The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study)

OBJECTIVE To examine for a legacy effect of early glycemic control on diabetic complications and death. RESEARCH DESIGN AND METHODS This cohort study of managed care patients with newly diagnosed type 2 diabetes and 10 years of survival (1997-2013, average follow-up 13.0 years, N = 34,737) examined associations between HbA(1c) <6.5% (<48 mmol/mol), 6.5% to <7.0% (48 to <53 mmol/mol), 7.0% to <8.0% (53 to <64 mmol/mol), 8.0% to <9.0% (64 to <75 mmol/mol), or >= 9.0% (>= 75 mmol/mol) for various periods of early exposure (0-1, 0-2, 0-3, 0-4, 0-5, 0-6, and 0-7 years) and incident future microvascular (end-stage renal disease, advanced eye disease, amputation) and macrovascular (stroke, heart disease/failure, vascular disease) events and death, adjusting for demographics, risk factors, comorbidities, and later HbA(1c). RESULTS Compared with HbA(1c) <6.5% (<48 mmol/mol) for the 0-to-1-year early exposure period, HbA(1c) levels >= 6.5% (>= 48 mmol/mol) were associated with increased microvascular and macrovascular events (e.g., HbA(1c) 6.5% to <7.0% [48 to <53 mmol/mol] microvascular: hazard ratio 1.204 [95% CI 1.063-1.365]), and HbA(1c) levels >= 7.0% (>= 53 mmol/mol) were associated with increased mortality (e.g., HbA(1c) 7.0% to <8.0% [53 to <64 mmol/mol]: 1.290 [1.104-1.507]). Longer periods of exposure to HbA(1c) levels >= 8.0% (>= 64 mmol/mol) were associated with increasing microvascular event and mortality risk. CONCLUSIONS Among patients with newly diagnosed diabetes and 10 years of survival, HbA(1c) levels >= 6.5% (>= 48 mmol/mol) for the 1st year after diagnosis were associated with worse outcomes. Immediate, intensive treatment for newly diagnosed patients may be necessary to avoid irremediable long-term risk for diabetic complications and mortality.