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, HbA_1c 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

中文翻译：

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三周的限时饮食可改善 2 型糖尿病成人的葡萄糖稳态，但不会改善胰岛素敏感性：一项随机交叉试验

目标/假设

限时进食 (TRE) 建议通过将食物摄入量限制在规定的时间窗口来改善代谢健康，从而延长禁食时间。预计这种长时间的禁食会导致肝糖原储存在一夜之间更明显的消耗，并且由于补充营养储存的需求增加，可能会提高胰岛素敏感性。先前的研究表明，在受控条件下，6-8 小时 TRE 方案对健康、超重的成年人具有有益的代谢作用。然而，TRE 对 2 型糖尿病患者葡萄糖稳态的影响尚不清楚。在这里，我们广泛研究了 TRE 对 2 型糖尿病患者肝糖原水平和胰岛素敏感性的影响。

方法

14 名患有 2 型糖尿病的成年人（BMI 30.5±4.2 kg/m ²，HbA _1c46.1±7.2 mmol/mol [6.4±0.7%]）在随机交叉试验设计中参与了 3 周的 TRE（每天 10 小时内的食物摄入）与对照组（在 ≥14 小时内传播食物）方案。该研究在荷兰马斯特里赫特大学进行。资格标准包括 2 型糖尿病的诊断、中间表型和不存在可能干扰研究执行和/或结果的医疗条件。随机化由独立于研究的研究者进行，确保相同数量的参与者从 TRE 和 CON 开始。由于研究的性质，无论是志愿者还是研究人员都对研究干预不知情。在不了解干预分配的情况下检查数据的质量。^用13评估肝糖原水平C-MRS 和胰岛素敏感性使用高胰岛素-正常血糖两步钳进行评估。此外，使用 24 小时连续血糖监测设备评估血糖稳态。次要结果包括 24 小时能量消耗和底物氧化、肝脂质含量和骨骼肌线粒体容量。

结果

结果被描述为平均值±SEM。TRE 和对照条件之间的肝糖原含量相似（0.15±0.01 vs 0.15±0.01 AU，p = 0.88）。M值不受 TRE 的显着影响（TRE 与对照分别为19.6±1.8 对 17.7±1.8 μmol kg ^-1 min ^{-1 ，} p = 0.10）。肝脏和外周胰岛素敏感性也不受 TRE 影响（分别为p =0.67 和p =0.25）。然而，胰岛素诱导的非氧化葡萄糖处理随着 TRE 增加（非氧化葡萄糖处理 4.3±1.1 vs 1.5±1.7 μmol kg ^-1 min ^-1，p=0.04)。TRE 增加了在正常血糖范围内的时间（每天 15.1±0.8 对 12.2±1.1 小时，p = 0.01），并降低空腹血糖（7.6±0.4 对 8.6±0.4 mmol/l，p = 0.03）和 24 小时血糖水平（6.8±0.2 vs 7.6±0.3 mmol/l，p <0.01）。超过 24 小时的能量消耗不受影响；尽管如此，TRE 减少了 24 小时葡萄糖氧化（260.2±7.6 对 277.8±10.7 g/天，p = 0.04）。没有报告与干预措施相关的不良事件。

结论/解释

我们表明，10 小时 TRE 方案是一种可行、安全和有效的方法，可以改善自由生活的 2 型糖尿病成人的 24 小时葡萄糖稳态。然而，这些变化并未伴随胰岛素敏感性或肝糖原的变化。

试用注册

ClinicalTrials.gov NCT03992248

资金

中MW, 459001013

图形概要