Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy

Hu, Xiaoli; Buhl, Christian Selmer; Sjogaard, Marie Balle; Schousboe, Karoline; Mizrak, Hatice Isik; Kufaishi, Huda; Jensen, Troels Staehelin; Hansen, Christian Stevns; Yderstræde, Knud Bonnet; Zhang, Ming-Dong; Ernfors, Patrik; Nyengaard, Jens Randel; Karlsson, Pall

doi:10.1007/s00125-023-06009-z

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…Sample size was determined based on a recent study applying the same cohort. 12 In the previous study, a sample size of 20–25 participants in each group was found to be sufficient with a power of 80% and an alpha of 0.05. To enhance the sensitivity in the study, we doubled the sample size to 40–50 participants per group to show group differences, incorporating various tests for DPN.…”

Section: Methodsmentioning

confidence: 94%

Assessment of neuropathy subtypes in type 1 diabetes

Karlsson,

Sjogaard,

Schousboe

et al. 2024

BMJ Open Diab Res Care

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IntroductionDiabetic polyneuropathy (DPN), a common complication of diabetes, can manifest as small, large, or mixed fiber neuropathy (SFN, LFN, and MFN, respectively), depending on the type of fibers involved. Despite evidence indicating small fiber involvement prior to large fiber involvement in type 1 diabetes mellitus (T1DM)-associated DPN, no evidence has been produced to determine the more prevalent subtype. We aim to determine the more prevalent type of nerve fiber damage—SFN, LFN, and MFN—in T1DM-associated DPN, both with and without pain.Research design and methodsIn this cross-sectional study, participants (n=216) were divided into controls; T1DM; T1DM with non-painful DPN (NP-DPN); and T1DM with painful DPN (P-DPN). DPN was further subgrouped based on neuropathy severity. The more prevalent type of fiber damage was determined applying small and large fiber-specific tests and three diagnostic models: model 1 (≥1 abnormal test); model 2 (≥2 abnormal tests); and model 3 (≥3 abnormal tests).ResultsMFN showed the highest prevalence in T1DM-associated DPN. No differences in neuropathy subtype were found between NP-DPN and P-DPN. DPN, with prevalent SFN plateaus between models 2 and 3. All models showed increased prevalence of MFN according to DPN severity. Model 3 showed increased DPN with prevalent LFN in early neuropathy. DPN with prevalent SFN demonstrated a similar, but non-significant pattern.ConclusionsDPN primarily manifests as MFN in T1DM, with no differentiation between NP-DPN and P-DPN. Additionally, we propose model 2 as an initial criterion for diagnosing DPN with a more prevalent SFN subtype in T1DM. Lastly, the study suggests that in mild stages of DPN, one type of nerve fiber (either small or large) is more susceptible to damage.

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Section: Methodsmentioning

confidence: 94%

Assessment of neuropathy subtypes in type 1 diabetes

Karlsson,

Sjogaard,

Schousboe

et al. 2024

BMJ Open Diab Res Care

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“…Several laboratories have reported that inhibition of PKCβ improves vascular and neural function in diabetic rodents ( 51 – 54 ). In addition, dysregulation of Schwann cells in part through altered PKC activity can contribute to DPN ( 50 , 55 – 58 ). In streptozotocin-induced diabetic rats’ activity of PKCα was decreased in neurons and Schwann cells that was corrected by treatment with methylcobalamin ( 59 ).…”

Section: Protein Kinase C Pathwaymentioning

confidence: 99%

Combination therapy is it in the future for successfully treating peripheral diabetic neuropathy?

Yorek

2024

Front. Endocrinol.

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In 2022, the Center for Disease Control and Prevention reported that 11.3% of the United States population, 37.3 million people, had diabetes and 38% of the population had prediabetes. A large American study conducted in 2021 and supported by many other studies, concluded that about 47% of diabetes patients have peripheral neuropathy and that diabetic neuropathy was present in 7.5% of patients at the time of diabetes diagnosis. In subjects deemed to be pre-diabetes and impaired glucose tolerance there was a wide range of prevalence estimates (interquartile range (IQR): 6%-34%), but most studies (72%) reported a prevalence of peripheral neuropathy ≥10%. There is no recognized treatment for diabetic peripheral neuropathy (DPN) other than good blood glucose control. Good glycemic control slows progression of DPN in patients with type 1 diabetes but for patients with type 2 diabetes it is less effective. With obesity and type 2 diabetes at epidemic levels the need of a treatment for DPN could not be more important. In this article I will first present background information on the “primary” mechanisms shown from pre-clinical studies to contribute to DPN and then discuss mono- and combination therapies that have demonstrated efficacy in animal studies and may have success when translated to human subjects. I like to compare the challenge of finding an effective treatment for DPN to the ongoing work being done to treat hypertension. Combination therapy is the recognized approach used to normalize blood pressure often requiring two, three or more drugs in addition to lifestyle modification to achieve the desired outcome. Hypertension, like DPN, is a progressive disease caused by multiple mechanisms. Therefore, it seems likely as well as logical that combination therapy combined with lifestyle adjustments will be required to successfully treat DPN.

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Molecular mechanisms of neuropathic pain

Pacifico,

Menichella

2024

International Review of Neurobiology

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Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy

Cited by 5 publications

References 26 publications

Assessment of neuropathy subtypes in type 1 diabetes

Assessment of neuropathy subtypes in type 1 diabetes

Combination therapy is it in the future for successfully treating peripheral diabetic neuropathy?

Molecular mechanisms of neuropathic pain

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