Study design
This study was designed as a prospective, open, multicenter, 6-month randomized, controlled clinical trial registered at the Chinese Clinical Trial Registry (ChiCTR1800017463) and approved by the First Affiliated Hospital Ethics Committee of the Nanjing Medical University School (Nanjing city, Jiangsu Province, China) (2018-SR-069). The recruitment period was August 1, 2018, to June 31, 2019. Recruitment strategies included advertisements in social media, such as WeChat, along with posters and referrals from the outpatient clinic. Written informed consent was obtained from all study participants.
Study settings
The trial was conducted primarily at 11 tertiary care hospitals across China, including The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital, Primary center), The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, The First Affiliated Hospital of Soochow University, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, The Affiliated Suzhou Science &Technology Town Hospital of Nanjing Medical University, Affiliated Hospital of Jiangsu University, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai'an Hospital Affiliated to Xuzhou Medical University and Huai'an Second People’s Hospital, Northern Jiangsu People’s Hospital, The First People’s Hospital of Chuzhou, and The Second Affiliated Hospital of Dalian Medical University. The duration of the study was July 1, 2018, to December 30, 2019.
Inclusion and exclusion criteria
Eligible adults with obesity aged between 18 and 50 years with BMI ≥28.0 kg/m2 capable of using smartphones and operating the mobile application “Medical Weight Management” were included. Participants additionally needed to follow the guidance of dietitians and health managers and monitor relevant indicators in accordance with the program requirements throughout the study. The complete inclusion and exclusion criteria are presented in Figure 1.
Intervention
A multi-aspect team comprising physicians, dietitians, and health managers delivered the program over a 3-month period. Participants in the CIMWM group were provided with two Fit Nutrition Bars (Guangzhou ND-fit Nutrition and Health Consulting Co. Ltd) per day in the first 3 months as well as monthly face-to-face guidance and daily online instructions via the mobile application “Medical Weight Management,” which allowed uploading of daily weight data and food diaries. This information helped our team of experts to manage and guide the subjects online in real time. The TMWM group underwent a separate program with monthly face-to-face guidance by the same multi-aspect team and daily self-monitoring. In the final 3 months, all participants were transferred to the self-monitoring aspect of the program. All participants were followed up at 1, 2, 3, and 6 months after randomization for assessment. Details of the interventions are presented in Figure 1.
Features of the diet and exercise intervention programs are described below. Based on age, sex, standard body weight, typical caloric intake, and physical activities, participants received a calorie-restricted diet (CRD)[13] plan of 1200–1800 calories per day developed by registered dietitians that was designed to provide 40–55% of daily calories from carbohydrates, 20–30% from fat, and 15–20% from protein. Fit Nutrition Bars consisting of whey protein, soy protein isolate, chia seeds, oligosaccharides, collagen, and konjac extract rich in dietary fiber and γ-aminobutyric acid were provided as meal replacements for participants from the CIMWM group in the first 3 months. A single bar weighed 30 g and provided 111 kcal with 9.15 g protein, 1.8 g fat, 12.48 g carbohydrate, and 3.93 g dietary fiber. Subjects in the CIMWM group were additionally provided calcium, vitamin D, and multivitamin mineral tablets.
Individualized exercise plans were created by health managers based on the health status and exercise capacity of each participant. The exercise plan included a weekly 160 min group exercise session. Over 6 months, participants were instructed to exercise for 40 min, 4 days a week, starting with 5 min warm-up exercises, followed by 10 min and 30 min of resistance and aerobic exercise, respectively, and ending with 5 min muscle stretching exercises.
Assessments
Assessments were conducted face-to-face at baseline, 1, 2, 3, and 6 months by physicians.
Primary Outcomes
Body mass index (BMI), body weight (BW), body fat percentage (BFP), body fat mass (BFM), free-fat weight (FFW), skeletal muscle mass (SMM), and visceral fat area (VFA) were measured in participants while standing on an automated hand-to-foot bioelectrical impendence device (JAWON IOI353 Body composition analyzer, Korea) with bare feet and light clothing.
Secondary Outcomes
Anthropometric measurements, such as height and waist (WC) and hip circumference (HC) accurate to the nearest 0.01 cm, were obtained using standard techniques. Blood pressure (while seated) was recorded as the average of two measures. Blood samples were obtained on the morning after an overnight fast. The BECKMAN-AU5800 automatic biochemical analyzer was used for determination of fasting plasma glucose (FPG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], creatinine (Cr), uric acid (UA), platelet (PLT), and albumin (ALB) levels. Fasting insulin (FINS) and C peptide (FCP) contents were determined via chemiluminescence, and glycated hemoglobin (HbA1c) detected using high-performance liquid chromatography (Bole, USA). The non-alcoholic fatty liver disease score (NFS) was calculated as follows:
-1.675+0.037×age (years)+0.094×BMI (kg/m2)+1.13×impaired fasting glucose/diabetes (yes=1, no=0)+0.99×AST/ALT ratio−0.013×platelet count (×109/L)−0.66×albumin (g/dL)[14].
Advanced fibrosis was accurately excluded by applying the NFS low cut-off point (-1.455) while its presence was diagnosed with high accuracy by applying the NFS high cut-off point (0.676) [14]. HOMA-IR was calculated using the formula: FPG (mmol/L) ×FINS (mIU/L)/22.5.
Diabetes mellitus was defined as either FPG ≥7 mmol/L or 2 h oral glucose tolerance test (OGTT) blood glucose ≥11.1 mmol/L, while impaired fasting glucose was defined as 6.1 mmol/L≤FPG<7 mmol/L[15].
Statistical analysis
Using data from a previous weight management study [16], a power analysis was conducted using SAS, with alpha of 0.05 and power of 0.80. Sample size calculations indicated that recruitment of 72 participants in the primary center was required to achieve 80% power. Accordingly, competitive enrollment was initiated at branch centers. Enrolled patients were numbered in adjacent sequences using the randomized block design (block size=4). Random assignment codes were generated by statistics professionals using the SAS 9.12 software proc plan program according to a 1:1 allocation ratio [7].
All analyses were performed using SPSS for Macintosh version 25.0 (SPSS Inc, Chicago, IL, USA). Demographic and baseline characteristics were evaluated with the aid of descriptive statistics. Normally distributed and continuous variables were presented as mean and standard deviation (SD) while median and interquartile range for variables were determined in cases where normality criteria were not satisfied. Categorical variables were presented as frequencies and percentages. Data sets involving the baseline, 3-month, and 6-month index of all participants were assessed using the Kruskal-Wallis test owing to frequent non-normal distribution of variables. All indicator changes were not normally distributed and Spearman’s rank correlation performed to evaluate the relationship between the physical examination and hematology indices at the 6-month point. To compare the characteristics of continuous variables between the two groups, the appropriate parametric (independent samples t-test) and nonparametric (Mann-Whitney U) tests were utilized. For categorical variables, the chi-square test was used. Two-sided P values <0.05 were considered statistically significant.