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Coprogression of Cardiovascular Risk Factors in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

ABSTRACT: OBJECTIVE:The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study has demonstrated the beneficial effect of intensive therapy on atherosclerosis and clinical cardiovascular outcomes, while identifying hyperglycemia as a dominant risk factor for type 1 diabetes. The current analyses evaluate the extent to which glycemic exposure influences long-term changes in established risk factors for cardiovascular disease (CVD) among patients with type 1 diabetes. RESEARCH DESIGN AND METHODS:The DCCT study randomized 1,441 participants to receive intensive or conventional diabetes therapy; and after an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study for an additional 20 years of follow-up. Annual visits included a detailed medical history and physical examination. Blood and urine samples were collected and assayed centrally. Longitudinal models for repeated measurements were used. RESULTS:Higher HbA1c level was a significant correlate of the longitudinal changes in all of the traditional CVD risk factors over the 30-year follow-up. The strongest longitudinal associations were among the lipid measurements and concurrent glycemia. CONCLUSIONS:A better understanding of the interrelationships between diabetes-related risk factors and traditional CVD risk factors may assist with the development of targeted treatment regimens for persons with type 1 diabetes who are at risk for CVD.

SUBMITTER: Writing Group for the DCCT/EDIC Research Group

PROVIDER: S-EPMC5001148 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Coprogression of Cardiovascular Risk Factors in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

Diabetes care 20160719 9

<h4>Objective</h4>The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study has demonstrated the beneficial effect of intensive therapy on atherosclerosis and clinical cardiovascular outcomes, while identifying hyperglycemia as a dominant risk factor for type 1 diabetes. The current analyses evaluate the extent to which glycemic exposure influences long-term changes in established risk factors for cardiovascular disease (CVD) among ...[more]

PMID: 27436274

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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 OBJECTIVES:In 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, & MEASUREMENTS:We 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. RESULTS:At 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. CONCLUSIONS:In 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

Coprogression of Cardiovascular Risk Factors in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

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Coprogression of Cardiovascular Risk Factors in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

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