medwireNews: Among people with type 2 diabetes, those with hypoglycemic events, microvascular complications, or high or unstable glycated hemoglobin (HbA1c) levels might have an increased risk for dementia, researchers report.
Using the UK Clinical Practice Research Datalink GOLD database Lefkos Middleton (Imperial College London, UK) and co-authors obtained individual data from 457,902 people (52.1% men, mean age 64.5 years) between 1987 and 2018. During a median follow-up of 6 years, 6.3% of these people developed dementia.
The researchers report that individuals with hypoglycemic events (n=17,524) or microvascular complications (n=103,188) were at higher risk for dementia compared with those without, at adjusted hazard ratios (aHR) of 1.30 and 1.10, respectively. When looking at the association between individual complications and risk for dementia, individuals with neuropathy (n=41,920) or nephropathy (n=8660) were at higher risk for dementia than those with retinopathy (n=73,615), at aHRs of 1.25, 1.23, and 1.07, respectively, relative to those without these complications.
A total of 372,287 individuals with post-diagnosis HbA1c data were included in analyses of longitudinal HbA1c; among those people, 6.4% developed dementia. HbA1c level was significantly associated with higher risk for dementia incidence, with an aHR of 1.08 per 1% increment of HbA1c.
The investigators also observed that when HbA1c level was modelled as a time-varying exposure and taking 6–7% (42–53 mmol/mol) as the reference group, individuals with well-controlled HbA1c (<6%; [<42 mmol/mol]) had a significantly lower risk for dementia incidence, at a HR of 0.86, while those with HbA1c levels of 8–9% (64–75 mmol/mol), 9–10% (75–86 mmol/mol), and 10% or higher had a significantly elevated risk, at HRs of 1.15, 1.26 and 1.40, respectively.
In order to assess the long-term glycemic variability, the authors calculated the 3-year coefficient of variation (CV) of HbA1c, which was also independently associated with higher risk for dementia incidence, at an aHR of 1.03 per 1 standard deviation increment of CV, after controlling for the 3-year mean HbA1c level. Individuals in the second, third and fourth quartiles of glycemic variability were at increased risk for dementia compared with individuals in the lowest quartile, with aHRs of 1.06, 1.12 and 1.13, respectively.
"[T]his large-scale cohort study provides strong evidence that higher or unstable HbA1c levels and the presence of diabetic complications in patients with type 2 diabetes are associated with higher dementia incidence,” writes the team in Diabetes Care.
They conclude: “Future adequately powered randomized controlled trials on long-term glycemic control and dementia prevention in patients with diabetes are further warranted.”
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