -1.7 +/- 3.5, -2.1 +/- 3.5 mg/L). After adjustment for changes in body weight, significant increases in adiponectin were detected with rosiglitazone, whereas glimepiride alone did not induce a comparable effect (-0.5 +/- 5.8, 8.8 +/- 22.9, 14.3 +/- 19.9 mg/L). The number of insulin-resistant patients decreased in both rosiglitazone treatment groups, whereas no change was seen with glimepiride alone. Next to the reported effects on glucose control, rosiglitazone provided an additional beneficial effect on insulin resistance, beta-cell function, and cardiovascular risk markers. In conclusion, our short-term investigation of rosiglitazone action provides further experimental support for the rationale of combining rosiglitazone with sulfonylurea drugs in patients with type 2 diabetes.
Pfützner
Andreas
A
IKFE Institute for Clinical Research and Development, Mainz, Germany. andreasp@ikfe.de
Schöndorf
Thomas
T
Seidel
Daniela
D
Winkler
Karl
K
Matthaei
Stephan
S
Hamann
Andreas
A
Forst
Thomas
T
D052242:Adiponectin / Q000097:blood*; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010186:Pancreatic Function Tests; D011384:Proinsulin / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
D052242:Adiponectin; D002097:C-Reactive Protein; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D011384:Proinsulin; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C057619:glimepiride