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Brain Structure among Middle-aged and Older Adults with Longstanding Type 1 Diabetes in the DCCT/EDIC Study

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posted on 2022-06-14, 15:20 authored by Alan M. Jacobson, Barbara H. Braffett, Guray Erus, Christopher M. Ryan, Geert J. Biessels, José A. Luchsinger, Ionut Bebu, Rose A. Gubitosi-Klug, Lisa Desiderio, Gayle M. Lorenzi, Victoria R. Trapani, John M. Lachin, R. Nick Bryan, Mohamad Habes, Ilya M. Nasrallah, the DCCT/EDIC Study Group

  

Objective: Individuals with type 1 diabetes (T1DM) are living to ages when neuropathological changes are increasingly evident. We hypothesized that middle-aged and older adults with long-standing T1DM will show abnormal brain structure in comparison to non-diabetic controls.

Research Design and Methods: Magnetic resonance imaging (MRI) was used to compare brain structure among 416 T1DM participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study with 99 demographically similar non-diabetic controls at 26 U.S. and Canadian sites. Assessments included total brain (TBV, primary outcome), gray matter (GMV), white matter (WMV), ventricle and white matter hyperintensity (WMH) volumes and white matter fractional anisotropy (FA). Biomedical assessments included HbA1c and lipid levels, blood pressure, and cognitive assessments of memory and psychomotor and mental efficiency (PME). Among EDIC participants, HbA1c, severe hypoglycemia history, and vascular complications were measured longitudinally. 

Results: Mean age of EDIC participants and controls was 60 years. T1DM participants showed significantly smaller TBV (1206 ± 1.7 vs. 1229 ± 3.5 cm3, p<0.0001), GMV and WMV, larger ventricle and WMH volumes, but no differences in mean white matter FA versus controls. Structural MRI measures in T1DM were equivalent to controls who are 4 to 9 years older. Lower PME scores were associated with altered brain structure on all MRI measures in T1DM participants. 

Conclusions: Middle-aged and older adults with T1DM showed brain volume loss and increased vascular injury in comparison to non-diabetic controls, equivalent to 4 to 9 years of brain aging.

Funding

The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017, 2017-2022), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA.

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