Study Details Brain Matter Changes, Cortical Thinning Among Patients With T1D, Neuropathy

Researchers found individuals with type 1 diabetes and neuropathy exhibit altered gray matter volume and cortical thickness compared with healthy controls.

Adults with type 1 diabetes (T1D) and neuropathy exhibited reduced total gray matter volume (GMV) compared with healthy controls, while total GMV loss seems to be related to the severity of neuropathy in this population, results of a brain morphology study indicate. Findings were published in Neuroscience Research.

Diabetic neuropathy affects both the peripheral and central nervous systems, and previous research has indicated hyper/hypoglycemia has an impact on total GMV and brain atrophy may be associated with microvascular complications and neuropathy, authors explained.

Although regional GMV loss has been identified in specific brain regions in patients with T1D and polyneuropathy, few studies with small sample sizes have investigated cortical thickness in this cohort. Specifically, these studies revealed “reduced cortical thickness in the right postcentral gyrus was associated with the presence of peripheral neuropathy, and reduced cortical thickness in the somatosensory cortex was shown in adults with severe painful distal symmetric polyneuropathy (DSPN),” they said.

To better understand neuronal loss/dysfunction among those with T1D and severe DSPN, the researchers characterized total GMV compared with healthy controls and explored associations with clinical characteristics and parietal N-acetylaspartate/creatine (NAA/cre)—a potential surrogate marker for overall brain atrophy.

Forty-six adults with T1D and DSPN and 28 healthy controls underwent MRI scans; all were over the age of 18, and patients had received their T1D diagnosis at least 2 years prior. Participants were recruited from a hospital in Denmark between 2014 and 2017.

Analyses revealed:

  • Adults with DSPN and T1D had reduced mean (SD) total GMV compared with controls (627.4 [4.1] mL vs 642.5 [5.2] mL; P = .026)
  • GMV loss was more pronounced for participants with painful neuropathy compared with controls (619.1 [8.9] mL vs 642.4 [5.2] mL; P = .026) and for those with proliferative vs nonproliferative retinopathy (609.9 [6.8] mL vs 636.0 [4.7] mL, P = .003)
  • Characteristics such as severity of neuropathy and decreased parietal NAA/cre metabolite concentration seem to be related to GMV loss
  • Regional GMV loss was confined to the bilateral thalamus/putamen/caudate, occipital, and precentral regions, and decreased cortical thickness was identified in frontal areas

“Besides age as a predictor for GMV loss, the severity of neuropathy and decreased parietal NAA/cre metabolite level were explanatory characteristics, even though the associations with brain atrophy were only borderline,” the researchers wrote.

Because reduction in the parietal NAA/cre metabolite ratio was associated with gray matter atrophy, this measure could be used as a marker to indicate neuronal integrity in patients with T1D.

The investigators were unable to determine if the observed brain changes were due to diabetes, the presence of diabetic neuropathy, or macroangiopathy leading to proliferative retinopathy, marking a limitation to the study. Future studies should assess the role of aging and other disease related co-factors and clinical characteristics.

“We confirmed that structural brain alteration is a key finding in diabetic neuropathy. Exploration of the brain in diabetes could play a key role in establishing a deeper understanding and better characterization of diabetic neuropathy,” the authors concluded.

“Such better phenotyping, including imaging biomarkers of the brain, could in the future help to understand neuropathy development, potentially identify early neuropathy, and optimize and monitor future interventions targeting the neuropathy,” they said.


Hansen TM, Muthulingam JA, Brock B, et al. Reduced gray matter brain volume and cortical thickness in adults with type 1 diabetes and neuropathy. Neurosci Res. Published online October 14, 2021. doi:10.1016/j.neures.2021.10.002

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