인슐린 저항성이 있는 제 2형 당뇨병 환자에서 Rosiglitazone의 치료 효과 및 반응도 예측인자의 분석

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.