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Identification of factors associated with sural nerve regeneration and degeneration in diabetic neuropathy.
Diabetes Care 2013; 36(12):4043-9DC

Abstract

OBJECTIVE

Patients with diabetic neuropathy (DN) demonstrate variable degrees of nerve regeneration and degeneration. Our aim was to identify risk factors associated with sural nerve degeneration in patients with DN.

RESEARCH DESIGN AND METHODS

Demographic, anthropometric, biochemical, and anatomical data of subjects with DN from a 52-week trial of acetyl-L-carnitine were retrospectively examined. Based on the change in sural nerve myelinated fiber density (ΔMFD%), subjects were divided into three groups: regenerator (top 16 percentiles, n = 67), degenerator (bottom 16 percentiles, n = 67), and intermediate (n = 290), with dramatically increased, decreased, and steady ΔMFD%, respectively. ANOVA, Fisher exact test, and multifactorial logistic regression were used to evaluate statistical significance.

RESULTS

ΔMFD%s were 35.6 ± 17.4 (regenerator), -4.8 ± 12.1 (intermediate), and -39.8 ± 11.0 (degenerator). HbA1c at baseline was the only factor significantly different across the three groups (P = 0.01). In multifactorial logistic regression, HbA1c at baseline was also the only risk factor significantly different between regenerator (8.3 ± 1.6%) and degenerator (9.2 ± 1.8%) (odds ratio 0.68 [95% CI 0.54-0.85]; P < 0.01). Support Vector Machine classifier using HbA1c demonstrated 62.4% accuracy of classifying subjects into regenerator or degenerator. A preliminary microarray experiment revealed that upregulated genes in the regenerator group are enriched with cell cycle and myelin sheath functions, while downregulated genes are enriched in immune/inflammatory responses.

CONCLUSIONS

These data, based on the largest cohort with ΔMFD% information, suggest that HbA1c levels predict myelinated nerve fiber regeneration and degeneration in patients with DN. Therefore, maintaining optimal blood glucose control is likely essential in patients with DN to prevent continued nerve injury.

Authors+Show Affiliations

Corresponding author: Eva L. Feldman, efeldman@umich.edu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24101696

Citation

Hur, Junguk, et al. "Identification of Factors Associated With Sural Nerve Regeneration and Degeneration in Diabetic Neuropathy." Diabetes Care, vol. 36, no. 12, 2013, pp. 4043-9.
Hur J, Sullivan KA, Callaghan BC, et al. Identification of factors associated with sural nerve regeneration and degeneration in diabetic neuropathy. Diabetes Care. 2013;36(12):4043-9.
Hur, J., Sullivan, K. A., Callaghan, B. C., Pop-Busui, R., & Feldman, E. L. (2013). Identification of factors associated with sural nerve regeneration and degeneration in diabetic neuropathy. Diabetes Care, 36(12), pp. 4043-9. doi:10.2337/dc12-2530.
Hur J, et al. Identification of Factors Associated With Sural Nerve Regeneration and Degeneration in Diabetic Neuropathy. Diabetes Care. 2013;36(12):4043-9. PubMed PMID: 24101696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of factors associated with sural nerve regeneration and degeneration in diabetic neuropathy. AU - Hur,Junguk, AU - Sullivan,Kelli A, AU - Callaghan,Brian C, AU - Pop-Busui,Rodica, AU - Feldman,Eva L, Y1 - 2013/10/07/ PY - 2013/10/9/entrez PY - 2013/10/9/pubmed PY - 2014/12/17/medline SP - 4043 EP - 9 JF - Diabetes care JO - Diabetes Care VL - 36 IS - 12 N2 - OBJECTIVE: Patients with diabetic neuropathy (DN) demonstrate variable degrees of nerve regeneration and degeneration. Our aim was to identify risk factors associated with sural nerve degeneration in patients with DN. RESEARCH DESIGN AND METHODS: Demographic, anthropometric, biochemical, and anatomical data of subjects with DN from a 52-week trial of acetyl-L-carnitine were retrospectively examined. Based on the change in sural nerve myelinated fiber density (ΔMFD%), subjects were divided into three groups: regenerator (top 16 percentiles, n = 67), degenerator (bottom 16 percentiles, n = 67), and intermediate (n = 290), with dramatically increased, decreased, and steady ΔMFD%, respectively. ANOVA, Fisher exact test, and multifactorial logistic regression were used to evaluate statistical significance. RESULTS: ΔMFD%s were 35.6 ± 17.4 (regenerator), -4.8 ± 12.1 (intermediate), and -39.8 ± 11.0 (degenerator). HbA1c at baseline was the only factor significantly different across the three groups (P = 0.01). In multifactorial logistic regression, HbA1c at baseline was also the only risk factor significantly different between regenerator (8.3 ± 1.6%) and degenerator (9.2 ± 1.8%) (odds ratio 0.68 [95% CI 0.54-0.85]; P < 0.01). Support Vector Machine classifier using HbA1c demonstrated 62.4% accuracy of classifying subjects into regenerator or degenerator. A preliminary microarray experiment revealed that upregulated genes in the regenerator group are enriched with cell cycle and myelin sheath functions, while downregulated genes are enriched in immune/inflammatory responses. CONCLUSIONS: These data, based on the largest cohort with ΔMFD% information, suggest that HbA1c levels predict myelinated nerve fiber regeneration and degeneration in patients with DN. Therefore, maintaining optimal blood glucose control is likely essential in patients with DN to prevent continued nerve injury. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/24101696/full_citation L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=24101696 DB - PRIME DP - Unbound Medicine ER -