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

Abstract

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.

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

“…These results are consistent with CRAE measures, but not CRVE measures, being associated with microvascular complications in an earlier study of middle-aged Danish T1D patients 39 and with cognitive performance in T1D participants of the Wisconsin Epidemiologic Study of Diabetes Retinopathy. 6 We also replicated results of the Beaver Dam Eye Study showing CRVE was related to older age in our T1D participants. 40 The reasons for these disparate relationships between CRAE and CRVE are not known and deserve further study.…”

“…5 The Wisconsin Epidemiologic Study of Diabetic Retinopathy recently reported a cross-sectional association between retinal vascular measures and CI in adults with T1D. 6 Whether longitudinal changes in these retinal vascular measures (e.g. narrowing or widening over time) could be detectable prior to the onset of CI in adults with T1D remains unknown.…”

A systematic review of the effect of prior hypoglycaemia on cognitive function in type 1 diabetes

“…Recent SH (<1 year) reduced mental efficiency and executive functioning in older people (mean age 55 years) with a long duration of childhood-onset disease. 43 Of the 14 cross-sectional studies, 6 did not find an association between SH and CD but recruited at an older mean age (3/6 recruited at ⩾25 years) and had in general lower thresholds for defining hypoglycaemia as discussed earlier. 19,18,27,34,39,42 Thus, studies that recruited younger participants and defined SH as more severe manifestations of hypoglycaemia were more likely to find a significant association with CD…”

“…SH in the older age group was associated with larger deficits in overall cognition and cognitiveprocessing speed (effect size 6.6 SD). 43,54,56,57 Strengths and limitations The strengths of this study include the use of a multidatabase search culminating in the summary of 62 relevant articles. To the best of our knowledge, this is the first systematic review focusing specifically on the relation between hypoglycaemia and CF in type 1 diabetes across all age groups and thus providing an in-depth review of this topic.…”

The cognitive and psychological effects of living with type 1 diabetes: a narrative review

“…A recent cross-sectional study in older people with type 1 diabetes confirmed that hypoglycaemia, in addition to preexisting microangiopathy was associated with cognitive decrements [23]. The role of hypoglycaemia in type 1…”