Ketogenic Diet Boosts Metabolic Health in Diabetic Patients

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

Background
Type 2 diabetes (T2DM) is a common chronic illness that is commonly associated with obesity, particularly visceral obesity. It is caused by reduced insulin action and secretion, which leads to high blood sugar and inflammation, as well as serious complications such cardiovascular and renal disease.

T2DM risk factors include genetic susceptibility, sedentary behavior, poor diets high in processed sugars, and insufficient intake of fruits and vegetables. Recent research has demonstrated that the gut microbiota is an important factor in metabolic health. The gut microbiota regulates a variety of physiological processes, including immune response, inflammation, and insulin sensitivity, via mechanisms such as bile acid regulation and bioactive metabolite synthesis.

Altered gut microbiota composition has also been linked to metabolic illnesses, implying that some diets may restore balance and promote metabolic health. While the Mediterranean diet is well-known for its cardiometabolic benefits, research into the long-term impact of very low-calorie ketogenic diets on gut flora and metabolic outcomes is scarce. The report highlights concerns about VLCKD’s long-term viability and the need for additional research.

The current study

The current study initially tracked 11 patients, however due to attrition, only 8 participants finished the entire 12 months. These newly diagnosed diabetes patients, aged 45 to 65, had not started medication. Patients were randomly randomized to either the very low-calorie ketogenic diet (VLCKD) or the low-calorie Mediterranean diet (MD).

The patients in the VLCKD group started with protein-based meal replacements and low carbs (less than 30 g/day) for two months before progressively transitioning to a Mediterranean diet by the fourth month. The MD program stressed plant-based diets, modest protein intake, and macronutrient balance. From month four on, all subjects followed the MD protocol.

Clinical, anthropometric, and microbiota composition assessments were performed at baseline and again at six and twelve months. Body weight, body mass index (BMI), and waist circumference were among the anthropometric measurements taken. The researchers used bioimpedance analysis to collect information about body composition, such as fat and lean mass. Fasting blood samples were also utilized to assess metabolic markers like glucose and cholesterol, while validated questionnaires were employed to monitor physical activity and nutritional adherence.

The gut microbiota was studied using genetic material obtained from stool samples. The researchers used the bacterial 16S ribosomal ribonucleic acid (rRNA) gene to sequence and identify the gut microbiota. The researchers then utilized various bioinformatics methods to examine the taxonomic content and diversity of the gut microbiome. Alpha diversity (species richness) was consistent across interventions, whereas beta diversity demonstrated significant alterations in microbial communities in the VLCKD group.

Furthermore, statistical tools, such as generalized linear models, were utilized to assess changes in microbial abundance over time and correlate them with clinical variables. Every month, the researchers interviewed participants and kept diet diaries to track their nutritional compliance. Metabolic, anthropometric, and lifestyle improvements were compared between groups at each time point to see whether VLCKD and MD had distinct effects on gut microbiota and health outcomes.

Major Findings

The results showed that both diets improved anthropometric and metabolic markers, although VLCKD outperformed MD in terms of weight loss, glycemic management, and gut microbiota composition. By six months, the VLCKD group had significantly lower BMI, waist circumference, and HbA1c compared to the baseline. BMI decreased by -5.8 kg/m² (p = 0.006), whereas HbA1c decreased by 1.2% (p = 0.02).

These gains were less noticeable in the MD group. Furthermore, significant microbial changes in the VLCKD group included an increase in beneficial taxa such as Akkermansia, which is known for its involvement in gut barrier integrity and metabolic health. However, the abundance of Akkermansia and other beneficial taxa had declined by the 12-month point.

Furthermore, while there was no significant difference in alpha diversity measurements between the diets, beta diversity assessments revealed unique microbial community alterations in the VLCKD group during the ketogenic phase. Surprisingly, no substantial changes were seen in the Firmicutes/Bacteroidota ratio, a widely investigated metric in microbiome research.

While the VLCKD approach led in temporary elevations in taxa associated with health, the MD showed little microbial changes. Furthermore, anthropometric and metabolic markers such as fasting glucose and triglycerides improved in both groups, but the MD group experienced less long-term improvements.

Conclusions
Overall, the study discovered that VLCKD provided better mid-term advantages than MD for metabolic health, gut microbiota composition, and weight control in diabetes patients. While moving to MD maintained some of the gains, the microbial changes linked with VLCKD declined over time. The study also emphasized the importance of customized dietary choices and careful monitoring, particularly in light of potential concerns such as decreased muscle mass and elevated cholesterol levels during VLCKD.

These findings suggested that by combining ketogenic techniques with Mediterranean diet principles, individualized dietary regimens could significantly improve metabolic and gastrointestinal health. However, the researchers believe that longer-term studies are required to corroborate these findings and investigate sustainable dietary approaches.

More information: Palmas, V., Deledda, A., Heidrich, V., Sanna, G., Cambarau, G., Fosci, M., Puglia, L., Cappai, E. A., Lai, A., Loviselli, A., Manzin, A., & Velluzzi, F. (2024). Impact of Ketogenic and Mediterranean Diets on Gut Microbiota Profile and Clinical Outcomes in Drug-Naïve Patients with Diabesity: A 12-Month Pilot Study. Metabolites, 15(1), 22. DOI: 10.3390/metabo15010022, https://www.mdpi.com/2218-1989/15/1/22