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


Different dietary approaches were able to improve the state of health in patients with type 2 diabetes (T2D), with very-low-calorie ketogenic diets demonstrating better results on gut microbiota profile.

Gut microbiota (GM) profile was affected 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 to this diet appeared to be higher than a classical Mediterranean diet for weight loss and impact on GM.

GM has been found to be a primary factor in the pathogenesis of insulin resistance and T2D. Different diets have been identified as ways to modulate GM composition. Specifically, the Mediterranean diet and the VLCKD have been effective in patients who are overweight or obese and have 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 of the Obesity Unit of the AOU of Cagliari and the Diabetology Unit of the PO Binaghi in Cagliari, Italy, from March to May of 2020. Patients were included if they had a new diagnosis of T2D, a glycosylated hemoglobin (HbA1C) value of 6.5% to 8.9%, and were drug naïve for T2D.

Patients were excluded if they had type 1 diabetes; serious heart disease; severe or uncontrolled hypertension; severe or uncompensated kidney, liver, or thyroid disease; painful pathologies; tumors being 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 the sample collection.

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

Clinical examinations included a full medical history, physical examination, standard blood pressure and heart rate measurement, and a quality of life assessment.

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

There were 11 patients included in the study, 6 men and 5 women, split evenly into 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 achieved significant progress in total weight reduction (–14.3 vs –3.04 kg), body mass index (–5.3 vs –1.1 kg/m2), waist circumference (–12.9 vs –4.7 cm) and fat mass (–7% vs –3.1%) reduction compared with the MEDI group; differences in fat-free mass kg, fasting plasma glycemia levels, HbA1C values, lipid status, and bloodpressure values were not significant.

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

There was no significant differences between the 2 diet groups when evaluating the GM of each participant through different analyses. The researchers found that the KETO diet was associated with steroid biosynthesis, carotenoid biosynthesis, and nonhomologous end-joining pathways in T2 and T3 compared with 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 benefits of VLCKD protocol in drug-naïve patients with T2D were significant in the short term. The benefits were more significant than patients following a classic Mediterranean diet in terms of weight loss and the impact on GM.


Deledda A, Palmas V, Heidrich V, et al. Dynamics of gut microbiota and clinical variables after 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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