Pioglitazone Improved Insulin Sensitivity and First Phase Insulin Secretion Among Obese and Lean People with Diabetes: A Multicenter Clamp Study

Xin Qian; Hui Wang; Gangyi Yang; Zhengnan Gao; Yong Luo; Aimei Dong; Fang Zhang; Mingtong Xu; Shiping Liu; Xin Yang; Yanyan Chen; Guangwei Li

doi:10.1007/s13300-018-0401-9

Pioglitazone Improved Insulin Sensitivity and First Phase Insulin Secretion Among Obese and Lean People with Diabetes: A Multicenter Clamp Study

Diabetes Ther. 2018 Apr;9(2):815-826. doi: 10.1007/s13300-018-0401-9. Epub 2018 Mar 13.

Authors

Xin Qian¹, Hui Wang¹, Gangyi Yang², Zhengnan Gao³, Yong Luo⁴, Aimei Dong⁵, Fang Zhang⁶, Mingtong Xu⁷, Shiping Liu⁸, Xin Yang⁹, Yanyan Chen¹, Guangwei Li¹⁰

Affiliations

¹ Endocrinology and Cardiovascular Diseases Center, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167 North Lishi Road, Xicheng District, Beijing, China.
² Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, No. 76 Linjiang Road, Chongqing, China.
³ Department of Endocrinology, Dalian Municipal Central Hospital, No. 42 Xuegong Street, Shahekou District, Dalian, China.
⁴ Department of Endocrinology, Chongqing Three Gorges Central Hospital, No. 165 Xincheng Road, Wanzhou District, Chongqing, China.
⁵ Department of Endocrinology, Peking University First Hospital, No. 8 Xishiku Road, Xicheng District, Beijing, China.
⁶ Department of Endocrinology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Futian District, Shenzhen, China.
⁷ Department of Endocrinology, Second Affiliated Hospital of Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, China.
⁸ Department of Endocrinology, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha, Hunan, China.
⁹ Department of Information Systems, Statistics, and Management Science, Culverhouse College of Commerce and Business Administration, The University of Alabama, Tuscaloosa, AL, USA.
¹⁰ Endocrinology and Cardiovascular Diseases Center, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167 North Lishi Road, Xicheng District, Beijing, China. guangwei_li45@126.com.

Abstract

Introduction: To investigate the effects of pioglitazone (PIO) on insulin resistance and first phase insulin secretion among obese and lean Chinese people with type 2 diabetes mellitus (T2DM).

Methods: Sixty-eight drug-naïve patients with T2DM were treated with PIO for 16 weeks. Before and after the treatment, insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test. Plasma insulin levels at 0, 3, 5, 7, and 10 min during intravenous glucose tolerance test were determined to calculate the first phase insulin secretion and pancreatic β-cell function. Circulating adiponectin levels were quantified.

Results: In both the lean and the obese patients with T2DM, the reduction of HbA_1c following the PIO treatment was more than 1% (P < 0.001) and glucose infusion rate, acute insulin response, glucose disposal index, and β-cell glucose sensitivity increased significantly (P < 0.001). A multiple linear regression analysis showed that the improvements of first phase insulin secretion and insulin sensitivity were independently associated with the changes of HbA_1c, but the change of first phase insulin secretion exhibited a higher correlation coefficient (R² = 0.20, P = 0.001) than the change of insulin sensitivity did (R² = 0.07, P = 0.040). The PIO treatment led to a significant increase in adiponectin levels only in the obese group (P < 0.05).

Conclusion: A 16-week treatment of PIO significantly increased insulin sensitivity and β-cell function in the lean group as well as in the obese group among Chinese T2DM patients, demonstrating that both lean and obese diabetic adults would profit from PIO.

Trial registration: The ChiCTR registry number is ChiCTR-OPC-17011571.

Funding: Takeda Pharmaceutical Co. Ltd. and Pfizer Pharmaceutical Co. Ltd.

Keywords: First phase; Insulin resistance; Insulin secretion; Pioglitazone.