Low-Calorie Ketogenic Diet Improved Body Composition, Gut Microbiota Profile in T2D

Several nutritional approaches were able to improve the health status of patients with type 2 diabetes (T2D), with very low-calorie ketogenic diets showing better results on the profile of the gut microbiota.

Gut microbiota (GM) profile was influenced by dietary approaches, namely a very low-calorie ketogenic diet (VLCKD), in patients with type 2 diabetes (T2D), according to a new study published in Metabolites. The benefit of this diet proved to be greater than a classic Mediterranean diet for weight loss and impact on GM.

GM has been shown to be a primary factor in the pathogenesis of insulin resistance and T2D. Several diets have been identified as ways to modulate GM composition. In particular, the Mediterranean diet and VLCKD have been effective in overweight or obese patients with T2D. The aim of the present study was to evaluate the short-term effects on GM using 2 dietary models, the Mediterranean diet and VLCKD, in patients with newly diagnosed T2D.

Study participants were outpatients from the Obesity Department of the AOU of Cagliari and the Diabetology Department of the PO Binaghi in Cagliari, Italy, from March to May 2020. Patients were included if they had a new diagnosis of T2D, a glycosylated hemoglobin (HbA1C) value from 6.5% to 8.9%, and were drug-naive for T2D.

Patients were excluded if they had type 1 diabetes; severe heart disease; severe or uncontrolled hypertension; severe or uncompensated kidney, liver, or thyroid disease; painful pathologies; tumors treated with chemotherapy or radiotherapy; sever psychopathology; gastrointestinal disease; therapy with corticosteroids; proton pump inhibitors; prebiotic or probiotic intake; or any dietary supplements or participation in other dietary regimens within 3 months of sample collection.

Baseline evaluations (T0) were performed 3 months after baseline evaluation (T3) for comparison. Nutritional intervention took place during the first (T1) and second (T2) months to evaluate adherence to the feeding program.

Clinical examinations include a complete medical history, physical examination, standard blood pressure and heart rate monitoring, and a quality of life assessment.

There were 2 study groups: KETO underwent a VLCKD and MEDI followed a low-calorie Mediterranean diet protocol. The MEDI group had a Mediterranean diet with macronutrient intake, while the KETO group had a multiphase model with protein-rich meal replacement products.

There were 11 patients in the study, 6 men and 5 women, evenly divided between the MEDI and KETO groups. The researchers found that both diets improved anthropometric and metabolic status, but found significant success in the KETO group.

Participants in the VLCKD group made significant progress in total weight reduction (–14.3 versus –3.04 kg), body mass index (–5.3 versus –1.1 kg/m2), waist circumference (–12.9 vs. –4.7 cm) and fat mass (–7% vs. –3.1%) decrease compared to the MEDI group; differences in fat-free mass kg, fasting plasma glycaemia values, HbA1C values, lipid status and blood pressure values ​​were not significant.

The KETO group significantly increased protein intake (19.7% [2.1%] versus 26.7% [2.6%]) and Mediterranean diet scores relative to fish (1.7 [0.8] versus 2.8 [0.7]) and vegetables (3.3 [1.5] against 5[0]) intake. A reduction in body weight, body mass index and waist circumference was found in the VLCKD protocol in the short evaluation at T2 compared to the KETO group. The MEDI group saw a significant reduction in waist circumference, but not in body weight and body mass index over the same period.

There were no significant differences between the 2 diet groups when evaluating each participant’s GM through different analyses. The researchers found that the KETO diet was associated with steroid biosynthesis, carotenoid biosynthesis, and non-homologous end-joining pathways in T2 and T3 compared to baseline.

The small sample size due to the COVID-19 pandemic was the main limitation of this study; the pandemic also interrupted the enrollment of patients whose data could be used for additional analysis.

The researchers concluded that the short-term benefits of the VLCKD protocol in previously untreated patients with T2D were significant. The benefits were greater than in patients following a classic Mediterranean diet in terms of weight loss and impact on GM.


Deledda A, Palmas V, Heidrich V, et al. Gut microbiota dynamics and clinical variables following ketogenic and Mediterranean diets in drug-naïve patients with type 2 diabetes mellitus and obesity. Metabolites. Published online November 10, 2022. doi:10.3390/metabo12111092

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