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 .
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.
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 serum insulin (FINS), lipid profile [triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], and HbA1c.
Also, the total energy and the daily intake of carbohydrate, fat, protein, and fiber in the diet were recorded at baseline. Patients were followed up by anthropometric and laboratory index at 24 and 48 weeks.
Homeostasis model assessment of β-cell function (HOMA-β) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated by using the following equations: HOMA-β = 20 × FINS (mIU/L)/[FBG (mmol/L) − 3.5], HOMA-IR = [FBG (mmol/L) × FINS (mIU/L)/22.5] [13, 14].
The improvement of HOMA-β was evaluated using ∆HOMA-β: 48-week HOMA-β − baseline HOMA-β; and the improvement of HOMA-IR was evaluated using ∆HOMA-IR: baseline HOMA-IR − 48 weeks HOMA-IR.
Distribution of Patients
At 48-week follow-up, the subjects were categorized into three groups, lowly improved (LI), mediumly improved (MI), and highly improved (HI), based on the tertiles of change noted in HOMA-β (∆HOMA-β) and HOMA-IR (∆HOMA-IR).
In relation to HOMA-β, the LI group had ∆HOMA-β <− 13.9, the MI group had − 13.9 ≤ ∆HOMA-β < 13.9, and the HI group had ∆HOMA-β ≥ 13.9. The LI group in ∆HOMA-IR was assessed at < 0.6, the MI group had 0.6 ≤ ∆HOMA-IR < 2.9, and the HI group had ≥ 2.9 resistance.
SPSS version 21.0 was used to perform statistical analysis of the study. Continuous variables that had normal distributions were expressed as mean ± standard deviation (SD). Student t test and one-way ANOVA were adopted to analyze the differences in characteristics between the groups. Continuous variables that did not have normal distribution were expressed as median with a range of upper and lower quartiles and analyzed using a non-parametric test. Discontinuous variables were expressed as a percentage and analyzed using Chi-square test. In addition, logistic regression was performed to analyze the factors that may influence ∆HOMA-β and ∆HOMA-IR. Statistical significance was defined as p < 0.05.
Compliance with Ethics Guidelines
All procedures performed in the study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.