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 HbA1c <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 HbA1c. RESULTS Compared with HbA1c <6.5% (<48 mmol/mol) for the 0-to-1-year early exposure period, HbA1c levels ≥6.5% (≥48 mmol/mol) were associated with increased microvascular and macrovascular events (e.g., HbA1c 6.5% to <7.0% [48 to <53 mmol/mol] microvascular: hazard ratio 1.204 [95% CI 1.063–1.365]), and HbA1c levels ≥7.0% (≥53 mmol/mol) were associated with increased mortality (e.g., HbA1c 7.0% to <8.0% [53 to <64 mmol/mol]: 1.290 [1.104–1.507]). Longer periods of exposure to HbA1c 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, HbA1c 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.