Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort

Abstract

Aims/hypothesis In patients with type 1 diabetes, there has been concern about the effects of recurrent hypoglycaemia and chronic hyperglycaemia on cognitive function. Because other biomedical factors may also increase the risk of cognitive decline, this study examined whether macro-vascular risk factors (hypertension, smoking, hypercholesterolaemia, obesity), sub-clinical macrovascular disease (carotid intima–media thickening, coronary calcification) and microvascular complications (retinopathy, nephropathy) were associated with decrements in cognitive function over an extended time period. Methods Type 1 diabetes patients (n=1,144) who had completed a comprehensive cognitive test battery at entry into the Diabetes Control and Complications Trial were reassessed at a mean of 18.5 (range: 15–23) years later. Univariate and multivariable models examined the relationship between cognitive change and the presence of micro-and macrovascular complications and risk factors. Results Univariate modelling showed that smoking history was modestly associated with decrements in learning, memory, spatial information-processing and psychomotor efficiency; hypertension was associated with only psychomotor slowing. Multivariable modelling demonstrated that HbA1c level, and retinal and renal complications were each independently associated with decrements in psychomotor efficiency. In contrast, no macrovascular risk factors were significant after correcting for multiple comparisons. No interactions were found between these predictors and sex, severe hypoglycaemic events or presence of the APOE ε4 allele. Conclusions/interpretation In relatively healthy, middle-aged adults with type 1 diabetes who had been followed for an average of 18.5 years, long-term metabolic control and microvascular factors are independently associated with a decline in cognitive function specifically affecting measures of psychomotor efficiency.

Ventral Striatum, but Not Cortical Volume Loss, Is Related to Cognitive Dysfunction in Type 1 Diabetic Patients With and Without Microangiopathy

“…Indeed, exposure to the similar cumulative hyperglycemic load does not affect the same organ systems, including the microvasculature, to the same extent in all patients. Thus, although proliferative retinopathy has previously been found to be a proxy for type 1 diabetes-related cerebral and cognitive changes (4,7,8), this does not seem to be the case for subcortical structures.…”

“…in type 1 diabetes (4)(5)(6)(7)(8), has been identified as a surrogate marker for cumulative hyperglycemic exposure (9).…”

Cognitive Dysfunction in Older Adults With Diabetes: What a Clinician Needs to Know

“…However, more work is needed to identify the impact of glycemic and nonglycemic factors associated with diabetes on the progression of cognitive dysfunction. Patients with type 1 diabetes enrolled in the DCCT trial were reassessed after 18 years and this assessment showed that long-term poor metabolic control was associated with cognitive decline (23). The ACCORD-MIND study evaluated this relationship in patients with type 2 diabetes and also showed an association between the poor glycemic control and lower cognitive function (24).…”

Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus

“…137 Retinopathy is a microvascular complication of longstanding diabetes mellitus 138 that is associated with cognitive decline in adults. 139 Estimates of the incidence of retinopathy in youth with T1DM vary from 9% 140 to ≈15% per 100 personyears. 141,142 There are limited data in youth with adolescents with T2DM, but these data suggest similar retinal abnormalities are developing.…”