Participants
This study is a quantitative clinical trial of advantages and disadvantages. According to our pre-trial data and the following formula, 46 samples are required. Considering about 10% of the patients lost to follow-up, no less than 51 patients are included.
This trial was conducted in Chongqing, China, during December 2019 to November 2020.We screened more than 1000 patients from the chronic disease management system of Chongqing Nan’an District People’s Hospital, China. Hypertensive patients with type II diabetes who were being treated as outpatients and were currently taking antihypertensive and antidiabetic drugs were enrolled in this prospective intervention study according to the following criteria: age between 35 and 75 years, no plan to move out of their community in the following 3 months, residence near the indicated hospital for regular follow-up visits, and ability to strictly follow the salt reduction and dietary recommendations during the trial. Additionally, the participants and the family members with whom they were living were required to agree to the terms of the study and sign an informed consent form.
Participants were excluded if they had been diagnosed as having serious complications of hypertension or diabetes, hypercortisolism or hyperaldosteronism, or an acute disease, such as upper respiratory infection, fever, or diarrhea. Participants were also excluded if they used potassium-retaining diuretics, they were pregnant, it was not suitable for them to take the test product, or if they or their family members had abnormal kidney or liver function.
Study design
This study was designed and conducted as a randomized, controlled, single-blind trial(the patients do not know the specific grouping). After baseline investigation and physical examination, we randomly assigned the participants to the intervention group (52% sodium-limited formula salt and CM-DASH) and control group (traditional salt and CM-DASH diet) by using a random number table. From the day of their admission onwards, all participants were subjected to salt restriction (less than 5 g/day) and food intake according to the CM-DASH diet. The 8-week diet intervention was divided into three stages: DASH diet adaptation at home (weeks 1–2), centralized feeding in the hospital (weeks 3–4), and dietary behavior intervention at home (weeks 5–8).
Participants attended follow-ups at the hospital once a week to collect information on salt intake, office BP, drug use, and the incidence of adverse events. For safety considerations, the participants measured their BP by themselves at home every day. In addition, general inspection, blood samples, 24-hour urine samples, and casual urine samples were measured at baseline, in the fourth week, and at the end of the intervention.
The study protocol was approved by the Ethics Committee of Second Affiliated Hospital of Chongqing Medical University,review date:2021.5.26,ethics code: 2021(54),which means that all methods were performed in accordance with the relevant guidelines and regulations.And all participants and their families signed the written informed consent before enrollment in the trial.
Salt distribution, restriction, and surveillance
The intervention group was given 52% sodium-limited formula salt (Gu Da Chu, developed by Shanghai Institute of Ecological Health Sciences: solid compound condiment; standard of execution, Q/BAAM0009S; food production license number, SC10334042205441; main ingredients, potassium chloride [KCl] [31%], sodium chloride [NaCl] [52%], carbohydrates [9.2%], protein [4.4%]). The control group was given traditional salt (Jing Xin, developed by Chongqing Salt Industry Group Co., Ltd: purified salt; product standard, NY/T1040; sodium chloride content, >99%). All participants were subjected to salt restriction (less than 5 g/day). The patients were given a week’s supply of salt (according to the number of family members) and a regular salt shaker (a flat teaspoon is ~ 1 g). We instructed patients to reduce the use of salty seasonings and eat less pickles and other salted products. Professional staff measured salt intake weekly at the hospital by using an electronic kitchen scale (accuracy, 0.1 g).
CM-DASH diet
We modified the DASH dietary requirements of the participants according to the DASH dietary energy estimate sheet and sample recipes, the dietary pagoda for Chinese residents, and the dietary habits of Chinese people. Food selections were recommended as follows: staple foods, coarse grain–fine grain ratio of 1:1; lean meat and white meat; vegetables and fruits with low sugar; low-fat/nonfat milk; low-fat nuts; low sodium and high potassium foods; plant oils; and less than 5 g of salt.
BP measurement
Professional staff measured BP weekly in the hospital by using an upper arm electronic BP monitor (Omron HEM-7130 electronic sphygmomanometer upper arm type;registration certificate number: liaoji note 20192070081;executive standard: GB/T 14710-2009;Omron [Dalian] Co., Ltd.). All measurements were performed three times in the sitting position, and the average of the last two BP measurements was used for the analysis. PP was computed as systolic BP (SBP) minus diastolic BP (DBP) (i.e., PP = SBP − DBP), and MAP was computed as the sum of DBP and one-third of PP (i.e., MAP = DBP + PP/3).
Twenty-four-hour urine collection
The participants were carefully instructed on how to collect their urine. To minimize deviation, we asked the participants not to change their diet both before and on the day of urine collection. Each participant was given a notepad to record the start and end of urine collection and any urine missed during the collection process. The urine samples were discarded on the first morning of the first day and then collected in appropriate 3-L containers throughout the day, overnight, and upon waking in the morning. After the 24-hour collection, the total amount of urine was measured, and samples were taken and stored in a cool place. All samples were sent to the laboratory immediately after collection.
Laboratory measurements
Twenty-four-hour urine samples, casual urine samples, and blood samples were measured according to the methods of the Second Affiliated Hospital of Chongqing Medical University at baseline, the fourth week, and the end of the intervention, respectively.
General inspection
Height, weight, body mass index(BMI), SBP, DBP, pulse, waist circumference, hip circumference, and waist–hip ratio were measured at baseline, the fourth week, and the end of intervention at the Second Affiliated Hospital of Chongqing Medical University.
Statistical analysis
Double data entry and logical error checking. Quantitative data are shown as Mean ± SD if normally distributed and as median and inter-quartile ranges (25th and 75th percentile) if nonnormally distributed. Qualitative data are expressed as a frequency. Changes in the normally distributed quantitative data are expressed as the difference between the baseline and the weekly mean and as the lower and upper 95% confidence intervals of the difference. An independent-samples t-test was used to compare the difference between the intervention and control groups. Categorical variables were compared using Pearson’s chi-squared test or Fisher’s exact test. Quantitative nonnormally distributed data (baseline fasting blood glucose(FBG)) were compared using an independent-samples Mann–Whitney U test. Multiple measurements of the same observation index of the same object at different time points, if normally distributed, were compared using ANOVA of repeated measurements, a general linear model, and a group comparison by least-significant difference. A P value of <0.05 was considered significant in all the analyses. All statistical analyses were performed using SPSS 24.0 (IBM, Armonk, NY, USA).