Influence of Statins on Glucose Tolerance in Patients with Type 2 Diabetes Mellitus: Subanalysis of the Collaborative Study on Hypercholesterolemia Drug Intervention and their Benefits for Atherosclerosis Prevention (CHIBA Study)

Abstract

the atorvastatin group (p=0.026), whereas no significant difference was observed in the pitavastatin group (Table 1). In the atorvastatin group, but not in pitavastatin group, the HbA1c level also tended to increase (p=0.098). Since glycoalbumin is known to reflect glycemic control over a shorter period of time than HbA1c, only glycoalbumin might have detected a slight glycemic change during a treatment period of 12 weeks in this relatively small study. There were no significant changes in fasting plasma glucose, insulin or the homeostasis model assessment ratio, but all of these values tended to decrease in the pitavastatin group. To date, adverse effects of atorvastatin on glucose tolerance have not been clearly demonstrated in clinical studies carried out in Western countries; however, several reports have suggested the deterioration of glycemic control with atorvastatin use for 3 to 4 months in Japanese diabetic patients as referred to by Yamakawa et al.. Recently, a PROVE-IT substudy has shown that high-dose atorvastatin treatment is associated with worse glycemic control. An in vitro study demonstrated that atorvastatin near the physiological concentrations suppressed glucose transporter GLUT4 expression in 3T3-L1 adipose cells. Since it has been suggested that the insulin-secreting capacity of pancreatic β-cells is lower in Japanese than Caucasians, even a slight negative influence on insulin sensitivity in the peripheral tissue may affect glycemic control in Japanese patients. Previous reports, together with our findings suggest that atorvastatin, but not pitavastatin, affects glycemic control in some Japanese diabetic patients. Larger clinical trials are required to draw a conclusion. In the previous issue of J Atheroslcer Thromb, Yamakawa et al. showed a significant increase in glycohemoglobin A1c (HbA1c) level in diabetic patients treated with atorvastatin, but not in patients given pitavastatin or pravastatin. Although the finding is intriguing, their study could not exclude bias because it was retrospective and recruited subjects only at a single hospital. Here we report the results of glycemic control subanalysis in a multicenter prospective comparative study of pitavastatin and atorvastatin (CHIBA study). In the original study, 204 Japanese patients with hypercholesterolemia recruited at 39 medical facilities were randomized to receive either 2 mg pitavastatin or 10 mg atorvastatin daily for 12 weeks, and the percent change from baseline in lipid parameters after 12 weeks of treatment was evaluated . Among 99 patients with type 2 diabetes included in the study, 45 patients (23 on pitavastatin and 22 on atorvastatin) at 16 centers were subjected to the evaluation of parameters related to glucose tolerance. Serum lipid levels at the baseline were similar between groups. No changes were made in types or doses of medications used to treat diabetes or hypertension, or in lifestyle guidance throughout the study period. After 12 weeks of statin treatment, serum glycoalbumin had significantly increased by 0.67±1.31% compared to the baseline in