Factors That Influence Pancreatic Beta Cell Function and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Patients: A Sub-Analysis of the MARCH Trial

Diabetes Ther (2018) 9:743–752 https://doi.org/10.1007/s13300-018-0393-5 ORIGINAL RESEARCH Factors That Influence Pancreatic Beta Cell Function and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Patients: A Sub-Analysis of the MARCH Trial Yan Duan . Jia Liu . Yuan Xu . Ning Yang . Wenying Yang . Guang Wang Received: December 26, 2017 / Published online: March 9, 2018 Ó The Author(s) 2018. This article is an open access publication ABSTRACT Introduction: The Metformin and Acarbose in Chinese as the initial Hypoglycemic treatment (MARCH) trial has demonstrated a similar efficacy in HbA1c reduction between acarbose and metformin treatments in newly diagnosed type 2 diabetes mellitus (T2DM) patients. The current sub-analysis of the MARCH trail aims to evaluate the baseline characteristics that may influence the improvement of pancreatic b-cell function and insulin resistance after acarbose therapy in Chinese patients with newly diagnosed T2DM. Methods: Of the 784 patients who entered the MARCH trail, 391 were assigned to the acarbose therapy group; 304 of these completed 48 weeks Yan Duan, Jia Liu, and Yuan Xu contributed equally to this work. Enhanced content To view enhanced content for this article go to https://doi.org/10.6084/m9.figshare. 5858112. Y. Duan
J. Liu
Y. Xu
N. Yang
G. Wang (&) Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China e-mail: W. Yang (&) Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of China e-mail: of follow-up of acarbose therapy. At 48 weeks, on the basis of the tertiles of change in homeostasis model assessment–beta cell function (DHOMA-b) and homeostasis model assessment–insulin resistance (DHOMA-IR), the subjects were divided into lowly, mediumly, and highly improved groups. Results: In the highly improved HOMA-b group, patients had higher systolic blood pressure (SBP), 2-h postprandial blood glucose (PBG), hemoglobin A1c (HbA1c), and lower high-density lipoprotein cholesterol (HDL-c), fasting serum insulin (FINS) concentration, and HOMA-IR in comparison to the lowly improved group (p \ 0.05). A positive correlation was observed between HbA1c, SBP, and highly improved DHOMA-b (p \ 0.05), while an inverse correlation was evident between HDL-c and highly improved DHOMA-b (p \ 0.05). The highly improved HOMA-IR group had a significantly higher body mass index (BMI), fasting blood glucose (FBG), FINS concentration, and HOMA-b in comparison to the lowly improved group (p \ 0.05). A positive correlation was observed between FBG, waist circumference, and highly improved HOMA-IR (p \ 0.05). Conclusion: Newly diagnosed T2DM Chinese patients with lower baseline HDL-c and higher HbA1c and SBP values are more likely to achieve improvement in beta cell function whereas baseline fasting blood glucose and waist circumference were the significant factors Diabetes Ther (2018) 9:743–752 744 associated with improvement in insulin resistance with acarbose therapy. Trial Registration: The clinical trial registry number was ChiCTR-TRC-08000231. Keywords: Acarbose; Beta cell function; Diabetes; HOMA-b; HOMA-IR; Insulin resistance INTRODUCTION Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease that has become a silent epidemic and a major global health burden over the years. China has the largest number of diabetic patients with a growing population of approximately 92.4 million [1, 2]. Metformin is the most commonly prescribed oral antidiabetic drug, taken by more than 150 million people annually [3]. The American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD), as well as many other authoritative clinical practice guidelines, have recommended metformin as the first-line therapy for the treatment of T2DM because of its hypoglycemic effect and long-term safety record [4, 5]. Besides metformin, alpha-glucosidase inhibitors (AGIs) are another class of ADA- and EASD-recommended oral hypoglycemic drugs, commonly prescribed in the East Asian population [6]. Several studies have reported postprandial hyperglycemia as a predominant contributor in newly diagnosed T2DM in China [7–9]. This may due to the high consumption of carbohydrate-rich white rice by the Chinese in comparison to other populations [10, 11]. Hence, acarbose is a widely prescribed hypoglycemic drug in China. The MARCH (Metformin and Acarbose in Chinese as the initial Hypoglycemic treatment) trial, conducted with 788 newly diagnosed Chinese type 2 diabetic patients, demonstrated a similar reduction of hemoglobin A1c (HbA1c) after 48 weeks of treatment with either acarbose or metformin [12]. However, the clinical features that impact the effectiveness of acarbose therapy in Chinese T2DM patients have not been previously studied. Hence, we used the data from the MARCH trial to determine the correlation between the baseline characteristics and the effectiveness of acarbose therapy by assessing the improvement in pancreatic beta cell functions and insulin resistance. The aim of the current study was to evaluate the baseline characteristics that may influence the improvement of pancreatic b-cell functions and insulin resistance after 48 weeks of acarbose therapy. METHODS Design and Participants This study is a sub-analysis of the MARCH trial, a randomized, open-label, non-inferiority trial (ChiCTR-TRC-08000231) that compared acarbose with metformin as an initial therapy in newly diagnosed T2DM patients. The enrollment criteria, baseline protocol, and diagnostic definitions have been reported previously [12]. Based on 1999 WHO diagnosis criteria, the study enrolled a total of 784 newly diagnosed T2DM patients, aged between 30 and 70 years, from 11 clinical sites. A total of 391 of the participants were assigned to the acarbose therapy group. The current study included 304 patients who completed follow-up at 48 weeks after acarbose therapy. Patients who had not received any oral antidiabetic drug or those who were previously treated for a short term and had discontinued 3 months before the enrollment were included in the study. Patients with a history of unstable angina, acute myocardial infarction, liver function impairment, renal function impairment, hematological diseases, chronic hypoxic diseases (emphysema and cor pulmonale), intestinal surgery, and infectious disease were excluded from the study. Measurements The baseline measurements included assessment of the body weight, waist circumference, hip circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), oral glucose tolerance test [fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG)], fasting Diabetes Ther (2018) 9:743–752 745 serum insulin (FINS), lipid profile [triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], and H (...truncated)