Rosiglitazone ; Insulin resistance ; Type 2 diabetes mellitus
Keywords
Rosiglitazone ; Insulin resistance ; Type 2 diabetes mellitus
Abstract
Background: Rosiglitazone, an insulin sensitizer of thiazolidinedione class, is known as a highly selective and potent agonist for the peroxisome proliferator-activated receptor-γ. This study was performed to evaluate the antidiabetic
activity
and insulin sensitizing effect of rosiglitazone combination therapy in insulin-resistant type 2 diabetic patients who were poorly controlled with oral agents such as metformin and/or sulfonylurea. The factors affecting response of rosiglitazone
were
also evaluated on the basis of the degree of glycemic control.
Methods: One hundred twenty insulin-resistant (glucose disposal rate, Kitt < 2.5%/min) type 2 diabetic patients (M:F=42:78, mean age 58.6±9.2 years, body mass index 24.2±2.8 ㎏/㎡) were enrolled and randomly divided into two groups. For
12
weeks, the treated group daily received 4 ㎎ of rosiglitazone and the control group had diet and exercise therapy in addition to previous medications. The responders were defined as more than 20% decrease of fasting plasma glucose level or more
than 1%
decrease of HbA1c. As for the indices of insulin resistance and insulin secretory function, Kitt (Kitt=0.693/t1/2 × 100) by insulin tolerance test, HOMAIR and HOMAβ-cell function by ‘HOMA index (Homeostasis
model
assessment)’ were evaluated.
Results: In rosiglitazone treated group (60 patients, M:F=19:45), 12 weeks of rosiglitazone treatment decreased fasting plasma glucose (28.2%), postprandial 2-hour glucose (23.2%), and HbA1c (12.2%). Rosiglitazone also significantly
decreased
HOMAIR (41.2%), and increased Kitt (53.3%) and HOMAβ-cell function (46.9%). Forty-five patients (75%) satisfied responder. Females and those who had higher body mass index and waist-hip ratio showed better response. The
basal
fasting plasma glucose, HbA1c, and systolic blood pressure were also higher in responders. The responders showed significantly higher fasting serum insulin level and HOMAIR, and also higher tendency of fasting serum C-peptide level and
HOMAβ-cell function than nonresponders.
Conclusion: From these results, rosiglitazone treatment can improve not only hyperglycemia and insulin resistance but also insulin secretory function in uncontrolled insulin-resistant type 2 diabetes. The factors that affect response of
rosiglitazone are female, obesity (especially central obesity), high insulin secretory function, and severe insulin resistance. As a conclusion, the therapeutic efficacy or response of rosiglitazone is likely to depend on the degree of preserved
pancreatic β-cell function and the severity of insulin resistance.