Ketogenic diet leads in metabolic health improvements for diabetic patients

By Dr. Chinta SidharthanReviewed by Susha Cheriyedath, M.Sc.Jan 7 2025

A 12-month pilot study reveals how ketogenic and Mediterranean diets uniquely shape gut microbiota and metabolic health in patients with diabesity, paving the way for personalized nutrition strategies.

Study: Impact of Ketogenic and Mediterranean Diets on Gut Microbiota Profile and Clinical Outcomes in Drug-Naïve Patients with Diabesity: A 12-Month Pilot Study. Image Credit: Yulia Furman / Shutterstock

In a recent study published in the journal Metabolites, a team of researchers in Brazil and Italy assessed microbial diversity, anthropometric measures, and metabolic outcomes over 12 months to investigate how very-low-calorie ketogenic and Mediterranean diets influence the gut microbiota and metabolic health in newly diagnosed patients with type 2 diabetes and obesity (diabesity).

Background

Type 2 diabetes mellitus (T2DM) is a prevalent chronic condition often linked to obesity, especially visceral obesity. It results from impaired insulin activity and secretion, leading to elevated blood sugar and inflammation, and contributes to severe complications such as cardiovascular and renal diseases.

The risk factors for T2DM include genetic predisposition, sedentary behavior, poor diets rich in processed sugars, and inadequate intake of fruits and vegetables. Recent evidence has shown that the gut microbiome is a key player in metabolic health. The gut microbiota influences various physiological processes, including immune response, inflammation, and insulin sensitivity, through mechanisms such as bile acid modulation and bioactive metabolite production.

Altered gut microbiome composition has also been found to correlate with metabolic disorders, suggesting that specific diets could restore balance and improve metabolic health. While the Mediterranean diet is known for its cardiometabolic benefits, research on the long-term effects of very-low-calorie ketogenic diets on gut microbiota and metabolic outcomes remains limited. The study also acknowledges concerns about the sustainability of VLCKD over extended periods and the need for further research.

The current study

The present study followed 11 patients initially, but due to attrition, only 8 participants completed the full 12 months. These newly diagnosed diabetes patients, aged between 45 and 65, had not begun treatment. The patients were randomly assigned to a very low-calorie ketogenic diet (VLCKD) or a low-calorie Mediterranean diet (MD).

The patients in the VLCKD group began with protein-based meal replacements and limited carbohydrates (less than 30 g/day) for two months and transitioned gradually to a Mediterranean diet by the fourth month. The MD protocol emphasized the consumption of plant-based foods, moderate protein, and balanced macronutrients. From month four onward, all participants followed the MD protocol.

Clinical, anthropometric, and microbiome composition evaluations occurred at baseline, and subsequently at six and 12 months. Anthropometric assessments included body weight, body mass index (BMI), and waist circumference. The researchers used bioimpedance analysis to obtain data on body composition, including fat and lean mass. Additionally, fasting blood samples were used to evaluate metabolic markers such as glucose and cholesterol, while physical activity and dietary adherence were tracked using validated questionnaires.

The gut microbiota was analyzed using genomic material extracted from stool samples. The researchers targeted the bacterial 16S ribosomal ribonucleic acid (rRNA) gene for sequencing and identification of the gut microbiota. Subsequently, the researchers used various bioinformatics tools to analyze the taxonomic composition and diversity of the gut microbiome. Alpha diversity (species richness) remained stable across interventions, while beta diversity revealed significant shifts in microbial communities in the VLCKD group.

Furthermore, statistical methods, including generalized linear models, were used to evaluate the changes in microbial abundance over time and correlate these changes with clinical parameters. The researchers also monitored nutritional compliance every month through interviews and diet diaries. Metabolic, anthropometric, and lifestyle improvements were compared between groups at each time point to identify distinct effects of VLCKD and MD on gut microbiota and health outcomes.

Major findings

The findings revealed that both diets improved anthropometric and metabolic measures, but VLCKD demonstrated greater mid-term benefits on weight loss, glycemic control, and gut microbiota composition compared to MD. By six months, the VLCKD group showed significant reductions in BMI, waist circumference, and HbA1c compared to baseline. These changes were statistically significant, with BMI reductions of -5.8 kg/m² (p = 0.006) and HbA1c reductions of 1.2% (p = 0.02).

These improvements were less pronounced in the MD group. Additionally, major microbial changes in the VLCKD group included an increase in beneficial taxa, such as Akkermansia, known for its role in gut barrier integrity and metabolic health. However, the abundance of Akkermansia and other beneficial taxa decreased by the 12-month mark.

Furthermore, the alpha diversity metrics did not differ significantly between the diets, but the beta diversity measures revealed distinct microbial community shifts in the VLCKD group during the ketogenic phase. Interestingly, no significant changes were observed in the Firmicutes/Bacteroidota ratio, a commonly studied marker in microbiome research.

While the VLCKD protocol resulted in transient increases in taxa linked to health, the MD showed minimal microbial shifts. Moreover, anthropometric and metabolic parameters, such as fasting glucose and triglycerides, improved in both groups, but sustained benefits were limited in the MD group.

Conclusions

Overall, the study found that VLCKD offered superior mid-term benefits over MD for metabolic health, gut microbiota composition, and weight management in diabesity patients. While transitioning to MD sustained some of the improvements, the microbial changes associated with VLCKD decreased over time. The study also highlighted the need for personalized dietary strategies and cautious monitoring, particularly regarding potential risks such as reduced muscle mass and increased cholesterol levels during VLCKD.

These findings suggested that combining ketogenic approaches with Mediterranean diet principles, personalized dietary strategies had significant potential to optimize metabolic and gut health. However, the researchers believe that long-term investigations are needed to validate these results and explore sustainable dietary models.