Reductions in Intestinal Taurine-Conjugated Bile Acids and Short-Chain Fatty Acid-Producing Bacteria Might be Novel Mechanisms of Type 2 Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats

Author(s):  
Xiaoyun Yang ◽  
Wenhui Jiang ◽  
Jingli Cheng ◽  
Jintong Hao ◽  
Fei Han ◽  
...  

Abstract Background The pathogenesis of spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, among the best models for human type 2 diabetes mellitus (T2DM), remains poorly defined. Therefore, we investigated the dynamic changes in taurine-conjugated bile acids (T-BAs) and intestinal microbiota during T2DM development in OLETF rats. Methods OLETF rats and corresponding diabetes-resistant Long Evans Tokushima Otsuka (LETO) rats were fed a normal baseline diet. The progress of T2DM was divided into four phases, including normal glycemia-normal insulinemia (baseline), normal glycemia-hyperinsulinemia, impaired glucose tolerance, and DM. Body weight, liver function, blood lipids, fasting plasma glucose, fasting plasma insulin, fasting plasma glucagon-like peptide (GLP)-1 and GLP-2, serum and fecal T-BAs, and gut microbiota were analyzed during the entire course of T2DM development. Results There were reductions in fecal T-BAs and short-chain fatty acids (SCFAs)-producing bacteria including Phascolarctobacterium and Lactobacillus in OLETF rats compared with those in LETO rats at baseline, and low levels of fecal T-BAs and SCFAs-producing bacteria were maintained throughout the whole course of the development of T2DM among OLETF rats compared with those in corresponding age-matched LETO rats. Fecal taurine-conjugated chenodeoxycholic acid correlated positively with Phascolarctobacterium. Fecal taurine-conjugated deoxycholic acid correlated positively with Lactobacillus and fasting plasma GLP-1 and inversely with fasting plasma glucose. Conclusion The fecal BAs profiles and microbiota structure among OLETF rats were different from those of LETO rats during the entire course of T2DM development, indicating that reductions in intestinal T-BAs and specific SCFA-producing bacteria may be potential mechanisms of T2DM in OLETF rats.

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e041269
Author(s):  
Tullaya Sitasuwan ◽  
Raweewan Lertwattanarak

ObjectivesAbout 11%–30% of individuals with impaired fasting plasma glucose (IFG) have type 2 diabetes mellitus (T2DM), diagnosed by the 75 g oral glucose tolerance test (75 g OGTT). This study investigated (1) the prevalence and cut-off levels for fasting plasma glucose (FPG) and glycated haemoglobin A1c (HbA1c) in IFG individuals that most effectively predict the presence of T2DM diagnosed by a 75 g OGTT; (2) the predictors associated with T2DM; and (3) the pathophysiological characteristics of patients with IFG.Materials and methodsA single-centre, cross-sectional study was conducted in a primary care setting. A standard 75 g OGTT was performed on 123 subjects with IFG. Their beta-cell function and insulin resistance were calculated through plasma glucose and insulin levels monitored during the 75 g OGTT.ResultsIn the IFG subjects, the prevalence of T2DM using the 2-hour postload plasma glucose (2hPG) criterion was 28.5%. Pre-diabetes and normal glucose metabolism were found in 48.7% and 22.8%, respectively, by 75 g OGTT. An HbA1c level ≥6.0% or FPG ≥5.9 mmol/L were the optimal cut-off thresholds for the prediction of the presence of T2DM. HbA1c had a sensitivity of 76.7% and specificity of 55.7% (95% CI 57.7% to 90.1% and 95% CI 43.3% to 67.6%, respectively), while FPG had a sensitivity of 85.7% and specificity of 23.9% (95% CI 69.7% to 95.2% and 95% CI 15.4% to 34.1%, respectively). The presence of metabolic syndrome, a higher HbA1c and higher FPG levels were associated with the risk of T2DM in the Thai IFG population.ConclusionsAlmost one-third of the people with IFG had T2DM diagnosed by the 2hPG criterion. HbA1c was more effective than FPG in predicting the presence of T2DM in the IFG subjects. IFG individuals with HbA1c≥6.0% or FPG≥5.9 mmol/L should be advised to undergo a 75 g OGTT to detect T2DM earlier than otherwise.


Author(s):  
Mukul Sharma ◽  
Kapil Bhatia ◽  
Pratibha Misra ◽  
Sibin MK ◽  
Vivek N Ambade ◽  
...  

Introduction: Diabetes mellitus (DM) is a metabolic disorder occurring due to either defect in the secretion of insulin or defect in the action of insulin characterized by hyperglycemia. Hyperglycemia causes oxidative stress due to increased production of mitochondrial Reactive oxygen species (ROS) in T2DM. Ceruloplasmin (Cp) acts as an antioxidant through its ferroxidase activity. There is an association between the raised serum Cp levels and elevated plasma glucose levels in Type-2 Diabetes mellitus (T2DM) patients. Aim and objectives: The aim of this study is to evaluate the correlation between the fasting plasma glucose (FPG), 2hour plasma glucose (2hPG), and serum Cp level in T2DM patients as compared to non diabetics. Materials and methods: 165 cases of T2DM were recruited along with the 40 healthy age and sex matched controls. The blood samples were analyzed for serum Cp and FPG and 2hPG after 75-gram oral glucose. Results: The serum Cp levels of the patient group with T2DM were significantly higher than the control group (p = 0.000). There was a significant positive association between serum Cp level and 2hPG level of the patient population (r = 0.283, p = 0.000), but there was no significant correlation found between serum Cp levels and fasting plasma glucose levels in patients (r = 0.146, p =0.061). Similar findings were seen in the sub group analysis. Conclusion: Our study concludes a significant positive correlation between serum Cp and 2hPG levels in T2DM patients. Hence Cp levels may be considered as a part of the routine diagnostic panel to assess diabetes mellitus. Keywords: Serum Ceruloplasmin, Type-2 Diabetes Mellitus, Fasting plasma glucose, 2hour plasma glucose


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