Type 2 diabetes in youth: Rationale for use of off-label antidiabetic agents.
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ABSTRACT:
SUBMITTER: Kelsey MM
PROVIDER: S-EPMC9378434 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Publications
Type 2 diabetes in youth: Rationale for use of off-label antidiabetic agents.
Kelsey Megan M MM Zeitler Philip S PS Nadeau Kristen J KJ Shah Amy S AS
Pediatric diabetes 20220516 6
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Project description:Telomere length and telomere shortening rate (TSR) are accepted indicators of aging in cross-sectional population studies. This study aimed to investigate the potential influence of common antidiabetic agents on telomere length and TSR in patients with type 2 diabetes mellitus (T2DM). Leukocyte telomere length was measured through terminal restriction fragment analysis, and TSR was calculated in 388 T2DM patients. Depending on whether or not they received antidiabetic medication, patients were first divided into a treatment group and a nontreatment group. Treated patients were further subdivided into an acarbose-free group (patients taking antidiabetic agents without acarbose) and an acarbose group (patients using acarbose for more than 3 months). Results showed that untreated patients had higher TSRs than patients on antidiabetic drugs. Interestingly, patients in the acarbose group had significantly higher TSRs than patients in the acarbose-free group. Compared to the nontreatment group, the acarbose group showed better glycemic control of HbA1c, but the TSR was also higher. Our results suggest that antidiabetic treatments without acarbose can slow aging. By contrast, acarbose may accelerate biological aging in patients with T2DM, independently of glycemic control.
| S-EPMC6366988 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The latter is a pandemic that has the potential of developing into a severe illness manifesting as systemic inflammatory response syndrome, acute respiratory distress syndrome, multi-organ involvement and shock. In addition, advanced age and male sex and certain underlying health conditions, like type 2 diabetes mellitus (T2DM), predispose to a higher risk of greater COVID-19 severity and mortality. This calls for an urgent identification of antidiabetic agents associated with more favourable COVID-19 outcomes among patients with T2DM, as well as recognition of their potential underlying mechanisms. It is crucial that individuals with T2DM be kept under very stringent glycaemic control in order to avoid developing various cardiovascular, renal and metabolic complications associated with more severe forms of COVID-19 that lead to increased mortality. The use of novel antidiabetic agents dipeptidyl peptidase 4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) in subjects with T2DM may have beneficial effects on COVID-19 outcomes. However, relevant studies either show inconsistent results (DPP4i) or are still too few (SGLT2i and GLP-1RAs). Further research is therefore needed to assess the impact of these agents on COVID-19 outcomes.
| S-EPMC8546380 | biostudies-literature
Project description:Heart failure is the most common comorbidity of diabetes. The incidence of heart failure in patients with diabetes is about 9%-22%, which is four times higher Than that in patients without diabetes. Heart failure and diabetes are collectively associated with increased morbidity and mortality compared to either condition alone. Several epidemiological studies have demonstrated an increased risk of heart failure in patients with diabetes; moreover, poor glycemic control accounts for the increased risk of heart failure. At present, several oral (metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, etc.) as well as injectable (insulins, glucagon-like peptide 1 receptor agonists) antidiabetic agents are available. However, optimal treatment strategy to achieve adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) and heart failure has not been well studied. In the view of rising prevalence of heart failure in patients with diabetes mellitus, clinicians need to understand the potential implications of antidiabetic agents in patients with heart failure. A group of experts from across India were involved in a consensus meeting in Pondicherry during the National Insulin Summit in November 2015. They evaluated agents currently available for the treatment of diabetes looking at existing scientific evidence relevant to each class of therapy. In addition, the existing guidelines and prescribing literature available with all these agents were also reviewed. Findings from the expert evaluations were then factored into the national context incorporating personal experience and common clinical practices in India. The purpose of this consensus document is to assist the clinicians while treating patients with T2DM and heart failure.
| S-EPMC5477452 | biostudies-other
Project description:AimsTo quantify patterns of conventional and newer antidiabetic medication use in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).MethodsWe used data from a large claims and integrated dataset that includes employed and commercially insured patients in the US to select patients who had T2DM and CKD with information on laboratory values and prescriptions for antidiabetic medications from January 1, 2014 to January 1, 2015. We stratified the analyses by sociodemographic variables.ResultsIn a cohort of 38,577 patients with T2DM and CKD, we found wide variation in the treatment of T2DM by CKD stage as well as by several sociodemographic factors. Although metformin was the most commonly prescribed medication, only about half of patients in the cohort and fewer than two-thirds of patients with early stage CKD were prescribed metformin. Approximately 10.6% of patients with CKD stage 4 and 2.1% of the patients with CKD stage 5 were prescribed metformin. Sulfonylureas with active metabolites that accumulate with impaired kidney function were prescribed in more than one-third of patients with CKD stages 3b, 4, and 5. Only 3.4% and 12.3% of patients were prescribed GLP-1 and DPP-4 respectively.ConclusionsPrescriptions for metformin were lower than expected among patients with mild to moderate CKD. Prescriptions for newer antidiabetic medications with known safety and efficacy across the spectrum of CKD remained low. Prescriptions for agents contraindicated in advanced CKD continued to be written in a sizeable fraction of patients.
| S-EPMC6823164 | biostudies-literature
Project description:Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups; N = 8) and 24 healthy control subjects were enrolled in this study, and intestinal bacterial microbiota was investigated by analyzing V3-V4 regions of 16S rRNA gene sequence. Numerous alterations were observed in the gut microbial community of diabetic individuals. These changes were characterized by a significant lowered abundance of Faecalibacterium, Fusobacterium, Dialister, and Elusimicrobium in the nontherapeutic subgroup compared to the healthy control group. Likewise, correlation analysis showed a substantial decline in gut microbiota richness and diversity with the duration of illness. Furthermore, antidiabetic agents restored to some extent the richness and diversity of gut microbiota and improved the abundance of many beneficial bacteria with a significant increase of Methanobrevibacter in the metformin subcategory compared to the nontherapeutic subgroup. In return, they decreased the abundance of some opportunistic pathogens. The findings of this study have added a novel understanding about the pathogenesis of the disease and the mechanisms underlying antidiabetic therapy, which are of potential interest for therapeutic lines and further studies.
| S-EPMC7539102 | biostudies-literature
Project description:AimThe efficacy and safety of insulin degludec (IDeg), a new basal insulin with an ultra-long duration of action, was compared to sitagliptin (Sita) in a 26-week, open-label trial.MethodsInsulin-naïve subjects with type 2 diabetes [n = 458, age: 56 years, diabetes duration: 7.7 years, glycosylated haemoglobin (HbA1c): 8.9% (74 mmol/mol)] were randomized (1 : 1) to once-daily IDeg or Sita (100 mg orally) as add-on to stable treatment with 1 or 2 oral antidiabetic drugs (OADs).ResultsSuperiority of IDeg to Sita in improving HbA1c and fasting plasma glucose (FPG) was confirmed [estimated treatment difference (ETD) IDeg-Sita for HbA1c: -0.43%-points [95% confidence interval (CI): -0.61; -0.24, p < 0.0001] and for FPG: -2.17 mmol/l (95% CI: -2.59; -1.74, p < 0.0001)]. HbA1c < 7% (<53 mmol/mol) was achieved by 41% (IDeg) versus 28% (Sita) of patients, estimated odds ratio IDeg/Sita: 1.60 (95% CI: 1.04; 2.47, p = 0.034). There was no statistically significant difference in the rate of nocturnal confirmed hypoglycaemia between IDeg and Sita [0.52 vs. 0.30 episodes/patient-year, estimated rate ratio (ERR): IDeg/Sita: 1.93 (95% CI: 0.90; 4.10, p = 0.09)]. Rates of overall confirmed hypoglycaemia were higher with IDeg than with Sita [3.1 vs. 1.3 episodes/patient-year, ERR IDeg/Sita: 3.81 (95% CI: 2.40; 6.05, p < 0.0001)]. IDeg was associated with a greater change in body weight than Sita [ETD IDeg-Sita: 2.75 kg (95% CI: 1.97; 3.54, p < 0.0001)]. The overall rates of adverse events were low and similar for both groups.ConclusionsIn patients unable to achieve good glycaemic control on OAD(s), treatment intensification with IDeg offers an effective, well-tolerated alternative to the addition of a second or third OAD.
| S-EPMC3799217 | biostudies-literature
Project description:Background & aimsThere is intense research for drugs able to reduce disease progression in nonalcoholic fatty liver disease. We aimed to test the impact of novel antidiabetic drugs (dipeptidyl-peptidase-4 inhibitors - DPP-4Is, glucagon-like peptide-1 receptor agonists - GLP-1RAs, sodium-glucose cotransporter-2 inhibitors - SGLT-2Is) on non-invasive biomarkers of steatosis (fatty liver index, FLI) and fibrosis (Fibrosis-4 score, FIB-4) in patients with type 2 diabetes (T2D).MethodsClinical, anthropometric and biochemical parameters were retrospectively analysed in 637 consecutive T2D patients switched from metformin w/wo sulfonylureas and/or pioglitazone to DPP-4Is, GLP-1RAs and SGLT-2Is in a tertiary care setting. 165 patients maintained on original treatments served as controls. The effects on FLI and FIB-4 at 6- and 12-month follow-up were analysed by logistic regression after adjustment for baseline differences, computed by propensity scores, and additional adjustment for changes in glycosylated hemoglobin (HbA1c) and body mass index.ResultsBody mass index, HbA1c and aminotrasferases significantly decreased following switching to GLP-1RAs and SGLT2-Is, compared with both controls and DPP-4Is, whereas only HbA1c was reduced on DPP-4Is. FLI and FIB-4 were reduced on GLP-1RA and SGLT-2I; logistic regression analysis confirmed a significant improvement of both biomarkers after adjustment for propensity score. The shift of FIB-4 values towards the category ruling out advanced fibrosis was maintained after additional adjustment for confounders. These effects were confirmed in a sensitivity analysis on effect size.ConclusionsGlucagon-like peptide-1 receptor agonists and SGLT-2Is improve biomarkers of steatosis and fibrosis, in keeping with beneficial effects on liver disease progression, and should be considered the treatment of choice in T2D.
| S-EPMC8248247 | biostudies-literature
Project description: Not available
| S-EPMC8785330 | biostudies-literature
Project description:The incidence of type 2 diabetes in children and adolescents in the United States rose at an annual rate of 4.8% between 2002-2003 and 2014-2015. Type 2 diabetes progresses more aggressively to complications than type 1 diabetes. For example, in one large epidemiological study, proliferative retinopathy affected 5.6% and 9.1% of children with type 1 and type 2 diabetes, respectively. Screening begins at age 10 or at onset of puberty, and is recommended among children with a BMI% ≥85 with risk factors such as a family history and belonging to a high risk racial or ethnic or racial group. HbA1C% is preferred for screening as it does not require fasting. As distinguishing between type 1 and type 2 diabetes is not straightforward, all children with new onset disease should undergo autoantibody testing. Results of lifestyle interventions for control of type 2 diabetes have been disappointing, but are still recommended for their educational value and the potential impact upon some participants. There is limited evidence for the benefit of newer mediations. Liraglutide, a GLP-1 agonist, however, has been shown to significantly reduce HbA1C% in one study and is now approved for children. Liraglutide should be considered as second line therapy.
| S-EPMC8126957 | biostudies-literature
Project description:ImportanceAccess to necessary prenatal care is not guaranteed through Medicaid for some people with low income based on their immigration status. Although states have the option to extend emergency Medicaid coverage for prenatal care, many states have not expanded coverage.ObjectiveTo evaluate whether the receipt of prenatal care services through the extension of emergency Medicaid coverage is associated with an increase in antidiabetic medication use among Latina patients with gestational diabetes.Design, setting, and participantsThis cohort study used linked Medicaid claims and birth certificate data on live births to 4869 Latina patients from October 1, 2010, to December 31, 2019, with a difference-in-differences design to compare the rollout of prenatal care and services in Oregon in 2013 with a comparison state, South Carolina, that did not cover prenatal or postpartum care.ExposureMedicaid coverage of prenatal care.Main outcomes and measuresThe main outcome was the receipt of antidiabetic agents. Secondary outcomes included hypertensive disorders, cesarean delivery, postpartum contraception, and a newborn morbidity composite outcome (large size for gestational age, neonatal intensive care unit admission, and preterm birth).ResultsThe study sample included live births to 4869 Latina patients (mean [SD] age, 32.7 [5.5] years [range, 12-44 years]) enrolled in emergency Medicaid who were mainly aged 25 to 34 years (1499 of 2907 [51.6%]), multiparous (2626 of 2907 [90.3%]), and living in urban areas (2299 of 2907 [79.1%]). After Oregon's policy change to offer prenatal coverage to individuals receiving emergency Medicaid, there was a large and significant increase in the receipt of antidiabetic agents among all people with diabetes during pregnancy (gestational diabetes). Prior to the policy, only 0.3% of all Latina emergency Medicaid recipients with gestational diabetes (2 of 617) received any medication (oral agents or insulin) to manage their blood glucose level. After the policy change, 28.8% of all patients with gestational diabetes (295 of 1023) received medication to manage their blood glucose level, translating to a 27.9-percentage-point increase (95% CI, 24.5-31.2 percentage points) in the receipt of antidiabetic agents in the adjusted model. The policy was also associated with a 10.4-percentage-point (95% CI, 5.3-15.5 percentage points) increase in insulin use during pregnancy among all patients with gestational diabetes. We observed an increase in postpartum contraceptive use (21.2 percentage points; 95% CI, 14.9-27.5 percentage points), the majority of which was due to postpartum sterilization (increase of 16.1 percentage points; 95% CI, 10.4-21.8 percentage points). We did not observe a significant association with gestational hypertension, cesarean births, or newborn health.Conclusions and relevanceThis retrospective cohort study suggests that expanded emergency Medicaid benefits that included prenatal care were associated with an increased use of antidiabetic medications and postpartum contraception during pregnancy.
| S-EPMC9055460 | biostudies-literature