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Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes

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posted on 12.05.2021, 18:52 by Rose Gubitosi-Klug, Xiaoyu Gao, Rodica Pop-Busui, Ian H de Boer, Neill White, Lloyd P Aiello, Ryan Miller, Jerry Palmer, William Tamborlane, Amisha Wallia, Mikhail Kosiborod, John M Lachin, Ionut Bebu, DCCT/EDIC Research Group
Objective: We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study followed for over 35 years.

Research Design and Methods: Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally-graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on ECG, confirmed angina, or coronary artery revascularization. Cox proportional hazard models assessed the association of microvascular complications with subsequent risk of CVD.

Results: 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively); associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with eGFR<60 ml/min/1.73m, and the presence of both retinal and kidney disease remained associated with CVD.

Conclusions: Advanced microvascular disease, especially moderate to severe albuminuria or eGFR<60 ml/min/1.73m2, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort.


The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017, 2017-2022), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA.