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

Abstract

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.

Figure 1

Definitions of early exposure periods and subsequent follow-up periods for the research design.

Figure 2

A: Microvascular events (vs. HbA_1c <6.5% [<48 mmol/mol]). B: Macrovascular events (vs. HbA_1c <6.5% [<48 mmol/mol]). C: Mortality (vs. HbA_1c <6.5% [<48 mmol/mol]). HRs adjusted for year of diagnosis, age at diagnosis, sex, race/ethnicity, BMI, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, smoking status, HbA_1c after each early exposure period, and comorbidity.