Association of short-chain fatty acids and the gut microbiome with type 2 diabetes: Evidence from the Henan Rural Cohort.

BACKGROUND AND AIMS: Human studies about short-chain fatty acids (SCFAs), the gut microbiome, and Type 2 diabetes (T2DM) are limited. Here we explored the association between SCFAs and T2DM and the effects of gut microbial diversity on glucose status in rural populations. METHODS AND RESULTS: We performed a cross-sectional study from the Henan Rural Cohort and collected stool samples. Gut microbiota composition and faecal SCFA concentrations were measured by 16S rRNA and GC-MS. The population was divided based on the tertiles of SCFAs, and logistic regression models assessed the relationship between SCFAs and T2DM. Generalized linear models tested the interactions between SCFAs and gut microbial diversity on glucose indicators (glucose, HbAlc and insulin). Compared to the lowest tertile of total SCFA, acetate and butyrate, the highest tertile exhibited lower T2DM prevalence, with ORs and 95% CIs of 0.291 (0.085-0.991), 0.160 (0.044-0.574) and 0.171 (0.047-0.620), respectively. Restricted cubic spline demonstrated an approximately inverse S-shaped association. We also noted interactions of the ACE index with the highest tertile of valerate on glucose levels (P-interaction = 0.022) and the Shannon index with the middle tertile of butyrate on insulin levels (P-interaction = 0.034). Genus Prevotella_9 and Odoribacter were inversely correlated with T2DM, and the genus Blautia was positively associated with T2DM. These bacteria are common SCFA-producing members. CONCLUSIONS: Inverse S-shaped associations between SCFAs (total SCFA, acetate, and butyrate) and T2DM were observed. Valerate and butyrate modify glucose status with increasing gut microbial diversity.

Association of low-carbohydrate diet scores and type 2 diabetes in Chinese rural adults: The Henan Rural Cohort Study.

PURPOSE: To investigate the association between low-carbohydrate diet scores (LCDs) and the risk of type 2 diabetes in rural China. METHODS: A total of 38,100 adults were included in the Henan Rural Cohort Study. Macronutrient intake was assessed via a validated food-frequency questionnaire to create low-carbohydrate diet (LCD) scores. Multivariate logistic regression models and subgroup analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: After multivariable adjustment, participants with a high total low-carbohydrate diet score have a high risk of T2D (extreme-quartile OR = 1.23, 95% CI: 1.04-1.41; P = 0.007), whereas plant-based LCD score is not related to T2D risk. Among individuals with a BMI < 24 (extreme-quartile OR = 1.22, 95% CI: 1.01-1.47; P < 0.001) or high levels of physical activity (extreme-quartile OR = 1.42, 95% CI: 1.17-1.72; P < 0.001), the animal-based LCD score is positively correlated with the risk of T2D. CONCLUSION: Among Chinese rural populations, high-fat-low carbohydrate diet is associated with an increased risk of type 2 diabetes. High intake of animal protein and fat also increases T2D risk in those who are overweight or have high physical activity.

Association of the short-chain fatty acid levels and dietary quality with type 2 diabetes: a case-control study based on Henan Rural Cohort.

Evidence of the relationship between fecal short-chain fatty acids (SCFA) levels, dietary quality and type 2 diabetes mellitus (T2DM) in rural populations is limited. Here, we aimed to investigate the association between fecal SCFA levels and T2DM and the combined effects of dietar quality on T2DM in rural China. In total, 100 adults were included in the case-control study. Dietary quality was assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), and SCFA levels were analysed using the GC-MS system. Generalised linear regression was conducted to calculate the OR and 95 % CI to evaluate the effect of SCFA level and dietary quality on the risk of T2DM. Finally, an interaction was used to study the combined effect of SCFA levels and AHEI-2010 scores on T2DM. T2DM participants had lower levels of acetic and butyric acid. Generalised linear regression analysis revealed that the OR (95 % CI) of the highest acetic and butyric acid levels were 0·099 (0·022, 0·441) and 0·210 (0·057, 0·774), respectively, compared with the subjects with the lowest tertile of level. We also observed a significantly lower risk of T2DM with acetic acid levels > 1330·106 µg/g or butyric acid levels > 585·031 µg/g. Moreover, the risks of higher acetic and butyric acid levels of T2DM were 0·007 (95 % CI: 0·001, 0·148), 0·005 (95 % CI: 0·001, 0·120) compared with participants with lower AHEI-2010 scores (all P < 0·05). Acetate and butyrate levels may be important modifiable beneficial factors affecting T2DM in rural China. Improving dietary quality for body metabolism balance should be encouraged to promote good health.

Dietary Potassium and Magnesium Intake with Risk of Type 2 Diabetes Mellitus Among Rural China: the Henan Rural Cohort Study.

Previous studies exploring the relationship between dietary potassium and magnesium intake and the risk of type 2 diabetes mellitus (T2DM) have yielded inconsistent results and the lack evidence from rural China. Therefore, we aimed to investigate the association between dietary potassium and magnesium intake and the risk of T2DM in rural China. Data was collected from the Henan Rural Cohort Study in 2017. A validated semi-quantitative food frequency questionnaire assessed dietary potassium and magnesium intake. Logistic regression models were used to calculate odds ratio (ORs) and 95% confidence intervals (CIs) to evaluate the effect of dietary potassium, magnesium and the potassium-magnesium ratio on the risk of T2DM. A total of 38384 individuals were included in the study, and 3616 participants developed T2DM. Logistic regression analysis revealed that the OR (95% CI) of the highest versus dietary potassium and magnesium and potassium-magnesium ratio intakes were 0.67 (0.59, 0.75), 0.76 (0.67, 0.88), and 0.57 (0.50, 0.66), respectively, compared to the subjects with the lowest quartile of intakes. In addition, gender partially influences the relationship between dietary magnesium and T2DM prevalence (P-interaction = 0.042). The group with the highest dietary potassium and dietary magnesium intake had the lowest risk of T2DM, with an OR (95% CI) of 0.63 (0.51-0.77). Dietary potassium and magnesium intake are important modifiable risk factors for T2DM in rural China. Dietary potassium intake > 1.8g/day, dietary magnesium intake > 358.6mg/day and < 414.7mg/day and potassium-magnesium ratio >5.1 should be encouraged to prevent better and manage T2DM.

Genetic prediction of age at menarche, age at natural menopause and type 2 diabetes: A Mendelian randomization study.

BACKGROUND AND AIMS: The relationship between reproductive factors and type 2 diabetes (T2D) is controversial; therefore, we explored the causal relationship of age at menarche (AAM), age at natural menopause (ANM), with the risk of T2D and glycemic traits using two-sample Mendelian randomization. METHODS AND RESULTS: We used publicly available data at the summary level of genome-wide association studies, where AAM (N = 329,345), ANM (N = 69,360), T2D (N = 464,389). The inverse variance weighting (IVW) method was employed as the primary method. To demonstrate the robustness of the results, we also conducted various sensitivity analysis methods including the MR-Egger regression, the weighted median (WM) and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. After excluding IVs associated with confounders, we found a causal association between later AAM and reduced risk of T2D (OR 0.81 [95% CI 0.75, 0.87]; P = 2.20 × 10-8), lower levels of FI (ß -0.04 [95% CI -0.06, -0.01]; P = 2.19 × 10-3), FPG (ß -0.03 [95% CI -0.05, -0.007]; P = 9.67 × 10-5) and HOMA-IR (ß -0.04 [95% CI -0.06, -0.01]; P = 4,95 × 10-3). As for ANM, we only found a causal effect with HOMA-IR (ß -0.01 [95% CI -0.02, -0.005]; P = 1.77 × 10-3), but not with T2D. CONCLUSIONS: Our MR study showed a causal relationship between later AAM and lower risk of developing T2D, lower FI, FPG and HOMA-IR levels. This may provide new insights into the prevention of T2D in women.

Association of intestinal microbiota markers and dietary pattern in Chinese patients with type 2 diabetes: The Henan rural cohort study.

Studies on intestinal microbiota in Chinese type 2 diabetes mellitus (T2DM) patients are scarce and correlation studies with dietary intake are lacking. The case-control study included 150 participants (74 T2DM patients and 76 controls) and microbiome analysis was performed using 16S rDNA sequencing. Principal component analysis was used to determine dietary patterns and correlation analysis was used to evaluate the associations between microbiota diversity, T2DM indicators and dietary variables. Compared to controls, the T2DM group had different gut flora characteristics, including lower alpha diversity, higher Firmicutes/Bacteroidetes ratios, statistically significant beta diversity and other specific bacterial species differences. Gut microbiota was associated with several diabetes-related metabolic markers including HOMA2-ß, fasting plasma glucose, HbA1c and fasting insulin. Significant associations were also observed between dietary intake pattern and gut flora. The animal foods pattern scores were positively correlated with the relative abundance of the phylum Fusobacteria, and the vegetarian diet pattern scores were positively correlated with the relative abundance of the phylum Actinobacteria. Phylum Actinobacteria mediated the association of vegetarian diet pattern with fasting insulin and HOMA2-ß (all P < 0.05). Composition of intestinal microbiota in Chinese T2DM patients differs from that of control population, and the intestinal flora is affected by dietary intake while being associated with several diabetes-related metabolic markers. The gut microbiota may play an important role in linking dietary intake and the etiology of T2DM.

Extraction of Flavonoids from Scutellariae Radix using Ultrasound-Assisted Deep Eutectic Solvents and Evaluation of Their Anti-Inflammatory Activities.

Deep eutectic solvents (DESs) play important roles in the extraction of active constituents in traditional Chinese medicine. Ultrasound-assisted DES has been used to extract flavonoids from Scutellaria baicalensis. Using the contents of scutellarin, baicalin, baicalein, wogonoside, wogonin, and oroxylin A as quantitative indices, different kinds of DESs have been optimized for extraction and betaine/acetic acid has shown the highest yield. The Box-Behnken response surface method (RSM) was utilized to select the extraction conditions with the highest yields. The optimal extraction conditions were as follows: the molar ratio of betaine/acetic acid was 1:4, the water content was 40%, the solid/liquid ratio was 1:100 g/mL, the extraction temperature was 52 °C, and the extraction time was 23 min. Compared with traditional reflux extraction using 70% ethanol as the solvent, ultrasound-assisted DES has a shorter extraction time and higher yields. Furthermore, anti-inflammatory activities of the two extracts by ultrasound-assisted DES and reflux were compared using RAW264.7 cells and the methyl thiazolyl tetrazolium (MTT) method, and they showed equal anti-inflammatory activities. The results demonstrated that the ultrasound-assisted DES method for extraction of flavonoids from scutellariae radix is simple, green, efficient, and reproducible. This research provides good method guides for the rapid and efficient extraction of flavonoids from natural sources.