The Impact of Diabetes on Cerebral Structure and Function

Abstract

Diabetes alters cerebral metabolism, structure, and function. Both hyperglycemia and therapy-associated hypoglycemia are believed to have an impact on the brain, and this impact may depend on the age of the individual, their stage of neurological development, and whether they have Type 1 or Type 2 diabetes. Hypoglycemia in children with Type 1 has consistently been associated with a reduction in neurocognitive function, but such a finding has not been seen in adults with Type 1 diabetes. Both hypoglycemia and hyperglycemia have been linked with dementia in adults with Type 2 diabetes. In both Type 1 and Type 2 diabetes, recurrent episodes of treatment-associated hypoglycemia impair how well the brain can sense and respond to subsequent episodes of hypoglycemia. In this brief review, we will review how diabetes affects the brain with a focus on investigations done in our own laboratory. We have focused on using high magnetic field imaging and spectroscopy to identify subtle changes in brain structure and metabolism that may contribute to the long-term cerebral complications of diabetes. We have found evidence of microstructural changes in white matter regions, reduced gray matter density, and reduced activation of the thalamus in response to recurrent hypoglycemia in patients with Type 1 diabetes.

FIGURE 1

How does diabetes affect the brain? Effects of hyper- and hypoglycemia.

FIGURE 2

Comparison of neurochemical profiles of patients with T1DM (n = 13) relative to nondiabetic controls (n = 32). Metabolite concentrations were measured from the gray matter–rich occipital lobe (A) and white matter–rich parieto-occipital region (B). Error bars indicate significance levels: *p < .05 and **p < .01. MM is quantified in arbitrary units. T1DM = Type 1 diabetes; MM = macromolecules; Asp = aspartate; Asc = ascorbate; Cr = creatine; GABA = g-aminobutyric acid; Glc = glucose; Gln = glutamine; Glu = glutamate; GSH = glutathione; myo-Ins = myo-inositol; scyllo-Ins = scyllo-inositol; Lac = lactate; NAA = N-acetylaspartate; NAAG = N-acetylaspartylglutamate; PE = phosphoethanolamine; Tau = taurine; GPC+PC = the sum of glycerophosphocholine and phosphocholine; Cr = creatine; PCr = phosphocreatine. Reprinted by permission from Macmillan Publishers Ltd: Journal of Cerebral Blood Flow and Metabolism (18).

FIGURE 3

Cerebral blood flow responses to hypoglycemia in 12 controls (C) and 11 participants with Type 1 diabetes and hypoglycemia unawareness (D). t Scores were evaluated where the change in %SI differed from zero. Red to yellow (green to blue) indicates larger (smaller) changes in cerebral blood flow in hypoglycemia versus euglycemia. %SI = signal intensity. Reprinted with permission from Macmillan Publishers Ltd: Journal of Cerebral Blood Flow and Metabolism (21).