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Recent trends over time in vascular disease in type 1 diabetes: insights from the Pittsburgh Epidemiology of Diabetes Complications study.

ABSTRACT: Aims:To evaluate recent trends, by diagnosis year, in the cumulative incidence of vascular type 1 diabetes (T1D) complications and their risk factors up to 35 years duration. Methods:Participants from the Epidemiology of Diabetes Complications study of childhood-onset T1D were categorized into three calendar year onset cohorts: 1965-69, 1970-74, and 1975-80. All-cause, cardiovascular and renal mortality were determined both on the complete cohort (n=440) as well as in the subset with clinical examinations (n=363). Coronary artery disease (CAD, CAD death, myocardial infarction, revascularization, angina and ischemic ECG abnormalities); lower extremity arterial disease (LEAD, abnormal Ankle Brachial Index/amputation/intermittent claudication); distal symmetric polyneuropathy (DSP, clinical exam); cardiac autonomic neuropathy (CAN, abnormal heart rate response to deep breathing); overt nephropathy (ON, albumin excretion rate>200 ?g/min) and proliferative retinopathy (PR, fundus photography) were assessed on the subset with clinical examinations. Results:While all-cause, cardiovascular and renal mortality improved with a more recent diagnosis in the overall cohort, no univariate differences were observed for complications requiring examination (CAD, DSP, CAN, ON), although a borderline trend toward improved complication-free survival with a more recent onset was observed for PR (p=0.06). LEAD incidence showed an anomalous pattern, being highest in the 1975-80 and lowest in the 1970-74 cohort (p=0.009). Allowing for risk factors over time did not materially change these results. Conclusions:Despite declines in all-cause, cardiovascular and renal mortality in the total cohort, no improvements were observed in either mortality or complication incidence with a more recent onset in the examined cohort.

SUBMITTER: Costacou T

PROVIDER: S-EPMC6739893 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Recent trends over time in vascular disease in type 1 diabetes: insights from the Pittsburgh Epidemiology of Diabetes Complications study.

Costacou Tina T Orchard Trevor J TJ

Cardiovascular endocrinology & metabolism 20190301 1

<h4>Aims</h4>To evaluate recent trends, by diagnosis year, in the cumulative incidence of vascular type 1 diabetes (T1D) complications and their risk factors up to 35 years duration.<h4>Methods</h4>Participants from the Epidemiology of Diabetes Complications study of childhood-onset T1D were categorized into three calendar year onset cohorts: 1965-69, 1970-74, and 1975-80. All-cause, cardiovascular and renal mortality were determined both on the complete cohort (n=440) as well as in the subset w ...[more]

PMID: 31531415

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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: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.

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Recent trends over time in vascular disease in type 1 diabetes: insights from the Pittsburgh Epidemiology of Diabetes Complications study.

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Recent trends over time in vascular disease in type 1 diabetes: insights from the Pittsburgh Epidemiology of Diabetes Complications study.

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