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White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes
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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.
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Neurocognitive changes have been associated with microvascular and macrovascular alterations, brain structural changes, neuronal loss, and cerebral atrophy.
“their development has been linked with both microvascular and macrovascular changes and changes in brain structure, neuronal loss, and cerebral atrophy.123,124”
From Type 1 diabetes (2018) · cites this paper as [123]
The Results and Discussion (page not supplied) link white matter hyperintensities, a brain structural finding, with slower information processing in middle-aged adults with childhood-onset type 1 diabetes. The paper does not establish the claimed links with macrovascular changes, neuronal loss, or cerebral atrophy. (LLM, conf=0.87)
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DiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31320-5 · Cited by 1,561
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Metadata
- Authors
- Nunley, K. A., Ryan, C. M., Orchard, T. J., Aizenstein, H. J., Jennings, J. R., Ryan, J., Zgibor, J. C., Boudreau, R. M., Costacou, T., Maynard, J. D., Miller, R. G., & Rosano, C.
- Affiliations
- University of Pittsburgh (US)
- ORCID
- Venue
- Neurology
- Published
- 2015-05-19
- Volume
- 84
- Issue
- 20
- Pages
- 2062-2069
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4442104
- OpenAlex
- W2092829693
- Cited by
- 68
- References
- 41
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 2 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 9 · 2015: 2
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag037451-05)
- National Institute on Aging (R01-AG037451, AG044474, RF1AG025516, R01AG044474, AG025516, R01AG014116, AG037451, R37AG025516, P30AG024827, R01AG025516)
- National Heart, Lung, and Blood Institute (R01HL101959, R01HL105647, R01HL111802)
- National Institute of Mental Health (R01MH076079, R01MH101088, R01MH084938, MH085722, R01MH085722, MH0-76079)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK034818, K01DK095759, R01DK034818, R01DK089028)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- white matter hyperintensities, childhood-onset type 1 diabetes, processing speed, peripheral neuropathy, smoking, middle-aged adults, cognitive impairment, cerebral infarction, Fazekas score
- MeSH terms
- Adult, Brain, Diabetes Mellitus, Type 1, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Risk Factors, White Matter
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