Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

Nunley, Karen A.; Rosano, Caterina; Jennings, J. Richard; Aizenstein, Howard J.; Zgibor, Janice C.; Costacou, Tina; Boudreau, Robert M.; Miller, Rachel G.; Orchard, Trevor J.; Saxton, Judith

doi:10.2337/dc15-0041

Cited by 106 publications

(118 citation statements)

References 39 publications

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“…The strongest predictors of cognitive dysfunction include a history of chronic hyperglycemia, indexed by elevated glycosylated hemoglobin (HbA1c) values, and retinal and renal microvascular complications (Jacobson et al, 2011; Ryan, Geckle, & Orchard, 2003). In contrast, episodes of recurrent severe hypoglycemia have not been found to be associated with cognitive changes – at least in the large cohorts of young and middle-aged adults who participated in the Diabetes Control and Complications Trial (DCCT) (DCCT/EDIC Research Group, 2007) or the Epidemiology of Diabetes Complications study (Nunley et al, 2015). These null results are puzzling, given recent reports that hypoglycemia is associated with an increased risk of cognitive dysfunction and dementia in older adults with type 2 diabetes (Lin & Sheu, 2013; Whitmer, Karter, Yaffe, Quesenberry, & Selby, 2009).…”

Section: Introductionmentioning

confidence: 99%

Associations between recent severe hypoglycemia, retinal vessel diameters, and cognition in adults with type 1 diabetes

Ryan

Klein

Lee

et al. 2016

Journal of Diabetes and its Complications

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Aims Mild cognitive dysfunction has been identified in children and adults with type 1 diabetes, but most studies have failed to find a relationship between severe hypoglycemia and cognition, despite reports of such associations in older adults with type 2 diabetes. Focusing on older adults with type 1 diabetes, we examined associations between cognitive performance and recent episodes of severe hypoglycemia, retinal vessel diameters and the presence of micro- and macrovascular complications. Methods Cognitive functioning was assessed in 244 participants enrolled in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. The mean (SD; range) age at assessment in 2012 – 14 was 55.2 (8.3; 37 – 82) years and the mean (SD) duration of diabetes was 41.1 (5.6) years. Three cognitive domains were assessed in this cross-sectional study: mental efficiency and executive function, nonverbal memory, and verbal memory. Results Multivariate modeling demonstrated that although age and/or education are most strongly associated with performance on measures of mental efficiency, three diabetes-related variables were also associated with poorer test scores: an episode of severe hypoglycemia in the past year (β = −0.360 [95% CI, −0.672, −0.047]), retinal arteriolar and venular diameters (β = 0.140 [95% CI, 0.062, 0.219]; β = −0.127 [95% CI −0.207, −0.047]), and carotid artery plaque (β = −0.372 [95% CI −0.741, −0.003]). In addition, recent severe hypoglycemia was associated with poorer nonverbal memory (β = −0.522 [95% CI, −0.849, −0.194]). Conclusions For middle-aged and older adults with long-duration type 1 diabetes, poorer cognition was associated with a recent episode of severe hypoglycemia as well as with the presence of micro- and/or macrovascular conditions. Given the increasing numbers of aging adults with type 1 diabetes, future longitudinal studies are needed to identify causality and to determine whether diabetes management techniques that reduce the onset or severity of vascular complications and hypoglycemia can also reduce the risk of cognitive dysfunction in this population.

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Section: Introductionmentioning

confidence: 99%

Associations between recent severe hypoglycemia, retinal vessel diameters, and cognition in adults with type 1 diabetes

Ryan

Klein

Lee

et al. 2016

Journal of Diabetes and its Complications

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“…Hyperglycaemia is a risk factor for the development of microvascular disease in the brain 27,28 and in the eye, 29 as well as CI in adults with T1D. [1][2][3]30,31 It has been suggested that hyperglycaemia induces systemic microand macrovascular damage 32 through a variety of mechanisms including oxidative stress, 33 accumulation of advanced glycation end products 34 and inhibition of endothelial nitric oxide synthase activity. 35 However, in this report, associations between CRAE longitudinal measures and CI did not differ by severity of hyperglycaemia.…”

Section: Discussionmentioning

confidence: 99%

“…1 On average, participants were diagnosed with T1D at 9 years of age. At time of neurocognitive testing, participants ranged in age from 32.2 to 61.7 years, with T1D duration ranging from 31.5 to 48.5 years.…”

Section: Sample Characteristicsmentioning

confidence: 99%

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

Nunley

Metti

Klein

et al. 2018

Diabetes and Vascular Disease Research

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Objective: To assess associations between cognitive impairment and longitudinal changes in retinal microvasculature, over 18 years, in adults with type 1 diabetes. Research design and methods: Participants of the Pittsburgh Epidemiology of Diabetes Complications Study received ≥3 fundus photographs between baseline (1986)(1987)(1988) and time of cognitive assessment (2010)(2011)(2012)(2013)(2014)(2015): N = 119; 52% male; mean age and type 1 diabetes duration 43 and 34 years, respectively). Central retinal arteriolar equivalent and central retinal venular equivalent were estimated via computer-based methods; overall magnitude and speed of narrowing were quantified as cumulative average and slope, respectively. Median regression models estimated associations of central retinal arteriolar equivalent and central retinal venular equivalent measures with cognitive impairment status, adjusted for type 1 diabetes duration. Interactions with HbA1c, proliferative retinopathy and white matter hyperintensities were assessed. Results: Compared with participants without cognitive impairment, those with clinically relevant cognitive impairment experienced 1.8% greater and 31.1% faster central retinal arteriolar equivalent narrowing during prior years (t = −2.93, p = 0.004 and t = −3.97, p < 0.0001, respectively). Interactions with HbA1c, proliferative retinopathy and white matter hyperintensities were not significant. No associations were found between central retinal arteriolar equivalent at baseline, at time of cognitive testing, or any central retinal venular equivalent measures, and cognitive impairment. Conclusion: Long-term arterial retinal changes could indicate type 1 diabetes-related cognitive impairment. Studies examining longitudinal central retinal arteriolar equivalent changes as early biomarkers of cognitive impairment risk are warranted.

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“…Además, el mayor deterioro se asoció con el mal control metabólico medido por hemoglobina glicosilada (HbA1c) y mayor prevalencia de compromiso cardiovascular 13 . Por otra parte, el seguimiento a largo plazo del sub grupo de pacientes jóvenes con edades entre 13 y 19 años que participó en el clásico estudio DCCT ("Diabetes control and complication trial" ), ha demostrado que los sujetos que tenían HbA1c más elevadas en la década del noventa, han desarrollado mayor deterioro en las áreas psicomotoras y de eficiencia mental [14][15][16] .…”

Section: Introductionunclassified

Control metabólico y rendimiento escolar en niños con diabetes tipo 1

Román

Garrido

Novoa

et al. 2017

Rev. chil. pediatr.

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ResumenEl impacto de la diabetes tipo 1 (DM1) en el rendimiento escolar es controversial. Objetivo: Evaluar la relación entre rendimiento escolar y control metabólico en niños con DM1 (N-DM1) y comparar sus resultados con niños de la población general (N-PG). Pacientes y Método: Se revisaron datos clínicos de 66 N-DM1. Se compararon las calificaciones de N-DM1 según Hemoglobina Glicosilada (HbA1c) < 7,5% y ≥ 7,5% con N-PG del mismo nivel, comuna, tipo de colegio (municipal, particular subvencionado y particular pagado) y localidad. Para la comparación de los grupos se utilizó la regresión lineal simple y el test de suma de los rangos de Wilcoxon (Mann y Whitney) previa comprobación de incumplimiento de normalidad con el test de Shapiro-Wilk según el caso. Se consideró un valor de p < 0,05 como estadísticamente significativo con una confiabilidad del 95%. Resultados: La edad fue 13,4 ± 2,9 años, tiempo de evolución DM1 5,3 ± 3,2 años, HbA1c 8,6 ± 1,9% y controles de glicemia capilar 3,2 ± 1,2 veces por día. Las calificaciones no mostraron correlación con HbA1c, duración de DM1, hipotiroidismo, problemas de salud mental, antecedentes de hipoglicemia ni de cetoacidosis. N-DM1 de educación básica mostraron calificaciones inferiores a N-PG del mismo nivel 5,6 ± 0,7 vs 6,0 ± 0,2 (p = 0,0002). Las calificaciones se correlacionaron con el número de controles diarios de glicemia capilar, coeficiente de correlación de Pearson (r) de 0,25, 0,41, 0,52 y 0,58 con el promedio general, matemática, lenguaje e historia respectivamente (p < 0,05). Un 6,1% de N-DM1 y 4,8% de N-PG no fue promovido de curso (p = 0,65). La deserción escolar fue 10,5% en N-DM1 y 7,7% en N-PG (p = 0,47). Conclusión: N-DM1que cursaban educación básica tuvieron calificaciones inferiores a N-PG y los pacientes que controlaban su glicemia capilar con mayor frecuencia mostraron mejores calificaciones. La DM1 puede tener un impacto deletéreo en el rendimiento escolar.

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Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

Cited by 106 publications

References 39 publications

Associations between recent severe hypoglycemia, retinal vessel diameters, and cognition in adults with type 1 diabetes

Associations between recent severe hypoglycemia, retinal vessel diameters, and cognition in adults with type 1 diabetes

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

Control metabólico y rendimiento escolar en niños con diabetes tipo 1

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