| KEY POINTS |
Ask What are the optimal glycemic goals associated with a reduced risk of dementia in older people with type 2 diabetes? Findings In this cohort study of 253,211 people aged 50 years or older with type 2 diabetes, those with a majority (>50%) of glycated hemoglobin concentrations of 9% or greater had the highest risk of dementia. Meaning The results of this study support common clinical guideline recommendations for relaxed glycemic goals in older adults. |
Although type 2 diabetes is associated with an increased risk of dementia, it is unclear whether glycemic control mediates this risk in middle-aged or elderly people. Observational studies have reported that hyperglycemia and duration of diabetes are associated with increased risk of dementia. However, studies of interventions with aggressive glycemic targets suggest that attempting to achieve tight glycemic control may increase the risk of harm, including death, particularly in older patients.
The harm associated with intensive glucose control has led the American Diabetes Association, the American Geriatrics Society, the Endocrine Society, and the U.S. Department of Veterans Affairs to recommend that glycemic goals for people of Middle age are individualized and consider the risk of hypoglycemia, the number and severity of comorbidities, functional independence, cognitive impairment, and life expectancy. Each of these organizations differs regarding the exact therapeutic goal recommended and encourages it to be developed based on each person’s individual circumstances - dependency, cognitive impairment and life expectancy.
To help inform patient-centered glycemic goal setting, it is essential to understand the contribution of glycemic control to dementia risk.
Long-term glycemic control, measured using cumulative glycemic exposure across multiple glycated hemoglobin (HbA1c) measurements over time, provides a more nuanced understanding of glycemic control than mean HbA1c concentrations by incorporating concentration and frequency. of HbA1c at that concentration.
Because the influence of dementia risk factors may vary by sex and by race and ethnicity, it is important to understand whether associations between glycemic control and dementia risk vary among various groups. Therefore, we aimed to examine associations between cumulative exposure to various ranges of HbA1c with dementia risk across sex and racial/ethnic groups and explore the association of current therapeutic glycemic targets with dementia risk.
| Importance |
The levels of glycemic control associated with lower risk of dementia in people with type 2 diabetes are unknown. This knowledge is critical to inform the setting of patient-centered glycemic goals.
| Aim |
To examine associations between cumulative exposure to various ranges of glycated hemoglobin (HbA 1c) concentrations with dementia risk across sex and racial/ethnic groups and the association of current therapeutic glycemic targets with dementia risk.
| Design, environment and participants |
This cohort study included members of the Kaiser Permanente Northern California integrated health care system with type 2 diabetes who were 50 years of age or older during the study period from January 1, 1996 to September 30, 2015.
Individuals with less than 2 HbA 1c measurements during the study period, prevalent dementia at baseline, or less than 3 years of follow-up were excluded. Data was analyzed from February 2020 to January 2023.
| Exhibitions |
Updated cumulative exposure to HbA 1c thresholds. At each HbA 1c measurement, participants were classified according to the percentage of their HbA 1c measurements that fell into the following categories: less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, 9% to less than 10%, and 10% or more of total hemoglobin (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01).
| Main results and measures |
The diagnosis of dementia was identified using International Classification of Diseases, Ninth Revision codes from inpatient and outpatient encounters. Cox proportional hazards regression models estimated the association of time-varying cumulative glycemic exposure with dementia, adjusting for age, race and ethnicity, baseline health conditions, and number of HbA 1c measurements.
| Results |
A total of 253,211 participants were included . The mean (SD) age of participants was 61.5 (9.4) years and 53.1% were men. The mean (SD) duration of follow-up was 5.9 (4.5) years.
Participants with more than 50% of HbA 1c measurements at 9%, less than 10%, or 10% or more had a higher risk of dementia compared to those who had 50% or less of measurements in those categories. (HbA 1c 9% to <10%: adjusted hazard ratio [aHR], 1.31 [95% CI, 1.15-1.51]; HbA 1c ≥10%: aHR, 1.74 [95% CI %, 1.62-1.86]).
In contrast, participants with more than 50% HbA 1c concentrations less than 6%, 6% to less than 7%, or 7% to less than 8% had a lower risk of dementia (HbA 1c <6%). : aHR, 0.92 [95% CI, 0.88-0.97], HbA1c 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]).
| Discussion |
In this large sample of people with type 2 diabetes, we found that greater cumulative exposure to HbA1c concentrations in the range of 6% to less than 7% and 7% to less than 8% was associated with a lower risk of dementia.
Importantly, we did not observe significant changes in risk for individuals with HbA1c concentrations in the non-intensive glycemic control range recommended by the American Geriatrics Society and the US Department of Veterans Affairs for older patients with multiple comorbidities, poor health or limited life expectancy.
| Conclusions and relevance |
In this cohort study of a large sample of older people with type 2 diabetes, we found that greater exposure to HbA1c concentrations greater than or equal to 9% was associated with the greatest risk of dementia. Additional work is needed to examine whether the observational associations we report are causal and seen in other groups.
| Final message |
In this study, the risk of dementia was highest among adults with cumulative HbA 1c concentrations of 9% or greater. These results support the relaxed glycemic goals currently recommended for older people with type 2 diabetes.
