Association between the gut microbiota profile, fat oxidation capacity during exercise, and leptin sensitivity in patients with type 2 diabetes mellitus: The Edugution Project
Type 2 diabetes (T2D) is a cardiometabolic disorder characterized by chronic hyperglycemia due to insulin resistance or insufficient secretion. Individuals with T2D experience difficulties in the oxidation of fats and glucose, a phenomenon known as metabolic inflexibility, which negatively impacts their body composition and overall metabolic health. As maximal fat oxidation (MFO) is typically assessed with protocols requiring two separate sessions or estimations from non-specific tests, a one-day test has been validated to assess MFO, its intensity (FATmax), and maximal oxygen consumption (VO2max) in individuals with T2D (Study I). This study, which established the validity and reliability of the test, involved 20 adults with pre-diabetes or T2D (10 women). Participants underwent a single-day MFO-VO2max protocol, followed by the traditional VO2max test on a cycle ergometer 4 7 days later, with both assessments performed using indirect calorimetry. The single-day test commenced with the MFO test, involving 15 W per 3 min increments until the respiratory exchange rate reached 1.0. After a 5-minute (min) rest, the VO2max test was conducted, starting at the last load and increasing by 15 Wmin-1 until voluntary exhaustion. The traditional VO2max test involved a 15 Wmin-1n incremental protocol until voluntary exhaustion, followed by a verification test at 110% of the previous maximum load. The Bland-Altman method was employed to determine the limits of agreement between VO2max-A and VO2max-B. The intraclass correlation coefficient (ICC) with a 95% confidence interval was used to assess the reliability of VO2max. The standard error of measurement (SEM) was calculated to assess the measurement error of the VO2max-A test. Sensitivity was evaluated using the minimal detectable change at a 95% confidence interval (MDC95). The findings indicate that the single-day test is a valid and reliable method for assessing these health outcomes in this population, enhancing clinical applicability by significantly reducing the time and cost associated with traditional assessments. The gut microbiota also plays a key role in T2D, often exhibiting lower diversity and a higher proportion of pro-inflammatory bacteria. Moreover, these factors may contribute to the low-fat oxidation capacity observed in individuals with this condition. Consequently, we explored the relationship between fat oxidation and gut microbiota, considering sex differences among people with T2D (Study II). In this cross-sectional study a total of 146 adults with prediabetes or type 2 diabetes mellitus were included. The MFO, FATmax and VO2max were assessed through indirect calorimetry during a cycle ergometer test. Gut microbiota diversity and composition were analyzed from fecal samples, and body composition was evaluated using bioelectrical impedance analysis. Correlations between gut microbiota composition and fat oxidation and body composition were explored using Pearsons correlation coefficients, with analyses performed for the overall sample as well as separately for men and women. Associations were visualized using R Studios corrplot function, applying the False Discovery Rate (FDR) procedure to correct for multiple testing. The results show sex-based differences in the associations between gut microbiota and maximal fat oxidation, with these associations being significant in women. Additionally, FATmax was associated with gut microbiota, but in a sex-specific manner, differing between men and women. These findings highlight the potential for sex-specific microbiota-based strategies to optimize fat metabolism and metabolic health. Within the management of T2D, physical exercise and dietary interventions are highlighted as key strategies. While substantial evidence supports the positive effects of these interventions, more research is needed to determine which specific approaches are most effective for this population. Therefore, this doctoral thesis compares high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT), as well as dietary interventions, either in isolation or combined, on fat oxidation capacity (Study III) and gut microbiota profiles and leptin levels (Study IV) in individuals with T2D. A total of 147 adults with overweight or obesity and prediabetes or T2D participated in these randomized controlled trials, divided into six groups based on their assigned intervention: HIIT with Diet, HIIT without diet, MICT with Diet, MICT without diet, Inactive group with Diet, and Inactive group without diet. The interventions lasted 12 weeks with pre-post assessments. Both exercise interventions (HIIT and MICT) included three weekly supervised sessions conducted on a cycle ergometer. Dietary interventions included biweekly consultations, providing a balanced menu and a slight caloric deficit. The analyses included variables related to fat oxidation, such as MFO and FATmax, gut microbiota diversity and composition, VO2max, body composition, and leptin levels. Our results showed that, after the 12-week period, MICT without dietary intervention and HIIT with dietary intervention improved MFO, while both exercise modalities significantly increased FATmax, with noted sex-specific differences. Specifically, HIIT was more effective in improving FATmax in women, while MICT had a greater impact in men. However, no significant changes were observed in gut microbiota or leptin levels, suggesting that longer or more targeted interventions may be necessary to influence these variables effectively.
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