Study design and participants
This case-control study included the LC/GDM, Con/GDM, and Con/Healthy groups. Participants were classified into LC/GDM group if they were diagnosed as GDM at 24–28 gestational weeks and went on an initiative limit-carbohydrate diet (carbohydrate intake <130 g/d) for weight management before pregnancy for at least 12 months. Participants, diagnosed as GDM at 24–28 gestational weeks and having an conventional diet (carbohydrate intake >130 g/d ) before pregnancy , were classified into Con/GDM group. The Con/Healthy group included healthy women on a conventional diet (carbohydrate intake >130 g/d). The two control groups (Con/GDM and Con/Healthy) were matched to the LC/GDM group by 1:4 for age, pre-pregnancy BMI (underweight, normal, overweight, obese), parity and family history of diabetes, and they were enrolled in the nutrition clinic and obestetrical clinic, respectively. All participants were recruited at the clinic in the International Peace Maternity and Child Health Hospital (Figure 1 Patient workflow).
Subjects with the following criteria were excluded: 1) those with religious dietary restrictions or dietary intervention for other; 2) those diagnosed with type 2 diabetes mellitus (T2DM) before pregnancy ;3) those with history of polycystic ovary syndrome, unexplained recurrent spontaneous abortion, and other digestive tract disease, liver disease, and kidney disease.
Eventually, 20 participants were included in the LC/GDM group. 80 participants were included in the Con/GDM and Con/Healthy, respectively. After diagnosed as GDM, the LC/GDM and Con/GDM groups received medical nutritional treatment according to the diabetes medical treatment guidelines13. No intervention was performed in the Con/Healthy group.
The case-control study was conducted at Shanghai International Peace Maternity and Child Health Hospital (IPMCH) between January 2019 and January 2020. All participants were local residents of Shanghai, and had completed pregnancy diagnosis and treatment records. Cut-off points of BMI were adopted based on the Chinese population standards14.
Written informed consent was obtained from all participants. This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involing human subjects/patients were approved by the Institutional Review Board of the International Peace Maternity and Child Health Hospital (IPMCH) affiliated with the School of Medicine, Shanghai Jiao Tong University (GKLW2018-35).
Diagnosis of GDM
GDM was diagnosed by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria between 24 and 28 weeks of gestation. A one-step approach using 75-g OGTT was performed after at least an 8-h fast (cutoff values: fasting ≥5.1 mmol/L; 1 h ≥10.0 mmol; 2 h ≥8.5 mmol/L). GDM was defined as one or more abnormal OGTT values 15.
Information on habitual dietary intake before pregnancy was collected through a 24-h dietary recall about the average intake of major foods or food groups. Participants were also invited to complete a 24-h dietary recalls between 24 and 28 weeks of gestation. If a participant reported during a 24-h recall that she did not eat or drink normally the day before (e.g., because of fasting, illness, or other reasons), dietary data from that 24-h recall will be performed at another visit.
Trained dietitians administered the interview, using food models to access the food intake. The interview was conducted between 24 and 28 weeks of gestation. The intakes of energy and macronutrients were calculated by nutrient calculation software ZHEN DIN 2.0.
All participants underwent standard clinical care which included biomedical blood tests. Fasting blood glucose, serum glycated haemoglobin (HbA1c) and lipid profiles [total cholesterol (TC), triacylglycerol (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC)]were measured in the first trimester of pregnancy (10-12 weeks of gestation). Serum HbA1c, glycated albumin (GA) and levels of OGTT test were performed between 24-28 gestational weeks. All the blood samples were detected with Cobas 8000 modular analyzer series. The detection of ketones in the urine was performed through Sysmex UC-3500 urine chemistry analyzer.
The participants were weighed barefoot using a standardized digital height and weight scale calibrated to 0.1 kg (SECA-285). After resting for 5 min, an automated system (OMRON-HEM-1020) was used to measure the blood pressure once. Weighing and blood pressure measurements were performed during every routine check-up.
Given the exploratory nature of this study (the sample size of women with a strict LC diet was limited), we did not conduct a priori sample size estimation. We only used unadjusted data to compare the dietary composition data and biomarkers of the three study groups because we have matched the potential confounders in different groups. One-way analysis of variance was used to analyze difference in continuous variables, and pairwise comparisons between the three groups were performed using Tukey's studentized range test. Continuous variables were showed as means and SD. Chi-square test was used to analyze difference in categorical variables, and pairwise comparisons were performed using Bonferroni test. Statistical analysis was performed using SPSS statistical software, version 23. P values < 0.05 was considered statistically significant.