Non‐invasive in vivo measurements of metabolic alterations in the type 2 diabetic brain by ¹H magnetic resonance spectroscopy

Abstract

Type 2 diabetes (T2D) is a complex chronic metabolic disorder characterized by hyperglycemia because of insulin resistance. Diabetes with chronic hyperglycemia may alter brain metabolism, including brain glucose and neurotransmitter levels; however, detailed, longitudinal studies of metabolic alterations in T2D are lacking. To shed insight, here, we characterized the consequences of poorly controlled hyperglycemia on neurochemical profiles that reflect metabolic alterations of the brain in both humans and animal models of T2D. Using in vivo 1H magnetic resonance spectroscopy, we quantified 12 metabolites cross‐sectionally in T2D patients and 20 metabolites longitudinally in T2D db/db mice versus db+ controls. We found significantly elevated brain glucose (91%, p < 0.001), taurine (22%, p = 0.02), glucose+taurine (56%, p < 0.001), myo‐inositol (12%, p = 0.02), and choline‐containing compounds (10%, p = 0.01) in T2D patients versus age‐ and sex‐matched controls, findings consistent with measures in T2D db/db versus control db+ littermates. In mice, hippocampal and striatal neurochemical alterations in brain glucose, ascorbate, creatine, phosphocreatine, γ‐aminobutyric acid, glutamate, glutamine, glutathione, glycerophosphoryl‐choline, lactate, myo‐inositol, and taurine persisted in db/db mice with chronic disease progression from 16 to 48 weeks of age, which were distinct from control db+ mice. Overall, our study demonstrates the utility of 1H magnetic resonance spectroscopy as a non‐invasive tool for characterizing and monitoring brain metabolic changes with T2D progression.image

Preface: Special issue: 14thInternational Conference on Brain Energy Metabolism: Energy substrates and microbiome govern brain bioenergetics and cognitive function with aging

“…Aging and diseases associated with aging, diabetes, and obesity‐related alterations in brain metabolism focus on this increasingly important area of research. In‐Young Choi and Phil Lee's paper on “Noninvasive in vivo measurements of metabolic alterations in the type 2 diabetic brain by 1 H magnetic resonance spectroscopy” (Choi et al., 2023) highlights the potential importance of MRS as a clinical tool for identifying and monitoring changes in the brain. Dr. Lee's talk at the conference underscored the key role of beneficial lifestyle choices including adequate dietary choices and exercise in protecting brain health and cognitive function.…”