White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes

Abstract

Objective: Although microvascular complications are common in type 1 diabetes mellitus (T1DM), few studies have quantified the severity, risk factors, and implications of cerebral microvascular damage in these patients. As life expectancy in patients with T1DM increases, patients are exposed to age- and disease-related factors that may contribute to cerebral microvascular disease.

Methods: Severity and volume of white matter hyperintensities (WMH) and infarcts were quantified in 97 middle-aged patients with childhood-onset T1DM (mean age and duration: 50 and 41 years, respectively) and 81 non-T1DM adults (mean age: 48 years), concurrent with cognitive and health-related measures.

Results: Compared with non-T1DM participants, patients had more severe WMH (Fazekas scores 2 and 3 compared with Fazekas score 1, p < 0.0001) and slower information processing (digit symbol substitution, number correct: 65.7 ± 10.9 and 54.9 ± 13.6; pegboard, seconds: 66.0 ± 9.9 and 88.5 ± 34.2; both p < 0.0001) independent of age, education, or other factors. WMH were associated with slower information processing; adjusting for WMH attenuated the group differences in processing speed (13% for digit symbol, 11% for pegboard, both p ≤ 0.05). Among patients, prevalent neuropathies and smoking tripled the odds of high WMH burden, independent of age or disease duration. Associations between measures of blood pressure or hyperglycemia and WMH were not significant.

Conclusions: Clinically relevant WMH are evident earlier among middle-aged patients with childhood-onset T1DM and are related to the slower information processing frequently observed in T1DM. Brain imaging in patients with T1DM who have cognitive difficulties, especially those with neuropathies, may help uncover cerebral microvascular damage. Longitudinal studies are warranted to fully characterize WMH development, risk factors, and long-term effects on cognition.

Figure 1. Between-group differences in severity of white matter hyperintensities

(A) Percentage of participants with type 1 diabetes (black bars) and without type 1 diabetes (blue bars) for each level of WMH severity per Fazekas score; 1 = mild; 2 = moderate; 3 = severe. All differences are statistically significant (p < 0.01). (B) FLAIR image from a 49-year-old woman without type 1 diabetes with a notable absence of WMH in periventricular (indicated by arrows) or subcortical areas or other areas. (C) FLAIR image from a 49-year-old woman with type 1 diabetes since age 10 (Epidemiology of Diabetes Complications Study), with arrows indicating substantial WMH localized in anterior and posterior periventricular areas (arrows) as well as in subcortical areas. FLAIR = fluid-attenuated inversion recovery; WMH = white matter hyperintensity.