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 6 10.9 and 54.9 6 13.6; pegboard, seconds: 66.0 6 9.9 and 88.5 6 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. Patients with type 1 diabetes mellitus (T1DM) develop slower information processing speed earlier than adults without diabetes.1 In nondiabetic populations, slower information processing speed is strongly associated with white matter hyperintensities (WMH).2,3 Few studies, however, have characterized WMH in patients with T1DM. 4 Most of the knowledge about WMH comes from older populations without diabetes: WMH 5 are common in individuals older than 65 years, 6 with a prevalence ranging from 60% to 100%, 7 and are less frequent in middle-aged adults, with prevalence ranging from 0% to 50%. 8 Although they can remain silent, WMH predict greater incidence of stroke, dementia, disability, and death.2,9-11 In addition to older age, chronic exposure to hypertension and hyperglycemia are known risk factors for WMH in adults without diabetes, conditions that may predispose patients with T1DM to develop WMH. Considering the increasing life expectancy in T1DM 12 and the 1.5% to 3.0% annual increase in T1DM incidence, 13 determining the severity of, and risk factors for, WMH in patients with T1DM who are now aging deserves prompt...

Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia

“…Increased presence of cerebral small vessel disease such as white matter hyperintensities and lacunes have been reported among individuals with T1DM (mean age 50 years) (57,58); however, other studies among older T1DM patients (mean age ~60 years and with known microvascular complications) (59) have reported no significant differences in white matter lesions or microinfarcts compared with control subjects. While we cannot exclude the possibility that occult cerebrovascular disease may also contribute to the differences observed in the T1DM-Unaware individuals, this appears less likely given our participants had well-controlled diabetes, had no history of cerebrovascular disease or cardiovascular disease, and were significantly younger (mean age 30 and 40 years for T1DM-Aware and -Unaware, respectively) than the groups reported in the literature.…”

Long-term changes in retinal vascular diameter and cognitive impairment in type 1 diabetes

“…As previously described, WMH had no parenchymal loss, nor showed central suppression on the T2/FLAIR. 3 In addition, severity of WMH was visually rated using the Fazekas scale, with possible scores of 0 (no WMH/normal), 1 (mild), 2 (moderate) and 3 (severe). 19 As we have previously shown, none of these T1D participants were free of WMH; hence, Fazekas scores in this population ranged from 1 to 3.…”

“…19 As we have previously shown, none of these T1D participants were free of WMH; hence, Fazekas scores in this population ranged from 1 to 3. 3 …”

“…T1D-related CI appears to have a vascular origin as it is strongly related to cerebral microvascular disease, measured as white matter hyperintensities (WMHs) 3,4 on brain magnetic resonance imaging (MRI). However, obtaining a brain MRI is expensive and not always feasible, as many people with T1D are MRI ineligible.…”

The diabetic brain and cognition

“…It was shown that patients with T1DM have an increased risk of lacunar stroke (Luitse et al 2012) and those with additional microangiopathy had decreased structural connectivity in posterior brain regions (van Duinkerken et al 2012a) and impaired function in the ventral attention network (Van Duinkerken et al 2012b). However, the effect of vascular lesions on the cognitive decline in T1DM patients is not entirely clear Nunley et al 2015;Biessels and Reijmer 2014;Huang et al 2014). In contrast to T2DM, T1DM begins earlier in life and may influence brain development (Biessels et al 2008;de Felice and Benedict 2015) via insulin receptors in the hypothalamus, which play a key role in the memory system (De Felice et al 2014;de Felice and Benedict 2015).…”