Epidemiology of Diabetes Interventions and Complications (EDIC) Study

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Project Summary The Diabetes Control and Complications Trial (DCCT,1983-1993) compared intensive therapy aimed at near-normal glycemia versus conventional therapy with no specific glucose targets in 1441 subjects with type 1 diabetes (T1DM) over a mean follow-up of 6.5 years. Intensive therapy reduced the risks of retinopathy, nephropathy, and neuropathy by 35-76%. The level of glycemia was the primary determinant of complications. We also described the adverse effects of intensive therapy; assessed its effects on cardiovascular disease (CVD) risk factors, neurocognition and quality of life; and projected the lifetime health-economic impact. After the primary DCCT results were reported in 1993, intensive therapy aiming for a HbA1c <7% was adopted world-wide as standard-of-care for T1DM. The Epidemiology of Diabetes Interventions and Complications (EDIC, 1994-present) is the observational follow-up study of the DCCT cohort. Micro- and cardio-vascular complications and a wide range of established and putative risk factors, including genetic and epigenetic factors, have been measured with standardized methods, carefully documented and events adjudicated. EDIC has notably shown that the early beneficial effects of intensive versus conventional therapy on complications persisted for ~15 years despite the convergence of HbA1c levels in the two groups during EDIC, a novel concept termed metabolic memory. Prior intensive therapy was also shown to reduce substantially the risk of CVD events and mortality. The overarching goals for the next 5 years (2022-27) will be to study the occurrence and identify potentially modifiable risk factors of the more advanced microvascular and cardiovascular complications and physical and cognitive dysfunction that are occurring with increasing diabetes duration and age. With increasing longevity, the increased adiposity that has affected patients with T1DM, including EDIC participants, has potential adverse consequences. Thus, the impact of diabetes duration, aging and adiposity on morbidities and their underlying risk factors will be studied. The results will guide treatment priorities as T1DM patients age. The specific aims for 2022-2027 are to: 1) determine the incidence of advanced microvascular complications, investigate the order of their development and pattern of co-development, and identify glycemic and non-glycemic risk factors; 2) quantify impairment in functional and myocardial performance that presages heart failure (HF) and identify the risk factors for impairment in T1DM; 3) determine the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) and steatohepatitis-associated fibrosis (NASH) and symptoms suggestive of obstructive sleep apnea (OSA) in this increasingly overweight/obese T1DM study population and identify precedent risk factors and mechanisms; and 4) continue the longitudinal assessment of aging-sensitive morbidities such as cognitive and physical dysfunction, frailty, and their risk factors and their aggregate impact on quality of life, ability to self-manage T1DM, and health economic outcomes.