scholarly journals Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes

2021 ◽  
Vol 22 (23) ◽  
pp. 12846
Author(s):  
Lixiang Zhai ◽  
Jiayan Wu ◽  
Yan Y. Lam ◽  
Hiu Yee Kwan ◽  
Zhao-xiang Bian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Gut Microbiota ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites ◽  
High Blood Glucose ◽  
Gaseous Products ◽  
Glucose Levels ◽  
Novel Therapeutic Strategies

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.

scholarly journals A High Level of Circulating Valine Is a Biomarker for Type 2 Diabetes and Associated with the Hypoglycemic Effect of Sitagliptin

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaoyu Liao ◽  
Bingyao Liu ◽  
Hua Qu ◽  
LinLin Zhang ◽  
Yongling Lu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Aromatic Amino Acids ◽  
Gas Chromatography Mass Spectrometry ◽  
Glucose Levels ◽  
Increased Risk ◽  
Normal Glucose ◽  
Potential Strategy ◽  
High Level

Background. High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Methods. Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n=19), newly diagnosed T2D (n=20), placebo-treated T2D (n=7), or Sit-treated T2D (n=7). Biochemical parameters were also assessed in all participants. Results. Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p<0.05). Correlation analysis showed that the plasma valine concentration was positively correlated with the level of fasting plasma glucose (p<0.05). Moreover, the plasma valine concentrations were notably reduced after Sit treatment in T2D patients (p<0.05). Conclusions. Our findings demonstrate an important effect of Sit on the BCAA valine in T2D patients and HFD-fed mice, revealing a new hypoglycemic mechanism of it. Furthermore, the results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy.

Sitagliptin: A DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

2011 ◽  
Vol 3 ◽  
pp. CMT.S6227 ◽  
Author(s):  
Kathryn MS Johnson ◽  
Kathleen Schurr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetes Therapy ◽  
High Blood Glucose ◽  
Adverse Side Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) has become an epidemic, with worldwide projections indicating that more than 336 million people will be afflicted with the disease by 2030. T2DM is characterized by inappropriately high blood glucose levels due to a deficiency in insulin secretion, action, or both. Despite the horrific complications that occur with chronic elevations of blood glucose levels, less than half of those with T2DM do not maintain proper glycemic control. Sitagliptin (Januvia, Merck and Co., Whitehouse Station, New Jersey) is a novel diabetes therapy approved for use in the U.S. and Europe. This small molecule inhibits the activity of DPP-4, a peptidase that degrades the glucoregulatory hormone GLP-1. Sitagliptin increases glucoregulation in individuals with T2DM both as a monotherapy and in combination with other antihyperglycemic drugs, with a low risk of adverse side effects.

scholarly journals Berberine alleviates type 2 diabetic symptoms by altering gut microbiota and reducing aromatic amino acids

2020 ◽  
Vol 131 ◽  
pp. 110669
Author(s):  
Ye Yao ◽  
Han Chen ◽  
Lijing Yan ◽  
Wenbo Wang ◽  
Dongsheng Wang
Keyword(s):  
Amino Acids ◽  
Gut Microbiota ◽  
Aromatic Amino Acids ◽  
Type 2 Diabetic

scholarly journals Type-2-diabetes Alters CSF but not Plasma Metabolomic and AD Risk Profiles in Vervet Monkeys

2019 ◽  
Author(s):  
Kylie Kavanagh ◽  
Stephen M. Day ◽  
Morgan C. Pait ◽  
William R. Mortiz ◽  
Christopher B. Newgard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Cerebral Metabolism ◽  
Vervet Monkeys ◽  
Plasma Lactate ◽  
Glucose Levels ◽  
Highly Correlated ◽  
Lactate Levels ◽  
The Brain

AbstractEpidemiological studies suggest that individuals with type 2 diabetes (T2D) have a 2-4 fold increased risk for developing Alzheimer’s disease (AD), however the exact mechanisms linking the two disease is unknown. In both conditions, the majority of pathophysiological changes (including glucose and insulin dysregulation, insulin resistance, and AD-related changes in Aβ and tau) occur decades before the onset of clinical symptoms and diagnosis. In this study, we investigated the relationship between metabolic biomarkers associated with T2D and AD-related pathology, including Aβ levels, from cerebrospinal fluid (CSF) and fasting plasma of healthy, prediabetic (PreD), and T2D vervet monkeys (Chlorocebus aethiops sabeus). Consistent with the human disease, T2D monkeys have increased plasma and CSF glucose levels as they transition from normoglycemia to pre-diabetic and diabetic states. Although plasma levels of acylcarnitines and amino acids remained largely unchanged, peripheral hyperglycemia correlated with decreased CSF acylcarnitines and CSF amino acids, including branched chain amino acid (BCAA) concentrations, suggesting profound changes in cerebral metabolism coincident with systemic glucose dysregulation. Moreover, CSF Aβ40 and CSF Aβ42 levels decreased in T2D monkeys, a phenomenon observed in the human course of AD which coincides with increased amyloid deposition within the brain. In agreement with our previous studies in mice, CSF Aβ40 and CSF Aβ42 were highly correlated with CSF glucose levels, suggesting that glucose levels in the brain are associated with changes in Aβ metabolism. Interestingly, CSF Aβ40 and CSF Aβ42 levels were also highly correlated with plasma but not CSF lactate levels, suggesting that plasma lactate might serve as a potential biomarker of disease progression in AD. Moreover, CSF glucose and plasma lactate levels were correlated with CSF amino acid and acylcarnitine levels, demonstrating alterations in cerebral metabolism occurring with the onset of T2D. Together, these data suggest that peripheral metabolic changes associated with the development of T2D produce alterations in brain metabolism that lead to early changes in the amyloid cascade, similar to those observed in pre-symptomatic AD.

scholarly journals A Fermented Food Product Containing Lactic Acid Bacteria Protects ZDF Rats from the Development of Type 2 Diabetes

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2530 ◽  
Author(s):  
Miriam Cabello-Olmo ◽  
Maria Oneca ◽  
Paloma Torre ◽  
Neira Sainz ◽  
María J. Moreno-Aliaga ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Fasting Blood Glucose ◽  
Food Product ◽  
Tolerance Test ◽  
Glucose Absorption ◽  
Fermented Food ◽  
Glucose Levels ◽  
Zdf Rats

Type 2 diabetes (T2D) is a complex metabolic disease, which involves a maintained hyperglycemia due to the development of an insulin resistance process. Among multiple risk factors, host intestinal microbiota has received increasing attention in T2D etiology and progression. In the present study, we have explored the effect of long-term supplementation with a non-dairy fermented food product (FFP) in Zucker Diabetic and Fatty (ZDF) rats T2D model. The supplementation with FFP induced an improvement in glucose homeostasis according to the results obtained from fasting blood glucose levels, glucose tolerance test, and pancreatic function. Importantly, a significantly reduced intestinal glucose absorption was found in the FFP-treated rats. Supplemented animals also showed a greater survival suggesting a better health status as a result of the FFP intake. Some dissimilarities have been observed in the gut microbiota population between control and FFP-treated rats, and interestingly a tendency for better cardiometabolic markers values was appreciated in this group. However, no significant differences were observed in body weight, body composition, or food intake between groups. These findings suggest that FFP induced gut microbiota modifications in ZDF rats that improved glucose metabolism and protected from T2D development.

scholarly journals Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM)

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3719
Author(s):  
Daniela Maria Tanase ◽  
Evelina Maria Gosav ◽  
Ecaterina Neculae ◽  
Claudia Florida Costea ◽  
Manuela Ciocoiu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Microvascular Complications ◽  
Aromatic Amino Acids ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Inflammatory Status ◽  
New Findings

Type 2 diabetes mellitus (T2DM) remains one of the most problematic and economic consumer disorders worldwide, with growing prevalence and incidence. Over the last years, substantial research has highlighted the intricate relationship among gut microbiota, dysbiosis and metabolic syndromes development. Changes in the gut microbiome composition lead to an imbalanced gastrointestinal habitat which promotes abnormal production of metabolites, inflammatory status, glucose metabolism alteration and even insulin resistance (IR). Short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide, aromatic amino acids and their affiliated metabolites, contribute to T2DM via different metabolic and immunologic pathways. In this narrative review, we discuss the immunopathogenic mechanism behind gut dysbiosis, T2DM development and the major known diabetic microvascular complications (retinopathy, neuropathy and nephropathy), the beneficial use of pre- and pro-biotics and fecal microbiota transplantation in T2DM management and new findings and future perspectives in this field.

scholarly journals Metabolomic analysis of obesity, metabolic syndrome, and type 2 diabetes: amino acid and acylcarnitine levels change along a spectrum of metabolic wellness

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5410 ◽  
Author(s):  
Diane M. Libert ◽  
Amy S. Nowacki ◽  
Marvin R. Natowicz
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Amino Acids ◽  
Cluster Analysis ◽  
Amino Acid ◽  
Statistical Significance ◽  
Aromatic Amino Acids ◽  
Large Neutral Amino Acid ◽  
Metabolomic Analysis

Background Metabolic syndrome (MS) is a construct used to separate “healthy” from “unhealthy” obese patients, and is a major risk factor for type 2 diabetes (T2D) and cardiovascular disease. There is controversy over whether obese “metabolically well” persons have a higher morbidity and mortality than lean counterparts, suggesting that MS criteria do not completely describe physiologic risk factors or consequences of obesity. We hypothesized that metabolomic analysis of plasma would distinguish obese individuals with and without MS and T2D along a spectrum of obesity-associated metabolic derangements, supporting metabolomic analysis as a tool for a more detailed assessment of metabolic wellness than currently used MS criteria. Methods Fasting plasma samples from 90 adults were assigned to groups based on BMI and ATP III criteria for MS: (1) lean metabolically well (LMW; n = 24); (2) obese metabolically well (OBMW; n = 26); (3) obese metabolically unwell (OBMUW; n = 20); and (4) obese metabolically unwell with T2D (OBDM; n = 20). Forty-one amino acids/dipeptides, 33 acylcarnitines and 21 ratios were measured. Obesity and T2D effects were analyzed by Wilcoxon rank-sum tests comparing obese nondiabetics vs LMW, and OBDM vs nondiabetics, respectively. Metabolic unwellness was analyzed by Jonckheere-Terpstra trend tests, assuming worsening health from LMW → OBMW → OBMUW. To adjust for multiple comparisons, statistical significance was set at p < 0.005. K-means cluster analysis of aggregated amino acid and acylcarnitine data was also performed. Results Analytes and ratios significantly increasing in obesity, T2D, and with worsening health include: branched-chain amino acids (BCAAs), cystine, alpha-aminoadipic acid, phenylalanine, leucine + lysine, and short-chain acylcarnitines/total carnitines. Tyrosine, alanine and propionylcarnitine increase with obesity and metabolic unwellness. Asparagine and the tryptophan/large neutral amino acid ratio decrease with T2D and metabolic unwellness. Malonylcarnitine decreases in obesity and 3-OHbutyrylcarnitine increases in T2D; neither correlates with unwellness. Cluster analysis did not separate subjects into discreet groups based on metabolic wellness. Discussion Levels of 15 species and metabolite ratios trend significantly with worsening metabolic health; some are newly recognized. BCAAs, aromatic amino acids, lysine, and its metabolite, alpha-aminoadipate, increase with worsening health. The lysine pathway is distinct from BCAA metabolism, indicating that biochemical derangements associated with MS involve pathways besides those affected by BCAAs. Even those considered “obese, metabolically well” had metabolite levels which significantly trended towards those found in obese diabetics. Overall, this analysis yields a more granular view of metabolic wellness than the sole use of cardiometabolic MS parameters. This, in turn, suggests the possible utility of plasma metabolomic analysis for research and public health applications.

scholarly journals Parental History of Type 2 Diabetes Mellitus: A Lurking Genetic Threat

2020 ◽  
pp. 66-75
Author(s):  
Sheh Zano ◽  
Zil-a- Rubab ◽  
Saeeda Baig ◽  
Burhanuddin Tahir
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Parental History ◽  
High Blood Glucose ◽  
Association Analyses ◽  
Glucose Levels ◽  
Current Prevalence ◽  
History Of

Type-2 Diabetes Mellitus (T2DM) is presently the fastest growing disease and has been recognized to be caused by a collision between inherited parental genes and the environment. The current prevalence in Pakistan of type-2 diabetes mellitus is 26.3%. Out of them 19.2% had disease two to three decades back while 7.1% are recently diagnosed cases. Worldwide burden of disease was 415 million in 2015 and this number will increase to 642 million by 2040. Parental history of diabetes mellitus is a chief reason for the development of T2DM in children, but whether this association derives from shared genetic or environmental factors is unclear. Persistent high blood glucose levels can result in drastic outcomes like Diabetic Ketoacidosis and Hyperosmolar non ketotic syndrome. Genome-wide association analyses have uncovered multiple genomic regions associated with T2DM, but identification of the causal variants remains a challenge. This review will discuss the approach of diagnosing T2DM by analyzing the association of gene variants and family history.

scholarly journals Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
M. Nazmul Huda ◽  
Myungsuk Kim ◽  
Brian J. Bennett
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Disease Status ◽  
Short Chain Fatty Acids ◽  
Host Cells ◽  
Low Grade ◽  
Microbial Metabolites ◽  
Microbial Composition

Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.

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