Predictors of improved glycaemic control with rosiglitazone therapy in type 2 diabetic patients: A practical approach for the primary care physician

Objective - To determine predictors of improved glycaemic control in patients with type 2 diabetes mellitus during rosiglitazone therapy using basic clinical parameters that are readily available in daily clinical practice. Research design and methods - Thirty-seven type 2 diabetic patients (men/women = 18/19; age = 54±2 years; diabetes duration = 6±1 years; diet-/sulphonylurea-treated = 24/13) received a 75 g oral glucose tolerance test (OGTT) and determination of body fat before and after rosiglitazone (8 mg/day) for 12 weeks. Results - After rosiglitazone therapy, there were decreases in HbA_1C (8.6±0.2 to 7.2±0.2%, p<0.0001), fasting plasma glucose (FPG) (10.6±0.3 to 8.0±0.3 mmol/L [191±6 to 145±6 mg/dL], p<0.0001), fasting plasma insulin (FPI) (108±6 to 84±6 pmol/L [18±1 to 14±1 μU/ml], p<0.05), fasting free fatty acids (FFA) (760±39 to 611±33 μEq/l, p<0.05), mean plasma glucose (PG) - OGTT (16.2±0.39 to 12.7±0.33 mmol/L [291±7 to 230±6 mg/dL], p<0.001), and mean FFA-OGTT (604±27 to 445±23 μEq/l, p<0.01) despite increases in body weight (85±2 to 88±2 kg, p<0.01) and % fat mass (37.9±2.0 to 39.5±1.9%, p<0.01). The insulinogenic index (IGI) during 0-120 minutes OGTT (IGI_0-120) increased following rosiglitazone (0.19±0.03 to 0.30±0.05, p<0.01). Two different insulin sensitivity indices, calculated from PG and plasma insulin (PI) during OGTT, increased significantly: composite index of whole body insulin sensitivity (ISIcomposite): 2.3±0.3 to 3.4±0.4, p<0.05; oral glucose insulin sensitivity (OGIS): 248±5 to 294±6 ml/m²·min, p<0.001. Using clinical and laboratory variables obtained in daily clinical practice (age, gender, diabetes duration, sulphonylurea treatment, body mass index (BMI), % fat mass, fasting plasma insulin/C-peptide/FFA/lipids, IGI_0-30, IGI_0-120, and ISIcomposite or OGIS), stepwise regression analysis demonstrated that % fat mass (standard coefficient (S.C.) = -0.49, p=0.001) and OGIS (S.C. = 0.31, p=0.02) or ISIcomp (S.C. = 0.31, p=0.03) are significant predictors of the decrease in HbA_1C after rosiglitazone (adjusted R²=0.33, p=0.0004). Conclusions - Rosiglitazone improves insulin resistance and glycaemic control in type 2 diabetes. Obesity (more body fat mass) and reduced insulin sensitivity prior to treatment are the best predictors of glycaemic response to thiazolidinedione therapy in type 2 diabetes.