Dataset Information

Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

ABSTRACT: OBJECTIVE:The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes. RESEARCH DESIGN AND METHODS:A total of 1,441 participants were randomly assigned to intensive or conventional diabetes therapy during the DCCT. After an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study, which included annual visits with detailed medical history, physical examination, and laboratory testing. CVD events were adjudicated by a review committee. Generalized linear mixed models and Cox proportional hazards regression models were used to assess the association between insulin dose and cardiometabolic risk factors and CVD risk, respectively, over a total of 30 years. RESULTS:Higher insulin doses were significantly associated with a less favorable cardiometabolic risk profile (higher BMI, pulse rate, and triglycerides and lower HDL cholesterol) with the exception of lower diastolic blood pressure and lower LDL cholesterol. In a minimally adjusted model, a 0.1 unit/kg body wt/day increase in insulin dose was associated with a 6% increased risk of any CVD (95% CI 3, 9). However, the association with insulin dose was no longer significant after adjustment for other CVD risk factors. CONCLUSIONS:During DCCT/EDIC, higher insulin doses were associated with adverse trends in several cardiometabolic risk factors, even after multivariable adjustment, but not with incident CVD outcomes.

SUBMITTER: Braffett BH

PROVIDER: S-EPMC6429630 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

Braffett Barbara H BH Dagogo-Jack Samuel S Bebu Ionut I Sivitz William I WI Larkin Mary M Kolterman Orville O Lachin John M JM

Diabetes care 20190206 4

<h4>Objective</h4>The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes.<h4>Research design and methods</h4>A total of 1,441 participants were randomly assigned to intensive or co ...[more]

PMID: 30728218

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Project description:BackgroundWith improved treatment, individuals with type 1 diabetes are living longer but there is limited information on the effects of type 1 diabetes on cognitive ability as they become older adults. We followed up individuals with type 1 diabetes to identify independent risk factors for cognitive decline as people age.Methods1051 participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. Participants completed cognitive assessments at baseline (median age 27 years) and 2, 5, 18, and 32 years later (median age 59). HbA1c levels, frequency of severe hypoglycaemia, non-glycemic risk factors such as elevated blood pressure, and microvascular and macrovascular complications were assessed repeatedly. We examined the effects of these on measures of memory and psychomotor and mental efficiency. These studies are registered with clinicaltrials.gov, NCT00360815 (DCCT) and NCT00360893 (EDIC).FindingsOver 32 years of follow-up, we found substantive declines in memory and psychomotor and mental efficiency. Between 18 and 32 years of follow-up, the decline in psychomotor and mental efficiency was five times larger than the change from baseline to year 18. Independent of the other risk factors and comorbidities, exposure to higher HbA1c levels, more episodes of severe hypoglycaemia, and elevated systolic blood pressure were associated with greater decrements in psychomotor and mental efficiency that was most notable by year 32 (p<0·0001). The combined effect of the presence of these three risk factors is the equivalent to an additional 9·4 years of age.InterpretationCognitive function declines with ageing in type 1 diabetes. The association of glycaemia and blood pressure levels with cognitive decline suggests that better management might preserve cognitive function.FundingUnited States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease.

Project description:BackgroundHyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus.Methods and ResultsA random subcohort of 349 participants was selected from the DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT, and 1 to 2 years post‐DCCT (EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F isoprostanes, and its metabolite, 2,3 dinor‐8 prostaglandin F. Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 prostaglandin F, an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, <0.003; −5.3% risk for 10% higher 2,3 dinor‐8 prostaglandin F, =0.0092). In contrast, the oxidative markers myeloperoxidase and F isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments.ConclusionsHeightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00360815 and NCT00360893.

Project description:Background and objectivesIn trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes.Design, setting, participants, & measurementsWe studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30-299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m2 on two consecutive visits), and subclinical cardiovascular disease.ResultsAt least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification.ConclusionsIn type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.

Dataset Information

Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

Publications

Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

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