HbA1c and brain health across the entire glycaemic spectrum.

Victoria Garfield,Sophie V Eastwood,Rohini Mathur,Nish Chaturvedi,Liam Smeeth,Krishnan Bhaskaran,Christopher T Rentsch,Aliki-Eleni Farmaki

doi:10.1111/dom.14321

Abstract

AimTo understand the relationship between HbA1c and brain health across the entire glycaemic spectrum.Materials and MethodsWe used data from the UK Biobank cohort consisting of 500,000 individuals aged 40–69 years. HbA1c and diabetes diagnosis were used to define baseline glycaemic categories. Our outcomes included incident all‐cause dementia, vascular dementia (VD), Alzheimer's dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. The reference group was normoglycaemic individuals (HbA1c ≥35 & <42 mmol/mol). Our maximum analytical sample contained 449,973 individuals with complete data.ResultsPrediabetes and known diabetes increased incident VD (HR 1.54; 95% CI = 1.04, 2.28 and HR 2.97; 95% CI = 2.26, 3.90, respectively). Known diabetes increased all‐cause and AD risk (HR 1.91; 95% CI = 1.66, 2.21 and HR 1.84; 95% CI = 1.44, 2.36, respectively). Prediabetes and known diabetes elevated the risks of cognitive decline (OR 1.42; 1.48, 2.96 and OR 1.39; 1.04, 1.75, respectively). Prediabetes, undiagnosed and known diabetes conferred higher WMH volumes (3%, 22% and 7%, respectively) and lower HV (36, 80 and 82 mm3, respectively), whereas low‐normal HbA1c had 1% lower WMH volume and 12 mm3 greater HV.ConclusionBoth prediabetes and known diabetes are harmful in terms of VD, cognitive decline and AD risks, as well as lower HV. Associations appeared to be somewhat driven by antihypertensive medication, which implies that certain cardiovascular drugs may ameliorate some of the excess risk. Low‐normal HbA1c levels, however, are associated with more favourable brain health outcomes and warrant more in‐depth investigation.

Highlights

Type 2 diabetes and, more generally, hyperglycaemic states, have been associated with poorer cognitive function,[1,2] increased risk of dementia[2,3] and alterations in key brain structures, the hippocampus.[4]
Associations between hyperglycaemia and dementia are stronger for vascular dementia than for all-cause dementia and Alzheimer's dementia (AD)
We observed that prediabetes is associated with 1% slower reaction time (RT), whereas undiagnosed and known diabetes are associated with 2% slower RTs

Summary

| INTRODUCTION

Type 2 diabetes and, more generally, hyperglycaemic states, have been associated with poorer cognitive function (such as learning and memory),[1,2] increased risk of dementia[2,3] and alterations in key brain structures, the hippocampus.[4]. Our aim was to investigate, in a single large-scale study, the associations between five glycaemic states across the entire spectrum (low-normal HbA1c, normoglycaemia, prediabetes, undiagnosed diabetes and known diabetes) and a number of brain health outcomes including Alzheimer's dementia (AD) risk, vascular dementia (VD) risk, baseline cognitive function and cognitive decline, hippocampal volume and WMH volume in the UKB. We hypothesized that those individuals with increasingly higher HbA1c levels would have poorer outcomes compared with those individuals with normal glycaemic levels

| METHODS

| RESULTS

Findings

| DISCUSSION