Type 2 diabetes is related to neurochemical alterations in the default mode network: An exploratory cross-sectional magnetic resonance spectroscopy study.
Kia Puustinen, Jitske Vandersmissen, Tin Gojevic, Georg Oeltzschner, Helge J Zöllner, Kenneth Verboven, Dominique Hansen, Ilse Dewachter, Melina Hehl, Koen Cuypers
Neuroimage April 22, 2026 DOI: 10.1016/j.neuroimage.2026.121949 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional observational study Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Adults with type 2 diabetes and age- and sex-matched control subjects |
| Measures | Montreal Cognitive Assessment, proton magnetic resonance spectroscopy (1H-MRS) using HERCULES |
| Topics | Default mode network |
| Keywords | Humans Choline Creatine Aspartic acid Cross-sectional studies Middle aged Female Type 2 diabetes Cognitive impairment Brain metabolism 1h-mrs |
| Key findings | People with type 2 diabetes had lower total N-acetylaspartate and total choline in the medial prefrontal cortex, lower total creatine in the posterior cingulate cortex, and lower glutathione in the hippocampus than controls. Glycated hemoglobin was inversely correlated with prefrontal choline, N-acetylaspartate, and creatine and with posterior cingulate creatine, but positively correlated with prefrontal glutamate and with glutamate, glutamine, myo-inositol, and lactate in the left sensorimotor cortex. The authors propose these region-specific deficits may support a deficit model of brain energy metabolism in diabetic encephalopathy. |
Abstract
Background: 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 (1H-MRS) to help elucidate the link between altered glucose metabolism and neurodegeneration.
Method: Adults with T2DM (n = 20) and age- and sex-matched control subjects (n = 20) underwent fasted blood sampling, Montreal Cognitive Assessment, and 1H-MRS using a novel sequence HERCULES, allowing the reliable quantification of small and overlapping signals, adding to the number of quantifiable metabolites.
Results: 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.
Conclusion: 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.
Comparable studies
Other cross-sectional and survey studies on default mode network, most cited first.