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Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes.

ABSTRACT: OBJECTIVES:We aimed to assess association between abnormal LVEF, in the absence of coronary artery disease (CAD), and 25-year incidence of major outcomes of diabetes (MOD) in a cardiology substudy of the Pittsburgh Epidemiology of Diabetes Complications cohort of childhood-onset type 1 diabetes. METHODS:115 normotensive type 1 diabetes individuals without known CAD, underwent a baseline exercise radionuclide ventriculography. Abnormal LVEF was defined as a resting ejection fraction <50% or a failure to increase ejection fraction with exercise by >5% (men) or a fall in ejection fraction with exercise (women). Cox proportional hazards models were used to predict the composite endpoint of MOD (first instance of major CAD, stroke, end-stage renal disease, blindness, amputation or diabetes-related death). RESULTS:Mean baseline age was 28 and diabetes duration 19?years. In a mean follow-up of 19?years, 50 MOD events were identified. Allowing for established risk factors at baseline, abnormal LVEF (n?=?22) independently predicted MOD incidence (HR?=?2.12, 95% CI: 1.12-4.00, p?=?0.022) but not major CAD (HR?=?1.33, 95% CI: 0.53-3.33, p?=?0.539). CONCLUSIONS:An abnormal LVEF may identify diabetic cardiomyopathy and predict long term risk of MOD (but not CAD alone) in type 1 diabetes individuals, consistent with it reflecting microvascular disease.

SUBMITTER: Guo J

PROVIDER: S-EPMC5820228 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes.

Guo Jingchuan J Miller Rachel G RG Costacou Tina T Follansbee William P WP Orchard Trevor J TJ

Journal of diabetes and its complications 20171228 3

<h4>Objectives</h4>We aimed to assess association between abnormal LVEF, in the absence of coronary artery disease (CAD), and 25-year incidence of major outcomes of diabetes (MOD) in a cardiology substudy of the Pittsburgh Epidemiology of Diabetes Complications cohort of childhood-onset type 1 diabetes.<h4>Methods</h4>115 normotensive type 1 diabetes individuals without known CAD, underwent a baseline exercise radionuclide ventriculography. Abnormal LVEF was defined as a resting ejection fractio ...[more]

PMID: 29366734

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Project description:IntroductionDNA methylation (DNAme) has been cross-sectionally associated with type 2 diabetes and hemoglobin A1c (HbA1c) in the general population. However, longitudinal data and data in type 1 diabetes are currently very limited. Thus, we performed an epigenome-wide association study (EWAS) in an observational type 1 diabetes cohort to identify loci with DNAme associated with concurrent and future HbA1cs, as well as other clinical risk factors, over 28 years.Research design and methodsWhole blood DNAme in 683 597 CpGs was analyzed in the Pittsburgh Epidemiology of Diabetes Complications study of childhood onset (<17 years) type 1 diabetes (n=411). An EWAS of DNAme beta values and concurrent HbA1c was performed using linear models adjusted for diabetes duration, sex, pack years of smoking, estimated cell type composition variables, and technical/batch covariates. A longitudinal EWAS of subsequent repeated HbA1c measures was performed using mixed models. We further identified methylation quantitative trait loci (meQTLs) for significant CpGs and conducted a Mendelian randomization.ResultsDNAme at cg19693031 (Chr 1, Thioredoxin-Interacting Protein (TXNIP)) and cg21534330 (Chr 17, Casein Kinase 1 Isoform Delta) was significantly inversely associated with concurrent HbA1c. In longitudinal analyses, hypomethylation of cg19693031 was associated with consistently higher HbA1c over 28 years, and with higher triglycerides, pulse rate, and albumin:creatinine ratio (ACR) independently of HbA1c. We further identified 34 meQTLs in SLC2A1/SLC2A1-AS1 significantly associated with cg19693031 DNAme.ConclusionsOur results extend prior findings that TXNIP hypomethylation relates to worse glycemic control in type 1 diabetes by demonstrating the association persists over the long term. Additionally, the associations with triglycerides, pulse rate, and ACR suggest TXNIP DNAme could play a role in vascular damage independent of HbA1c. These findings strengthen potential for interventions targeting TXNIP to improve glycemic control in type 1 diabetes through its role in SLC2A1/glucose transporter 1-mediated glucose regulation.

Project description:ObjectivesThe goal of these studies was to determine the association between cardiovascular autonomic neuropathy (CAN) and indices of left ventricle (LV) structure and function in patients with type 1 diabetes (T1DM) in the DCCT/EDIC (Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications) study.BackgroundThe pathophysiology of LV dysfunction in T1DM remains unclear, especially when the LV ejection fraction (EF) is preserved. Whether CAN is associated with LV dysfunction is unclear.MethodsIndices of LV structure and function were obtained by cardiac magnetic resonance imaging (CMRI). CAN was assessed by cardiovascular reflex testing (R-R response to paced breathing, Valsalva ratio, and blood pressure response to standing). Analyses were performed in 966 DCCT/EDIC participants with valid CMRI and CAN data (mean age 51 years, 52% men, mean diabetes duration 29 years, and mean glycosylated hemoglobin 7.9%).ResultsSystolic function (EF, end-systolic and end-diastolic volumes, stroke volumes) was not different in 371 subjects with CAN compared with 595 subjects without CAN. In multiple-adjusted analyses, participants with either abnormal R-R variation or a composite of abnormal R-R variation, abnormal Valsalva ratio, and postural blood pressure changes had significantly higher LV mass, mass-to-volume-ratio, and cardiac output compared with those with normal tests (p < 0.0001 for all). After further adjustment for traditional cardiovascular risk factors, subjects with abnormal R-R variation had higher LV mass and cardiac output compared with those with a normal R-R variation (p < 0.05).ConclusionsIn this large cohort of patients with T1DM, CAN is associated with increased LV mass and concentric remodeling as assessed by CMRI independent of age, sex, and other factors. (Diabetes Control and Complications Trial [DCCT]; NCT00360815) (Epidemiology of Diabetes Interventions and Complications [EDIC]; NCT00360893).

Project description:BackgroundClinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM.MethodsAn analysis of the cumulative incidence of long-term complications was performed. The DCCT (1983-1993) assigned patients to conventional or intensive therapy. Since 1993, the DCCT has been observational, and intensive therapy was recommended for all patients. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is an observational study of patients with T1DM from Allegheny County, Pennsylvania. The study population comprised the DCCT T1DM cohort (N = 1441) and a subset of the EDC cohort (n = 161) selected to match DCCT entry criteria. In the DCCT, intensive therapy aimed for a near-normal glycemic level with 3 or more daily insulin injections or an insulin pump. Conventional therapy, with 1 to 2 daily insulin injections, was not designed to achieve specific glycemic targets. Main outcome measures included the incidences of proliferative retinopathy, nephropathy (albumin excretion rate >300 mg/24 h, creatinine level >or=2 mg/dL [to convert to micromoles per liter, multiply by 88.4], or renal replacement), and cardiovascular disease.ResultsAfter 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the EDC cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time.ConclusionThe frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically.

Project description:AimsRecent studies indicated that sodium glucose cotransporter-2 inhibitors (SGLT2i) reduced heart failure hospitalization in patients with type 2 diabetes mellitus (T2DM). However, whether SGTL2i can improve left ventricular (LV) systolic and diastolic function remained unclear. This study aimed to compare the change in echocardiographic parameters in T2DM patients receiving SGLT2i with a different baseline LV ejection fraction (LVEF). The change in echocardiographic parameters was also compared between T2DM patients treated with SGLT2i and those treated with dipeptidyl peptidase-4 inhibitor (DPP4i).Methods and resultsThis multicentre cohort study consecutively enrolled 665, 119, and 132 T2DM patients treated with SGLT2i with a preserved (≥50%), moderately reduced (40-50%), and reduced baseline LVEF (<40%), respectively, with paired baseline and post-treatment echocardiographic data available between 1 June 2016 and 31 May 2018. There were 212 patients treated with DPP4i with paired baseline and post-treatment echocardiographic data available at the same time. For those patients treated with DPP4i, 45 patients had impaired baseline LVEF of <50%. Echocardiographic parameters, including LVEF, LV end-diastolic volume, LV end-systolic volume (LVESV), and LV diastolic function, were analysed at baseline and after treatment. After a median SGLT2i treatment period of 230 days, patients with reduced LVEF were associated with an improvement in LVEF from 29.4 ± 7.4% to 42.2 ± 15.2% (P < 0.0001) and decrease in LVESV from 133.2 ± 49.2 to 117.4 ± 60.1 mL (P = 0.0002). Patients with moderately reduced LVEF were associated with an improvement in LVEF from 44.8 ± 2.9% to 49.7 ± 12.4% (P < 0.0001) and decrease in LVESV from 90.7 ± 31.1 to 80.0 ± 36.2 mL (P = 0.0017). Patients with preserved LVEF did not show an improvement in LVEF and LVESV after SGLT2i treatment. There were no significant changes of LV end-diastolic volume, LV diastolic function, and LV wall thickness in three study groups after SGLT2i treatment. In contrast, patients with impaired baseline LVEF (<50%) did not show any change in LVEF and LVESV after DPP4i treatment.ConclusionsSodium glucose cotransporter-2 inhibitor was associated with an improvement in LV systolic function in patients with T2DM with reduced and moderately reduced LVEF. In contrast, DPP4i treatment was not associated with any improvement in LVEF among patients with impaired LVEF.

Dataset Information

Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes.

Publications

Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes.

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