Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial,Diabetologia

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Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial
Diabetologia ( IF 8.4 ) Pub Date : 2022-01-07 , DOI: 10.1007/s00125-021-05628-8
Mads N Thomsen ₁ , Mads J Skytte ₁ , Amirsalar Samkani ₁ , Martin H Carl ₁ , Philip Weber ₁ , Arne Astrup ₂ , Elizaveta Chabanova ₃ , Mogens Fenger ₄ , Jan Frystyk _{5,

6} , Bolette Hartmann _{7,

8} , Jens J Holst _{7,

8} , Thomas M Larsen ₂ , Sten Madsbad ₉ , Faidon Magkos ₂ , Henrik S Thomsen ₃ , Steen B Haugaard ₁ , Thure Krarup _{1,

2}

Affiliation

Aims/hypothesis

Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes.

Methods

This open-label, parallel RCT included adults with type 2 diabetes, HbA_1c 48–97 mmol/mol (6.5–11%), BMI >25 kg/m², eGFR >30 ml min⁻¹ [1.73 m]⁻² and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA_1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev).

Results

Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA_1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m² were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA_1c (mean [95% CI] −1.9 [−3.5, −0.3] mmol/mol [−0.18 (−0.32, −0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] −0.8 [−1.2, −0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] −4.1 [−5.9, −2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] −18 [−29, −6]%, p < 0.01) and liver fat content (by mean [95% CI] −26 [−45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets.

Conclusions/interpretation

Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies.

Trial registration

ClinicalTrials.gov NCT03814694.

Funding

The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.

Graphical abstract

中文翻译：

限制饮食碳水化合物可增强 2 型糖尿病患者体重减轻引起的血糖控制和肝脏脂肪改善：一项随机对照试验

目标/假设

改变生活方式和减轻体重是 2 型糖尿病管理的基石。然而，碳水化合物限制可能对血糖控制产生与体重无关的有益影响。这很难证明，因为低碳水化合物饮食很容易降低体重。我们假设限制碳水化合物可增强 2 型糖尿病患者减肥的有益代谢作用。

方法

这项开放标签、平行 RCT 包括患有 2 型糖尿病、HbA _1c 48–97 mmol/mol (6.5–11%)、BMI >25 kg/m ²、eGFR >30 ml min ^-1 [1.73 m] ^-2的成人降糖治疗仅限于二甲双胍或二肽基肽酶 4 抑制剂。参与者由第三方随机分配，并被分配到为期 6 周的能量限制（提供所有食物），目标是通过减少碳水化合物的高蛋白饮食（CRHP，总能量摄入百分比 [E%] 减少约 6% 的体重） : CH30/P30/F40) 或传统的糖尿病饮食 (CD, E%: CH50/P17/F33)。空腹血样、连续血糖监测和磁共振波谱用于评估血糖控制、脂质代谢和肝内脂肪。HbA 的变化_1c是主要结果；循环和肝内甘油三酯的变化是次要结果。数据是在哥本哈根大学医院（Bispebjerg 和 Herlev）收集的。

结果

_{72 名患有 2 型糖尿病（平均病程 8 年，平均 HbA 1c} 57 mmol/mol [7.4%]）且平均 BMI 为 33 kg/m ²的成年人（CD 36，CRHP 36，全白人，38 名男性）为入组，其中 67 人（CD 33，CRHP 34）完成了研究。6 周后，两组的体重均减少了 5.8 kg (5.9%)。与 CD 饮食相比，CRHP 饮食进一步降低了 HbA _1c（平均 [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%]，p = 0.018）和昼夜平均葡萄糖（平均 [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001），通过降低葡萄糖 CV 稳定葡萄糖偏移（平均 [95% CI] -4.1 [-5.9, -2.2 ]%, p < 0.001），并增加了空腹甘油三酯浓度（平均 [95% CI] -18 [-29, -6]%，p < 0.01）和肝脂肪含量（平均 [95% CI] -26 [ −45, 0]%, p = 0.051)。然而，CRHP 对胰腺脂肪含量的降低程度低于 CD 饮食（平均 [95% CI] 33 [7, 65]%，p = 0.010）。空腹血糖、胰岛素、HOMA2-IR 和胆固醇浓度（总胆固醇、低密度脂蛋白和高密度脂蛋白）均显着降低且相似。