Higher HbA_1c Levels May Up Dementia Risk in Patients With Type 2 Diabetes

Cumulative glycated hemoglobin (HbA_1c) levels over 9% are associated with a greater risk for dementia in patients with type 2 diabetes, according to study findings published in JAMA Neurology.

Although a relative risk association has been established between type 2 diabetes and dementia, it is unknown whether strict glycemic control can attenuate this effect. Long term glycemic control, best measured by HbA_1c, may serve as a potential marker for risk-based assessment.

In an effort to establish optimal glycemic targets for risk reduction, researchers aimed to investigate the relationship between HbA_1c and its association with the development of dementia over time.

The researchers conducted a cohort study using data from Kaiser Permanente California (KPNC), a healthcare delivery system, from January 1, 1996 to September 30, 2015. Individuals aged >50 and diagnosed with type 2 diabetes according to International Classification of Disease, Ninth Revision (ICD-9), were included in the study. Those with less than 2 HbA_1c readings during the study period, or who have had dementia at baseline were excluded from the study. Covariates of age, race, sex and ethnicity were recorded at beginning of study.

Primary outcome was diagnosis of dementia, based on ICD-9 classification codes for Alzheimer disease (AD), nonspecific dementia and vascular dementia. HbA_1c levels were categorized by an increase of 1 percentile and ranged from less than 6% to greater than 10%.

Of 409,108 individuals evaluated, 253,211(mean age, 61.5 years; 53.1% men) were included in the study. The mean number of HbA_1c values which were evaluated for each participant was 11.6, and average follow-up time was 5.9 years.

Adjusting for age, race, sex, and ethnicity, HbA_1c concentrations <6% ,6% to 7% and 7% to 8% were associated with a decreased hazard of dementia compared with higher levels.

• HbA_1c <6%: adjusted hazard ratio [aHR], 0.92; 95% CI, 0.88- 0.97
• HbA_1c 6% to <7%: aHR, 0.79; 95% CI, 0.77-0.81
• HbA_1c 7% to <8%: aHR, 0.93; 95% CI, 0.89-0.97

HbA_1c levels ranging from less than 9% to 10% and 10% or more were associated with the highest hazard of dementia (aHR, 1.31; 95% CI, 1.15-1.51 and aHR, 1.74; 95% CI, 1.62-1.86, respectively). Similar patterns were found, compared with the overall sample when stratified by racial and ethnic groups.

Subgroup analysis found a HbA_1c of less than 6% associated a lower hazard of dementia in men (aHR, 0.88; 95% CI, 0.81-0.95), but this association was not found in women (aHR, 1.01; 95% CI, 0.94-1.09).

The lowest hazard of dementia risk was found in a proportion of patients who have had HbA_1c levels between 6% and 7% for at least 75% of the entire time evaluated (aHR, 0.69; 95% CI, 0.66-0.72). Conversely, those who spent 75% or more time in the HbA_1c bracket of >10% had the highest hazard of dementia (aHR, 1.76; 95% CI, 1.60-1.93).

Study limitations included lacking HbA_1c measurements in earlier life, which could lead to an underestimation of total exposure to HbA_1c over time.

“In this cohort study of a large sample of older people with type 2 diabetes, we found that increased exposure to HbA_1c concentrations greater than or equal to 9% was associated with the greatest hazard of dementia,” the researchers noted.

They concluded, “Importantly, we observed no significant change in hazard for individuals with HbA_1c concentrations in the range of relaxed glycemic control recommended by the American Geriatrics Society and US Department of Veterans Affairs for older patients with multiple comorbidities, poor health, or limited life expectancy.”