We thank Yoshioka, Yoshida, and Yoshikawa for their comments on our article (1) in this issue of Diabetes Care (2). We reported that serum adiponectin concentration increased after 3 months’ glimepiride treatment in type 2 diabetic patients (1). They indicated that baseline values of serum adiponectin (22.1 ± 2.7 μg/ml, mean ± SE) seem to be higher than those expected from subjects with greater BMI (26.5 ± 0.9 kg/m2) and homeostasis model assessment of insulin resistance (5.0 ± 0.8) levels. First, we must apologize for not having corrected the final results of serum adiponectin concentration by using the ratio of sample dilution. The correct results of our study (1) are as follows: serum adiponectin concentration increased from 11.1 ± 1.3 to 14.2 ± 1.4 μg/ml (29%, P = 0.015 by Wilcoxon’s sign-rank test) in the glimepiride-treated patients (n = 28), and the concentration also increased from 9.4 ± 1.5 to 10.3 ± 1.7 μg/ml (10%, P = 0.034) by metformin treatment in another group of type 2 diabetic patients (n = 12) matched with the glimepiride group for sex, age, BMI, glycemia, and insulinemia. Statistical analysis and data interpretation remained unchanged despite the changes in absolute values of serum adiponectin concentration.
Along with glimepiride (1,3), insulin-sensitizing thiazolidinediones are known to increase mRNA and circulating levels of adiponectin (4,5). We have also confirmed that serum adiponectin concentration increased from 9.1 ± 2.3 to 19.6 ± 2.0 μg/ml (123%, P < 0.001) in 15 type 2 diabetic patients (10 men and 5 women, aged 61 ± 2 years, BMI 27.2 ± 0.4 kg/m2) after 4 months’ pioglitazone treatment, which was concomitant with improvements in fasting glucose from 161 ± 6 to 137 ± 6 mg/dl (P = 0.023), HbA1c from 7.9 ± 0.2 to 7.2 ± 0.2% (P = 0.002), and homeostasis model of insulin resistance from 5.9 ± 3.0 to 3.8 ± 0.4 (P = 0.025). Very recently, blockade of the renin-angiotensin system was also shown to increase serum adiponectin concentration (15% by temocapril and 30% by candesartan, respectively) as well as insulin sensitivity in hypertensive men (6). Therefore, at least three kinds of therapeutic interventions are known to increase both adiponectinemia and insulin sensitivity in men. The mechanisms responsible for increased adiponectinemia by glimepiride and blockade of the renin-angiotensin system await further investigation. In addition, we agree with Yoshioka, Yoshida, and Yoshikawa in that further clinical study is also necessary to establish the long-term beneficial effects of such pharmacological interventions to increase adiponectinemia in type 2 diabetic patients.
