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

Abstract

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.

Keywords: Carbohydrate restriction; Dietary intervention; Dyslipidaemia; Glycaemic control; Low-energy diet; Non-alcoholic fatty liver disease; Nutritional therapy; Obesity; Type 2 diabetes mellitus; Weight loss.

Fig. 1

Participant flow diagram. The median (25th, 75th percentile) time from randomisation to initiation of dietary intervention upon which participants were unblinded was 22 (18, 30) days for the CRHP diet and 22 (19, 31) days for the CD diet

Fig. 2

Fasting measures of body weight (p = 0.83) (a), HbA_1c (p = 0.018) (b), plasma glucose (p = 0.64) (c), serum insulin (p = 0.92) (d) and serum triacylglycerol (TAG) (p < 0.01) (e) during 6 weeks of a CRHP (n = 34) or CD (n = 33) diet. Data are presented as mean with SEM error bars, including back-transformed data in (c–e) following log-transformation. Changes from baseline to week 6 were evaluated between diets, and p values for these differences are included