Hyperglycaemia is associated with changes in the regional concentrations of glucose and myo-inositol within the brain

Abstract

Aims/hypothesis The aim of the study was to assess the effect of hyperglycaemia on regional concentrations of glucose and other substrates within the brain in nondiabetic individuals and in patients with type 1 diabetes. Methods The brain metabolites of 17 men with type 1 diabetes and 12 age-matched non-diabetic men (22-43 years old) were studied after an overnight fast (plasma glucose 9.2±3.0 vs 4.8±0.5 mmol/l, respectively). N-Acetylaspartate (NAA), creatine, choline, myo-inositol (mI) and glucose in the frontal cortex, frontal white matter and thalamus were quantified with proton magnetic resonance spectroscopy. Results In the non-diabetic participants, the glucose level was 47% higher (p<0.01) in the frontal cortex than in the frontal white matter. In contrast, this regional variation was not observed in the diabetic participants, in whom the glucose level in the frontal white matter was 64% higher (p<0.001) and in the frontal cortex 25% higher (p=0.033) than that of the non-diabetic participants. In the diabetic participants, the glucose level in each of the three regions studied correlated with fasting plasma glucose (r=0.88-0.67, p<0.01). In addition, in the diabetic participants, mI was 20% higher (p<0.001) and NAA 6% lower (p=0.037) in the frontal white matter, and mI was 8% higher (p= 0.042) in the frontal cortex, than in the non-diabetic participants. Conclusions/interpretation In type 1 diabetes, hyperglycaemia is associated with accumulation of glucose and mI in the cortex and in the white matter.

Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

“…[3][4][5] In contrast, other studies found no changes of NAA level in left basal ganglion, thalamus, frontal cortex, WM-rich parieto-occipital cortex, and posterior frontal WM. [3][4][5][6] Increased myo-inositol (Ins) level was frequently observed in frontal lobe, basal ganglia, temporal, and frontal cortex, 2,3,6 but not in thalamus, occipital lobe, and WM-rich parieto-occipital region in T1DM patients. 3,5,6 These clinical studies suggested that T1DM-related cerebral metabolic changes may be region specific.…”

“…9,14,25 Absolute tCr concentration was also measured by in vivo 1 H-MRS in the basal ganglia, frontal lobe, temporal lobe, GM-rich occipital lobe, thalamus, posterior frontal WM, and WM-rich parieto-occipital region of clinical T1DM patients, and none of these studies reported any significant changes in the tCr level. 2,3,5,6 One previous study showed that absolute hyperglycemia tCr level in the hippocampus of STZ-treated rats were~10% higher than control at 30 days after induction. 8 However, it was reported that the brain water content was reduced in STZ-treated T1DM rats since 1 week after induction, 40 and such dehydration would potentially lead to overestimation of absolute concentration of cerebral metabolites in diabetic animals.…”

“…24 The reasons underlying the differential changes of Tau in the striatum and hippocampus are unclear, but could be related to the fact that STZ-induced T1DM results in more severely perturbed glucose metabolism in the hippocampus than in the striatum. 25 Visual Cortex A number of clinical studies have investigated T1DM-related metabolic changes in the frontal 3,6 and occipital 5,26 cortex. While the results from the frontal cortex are rather consistent, the observations from the occipital cortex appeared to be varied.…”

“…[3][4][5][6] Increased myo-inositol (Ins) level was frequently observed in frontal lobe, basal ganglia, temporal, and frontal cortex, 2,3,6 but not in thalamus, occipital lobe, and WM-rich parieto-occipital region in T1DM patients. 3,5,6 These clinical studies suggested that T1DM-related cerebral metabolic changes may be region specific. Metabolic alterations in the brain of type 2 DM (T2DM) patients also appeared to be region specific.…”

Alteration of Interaction Between Astrocytes and Neurons in Different Stages of Diabetes: a Nuclear Magnetic Resonance Study Using [1-13C]Glucose and [2-13C]Acetate

“…All these abnormalities are closely related to brain metabolic disorders [10]. For example, decreased N-acetyl aspartate (NAA) [11] and increased myo-inositol (m-Ins) [12] concentrations have been observed in the white matter of individuals with diabetes by using localized proton nuclear magnetic resonance ( 1 H NMR). In addition, streptozotocin (STZ)-induced diabetic rats exhibited increased cerebral lactate/choline (Lac/Cho) ratio [13].…”