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

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 macrovascular 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. 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 re-assessed 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. 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 HbA(1c) 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 epsilon 4 allele. 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. ClinicalTrials.gov NCT00360893 This study is supported by NIH grant number 5RO1 DK062218-02. The DCCT/EDIC project is supported by contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program, the Clinical and Translational Science Awards Program, the National Center for Research Resources and by Genentech through a Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases.