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The Mechanism of Metabolic Influences on the Endogenous GLP-1 by Oral Antidiabetic Medications in Type 2 Diabetes Mellitus.

ABSTRACT: Incretin-based therapy is now a prevalent treatment option for patients with type 2 diabetes mellitus (T2DM). It has been associated with considerably good results in the management of hyperglycemia with cardiac or nephron-benefits. For this reason, it is recommended for individuals with cardiovascular diseases in many clinical guidelines. As an incretin hormone, glucagon-like peptide-1 (GLP-1) possesses multiple metabolic benefits such as optimizing energy usage, maintaining body weight, ? cell preservation, and suppressing neurodegeneration. However, recent studies indicate that oral antidiabetic medications interact with endogenous or exogenous GLP-1. Since these drugs are transported to distal intestine portions, there are concerns whether these oral drugs directly stimulate intestinal L cells which release GLP-1, or whether they do so via indirect inhibition of the activity of dipeptidyl peptidase-IV (DPP-IV). In this review, we discuss the metabolic relationships between oral antihyperglycemic drugs from the aspect of gut, microbiota, hormones, ? cell function, central nervous system, and other cellular mechanisms.

SUBMITTER: Nguyen T

PROVIDER: S-EPMC7320283 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Mechanism of Metabolic Influences on the Endogenous GLP-1 by Oral Antidiabetic Medications in Type 2 Diabetes Mellitus.

Nguyen Thiquynhnga T Gong Min M Wen Song S Yuan Xinlu X Wang Chaoxun C Jin Jianlan J Zhou Ligang L

Journal of diabetes research 20200616

Incretin-based therapy is now a prevalent treatment option for patients with type 2 diabetes mellitus (T2DM). It has been associated with considerably good results in the management of hyperglycemia with cardiac or nephron-benefits. For this reason, it is recommended for individuals with cardiovascular diseases in many clinical guidelines. As an incretin hormone, glucagon-like peptide-1 (GLP-1) possesses multiple metabolic benefits such as optimizing energy usage, maintaining body weight, <i>β</ ...[more]

PMID: 32656265

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Project description:INTRODUCTION:Targeting better glycated hemoglobin (HbA1c) and blood pressure (BP) goals may endanger older adults with type 2 diabetes mellitus (T2DM). Overtreatment of T2DM and hypertension is a trending issue, although undertreatment is still common. We investigated the rates and predictors of overtreatment and undertreatment of glycemia and BP in older adults with T2DM and physicians' attitudes to deintensify or intensify treatment. METHODS:Data from older adults (≥ 65 years) enrolled in a large nationwide T2DM survey in 2017 across Turkey were analyzed. Overtreatment of glycemia was defined as HbA1c < 6.5% plus the use of ≥ 2 oral antihyperglycemics or insulin, and BP overtreatment was defined as systolic BP (SBP) < 120 mmHg or diastolic BP (DBP) < 65 mmHg plus the use of ≥ 2 drugs. Undertreatment of glycemia was defined as HbA1c > 9%, and BP undertreatment was defined as SBP > 150 mmHg or DBP > 90 mmHg. Deintensification or intensification rates were calculated according to treatment modification initiated by the treating physician(s). RESULTS:The rate of overtreatment in the glycemia group (n = 1264) was 9.8% (n = 124) and that in the BP group (n = 1052) was 7.3% (n = 77), whereas the rate of undertreatment was 14.2% (n = 180) and 15.2% (n = 160), respectively. In the adjusted model, use of oral secretagogues (sulfonylureas or glinides) (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.2-3.1) and follow-up at a private clinic (OR 1.81, 95% CI 1.0-3.3) were predictors of glycemia overtreatment. BP overtreatment was independently associated with the use insulin-based diabetes therapies (OR 1.86, 95% CI 1.14-3.04). There was no independent association of BP undertreatment to the study confounders. The deintensification and intensification rates were 25 and 75.6%, respectively, for glycemia and 10.9 and 9.2%, respectively, for BP. CONCLUSIONS:The results show that one in ten older adults with T2DM are overtreated while one in four require modification of their current antihyperglycemic and antihypertensive treatments. Physicians are eager to intensify medications while they largely ignore deintensification in diabetes management. These results warrant enforced measures to improve the care of older adults with T2DM. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT03455101.

Project description:IntroductionTwo studies were carried out to investigate the efficacy and safety of luseogliflozin added to existing oral antidiabetic drugs (OADs) in Japanese type 2 diabetic patients inadequately controlled with OAD monotherapy.Materials and methodsIn the trial involving add-on to sulfonylureas (study 03-1), patients were randomly assigned to receive luseogliflozin 2.5 mg or a placebo for a 24-week double-blind period, followed by a 28-week open-label period. In the open-label trial involving add-on to other OADs; that is, biguanides, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, glinides and ?-glucosidase inhibitors (study 03-2), patients received luseogliflozin for 52 weeks.ResultsIn study 03-1, luseogliflozin significantly decreased glycated hemoglobin at the end of the 24-week double-blind period compared with the placebo (-0.88%, P < 0.001), and glycated hemoglobin reduction from baseline at week 52 was -0.63%. In study 03-2, luseogliflozin added to other OADs significantly decreased glycated hemoglobin from baseline at week 52 (-0.52 to -0.68%, P < 0.001 for all OADs). Bodyweight reduction was observed in all add-on therapies, even with agents associated with weight gain, such as sulfonylureas and thiazolidinediones. Most adverse events were mild in severity. When added to a sulfonylurea, incidences of hypoglycemia during the double-blind period were 8.7% and 4.2% for luseogliflozin and placebo, respectively, but no major hypoglycemic episodes occurred. The frequency and incidences of adverse events of special interest for sodium glucose cotransporter 2 inhibitors and adverse events associated with combined OADs were acceptable.ConclusionsAdd-on therapies of luseogliflozin to existing OADs improved glycemic control, reduced bodyweight and were well tolerated in Japanese type 2 diabetic patients. These trials were registered with the Japan Pharmaceutical Information Center (add on to sulfonylurea: JapicCTI-111507; add on to other OADs: JapicCTI-111508).

Project description:BackgroundType 1 diabetes mellitus (T1DM), an autoimmune disease with a genetic tendency, has an increasing prevalence. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in disease pathogenesis. However, their roles in T1DM are poorly understood. The present study aimed at identifying signature lncRNAs and circRNAs and investigating their roles in T1DM using the competing endogenous RNA (ceRNA) network analysis.MethodsThe T1DM expression profile was downloaded from Gene Expression Omnibus (GEO) database to identify the differentially expressed circRNAs, lncRNAs, and mRNAs. The biological functions of these differentially expressed circRNAs, lncRNAs, and mRNAs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Targeting relationships of circRNA-miRNA, lncRNA-miRNA, and miRNA-mRNA were predicted, and the circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network was established. Finally, qRT-PCR was applied to identify the effect of hsa_circ_0002202 inhibition on the IFN-I induced macrophage inflammation.ResultsA total of 178 circRNAs, 404 lncRNAs, and 73 mRNAs were identified to be abnormally expressed in T1DM samples. Functional enrichment analysis results indicated that the differentially expressed genes were mainly enriched in extracellular matrix components and macrophage activation. CeRNA regulatory network showed that circRNAs and lncRNAs regulate mRNAs through integrate multiple miRNAs. In addition, in vitro experiments showed that hsa_circ_0002202 inhibition suppressed the type I interferon (IFN-I)-induced macrophage inflammation.ConclusionIn the present study, the circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network in T1DM was established for the first time. We also found that hsa_circ_0002202 inhibition suppressed the IFN-I-induced macrophage inflammation. Our study may lay a foundation for future studies on the ceRNA regulatory network in T1DM.

Project description:BackgroundMaternal gestational diabetes mellitus (GDM) had long-term influences on the health of their children. However, the influences of GDM on the oral microbiota, which was closely related to oral and systemic health in offspring, were less documented. The present study aimed to explore the oral microbiota of neonates born to mothers with GDM is differentially colonized compared with those born to mothers without GDM, and whether any such differences persist to 1 month of age.MethodsOral samples were collected from children of mothers with (n = 20) and without GDM (n = 34) at birth and again at an average age of 1 month. The oral microbiota was characterized by 16S rRNA sequencing (V3-V4). Differences in diversity and composition according to maternal GDM status were assessed, and different metabolic functional pathways and microbial ecological networks were also analyzed.ResultsAlthough no significant differences were observed in diversity metrics between GDM and non-GDM groups (P > 0.05), we found significant differences in the taxonomic composition of oral microbiota from phylum to genus level between the two groups, with the GDM group exhibiting less abundance of Veillonella in both "Day 1" (P < 0.001) and "Day 30" (P < 0.05) phases. Metabolic pathways analysis showed that 5-aminoimidazole ribonucleotide biosynthesis and inosine-5'-phosphate biosynthesis were enriched in GDM subjects in the "Day 30" phase. Moreover, ecological network analysis revealed apparent differences between GDM and control groups, with the non-GDM group containing more high-degree nodes and microbial interactions compared with the GDM group.ConclusionMaternal GDM was associated with an altered oral microbial composition in neonates, although the distinct difference between GDM and non-GDM groups diminished in infancy. The oral microbiota functions and ecological networks differed dramatically between the two groups, highlighting the importance of maternal GDM status on initial oral microbiota in offspring.

Dataset Information

The Mechanism of Metabolic Influences on the Endogenous GLP-1 by Oral Antidiabetic Medications in Type 2 Diabetes Mellitus.

Publications

The Mechanism of Metabolic Influences on the Endogenous GLP-1 by Oral Antidiabetic Medications in Type 2 Diabetes Mellitus.

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