A Low-Carbohydrate Diet in Type 2 Diabetes: Effects over six months on glycemic control, cardiovascular risk factors, vascular endothelial function and pro-inflammatory markers

Eva Gram-Kampmann

Research output: ThesisPh.D. thesis

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Diabetes affects over 9.3 % of the population worldwide, where, especially, the prevalence of type 2 diabetes (T2D) is increasing. A cornerstone in the management of T2D is lifestyle changes such as physical activity and diet to facilitate a good glycemic control and reduce risk of complications. During the last 20 years, carbohydrate-restricted diets (CRD) have gained increasing popularity, in particular, low-carbohydrate diets (LCDs) with an intake of carbohydrates between 10 and 25 E% (percentage of total energy intake). Recent meta-analyses have reached conflicting results regarding the impact of CRDs on glycemic control, body weight and markers of cardiovascular risk in T2D. This may be explained by variations in the interventions, such as combining the LCD and/or the control diet with calorie-restriction, exercise programs and reduction in antidiabetic medication. However, there is evidence that the greater the carbohydrate restriction, the greater the glucose-lowering effect in patients with T2D, whereas the effect of CRDs on other risk factors for cardiovascular disease (CVD) such as blood lipids, blood pressure and body composition are uncertain. There have been concerns that LCDs high in fat may increase the risk of cardiovascular disease (CVD). This may include worsening of the endothelial function, an early marker of atherosclerosis, mediated by increased levels of markers of chronic low-grade inflammation. This, however, remains to be established.
In this thesis, we aimed to test the hypotheses that a non-calorie–restricted LCD high in fat for 6 months 1) improves glycemic control and body composition and is safe with respect to risk factors of CVD such as blood lipid and blood pressure, and 2) adversely affects CVD risk factors such as endothelial function and markers of systemic chronic low-grade inflammation compared to a control diet in patients with T2D instructed to maintain their non-insulin glucose-lowering medication and level of physical activity.
In an open-label randomized controlled trial, 71 patients with T2D were randomized 2:1, to either a LCD diet (n = 49) or a control diet (n = 22) for six months. Both diets were non-calorie restricted. The LCD group were recommended a diet with < 20 E% carbohydrates, 50-60 E% fat (mainly monounsaturated) and 20-30 E% protein, while the control group was recommended 50-60 E% carbohydrates, 15-20 E% protein and < 30 E% fat. An internet-based food log was used. They attended three visits, at baseline, after three months and six months, where fasting blood samples were drawn and anthropometric data, blood pressure and compliance were assessed. At baseline and after six months, accelerometers were applied for seven consecutive days to asses level of physical activity, a dual energy x-ray absorptiometry scan (DXA) was done to assess body composition, along with measurements of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation(NID) of the brachial artery. Plasma and serum were analyzed for high-sensitive CRP (hsCRP) and Interleukin 6 (IL-6) as selected markers of low-grade inflammation. The mean differences in change (MDIC) between groups for these outcomes are reported.
The LCD group reduced their carbohydrate intake to ~13 E% and increased fat intake to ~63 E% (both p < 0.001). HbA1c decreased significantly with LCD at both three months ( -8.9 ± 1.7 mmol/mol; P < .0001) and at six months (-7.5 ± 1.8 mmol/mol; P < .0001) compared with control diet. There was a significant reduction of weight with LCD of -3.9± 1.0 kg, of BMI – 1.4 ± 0.4 kg/m2 and of waist circumference -4.9 ± 1.3 cm (all p < 0.01) compared with control diet. DXA-scan showed that the LCD group lost both fat mass and lean mass (both p < 0.05) compared with control diet. Apart for a transient improvement in HDL after three months on LCD (+0.1 ± 0.4, p = 0.03), there were no between-group differences in the change of blood lipids or blood pressure. The groups differed slightly at baseline, with the LCD group having slightly higher FMD and NID (both p < 0.05). However, there were no between-group differences in the changes of either FMD or NID. Moreover, the selected markers of systemic low-grade inflammation (hsCRP and IL-6) were not significantly changed in response to LCD compared with the control diet after six months. The LCD was generally well-tolerated, except for an increase in gastrointestinal complaints. The described changes were observed in spite of maintained level of physical activity, and there were no episodes of severe hypoglycemia.
In conclusion, in this open-label randomized controlled trial, a six-month LCD significantly reduced HbA1c and improved body composition in patients with T2D. Moreover, the LCD had no detectable negative impact on blood lipids, blood pressure, endothelial function or biomarkers of systemic low-grade inflammation, which indicate that a non-calorie-restricted LCD high in fat is safe with regard to cardiovascular risk factors. The improvements in glycemic control and body composition may have counteracted potential deleterious effects of a higher intake of saturated fat on CVD risk factors.
Translated title of the contributionLavkulhydratdiæt og Type 2 Diabetes: Effekt over seks måneder på glykæmisk kontrol, kardiovaskulære risikofaktorer, vaskulær endotelfunktion og proinflammatoriske markører
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
  • Højlund, Kurt, Principal supervisor
  • Beck-Nielsen, Henning, Supervisor
  • Olsen, Michael Hecht, Supervisor
  • Krag, Aleksander, Supervisor
Date of defence25. Aug 2023
Publication statusPublished - 27. Apr 2023


  • low-carbohydrate diet
  • type 2 diabetes
  • HbA1c
  • glycemic control
  • cardiovascular risk
  • body composition
  • pro-inflammatory markers
  • endothelial dysfunction
  • flow-mediated vasodilation
  • diet
  • LCHF


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