Editorial: Pharmacogenomics and pharmacomicrobiomics in type 2 diabetes mellitus (T2DM).
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ABSTRACT:
SUBMITTER: Luo JQ
PROVIDER: S-EPMC10545849 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
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Editorial: Pharmacogenomics and pharmacomicrobiomics in type 2 diabetes mellitus (T2DM).
Luo Jian-Quan JQ Shu Yan Y Zhang Wei W
Frontiers in endocrinology 20230918
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Project description:IntroductionMethylenetetrahydrofolate reductase (MTHFR) is essential in mediating folate metabolism, and thus plays an important role in diabetes and diabetic complications. MTHFR C677T (rs1801133 C>T) polymorphism has been proposed to be linked with type 2 diabetes mellitus (T2DM) susceptibility. However, the conclusions are inconsistent. Therefore, we rechecked their linkage aiming to obtain a more reliable estimation by performing an updated meta-analysis.MethodsWe searched electronic databases PubMed, EMBASE, CNKI, and Wanfang to obtain studies updated to October 2019.ResultsAfter carefully screening, we finally incorporated 68 studies with 10,812 cases and 8,745 controls. The genotype frequency of C677T polymorphism was analyzed pooled to generate odds ratios (ORs) and 95% confidence intervals (CIs). Pooled results presented that MTHFR C677T polymorphism was significantly associated with T2DM under homozygous (OR = 1.64, 95% CI = 1.39-1.94), heterozygous (OR = 1.38, 95% CI = 1.20-1.59), recessive (OR = 1.41, 95% CI = 1.23-1.61), dominant (OR = 1.47, 95% CI = 1.27-1.70), and allele (OR = 1.37, 95% CI = 1.23-1.52) genetic models. Stratified analysis demonstrated that C677T genotype was associated with T2DM in Asian populations, but not Caucasian and African populations.ConclusionOur results indicated that MTHFR C677T polymorphism confers to T2DM, especially in Asian populations. Much more large-scale case-control studies are needed to strengthen such conclusion in the future.
| S-EPMC6900375 | biostudies-literature
Project description:Advances in genotype technology in the last decade have put the pharmacogenomics revolution at the forefront of future medicine in clinical practice. Discovery of novel gene variations in drug transporters, drug targets, effector proteins and metabolizing enzymes in the form of single-nucleotide polymorphisms (SNPs) continue to provide insight into the biological phenomena that govern drug efficacy and toxicity. To date, novel gene discoveries extracted from genome-wide association scans and candidate gene studies in at least four antidiabetic drug classes have helped illuminate possible causes of interindividual variability in response. Inadequate protocol guidelines for pharmacogenomics studies often leads to poorly designed studies, making it hard to formulate a definitive conclusion regarding the clinical relevance of the information at hand. These issues, along with the ethical, social, political, legislative, technological, and economic challenges associated with pharmacogenomics have only delayed its entry to mainstream clinical practice. On the other hand, these issues are being actively pursued and rapid progress is being made in each area which assures the possibility of gaining widespread acceptance in clinical practice.
| S-EPMC3513204 | biostudies-literature
Project description:PurposeGenetic factors have a role in response to a target medication (personalized medicine). This study aimed to review available evidence about the relationship between gene variants and therapeutic response to sulfonylureas in type 2 diabetes, systematically.MethodsAn extensive search was done in Scopus, PubMed, and Web of Science with specific search strategy in the field from the beginning until the 1st of Jan. 2021. After sending records to endnote software and removing duplicate records remained documents were screened by title and abstract. Full texts of remained documents were assessed after removing un-related records. Required data was extracted from remained documents and records were categorized according to gene/SNP studied.ResultsFinally, 26 studies with 9170 T2DM patients with a mean age of 59.47 ± 6.67 (49.7-75.2 years) remained. The most contribution was from China, Slovakia and Greece, respectively and the most genes studied were CYP2C9, KCNJ11, and both KCNQ1 and ABCC8 with 10, 7, and 4 articles, respectively. Also, rs1799853 and rs1057910 (each with seven studies), rs5219 with six studies and CYP2C9*1(with four articles), respectively were the most common variants investigated. Studies about each gene obtained different positive or negative results and were not consistent.ConclusionConsidering heterogeneity between SFUs pharmacogenomic studies regarding the method, sample size, population, gene/variant studied, and outcome and findings, these studies are not conclusive and need further studies.
| S-EPMC9167353 | biostudies-literature
Project description:PurposeThe pancreatic islet specific microRNA-375 (miR-375) is overexpressed in type 2 diabetes mellitus (T2DM) patients suppressing the glucose-induced insulin secretion. Thus, miR-375 may serve as a biomarker for the early prediction of T2DM among high-risk individuals. We conducted this clinical study to assess the significance of miR-375 among type 2 diabetes mellitus (T2DM) patients and their first-degree relatives.Patients and methodsWe included 56 Han Chinese individuals (N: NGT = 21, T2DM = 10, FD-NGT =13 and FD-T2DM = 12) who received medical health check-ups from January 2018 to September 2018 at The Third Hospital of Yunnan Province, China. They were categorized as normal glucose tolerance (NGT), T2DM, first-degree relatives with normal glucose tolerance (FD-NGT) and first-degree relatives with T2DM (FD-T2DM). OGTT, C-peptide and Insulin tests were performed to confirm the diagnosis. The miR-375 levels were determined by Quantitative real-time RT-PCR (qRT-PCR).ResultsThe OGTT test showed a significant difference in T2DM and FD-T2DM groups compared with NGT and FD-NGT (p< 0.05). Similar results were observed during C-peptide and insulin tests. Interestingly, the 2-hour insulin test showed FD-NGT group having a significantly higher mean ± standard error of (64.240 ± 12.775) compared to NGT (28.836 ± 10.875). Assessment of miR-375 expression levels in 4 groups showed a significant up-regulation in T2DM and FD-T2DM compared with NGT and FD-NGT groups. A slight increase in miRNA expression was observed in FD-NGT compared with NGT group but was not statistically significant.ConclusionThe OGTT, C-peptide and insulin tests revealed a statistically significant difference in T2DM and FD-T2DM compared with NGT and FD-NGT groups. A significantly higher miR-375 expression was also observed in T2DM and FD-T2DM groups compared with NGT and FD-NGT and thus, miR-375 may serve as a stable biomarker for the early prediction of T2DM among high-risk individuals.
| S-EPMC8018570 | biostudies-literature
Project description:Objective: To analyze the factors associated with type 2 diabetes mellitus (T2DM) "remission" in non-bariatric Medicare patients 65 years and older. Research Design and Methods: A retrospective cohort analysis of a Medicare Advantage health plan was conducted using administrative data. An individual was identified as T2DM if the individual had: ≥ 2 medical claims for T2DM coded 250.xx excluding type 1 diabetes; or ≥ 2 pharmacy claims related to T2DM; or ≥ 2 combined medical claims, pharmacy claims for T2DM in 12 months. A T2DM individual was in "remission" if they had no T2DM related claims for more than 12 months continuously. This is different from the standard American Diabetes Association (ADA) definition of remission which includes HbA1c values and hence is represented in quotation (as "remission"). 10,059 T2DM individuals were evaluated over a period of 8 years from 2008 to 2015. Cox proportional hazards was used to identify significant variables associated with T2DM "remission." Results: 4.97% of patients studied met the definition of T2DM "remission" in the study cohort. After adjusting for covariates this study found a number of variables associated with T2DM "remission" that were not previously reported: no statin use; low diabetes complications severity index score; no hypertension; no neuropathy; no retinopathy; race (non-white and non-African American); presence of other chronic ischemic heart disease (IHD) and females (p < 0.05). Conclusion: T2DM "remission" in Medicare patients 65 years and older is observed in a community setting in a small proportion of non-bariatric patients.
| S-EPMC6473045 | biostudies-literature
Project description:BackgroundFinger prick blood glucose (BG) monitoring remains a mainstay of management in people with type 2 diabetes (T2DM) who take sulphonylurea (SU) drugs or insulin. We recently examined patient experience of BG monitoring in people with type 1 diabetes (T1DM). There has not been any recent comprehensive assessment of the performance of BG monitoring strips or the patient experience of BG strips in people with T2DM in the UK.MethodsAn online self-reported questionnaire containing 44 questions, prepared following consultation with clinicians and patients, was circulated to people with T2DM. 186 responders provided completed responses (25.5% return rate). Fixed responses were coded numerically (eg not confident = 0 fairly confident = 1).ResultsOf responders, 84% were treated with insulin in addition to other agents. 75% reported having had an HbA1c check in the previous 6 months. For those with reported HbA1c ≥ 65 mmol/mol, a majority of people (70%) were concerned or really concerned about the shorter term consequences of running a high HbA1c This contrasted with those who did not know their recent HbA1c, of whom only 33% were concerned/really concerned and those with HbA1c <65 mmol/mol of whom 35% were concerned. Regarding BG monitoring/insulin adjustment, only 25% of responders reported having sufficient information with 13% believing that the accuracy and precision of their BG metre was being independently checked. Only 9% recalled discussing BG metre accuracy when their latest metre was provided and only 7% were aware of the International Standardisation Organisation (ISO) standards for BG metres. 77% did not recall discussing BG metre performance with a healthcare professional.ConclusionThe group surveyed comprised engaged people with T2DM but even within this group there was significant variation in (a) awareness of shorter term risks, (b) confidence in their ability to implement appropriate insulin dosage (c) awareness of the limitations of BG monitoring technology. There is clearly an area where changes in education/support would benefit many.
| S-EPMC8917860 | biostudies-literature
Project description:BackgroundVarious studies suggest a comorbid association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) indicating that there could be shared underlying pathophysiological mechanisms.ObjectiveThis study aims to systematically model relevant knowledge at the molecular level to find a mechanistic rationale explaining the existing comorbid association between AD and T2DM.MethodWe have used a knowledge-based modeling approach to build two network models for AD and T2DM using Biological Expression Language (BEL), which is capable of capturing and representing causal and correlative relationships at both molecular and clinical levels from various knowledge resources.ResultsUsing comparative analysis, we have identified several putative "shared pathways". We demonstrate, at a mechanistic level, how the insulin signaling pathway is related to other significant AD pathways such as the neurotrophin signaling pathway, PI3K/AKT signaling, MTOR signaling, and MAPK signaling and how these pathways do cross-talk with each other both in AD and T2DM. In addition, we present a mechanistic hypothesis that explains both favorable and adverse effects of the anti-diabetic drug metformin in AD.ConclusionThe two computable models introduced here provide a powerful framework to identify plausible mechanistic links shared between AD and T2DM and thereby identify targeted pathways for new therapeutics. Our approach can also be used to provide mechanistic answers to the question of why some T2DM treatments seem to increase the risk of AD.
| S-EPMC5611890 | biostudies-literature
Project description:Type 2 Diabetes Mellitus (T2DM) is a complicated multifactorial illness involving hereditary and external environmental variables. The symptoms typically appear gradually over a number of years without realizing it. This viewpoint is further supported by the Ayurvedic constitution concept (Prakriti). Prakriti explains the biological variability that is observed in different individuals. This study was conducted a retrospective investigation to examine if there was a link between type 2 diabetes and an individual's constitution based on anthropometric and biochemical characteristics. Physical and mental characteristics and anthropometric and biochemical markers were used to determine reported cases' prevailing Dosha Prakriti (constitution). Based on biochemical and anthropometric data, significant differences in Prakriti were found between the case (T2DM patients) and control (person without diabetes) groups. The incidence of numerous secondary problems linked with T2DM patients was also evaluated according to their Prakriti types, which revealed a positive relationship. The three primary contributing parameters, such as waist-hip ratio, postprandial blood sugar, and serum creatinine, were correctly classified all person with or without diabetes subjects to 90.6% of the time, whereas the constitution-wise study classified person with diabetes and without diabetes individuals of Pitta and Kapha Prakriti to 94.3% and 90%, respectively. A discriminant function was created to predict a person with diabetes and without diabetes based on these three contributing factors. The primary contributing biochemical parameters discovered by Prakriti in the current study could be used as a biochemical disease diagnostic for predicting type 2 diabetes susceptibility.
| S-EPMC8947277 | biostudies-literature
Project description:BackgroundGlobally, type 2 diabetes mellitus (T2DM) is one of the fastest-growing noncommunicable multifactorial and polygenic diseases, which leads to many health complications and significant morbidity and mortality. South Asians have a high genetic predisposition to T2DM, with India being home to one in six diabetics. This study investigates the association of selected genetic polymorphisms with T2DM risk and develops a polygenic risk score (PRS).MethodsA case-control study recruited fully consented participants from a population of Jat Sikhs in north India. DNA samples were genotyped for a range of polymorphisms and odds ratios were calculated under several genetic association models. Receiver operating characteristic (ROC) curves were produced for combinations of the PRS and clinical parameters.ResultsThe GSTT1(rs17856199), GSTM1(rs366631), GSTP1(rs1695), KCNQ1(rs2237892), ACE(rs4646994), and TCF7L2(rs12255372; rs7903146; rs7901695) polymorphisms were associated with increased T2DM risk (p ≤ 0.05). No association was observed with IGF2BP2(rs4402960) or PPARG2(rs1801282). The weighted PRS was found to be significantly higher in patients (mean = 15.4, SD = 3.24) than controls (mean = 11.9, SD = 3.06), and t(454) = -12.2 (p < 0.001). The ROC curve analysis found the weighted PRS in combination with clinical variables to be the most effective predictor of T2DM (area under the curve = 0.844, 95%CI = 0.0.808-0.879).ConclusionsSeveral polymorphisms were associated with T2DM risk. PRS based on even a limited number of loci improves the prediction of the disease. This may provide a useful method for determining T2DM susceptibility for clinical and public health applications.
| S-EPMC9959290 | biostudies-literature
Project description:IntroductionMicroRNAs (miRNAs) have been shown to be altered in both CVD and T2DM and can have an application as diagnostic and prognostic biomarkers. miRNAs are released into circulation when the cardiomyocyte is subjected to injury and damage.ObjectivesMeasuring circulating miRNA levels in human plasma may be of great potential use for measuring the extent of damage to cardiomyocytes and response to exercise. This review is aimed to highlight the potential application of miRNAs as biomarkers of CVD progression in T2DM, and the impact of exercise on recovery.MethodsThe review aims to examine whether the health improvements following exercise in T2DM patients are reflective of changes in expression of plasma miRNAs. For this purpose, studies were identified from the literature that have established a correlation between diabetes, disease progression and plasma miRNA levels. We also reviewed studies which looked at the effect of exercise on plasma miRNA levels.ResultsThe review identified miRNA signatures that are affected by T2DM and DHD and a subset of these miRNAs that are also affected by different types of exercise. This approach helped us to identify those miRNAs whose expression and function can be altered by regular bouts of exercise.ConclusionsmiRNAs identified as part of this review can serve as tools to monitor the cardio-protective, anti-inflammatory and metabolic effects of exercise in people suffering from T2DM. Future research should focus on regulation of these miRNAs in T2DM and how they can be altered by appropriate exercise interventions.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-022-01066-4.
| S-EPMC9261151 | biostudies-literature