• T2DM group showed reduced tNAA and tCho (PFC), tCr (PCC), and GSH (hippocampus) • Various brain metabolite levels may be correlated to blood glucose control • Considering glucose control as a continuum might offer more sensitivity • HERCULES 1 H-MRS allowed more metabolites to be quantified simultaneously • Findings suggest regional alterations in brain energy metabolism in T2DM Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder linked to an increased risk for neurodegeneration and cognitive impairment. The current study set out to explore a wide range of indirect markers of neuronal function via proton magnetic resonance spectroscopy ( 1 H-MRS) to help elucidate the link between altered glucose metabolism and neurodegeneration. Adults with T2DM ( n = 20) and age- and sex-matched control subjects ( n = 20) underwent fasted blood sampling, Montreal Cognitive Assessment, and 1 H-MRS using a novel sequence HERCULES, allowing the reliable quantification of small and overlapping signals, adding to the number of quantifiable metabolites. Significant neurometabolic differences were observed in three brain regions. Namely, N-acetylaspartate (tNAA) and total choline (tCho) in the medial prefrontal cortex, total creatine (tCr) in the posterior cingulate cortex, and glutathione (GSH) in the hippocampus were lower in the T2D group than the control group. Glycated hemoglobin was inversely correlated with prefrontal tCho, tNAA, and tCr levels, as well as posterior cingulate tCr. In contrast, glycated hemoglobin was positively correlated with prefrontal concentrations of glutamate, along with left sensorimotor cortex glutamate, glutamine, myo-inositol, and lactate. The region-specific metabolic deficits in tNAA, tCho, tCr, and GSH observed in the default mode network add to our understanding of diabetic encephalopathy. These exploratory findings might support a deficit model of brain energy metabolism and raise clinically relevant research questions about the neuro-energetic underpinnings of cognitive impairment in T2DM.
Puustinen et al. (2026) studied this question.