Influence of diabetic peripheral polyneuropathy on long-term outcome in patients with type 2 diabetes

Background. Diabetic peripheral neuropathy (DPN) is recognized as the most prevalent microvascular complication of diabetes leading to the development of pain syndrome, sensory impairment, and motor function disturbance. The role of DPN as an independent factor influencing mortality in patients with type 2 diabetes mellitus (T2DM) remains insufficiently studied.

Aim. To assess the impact of DPN on the frequency of death in patients with T2DM over a period of five years.

Material and methods. A single-center uncontrolled study was conducted involving 496 patients with T2DM who were hospitalized in the endocrinology department. The evaluated outcome was all-cause mortality. The average follow-up period was 1701 ± 338 days. Clinical and anamnestic data were collected from the patients, laboratory studies of biochemical blood parameters were performed, and the severity of clinical symptoms and neurological deficits were assessed using special scales and questionnaires.

Results. During the five-year observation period, 81 patients (16.3%) died. Age over 70 years old, decrease in vibration perception threshold (VPT) by more than 2 points, and history of acute myocardial infarction (AMI) were associated with adverse outcomes. For patients aged over 70 years and those with previous AMI, there was a 2.5-fold increased risk of death. VPT scores exceeding 2 points were associated with an 1.8-fold increase in unfavorable outcomes. A scoring system for predictors of fatal outcomes was introduced. An ROC analysis was conducted for the predictive scoring model. The area under the ROC curve was 0.696 (95% CI: 0.629–0.760, p < 0.001).

Conclusion. Assessment of VPT is a simple test available in clinical practice that not only allows diagnosing DPN and predicting the risk of developing diabetic foot syndrome but also evaluating long-term prognosis in patients with T2DM. Based on measuring VPT, a point-based system for predicting the risk of death within 5 years has been proposed.

1. Lu Y, Xing P, Cai X, Luo D, Li R, Lloyd C et al. Prevalence and risk factors for diabetic peripheral neuropathy in type 2 diabetic patients from 14 countries: Estimates of the INTERPRET-DD Study. Front Public Health. 2020;8:534372. doi: 10.3389/fpubh.2020.534372.

2. Дедов И.И., Шестакова М.В., Викулова О.К. Эпидемиология сахарного диабета в Российской Федерации: клинико-статистический анализ по данным Федерального регистра сахарного диабета. Сахарный диабет. 2017;20(1):13–41. doi: 10.14341/DM8664.

3. Дедов И.И., Шестакова М.В., Майоров А.Ю., Мокрышева Н.Г., Андреева Е.Н., Безлепкина О.Б. с соавт. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 11-й выпуск. Сахарный диабет. 2023;26(S2):1–157. doi: 10.14341/DM13042.

4. Lazzarini PA, Raspovic KM, Meloni M, van Netten JJ. A new declaration for feet's sake: Halving the global diabetic foot disease burden from 2% to 1% with next generation care. Diabetes Metab Res Rev. 2024;40(3):e3747.doi: 10.1002/dmrr.3747.

5. Yu Y. Gold standard for diagnosis of DPN. Front Endocrinol (Lausanne). 2021;12:719356. doi: 10.3389/fendo.2021.719356.

6. Григорьева В.Н., Белова А.Н. Клиническое неврологическое обследование. Учебное пособие. М.: Практическая медицина. 2018; 400 c. ISBN: 978-5-98811-373-7.

7. Галстян Г.Р., Старостина Е.Г., Яхно Н.Н., Гурьева И.В., Чурюканов М.В., Строков И.А. с соавт. Диагностика и рациональная терапия болевой формы диабетической периферической нейропатии: междисциплинарный консенсус экспертов. Сахарный диабет. 2019;22(4):305–327. doi: 10.14341/DM9625.

8. Carmichael J, Fadavi H, Ishibashi F, Shore AC, Tavakoli M. Advances in screening, early diagnosis and accurate staging of diabetic neuropathy. Front Endocrinol (Lausanne). 2021;12:671257. doi: 10.3389/fendo.2021.671257.

9. Sacchetta L, Chiriaco M, Nesti L, Leonetti S, Forotti G, Natali A et al. Synergistic effect of chronic kidney disease, neuropathy, and retinopathy on all-cause mortality in type 1 and type 2 diabetes: A 21-year longitudinal study. Cardiovasc Diabetol. 2022;21(1):233. doi: 10.1186/s12933-022-01675-6.

10. Hicks CW, Wang D, Matsushita K, Windham BG, Selvin E. Peripheral neuropathy and all-cause and cardiovascular mortality in U.S. adults : A prospective cohort study. Ann Intern Med. 2021;174(2):167–74. doi: 10.7326/M20-1340.

11. Rastogi A, Goyal G, Kesavan R, Bal A, Kumar H, Mangalanadanam et al. Long term outcomes after incident diabetic foot ulcer: Multicenter large cohort prospective study (EDI-FOCUS investigators) epidemiology of diabetic foot complications study: Epidemiology of diabetic foot complications study. Diabetes Res Clin Pract. 2020;162:108113. doi: 10.1016/j.diabres.2020.108113.

12. Тюрюпов М.С., Однокол П.О., Кутелев Г.Г., Комарова У.А. Новый лик сахарного диабета – нарушения ритма и проводимости. Известия Российской Военно-медицинской академии. 2024;43(2):193–201. doi: 10.17816/rmmar627539.

13. Ando A, Miyamoto M, Saito N, Kotani K, Kamiya H, Ishibashi S, Tavakoli M. Small fibre neuropathy is associated with impaired vascular endothelial function in patients with type 2 diabetes. Front Endocrinol (Lausanne). 2021;12:653277. doi: 10.3389/fendo.2021.653277.

14. Шамхалова М.Ш., Викулова О.К., Железнякова А.В., Исаков М.А., Шестакова М.В., Дедов И.И., Мокрышева Н.Г. Эпидемиология хронической болезни почек у пациентов с диабетом в Российской Федерации по данным Федерального регистра сахарного диабета (2010–2022 гг.). Сахарный диабет. 2023;26(5):404–417. doi: 10.14341/DM13090.

15. Galiero R, Caturano A, Vetrano E, Beccia D, Brin C, Alfano M et al. Peripheral neuropathy in diabetes mellitus: Pathogenetic mechanisms and diagnostic options. Int J Mol Sci. 2023;24(4):3554. doi: 10.3390/ijms24043554.

16. Peto A, Toth LI, Hernyak M, Lorincz H, Molnar A, Nagy AC et al. Correlations between distal sensorimotor polyneuropathy and cardiovascular complications in diabetic patients in the North-Eastern region of Hungary. PLoS One. 2024;19(7):e0306482. doi: 10.1371/journal.pone.0306482.