Background. Subclinical peripheral polyneuropathy (PPN) frequently develops in prediabetes and obesity but often remains undetected. The contribution of cytokine–adipokine imbalance and microcirculatory dysfunction to early nerve injury requires clarification. Objective. To assess how cytokine–adipokine markers and microcirculatory parameters relate to subclinical PPN and to determine their independent predictive value. Materials and Methods. A cross-sectional study included 120 adults: 80 with prediabetes and obesity and 40 healthy controls. Subclinical PPN was defined by normal neurological scores combined with ≥2 abnormal tests (QST deviations, reduced IENFD, or decreased sensory conduction velocity). Serum leptin, adiponectin, IL-6, TNF-α, hsCRP, and the leptin-to-adiponectin ratio (L/A-ratio) were measured. Microcirculation was evaluated by laser Doppler flowmetry and nailfold capillaroscopy. Multivariable regression and ROC analysis were applied. Results. Subclinical PPN was found in 41.3% of the main group. Affected individuals had significantly higher L/A-ratio and inflammatory cytokines, along with reduced endothelial oscillations, post-occlusive hyperemia, and capillary density. L/A-ratio, IL-6, and endothelial oscillation amplitude were independently associated with PPN, and their combination showed high accuracy (AUC 0.88). Conclusions. Subclinical PPN in prediabetes with obesity is strongly linked to adipokine imbalance, systemic inflammation, and microvascular dysfunction. Combined biochemical and microcirculatory markers may improve early risk identification and warrant longitudinal validation.

Peripheral polyneuropathy, quantitative sensory testing, cytokine–adipokine profile, leptin-to-adiponectin ratio

Volkova L.Yu., Eliashevich S.O., Shepel R.N., Astanina S.Yu., Drapkina O.M. Structured approach to changing the nutritional model in obese adult patients in primary health care. Preventive medicine. 2023;26(2):94‑99. https://doi.org/10.17116/profmed20232602194

Golodnikov I.I., Podshivalova E.S., Chechekhin V.I., Zubritsky A.V., Matrosova A.A., Dvoryanchikov Ya.V., Samsonova M.D., Markelova E.K., Medvedeva Yu.A., Nikonova T.V., Bondarenko E.V., Popov S.V., Minniakhmetov I.R., Shestakova M.V. Transcriptional features of autoimmune diabetes mellitus: differential gene expression in CD4+ and CD8+ subpopulations of blood T-cells. Diabetes mellitus. 2025;28(2):124-135. https://doi.org/10.14341/DM13316

Dzugkoev S.G., Dzugkoeva F.S. Optimization of treatment and prevention of metabolic and functional disorders in diabetic nephropathy. Preventive medicine. 2022;25(3):18‑24. https://doi.org/10.17116/profmed20222503118

Kurilova O.V., Kiseleva A.V., Meshkov A.N., et al. Scales for assessing the genetic risk of developing type 2 diabetes mellitus. Preventive medicine. 2021;24(12):115‑122. https://doi.org/10.17116/profmed202124121115

Mehdiyev, T. V., Akhmedova, Z. B., Mamedov, M. N., & Askerov, E. I. (2022). Detection of diabetic neuropathies in patients with diabetes mellitus. Justification for medical rehabilitation. Spa Medicine, (1), 55-61.

Stepanova, A. P. (2021). Diabetic peripheral polyneuropathy and vitamin D provision in patients with type 2 diabetes mellitus: clinical and pathogenetic features, possibilities of therapy with cholecalciferol (Dissertation for the degree of Candidate of Medical Sciences). Saint Petersburg. https://www.almazovcentre.ru/wp-content/uploads/Диссертация-Степанова-А.П..pdf

Khramilin V.N., Davydov O.S. Pain diabetic polyneuropathy: diagnosis and treatment from the standpoint of evidence-based medicine. Russian Journal of Pain. 2021;19(4):44‑59. https://doi.org/10.17116/pain20211904144

Carmichael, J., Fadavi, H., Ishibashi, F., Shore, A. C., & Tavakoli, M. (2021). Advances in Screening, Early Diagnosis and Accurate Staging of Diabetic Neuropathy. Frontiers in endocrinology, 12, 671257. https://doi.org/10.3389/fendo.2021.671257

Chupryna, G. N., Dubynetska, V. N., Vashenyuk, O. L., & Vashenyuk, N. O. (2021). Features of clinical and paraclinic parameters and comorbidity in patients with diabetic polyneuropathy. Health of Society, 8(5), 174–178. https://doi.org/10.22141/2306-2436.8.5.2019.198386

Metsker, O., Magoev, K., Yakovlev, A. et al. Identification of risk factors for patients with diabetes: diabetic polyneuropathy case study. BMC Med Inform Decis Mak 20, 201 (2020). https://doi.org/10.1186/s12911-020-01215-w

Tokarenko О. I. ., Andreieva, I. O. ., Tokarenko, O. O. ., & Surmilo, M. M. . (2021). Effect of diet and exercise-induce weight loss on level of resistin in patient with obesity. Modern Medical Technology, (4), 11–15. https://doi.org/10.34287/MMT.4(51).2021.2

Velychko, V., Mykhailenko, V., Lahoda, D., Volokhova, G., & Liashenko, S. (2021). Screening for diabetes and prediabetes: the newest communication opportunities. Reproductive endocrinology, (62), 92–95. https://doi.org/10.18370/2309-4117.2021.62.92-95