Gray Matter Brain Alterations in Type 1 Diabetes – Findings Based on Detailed Phenotyping of Neuropathy Status

Abstract

Aims This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements. Methods Sixty individuals with type 1 diabetes and 20 healthy controls were included in the study. Nineteen individuals with type 1 diabetes and neuropathic pain, 19 with type 1 diabetes and DPN, 18 with type 1 diabetes without DPN, and 20 healthy controls were included in the brain analyses. We utilized structural brain magnetic resonance imaging to investigate total and regional gray matter volume. Results Significant lower gray matter volume was found in type 1 diabetes with neuropathic pain and in type 1 diabetes without DPN compared to healthy controls (p=0.024 and p=0.019, respectively). Lower insula volume was observed in all three diabetes groups (all p≤0.050). Thalamus and hippocampus volume was lower in type 1 diabetes with neuropathic pain, cerebellum volume was lower in type 1 diabetes with DPN, and somatosensory cortex volume was lower in type 1 diabetes without DPN (all p≤0.018). Attenuated memory was associated with lower gray matter volume in type 1 diabetes with DPN. No associations were found between gray matter volume and clinical/peripheral measurements. Conclusion We demonstrated lower gray matter volume in individuals with type 1 diabetes regardless of the presence of DPN and neuropathic pain. Hence, central gray matter alteration was not associated with peripheral alterations.

Diagnostic Accuracy of Perception Threshold Tracking in the Detection of Small Fiber Damage in Type 1 Diabetes

“…The study was conducted between August 2019 and February 2022 in participants from the "MEDON" (Methods for Early Detection Of diabetic peripheral Neuropathy)-cohort (clinicaltrials.gov: NCT04078516) [12][13][14]. This population is described in details elsewhere, but in short, the original cohort consisted of 80 participants equally divided into four groups: participants with T1DM and painful diabetic peripheral neuropathy (PDPN), participants with T1DM and DPN, participants with T1DM and no DPN, and healthy controls (HC) without diabetes or pain [12][13][14]. The four groups were matched 1:1:1:1 on age (+/-2 years) and sex.…”

“…Neuropathic pain severity (over the last 4 weeks) was derived from the PainDETECT questionnaire as average and peak pain intensity rated on a visual analog scale (VAS) ranging from 0-10, where 0 is no pain and 10 is the most intense pain imaginable [18]. Quantitative sensory testing and conventional nerve conduction studies were performed as previously described and reported [12][13][14].…”

Characterization of the central nervous system in diabetic peripheral neuropathy: Aspects of cognitive, structural, and functional brain alterations in type 1 diabetes

“…No significant differences in total GMV were observed between the three diabetes groups. (82) Overall, these data provide the knowledge that GMV is altered in T1DM regardless of the presence of DPN or neuropathic pain. This was further supported by the lack of association between total GMV and peripheral nerve function.…”

“…(94) In Paper II lower volume of thalamus was observed in the diabetes individuals experiencing neuropathic pain. (82) The structural changes may contribute to the development of neuropathic pain but also to the functional thalamic connectivity alterations observed in the same group in Paper III. This will be discussed later in section 6.3.…”

“…MRI has a high spatial resolution and can provide essential information on structural volume loss, including gray matter alterations. (20,21) Also, the functional activity of the brain can be obtained using functional MRI (fMRI), which utilizes a blood-oxygen-level-dependent (BOLD) signal. This approach may give valuable information about the infrastructure of the brain that otherwise may not be "visible".…”