Prediabetes and structural brain abnormalities: Evidence from observational studies

Abstract

Type 2 diabetes mellitus has been linked to structural brain abnormalities, but evidence of the association among prediabetes and structural brain abnormalities has not been systematically evaluated. Comprehensive searching strategies and relevant studies were systematically retrieved from PubMed, Embase, Medline and web of science. Twelve articles were included overall. Stratified analyses and regression analyses were performed. A total of 104 468 individuals were included. The risk of infarct was associated with continuous glycosylated haemoglobin (HbA_1c ) [adjusted odds ratio (OR) 1.19 (95% confidence interval [CI]: 1.05-1.34)], or prediabetes [adjusted OR 1.13 (95% CI: 1.00-1.27)]. The corresponding ORs associated with white matter hyperintensities were 1.08 (95%CI: 1.04-1.13) for prediabetes, and 1.10 (95%CI: 1.08-1.12) for HbA_1c . The association was significant between the decreased risk of brain volume with continuous HbA_1c (the combined OR 0.92, 95% CI: 0.87-0.98). Grey matter volume and white matter volume were inversely associated with prediabetes [weighted mean deviation (WMD), -9.65 (95%CI: -15.25 to -4.04) vs WMD, -9.25 (95%CI: -15.03 to -3.47)]. There were no significant association among cerebral microbleeds, hippocampal volume, continuous total brain volume, and prediabetes. Our findings demonstrated that (a) both prediabetes and continuous HbA_1c were significantly associated with increasing risk of infarct or white matter hyperintensities; (b) continuous HbA_1c was associated with a decreased risk of brain volume; (c) prediabetes was inversely associated with grey matter volume and white matter volume. To confirm these findings, further studies on early diabetes onset and structural brain abnormalities are needed.

Keywords: glycosylated haemoglobin; meta-analysis; prediabetes; structural brain abnormalities.

Figure 1

Results of systematic literature search

Figure 2

The association between continuous HbA_1c with infarct, A, and white matter hyperintensities, B. A, The association between continuous HbA_1c with infarct. B, The association between continuous HbA_1c with white matter hyperintensities. Where I ² is the variation in effect estimates attributable to heterogeneity, overall is the pooled fixed effect estimate of all studies. Subtotal is the pooled fixed effects estimate of sub‐group analysis studies. Weights are from fixed‐effects analysis. Percentage of weight is the weight assigned to each study, based on the inverse of the within‐ and between‐study variance. The size of the grey boxes around the point estimates reflects the weight assigned to each study. The summarized studies were adjusted for age, sex and BMI. Abbreviation: OR, odds ratio

Figure 3

The association between continuous HbA_1c with brain volume. Where I ² is the variation in effect estimates attributable to heterogeneity, overall is the pooled fixed effect estimate of all studies. Subtotal is the pooled fixed effects estimate of sub‐group analysis studies. Weights are from fixed‐effects analysis. Percentage of weight is the weight assigned to each study, based on the inverse of the within‐ and between‐study variance. The size of the grey boxes around the point estimates reflects the weight assigned to each study. The summarized studies were adjusted for age, sex and BMI. Abbreviation: OR, odds ratio

Figure 4

The association between prediabetes with infarct, A, and white matter hyperintensities, B. A, The association between prediabetes with infarct. B, The association between prediabetes with white matter hyperintensities. Where I ² is the variation in effect estimates attributable to heterogeneity, overall is the pooled fixed effect estimate of all studies. Subtotal is the pooled fixed effects estimate of sub‐group analysis studies. Weights are from fixed‐effects analysis. Percentage of weight is the weight assigned to each study, based on the inverse of the within‐ and between‐study variance. The size of the grey boxes around the point estimates reflects the weight assigned to each study. The summarized studies were adjusted for age, sex and BMI. Abbreviations: OR, odds ratio; WMD, weighted mean deviation

Figure 5

The association between prediabetes with continuous white matter volume, A, and continuous grey matter volume, B. A, The association between prediabetes with continuous white matter volume. B, The association between prediabetes with continuous grey matter volume. Where I ² is the variation in effect estimates attributable to heterogeneity, overall is the pooled fixed effect estimate of all studies. Subtotal is the pooled fixed effects estimate of sub‐group analysis studies. Weights are from fixed‐effects analysis. Percentage of weight is the weight assigned to each study, based on the inverse of the within‐ and between‐study variance. The size of the grey boxes around the point estimates reflects the weight assigned to each study. The summarized studies were adjusted for age, sex and BMI. Abbreviation: WMD, weighted mean deviation