Proliferative Retinopathy in Type 1 Diabetes Is Associated With Cerebral Microbleeds, Which Is Part of Generalized Microangiopathy

Woerdeman, Jorn; Duinkerken, Eelco van; Wattjes, Mike P.; Barkhof, Frederik; Snoek, Frank J.; Moll, Annette C.; Klein, Martin; Boer, Michiel P. de; IJzerman, Richard G.; Serné, Erik H.; Diamant, Michaëla

doi:10.2337/dc13-1586

Cited by 61 publications

(50 citation statements)

References 15 publications

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“…These results are consistent with one small case-control study of WMH volumes 14 ; however, other case-control studies reported nonsignificant between-group differences 16,18,22 or an absence of detectable WMH in both T1DM and non-T1DM participants. 15,17 Population characteristics varied across these studies, possibly contributing to the contradictory findings.…”

Section: Resultssupporting

confidence: 81%

“…36 Other diabetes-related factors such as proliferative retinopathy and age at diagnosis were not related to WMH volume, similar to earlier studies. 15,16,18,19,21,22 The 5-year interval between SIF measurement and ascertainment of diabetes-related complications and MRI acquisition may have contributed to these null findings because it may have led to an underestimation of these associations. However, glycated hemoglobin measures and blood pressure were taken periodically through time of MRI.…”

Section: Resultsmentioning

confidence: 76%

“…Among the studies investigating WMH in adults with T1DM, [14][15][16][17][18][19][20][21][22] few quantified the relationship between WMH, advancing age, and cardiovascular risk factors or with processing speed; only one study 16 examined patients older than 50 years.…”

mentioning

confidence: 99%

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

Nunley¹,

Orchard²,

Aizenstein³

et al. 2015

Neurology

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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 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...

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 76%

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

Nunley¹,

Orchard²,

Aizenstein³

et al. 2015

Neurology

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“…Moreover, although type 1 diabetes is an established risk factor for lacunar stroke (30), there are limited data on the occurrence of lacunes on brain MRI in people with type 1 diabetes (29). One recent study on microbleeds reported no difference in the overall occurrence of these lesions relative to control subjects in a small cohort of patients with type 1 diabetes but did observe an increased occurrence in the subgroup of patients with proliferative diabetic retinopathy (31).…”

Section: Type 1 Diabetesmentioning

confidence: 99%

Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?

2014

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Diabetes is associated with cognitive dysfunction and an increased risk of dementia. This article addresses findings with brain MRI that may underlie cognitive dysfunction in diabetes. Studies in adults with type 1 diabetes show regional reductions in brain volume. In those with a diabetes onset in childhood, these volume reductions are likely to reflect the sum of changes that occur during brain development and changes that occur later in life due to exposure to diabetes-related factors. Type 2 diabetes is associated with global brain atrophy and an increased burden of small-vessel disease. These brain changes occur in the context of aging and often also in relation to an adverse vascular risk factor profile. Advanced imaging techniques detect microstructural lesions in the cerebral gray and white matter of patients with diabetes that affect structural and functional connectivity. Challenges are to further unravel the etiology of these cerebral complications by integrating findings from different imaging modalities and detailed clinical phenotyping and by linking structural MRI abnormalities to histology. A better understanding of the underlying mechanisms is necessary to establish interventions that will improve long-term cognitive outcomes for patients with type 1 and type 2 diabetes.Interest in the effect of diabetes on the brain is growing. It is now clear that type 1 diabetes is associated with modest decrements in cognitive functioning, which are most marked in patients with an early childhood diabetes onset (1). These decrements in adults with type 1 diabetes are most evident in the domains of general intelligence, psychomotor speed, and mental flexibility (2). On these domains, the magnitude of the decrements is ;0.3 to 0.7 SD units relative to people without diabetes (2). This implies that, on average, the performance of people with diabetes on these domains is at the 30th to the 40th percentile of control values. The progression of cognitive decrements in adults with type 1 diabetes, relative to people without diabetes, is generally slow, except in subgroups of patients with marked microvascular complications, who may show more marked decline (1).Modest decrements in cognitive functioning, evident on the domains of verbal and visual memory, information processing speed, and executive functioning, have also been noted in people with type 2 diabetes across all age groups (3). Similar to type 1 diabetes, effect sizes are small to moderate (0.3 to 0.4 SD units) (4) and follow a slow progression over time, only modestly exceeding the rate of normal aging-related cognitive decline (3). In older people, however, particularly older than the age of 65, type 2 diabetes is also associated with more severe forms of cognitive impairment. Data from large epidemiological surveys link diabetes to an increased dementia risk. A meta-analysis estimated that people with type 2 diabetes have a relative risk of vascular dementia of 2.5 (95% CI 2.1-3.0) and that of Alzheimer disease is 1.5 (95% CI 1.2-1.8) relative to indiv...

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“…She championed and contributed greatly to the understanding of diabetic cardiomyopathy [1], cerebral changes in patients with type 1 diabetes [2], clinical use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) [3] and glucocorticoid-induced diabetes [4,5]. She collaborated with several national and international researchers on basic science topics that were carefully aligned to her translational research programme, and established deep friendships with numerous colleagues throughout the world [6][7][8].…”

mentioning

confidence: 99%

Michaela Diamant, 11 April 1962–9 April 2014

et al. 2014

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Proliferative Retinopathy in Type 1 Diabetes Is Associated With Cerebral Microbleeds, Which Is Part of Generalized Microangiopathy

Cited by 61 publications

References 15 publications

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

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

Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?

Michaela Diamant, 11 April 1962–9 April 2014

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