Three weeks of time-restricted eating improves glucose homeostasis in adults with type 2 diabetes but does not improve insulin sensitivity: a randomised crossover trial

Abstract

Aims/hypothesis Time-restricted eating (TRE) is suggested to improve metabolic health by limiting food intake to a defined time window, thereby prolonging the overnight fast. This prolonged fast is expected to lead to a more pronounced depletion of hepatic glycogen stores overnight and might improve insulin sensitivity due to an increased need to replenish nutrient storage. Previous studies showed beneficial metabolic effects of 6–8 h TRE regimens in healthy, overweight adults under controlled conditions. However, the effects of TRE on glucose homeostasis in individuals with type 2 diabetes are unclear. Here, we extensively investigated the effects of TRE on hepatic glycogen levels and insulin sensitivity in individuals with type 2 diabetes. Methods Fourteen adults with type 2 diabetes (BMI 30.5±4.2 kg/m2, HbA1c 46.1±7.2 mmol/mol [6.4±0.7%]) participated in a 3 week TRE (daily food intake within 10 h) vs control (spreading food intake over ≥14 h) regimen in a randomised, crossover trial design. The study was performed at Maastricht University, the Netherlands. Eligibility criteria included diagnosis of type 2 diabetes, intermediate chronotype and absence of medical conditions that could interfere with the study execution and/or outcome. Randomisation was performed by a study-independent investigator, ensuring that an equal amount of participants started with TRE and CON. Due to the nature of the study, neither volunteers nor investigators were blinded to the study interventions. The quality of the data was checked without knowledge on intervention allocation. Hepatic glycogen levels were assessed with 13C-MRS and insulin sensitivity was assessed using a hyperinsulinaemic–euglycaemic two-step clamp. Furthermore, glucose homeostasis was assessed with 24 h continuous glucose monitoring devices. Secondary outcomes included 24 h energy expenditure and substrate oxidation, hepatic lipid content and skeletal muscle mitochondrial capacity. Results Results are depicted as mean ± SEM. Hepatic glycogen content was similar between TRE and control condition (0.15±0.01 vs 0.15±0.01 AU, p=0.88). M value was not significantly affected by TRE (19.6±1.8 vs 17.7±1.8 μmol kg−1 min−1 in TRE vs control, respectively, p=0.10). Hepatic and peripheral insulin sensitivity also remained unaffected by TRE (p=0.67 and p=0.25, respectively). Yet, insulin-induced non-oxidative glucose disposal was increased with TRE (non-oxidative glucose disposal 4.3±1.1 vs 1.5±1.7 μmol kg−1 min−1, p=0.04). TRE increased the time spent in the normoglycaemic range (15.1±0.8 vs 12.2±1.1 h per day, p=0.01), and decreased fasting glucose (7.6±0.4 vs 8.6±0.4 mmol/l, p=0.03) and 24 h glucose levels (6.8±0.2 vs 7.6±0.3 mmol/l, p<0.01). Energy expenditure over 24 h was unaffected; nevertheless, TRE decreased 24 h glucose oxidation (260.2±7.6 vs 277.8±10.7 g/day, p=0.04). No adverse events were reported that were related to the interventions. Conclusions/interpretation We show that a 10 h TRE regimen is a feasible, safe and effective means to improve 24 h glucose homeostasis in free-living adults with type 2 diabetes. However, these changes were not accompanied by changes in insulin sensitivity or hepatic glycogen. Trial registration ClinicalTrials.gov NCT03992248 Funding ZonMW, 459001013 Graphical abstract

Time-restricted eating for patients with diabetes and prediabetes: A systematic review

“…Andriessen et al ( 12 ) investigated the effects of TRE on insulin sensitivity and hepatic glycogen levels in patients with diabetes. In their study, fourteen patients were included.…”

“…After excluding the duplications, 1,167 articles were screened by title and abstracts, and 336 full-text articles were reviewed. In addition, a recently published article (12) was included to make our study more comprehensive. In total, seven studies including five articles on patients with diabetes and two articles on patients with prediabetes, were included (11,12,(15)(16)(17)(18)(19).…”

“…In addition, a recently published article (12) was included to make our study more comprehensive. In total, seven studies including five articles on patients with diabetes and two articles on patients with prediabetes, were included (11,12,(15)(16)(17)(18)(19). The search flow is shown in Figure 1.…”

“…For example, Che et al ( 11 ) explored the effects of TRE over 12 weeks on weight changes and glycemic regulation in overweight patients with diabetes, and found that 10-h TRE could result in weight loss, improve blood glucose and insulin sensitivity, reduce the necessary dosage of hypoglycemic drugs, offer cardiovascular benefits and enhance the quality of life. Andriessen et al ( 12 ) determined the clinical tolerability and biochemical effects of short-term TRE for patients with type 2 diabetes, and the results showed that short-term daily TRE may be a tolerable and safe dietary intervention and may improve outcomes of postprandial variability, fasting glucose and body weight for patients with T2DM. However, these studies were not analyzed and summarized as a whole.…”

Design and Implementation of a Time-Restricted Feeding Intervention in a Randomized, Controlled Feeding Study

“…In particular, timing of feeding during the active period (daytime in humans), consistent with circadian rhythms, may improve metabolic outcomes [3][4][5][6] Several randomized clinical trials have evaluated the cardiometabolic effects of TRF in humans [7][8][9][10][11][12][13][14][15][16]. These prior trials of TRF were either not feeding studies [12][13][14][15][16][17][18][19] or feeding studies with substantial limitations including short duration of intervention [8,9,11], small sample size [10] and low retention rates [7,10,11], limiting the inferences that can be drawn. These limitations make it difficult to assess whether prior promising results of TRF are due to reductions in caloric intake or other confounding factors rather than timing of food intake.…”