Diabetes, Prediabetes, and Brain Volumes and Subclinical Cerebrovascular Disease on MRI: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Abstract

OBJECTIVETo examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology.RESEARCH DESIGN AND METHODSCross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011–2013. Participants were categorized by diabetes-HbA1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA1c ≥6.5%] <7.0% vs. ≥7.0%), with further stratification by diabetes duration (<10 vs. ≥10 years).RESULTSIn adjusted analyses, compared with participants without diabetes and HbA1c <5.7%, participants with prediabetes and those with diabetes and HbA1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05), but those with diabetes and HbA1c ≥7.0% had smaller total brain volume (β −0.20 SDs, 95% CI −0.31, −0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016). Among participants with diabetes, those with HbA1c ≥7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA1c <7.0%. Similarly, participants with longer duration of diabetes (≥10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05).CONCLUSIONSMore-severe diabetes (defined by higher HbA1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.

Assessing the severity of Type 2 diabetes using clinical data‐based measures: a systematic review

“…In studies using severity level categories (seven studies with 2640 participants), participants were categorized as having between two and six levels of severity according to predefined diabetes-related criteria [21,[27][28][29][30]33,35]. The categories were based on insulin use, diabetes therapy intensity, presence of diabetes-related microvascular and macrovascular complications, glucose and HbA 1c levels, diabetes duration, and history of hypoglycaemia.…”

“…Glycaemic control was the second most commonly included domain, with levels of blood glucose and/or HbA 1c used in eight (44%) severity measures [21,22,[26][27][28][29]32,35]. Other domains used to assess diabetes severity were: diabetes duration [26,35]; blood pressure levels [22,28]; presence of renal disease (levels of albuminuria [28] and/or serum creatinine) [19,22,25]; a composite score of quality-of-life indicators and counts of comorbidities and prescribed medications [20]; demographic variables (age, gender, ethnicity, marital status) [22]; BMI [22]; LDL cholesterol levels [22]; and a composite history of cerebrovascular and/or cardiovascular disease, severe obesity and renal failure before heart transplantation [24]. Other domains used to assess diabetes severity were: diabetes duration [26,35]; blood pressure levels [22,28]; presence of renal disease (levels of albuminuria [28] and/or serum creatinine) [19,22,25]; a composite score of quality-of-life indicators and counts of comorbidities and prescribed medications [20]; demographic variables (age, gender, ethnicity, marital status) [22]; BMI [22]; LDL cholesterol levels [22]; and a composite history of cerebrovascular and/or cardiovascular disease, severe obesity and renal failure before heart transplantation [24].…”

“…No studies were identified from other countries that are well-known for their high availability of national administrative data, such as the UK. Ten studies were cross-sectional [19,20,23,25,28,[31][32][33][34][35], six were retrospective [21,22,24,26,29,30], and only one had a prospective design, assessing the relationship between longitudinal severity and clinical outcome [27]. The study populations consisted mainly of people with Type 2 diabetes only (N=2889 in 10 studies, 59%), but seven studies (41%) included participants with other forms of diabetes (mainly Type 1 diabetes) in addition to those with Type 2 diabetes.…”

“…Microvascular complications (diabetic neuropathy, nephropathy and retinopathy) and macrovascular events were included. Glycaemic control was the second most commonly included domain, with levels of blood glucose and/or HbA 1c used in eight (44%) severity measures [21,22,[26][27][28][29]32,35]. The complexity of antidiabetic treatment domain was also used in four (22%) severity measures and was assessed as insulin use and/or the number of prescribed antidiabetic therapies (monotherapy vs drug combinations) [20,29,30].…”

Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance

“…Evidence in support of brain changes in relation to MVRFs is however mixed (Cavalieri et al, 2010). A meta-analysis on the role of blood pressure implicates loss of brain tissue in the frontal and temporal lobes (Beauchet et al, 2013;Schneider et al, 2017). A meta-analysis on the role of blood pressure implicates loss of brain tissue in the frontal and temporal lobes (Beauchet et al, 2013;Schneider et al, 2017).…”