Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes

Individuals with type 1 diabetes have experienced an increase in life expectancy, yet it is unknown what level of glycemic control is ideal for maintaining late-life brain health. We investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes.

We followed 3,433 members of a health care system with type 1 diabetes, aged ≥50 years, from 1996 to 2015. Repeated measurements of hemoglobin A_1c (HbA_1c), dementia diagnoses, and comorbidities were ascertained from health records. Cox proportional hazards models were fit to evaluate the association of time-varying glycemic exposure with dementia, with adjustment for age, sex, race/ethnicity, baseline health conditions, and frequency of HbA_1c measurement.

Over a mean follow-up of 6.3 years, 155 individuals (4.5%) were diagnosed with dementia. Patients with ≥50% of HbA_1c measurements at 8-8.9% (64-74 mmol/mol) and ≥9% (≥75 mmol/mol) had 65% and 79% higher risk of dementia, respectively, compared with those with <50% of measurements exposed (HbA_1c 8-8.9% adjusted hazard ratio [aHR] 1.65 [95% CI 1.06, 2.57] and HbA_1c ≥9% aHR 1.79 [95% CI 1.11, 2.90]). By contrast, patients with ≥50% of HbA_1c measurements at 6-6.9% (42-52 mmol/mol) and 7-7.9% (53-63 mmol/mol) had a 45% lower risk of dementia (HbA_1c 6-6.9% aHR 0.55 [95% CI 0.34, 0.88] and HbA_1c 7-7.9% aHR 0.55 [95% CI 0.37, 0.82]).

Among older patients with type 1 diabetes, those with majority exposure to HbA_1c 8-8.9% and ≥9% had increased dementia risk, while those with majority exposure to HbA_1c 6-6.9% and 7-7.9% had reduced risk. Currently recommended glycemic targets for older patients with type 1 diabetes are consistent with healthy brain aging.