Discussion
dyslipidaemia, overweight, hyperglucagonaemia, type 2 diabetes, weight loss, glucometabolic, diabetes
INSULIN RESISTANCE, ADIPOSITY, REMISSION, TYPE 2 DIABETES, INSULIN SENSITIVITY, DIABETES
This randomised controlled trial tested efficacy, feasibility and safety of a novel dietary strategy, named eTRC, which involves restricting carbohydrate-rich food intake to the morning and early afternoon to align carbohydrate consumption with the body’s circadian rhythm. In people with well-controlled type 2 diabetes under free-living conditions, eTRC induced no added glucometabolic benefits compared with a traditional Mediterranean-style diet matched for energy restriction and macronutrient composition. Furthermore, eTRC appeared to be as effective as conventional dieting for the management of multiple cardiometabolic risk factors, encompassing overweight, increased whole-body and visceral adiposity, insulin resistance, impaired insulin clearance and dyslipidaemia. These beneficial effects appear to be largely conveyed by body weight loss, which intrinsically improves metabolic health, and not related to the daily distribution of carbohydrate intake.The accurate matching of energy and nutrient prescription between the eTRC and Med diets, as well as the quantification of carbohydrate intake across the day, allowed us to dissect the effects deriving from the specific timing of carbohydrate consumption from those of body weight loss or diet composition. By study design, the two groups randomised to the eTRC or Med diet achieved equal improvements in body weight and composition after 12 weeks of intervention, in line with the prescribed energy restriction. This finding does not support additional benefits of eTRC on weight management as compared with conventional dieting. Consistently, even a stricter regimen of energy-restricted eTRF was not superior to energy restriction alone in reducing body weight and fat mass over a 12 month period [Previous acute studies under controlled conditions suggest that altering the daily distribution of carbohydrate intake can affect 24 h glycaemic control in people with type 2 diabetes [Supervised controlled feeding trials to test the metabolic effects of eTRF independent of body weight changes have shown large improvements in insulin sensitivity and beta cell responsiveness [Nevertheless, we demonstrated several beneficial changes after the dietary intervention. Measuring postprandial responses to a mixed-nutrient meal provides a more comprehensive assessment of glucose homeostatic mechanisms than simple fasting assessments, allowing the exploration of changes in the physiological gut hormone responses to food intake. In our study, plasma glucagon levels in response to the MMTT were significantly reduced by the diet, regardless of daily carbohydrate distribution. This finding is noteworthy as hyperglucagonaemia is a hallmark of type 2 diabetes, whose resolution has been proposed as a key mechanism of diabetes remission [This proof-of-concept study expands the current knowledge on the promising metabolic effects of time-restricted carbohydrate eating in individuals with type 2 diabetes under free-living conditions. However, some limitations should be acknowledged. First, our sample size was relatively small. This was in line with similar pilot studies and the statistical power was adequate to identify large and clinically meaningful effects on body weight and glucometabolic variables. Women and men were equally represented in the two study groups. However, the small sample size did not allow for subgroup analyses stratified by sex, which may reveal sex-related differences in the glucometabolic effects of eTRC. Second, adherence to the diet was evaluated from self-reported 3 day food diaries, which are prone to error and bias. To mitigate the risk of misinterpretations, food diaries were analysed independently by two investigators, and a third investigator was involved to resolve any dispute. Furthermore, flash glucose monitoring allowed the detection of any unprescribed carbohydrate assumption to confirm the strict adherence to the protocol during recording. Predicted and actual weight loss were also very similar, in the absence of significant changes in physical activity and sedentary behaviours, indicating adequate adherence at least to dietary energy prescriptions. Third, dedicated studies should be performed to assess the effects of a longer-term eTRC dietary intervention, compared with both conventional dieting and a more stringent eTRF. Finally, the therapeutic potential of eTRC should be tested in people with less controlled type 2 diabetes, greater habitual carbohydrate intake in the evening or different racial/ethnic background, who may achieve greater metabolic benefits from eTRC.In conclusion, this randomised controlled trial demonstrated that synchronising carbohydrate intake with the daily variations in glucose tolerance, while allowing for habitual fat and protein eating, does not amplify the glycometabolic benefits of an energy-matched Mediterranean diet in individuals with type 2 diabetes. Nonetheless, tailoring the dietary intervention to the individual’s preferences and habits promotes greater compliance and increases efficacy. Thus, this dietary regimen may offer a feasible and safe alternative nutritional strategy to conventional dieting to improve cardiometabolic risk management in type 2 diabetes.