Study design and overview
The study is designed as open, single centre and randomized. All procedures were conducted at the site of the investigating clinic, namely APSA Diabetes Care Centre (ADCC). Included subjects were required to undergo a two-phase intervention and observation period; phase 1 (day 1- day 5) whereby patients were instructed to continue with their usual dietary habits. Before embarking onto the second phase, that is, from day 6 to day 10, subjects were randomized into two groups; ‘low-GI sugar’, which comprises of individuals who received and consumed portioned food prepared with low-GI sugar, and ‘normal-GI sugar’ to indicate those who received portioned food but that included normal-GI sugar. Hence all subjects received the same food during the second phase, the only difference being that the novel low-GI sugar (DinaLife TM) was used for the preparation of the various plates.
The design of this study is justified and preferred over a typical cross-over trial for two main reasons: the CGM, once installed raises awareness among patients and intuitively leads to enhanced sugar levels in terms of trend and variation. Thus, while the first phase of the study makes it possible to observe the intrinsic glycemic control of the enrolled subjects, it also serves as an acclimatization period so that any effect due to the sugar being used is not confounded with the rise in consciousness.
Overall, subjects attended three (3) visits at the centre and under continuous study conditions for 10 days (from day 1 and day 10 inclusive). Due to the availability of sensors for the CGM and interruptions related to the COVID-19 pandemic, the dates for the First Subject In (FSI) and Last Subject Out (LSO), initially planned for March 2020 - July 2020 were shifted to July 2020 - Dec 2020.
Subject selection, consent and ethical considerations
In addition to the general eligibility criteria for participation in a study locally (capable to express and give written consent, eligible for free health care services, not serving imprisonment etc.), Mauritian subjects registered on the clinic’s database were screened and examined for the following study specific inclusion criteria; subjects had to be above 18 years of age, suffering from type 2 diabetes, ready to embark on a special diet and having a baseline HbA1c of 6.5% or above at screening. Study specific exclusion criteria included subjects with known allergy to food, having a history of bariatric surgery, had experienced microvascular and/or macrovascular complications of diabetes, undergoing hemodialysis or was on insulin treatment, regularly consumes alcohol, is a vegetarian, suffers from chronic psychiatric illness, on antipsychotic prescriptions or is a breastfeeding or pregnant women.
Eligible patients were explained about the study procedures, expected adverse events and reporting strategies put in place. An explanatory leaflet that also included the menu for the second phase of the study was handed over to them during the same visit. Foreseeable advantages for participation to the study were: free CGM for ten (10) consecutive days, including a smartphone for real-time visuals, free portioned food including home delivery, and follow-up by a physician during the study period (including assistance over the phone). Travel costs for the patients were also catered for by the study sponsor. Clearance for ethical considerations was obtained from a local independent committee (CEC, c/o Accrux, Port Louis, 13 March 2020). The study was conducted in the spirit of Good Clinical Practice (GCP).
Meal preparation and logistics
A full description of the menu for the second phase of the study is provided in table 1. Briefly described, the participants in the control group (normal-GI sugar) were provided with a portioned meal set for breakfast, mid-morning snack, lunch, afternoon snack and dinner that included sugar of GI 103 ± 3. The test group (low-GI sugar) received the same set of meals but prepared with sugar of GI 51, DinaLife TM. Irrespective of the group, the GI of the other ingredients used for the preparation of meals was primarily low whenever the choice was present. The total amount of carbohydrate per meal was also the same for both groups. Preparation and organization for home delivery were centralized. The meals were delivered in the evening for the consumption on the following day.
Continuous Glucose Monitoring
Each participant wore the CGM (The Guardian TM Connect System, Medtronic) for a total of 10 days; fitted on day 1, worn for 4 days, sensors changed on day 5 and worn for another 5 days. The CGMs were fitted according to the manufacturer’s instructions and assisted by the local brand representative in Mauritius. The participants were educated on handling measures and how to calibrate the system 12-hourly using the finger-prick method. Assistance was made available by phone
Oral Glucose Tolerance Tests (OGTT)
Two sets of OGTT were performed on thirteen participants to confirm the low-GI property of the novel sugar on glycemic control. The participants were instructed to consume normal meals or meals that contained approximately 150g of carbohydrates per day for three days preceding the test day. On the day of the test, a fasting blood sample was taken followed by a 1-hour and 2-hour sample after consuming 75 of sugar diluted in water; the participants attended two test sessions for the OGTT, low-GI sugar on OGTT test Day 1 and normal-GI sugar on OGTT test Day 2. The phlebotomy samples were sent to the laboratory for analysis.
Statistical considerations and efficacy variables
The analysis was conducted on a modified Intent to Treat population (mITT), comprising of all randomized subjects with available data. One subject’s data could not be retrieved from the application’s platform for downloading measurements. Thus, the data for 19 patients (10 normal-GI sugar and 9 low-GI-sugar) could be analyzed for efficacy assessment. The analysis method is inspired by Rodbard’s ‘systematic approach to analysis of CGM data’ , while also taking into consideration relevant clinical questions and degree of glycemic variation .
A graphical illustration of the daily average blood sugar level was provided to identify possible changes from baseline, by treatment group. Since initial analyses revealed a considerable change in behavior between Day 5 (last day of normal food intake) and Day 6 (first day of portioned food intake), this part of the data was further explored to understand hourly variations.
Measurements related to blood sugar collected over 5-minute intervals were averaged daily (or hourly) first at patient level, before aggregating and presented across individuals, by group. Line graphs by time and group represent means. Error bars are not provided since variation is thoroughly analyzed on its own.
Variations in blood sugar levels were analysed using the coefficient of variation  and computed in the same order as described for the means.
Results from OGTT are reported in a graphical illustration showing the means, by type of sugar and time.