Prediabetes, Not Just Full-Blown Diabetes, Increases Risk of Declining Neurological Health

Victoria Garfield, PhD

In the wake of many new studies outlining risks of worsening neurological health associated with poor glycemic control, new research suggests patients with prediabetes were also at a higher risk of cognitive decline and vascular dementia.

While investigators noted absolute rates of both conditions were low, higher than normal blood sugar levels were associated with a 42% increase in risk of cognitive decline over the next 4 years and a 54% higher risk of developing vascular dementia over the next 8 years.

"Previous research has found a link between poorer cognitive outcomes and diabetes but our study is the first to investigate how having blood sugar levels that are relatively high - but do not yet constitute diabetes - may affect our brain health,” said Victoria Garfield, lead investigator, and research associate at the University College London (UCL) Institute of Cardiovascular Science and the UCL MRC Unit for Lifelong Health & Ageing, in a statement.

To more fully understand the relationship between HbA1c levels and neurological health, Garfield and a team of colleagues designed their current study as an analysis of data from within the UK Biobank cohort. From the UK Biobank cohort, investigators identified data related to more 450,000 individuals, including 449,973 without dementia or cognitive impairment at baseline. From this cohort, investigators identified more than 50,000 patients with follow-up visual memory and exposure/covariate data or data related to structural MRI measures, which were used to assess cognitive decline.

Specific outcomes of interest for the analysis included incident all-cause dementia, vascular dementia, Alzheimer’s disease, hippocampal volume, white matter hyperintensity volume, and cognitive function and decline.

For the purpose of analysis, undiagnosed diabetes was defined as an HbA1c of 48 mmol/mol or greater, prediabetes was defined as 42-48 mmol/mol, and normoglycemia was defined as 35-42 mmol/mol. Of those included in the study, 210,309 had low-normal glycemic HbA1c levels, 198,969 were considered normoglycemic, 15,229 had prediabetes, 3279 had undiagnosed diabetes, and 22,187 had known diabetes.

In their analyses, investigators found a diagnosis of prediabetes (HR, 1.54; 95% CI, 1.04-2.28) or known diabetes (HR, 2.97; 95% CI, 2.26-3.90) was associated with incident vascular dementia. Additionally, known diabetes was associated with all-cause (HR, 1.91; 95% CI, 1.66-2.21) and Alzheimer’s dementia (HR, 1.84; 95% CI, 1.44-2.36) risk. When assessing cognitive decline, results suggested prediabetes (OR, 1.42; 95% CI, 1.48-2.96) and known diabetes (OR, 1.39; 95% CI, 1.04-1.75) were associated with increased risk of cognitive decline.

Further analysis indicated prediabetes, undiagnosed, and known diabetes were associated with higher white matter hyperintensity volumes (3%, 22%, and 7%, respectively) and lower hippocampal volume (36, 80, and 82 mm3, respectively). Investigators noted patients with normal HbA1c levels had 1% lower white matter hypertension volume and 12 mm3 greater hippocampal volume compared to their counterparts with increased HbA1c.

"In this relatively young age group, the risks of cognitive decline and of dementia are very low; the excess risks we observe in relation to elevated blood sugar only modestly increase the absolute rates of ill health. Seeing whether these effects persist as people get older, and where absolute rates of disease get higher, will be important,” added senior investigator Nishi Chaturvedi, PhD, professor in the UCL MRC Unit for Lifelong Health & Ageing.

This study, “HbA1c and brain health across the entire glycaemic spectrum,” was published in Diabetes, Obesity, and Metabolism.