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Bariatric Surgery

Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity



Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage.


Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery.


Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = –0.45, P = 0.04).


Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

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Fig. 1: Study design.
Fig. 2: Representetive examples of CCM images.
Fig. 3: Corneal nerve morphological parameters at baseline and 12 months visits.


  1. D’Souza MJ, Bautista RC, Wentzien DE. Data talks: obesity-related influences on US mortality rates. Res Health Sci. 2018;3:65–78.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Xia JY, Lloyd-Jones DM, Khan SS. Association of body mass index with mortality in cardiovascular disease: new insights into the obesity paradox from multiple perspectives. Trends Cardiovasc Med. 2018;29:220–5.

    Article  PubMed  Google Scholar 

  3. Asghar O, Petropoulos IN, Alam U, Jones W, Jeziorska M, Marshall A, et al. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014;37:2643–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dimova R, Tankova T, Guergueltcheva V, Tournev I, Chakarova N, Grozeva G, et al. Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance. J Diabetes Complications. 2017;31:537–43.

    Article  PubMed  Google Scholar 

  5. Ziegler D, Papanas N, Zhivov A, Allgeier S, Winter K, Ziegler I, et al. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes. 2014;63:2454–63.

    Article  PubMed  Google Scholar 

  6. Ziegler D, Winter K, Strom A, Zhivov A, Allgeier S, Papanas N, et al. Spatial analysis improves the detection of early corneal nerve fiber loss in patients with recently diagnosed type 2 diabetes. PLoS One. 2017;12:e0173832.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Smith AG, Singleton JR. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy. J Diabetes Complications. 2013;27:436–42.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Stino AM, Smith AG. Peripheral neuropathy in prediabetes and the metabolic syndrome. J Diabetes Investig. 2017;8:646–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Schlesinger S, Herder C, Kannenberg JM, Huth C, Carstensen-Kirberg M, Rathmann W, et al. General and abdominal obesity and incident distal sensorimotor polyneuropathy: insights into inflammatory biomarkers as potential mediators in the KORA F4/FF4 cohort. Diabetes Care. 2019;42:240–7.

    Article  CAS  PubMed  Google Scholar 

  10. Coppey L, Davidson E, Shevalye H, Torres ME, Yorek MA. Effect of dietary oils on peripheral neuropathy-related endpoints in dietary obese rats. Diabetes Metab Syndr Obes. 2018;11:117–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Coppey LJ, Shevalye H, Obrosov A, Davidson EP, Yorek MA. Determination of peripheral neuropathy in high-fat diet fed low-dose streptozotocin-treated female C57Bl/6J mice and Sprague-Dawley rats. 2018;9:1033–40.

  12. Davidson EP, Coppey LJ, Kardon RH, Yorek MA. Differences and similarities in development of corneal nerve damage and peripheral neuropathy and in diet-induced obesity and type 2 diabetic rats. Invest Ophthalmol Vis Sci. 2014;55:1222–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vincent AM, Hayes JM, McLean LL, Vivekanandan-Giri A, Pennathur S, Feldman EL. Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1. Diabetes. 2009;58:2376–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dias LS, Nienov OH, Machado FD, Ramos CP, Rodrigues D, Menguer RK, et al. Polyneuropathy in severely obese women without diabetes: prevalence and associated factors. Obes Surg. 2019;29:953–7.

    Article  PubMed  Google Scholar 

  15. Callaghan BC, Feldman EL. Measuring neuropathy in obese populations: challenge accepted. Reply to “Diagnostic accuracy of neuropathy tests in obese population remains elusive”. Clin Neurophysiol. 2018;129:1504–5.

    Article  PubMed  Google Scholar 

  16. Callaghan BC, Xia R, Reynolds E, Banerjee M, Burant C, Rothberg A, et al. Better diagnostic accuracy of neuropathy in obesity: a new challenge for neurologists. Clin Neurophysiol. 2018;129:654–62.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Smith AG, Russell J, Feldman EL, Goldstein J, Peltier A, Smith S, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006;29:1294–9.

    Article  PubMed  Google Scholar 

  18. Sjostrom L, Peltonen M, Jacobson P, Ahlin S, Andersson-Assarsson J, Anveden A, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA. 2014;311:2297–304.

    Article  PubMed  CAS  Google Scholar 

  19. Johnson BL, Blackhurst DW, Latham BB, Cull DL, Bour ES, Oliver TL, et al. Bariatric surgery is associated with a reduction in major macrovascular and microvascular complications in moderately to severely obese patients with type 2 diabetes mellitus. J Am Coll Surg. 2013;216:545–56. discussion 56-8

    Article  PubMed  Google Scholar 

  20. Coleman KJ, Haneuse S, Johnson E, Bogart A, Fisher D, O’Connor PJ, et al. Long-term microvascular disease outcomes in patients with type 2 diabetes after bariatric surgery: evidence for the legacy effect of surgery. Diabetes Care. 2016;39:1400–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Miras AD, Chuah LL, Khalil N, Nicotra A, Vusirikala A, Baqai N, et al. Type 2 diabetes mellitus and microvascular complications 1 year after Roux-en-Y gastric bypass: a case-control study. Diabetologia. 2015;58:1443–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schauer PR, Burguera B, Ikramuddin S, Cottam D, Gourash W, Hamad G, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238:467.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Müller-Stich BP, Fischer L, Kenngott HG, Gondan M, Senft J, Clemens G, et al. Gastric bypass leads to improvement of diabetic neuropathy independent of glucose normalization—results of a prospective cohort study (DiaSurg 1 study). Ann Surg. 2013;258:760–6.

    Article  PubMed  Google Scholar 

  24. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.

    Article  CAS  PubMed  Google Scholar 

  25. Quattrini C, Tavakoli M, Jeziorska M, Kallinikos P, Tesfaye S, Finnigan J, et al. Surrogate markers of small fiber damage in human diabetic neuropathy. Diabetes. 2007;56:2148–54.

    Article  CAS  PubMed  Google Scholar 

  26. Alam U, Jeziorska M, Petropoulos IN, Asghar O, Fadavi H, Ponirakis G, et al. Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy. PLoS One. 2017;12:e0180175.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Tavakoli M, Malik RA. Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies. J Vis Exp. 2011;47:e2194.

    Google Scholar 

  28. Kalteniece A, Ferdousi M, Adam S, Schofield J, Shazli A, Petropoulos I. Corneal confocal microscopy is a rapid reproducible ophthalmic technique for quantifying corneal nerve abnormalities. PLoS ONE. 2017;12:e0183040.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Dabbah MA, Graham J, Petropoulos IN, Tavakoli M, Malik RA. Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging. Med Image Anal. 2011;15:738–47.

    Article  CAS  PubMed  Google Scholar 

  30. Azmi S, Jeziorska M, Ferdousi M, Petropoulos IN, Ponirakis G, Marshall A, et al. Early nerve fibre regeneration in individuals with type 1 diabetes after simultaneous pancreas and kidney transplantation. Diabetologia. 2019;62:1478–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Becker DA, Balcer LJ, Galetta SL. The neurological complications of nutritional deficiency following bariatric surgery. J. Obes. 2012;2012:608534.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. O’Donnell KB, Simmons M. Early-onset copper deficiency following Roux-en-Y gastric bypass. Nutr Clin Pract. 2011;26:66–9.

    Article  PubMed  Google Scholar 

  33. Aasheim ET, Hofsø D, Hjelmesæth J, Sandbu R. Peripheral neuropathy and severe malnutrition following duodenal switch. Obes Surg. 2008;18:1640–3.

    Article  PubMed  Google Scholar 

  34. Panda S, Sharma K. Osteomalacia induced peripheral neuropathy after obesity reduction surgery. Ann Indian Acad Neurol. 2013;16:690.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kattalai Kailasam V, DeCastro C, Macaluso C, Kleiman A. Postbariatric surgery neuropathic pain (PBSNP): case report, literature review, and treatment options. Pain medicine (Malden, Mass). 2015;16:374–82.

    Article  Google Scholar 

  36. Thaisetthawatkul P, Collazo-Clavell ML, Sarr MG, Norell JE, Dyck PJ. A controlled study of peripheral neuropathy after bariatric surgery. Neurology. 2004;63:1462–70.

    Article  CAS  PubMed  Google Scholar 

  37. Casellini CM, Parson HK, Hodges K, Edwards JF, Lieb DC, Wohlgemuth SD, et al. Bariatric surgery restores cardiac and sudomotor autonomic C-fiber dysfunction towards normal in obese subjects with type 2 diabetes. PLoS One. 2016;11:e0154211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Petropoulos IN, Alam U, Fadavi H, Asghar O, Green P, Ponirakis G, et al. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care. 2013;36:3646–51.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tavakoli M, Mitu-Pretorian M, Petropoulos IN, Fadavi H, Asghar O, Alam U, et al. Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes. 2013;62:254–60.

    Article  CAS  PubMed  Google Scholar 

  40. Azmi S, Ferdousi M, Petropoulos IN, Ponirakis G, Fadavi H, Tavakoli M, et al. Corneal confocal microscopy shows an improvement in small-fiber neuropathy in subjects with type 1 diabetes on continuous subcutaneous insulin infusion compared with multiple daily injection. Diabetes Care. 2015;38:e3–e4.

    Article  PubMed  Google Scholar 

  41. Carlsson LMS, Sjoholm K, Karlsson C, Jacobson P, Andersson-Assarsson JC, Svensson PA, et al. Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study. Lancet Diabetes Endocrinol. 2017;5:271–9.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wiggin TD, Sullivan KA, Pop-Busui R, Amato A, Sima AA, Feldman EL. Elevated triglycerides correlate with progression of diabetic neuropathy. Diabetes. 2009;58:1634–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Callaghan BC, Feldman E, Liu J, Kerber K, Pop-Busui R, Moffet H, et al. Triglycerides and amputation risk in patients with diabetes: ten-year follow-up in the DISTANCE study. Diabetes Care. 2011;34:635–40.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yadav R, Hama S, Liu Y, Siahmansur T, Schofield J, Syed AA, et al. Effect of Roux-en-Y bariatric surgery on lipoproteins, insulin resistance, and systemic and vascular inflammation in obesity and diabetes. Front Immunol. 2017;8:1512.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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This study was supported by a research donation from AMGEN and the Lipid Disease Fund. The authors acknowledge support from The Manchester Comprehensive Local Research Network and The National Institute for Health Research/Wellcome Trust Clinical Research Facility in Manchester.

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S Azmi and MF were involved in acquisition of data, analysis and interpretation of data and wrote the manuscript. S Azmi, HS, GP, S Adam, AS, SD, ZI and JHH recruited patients and controls. MF, YL, TS, S Azmi, GP, IP, AK, AM, AS, BJA, HS and JHH contributed to acquisition and analysis of the data. YL, TS, JHH and S Adam performed biochemical analysis. HS conceived the hypothesis and is the chief investigator of the study. HS, PND and RAM designed the study and contributed to interpretation of the data. HS is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors were involved in revising the manuscript critically for important intellectual content and for final approval of the version to be published.

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Correspondence to Handrean Soran.

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Azmi, S., Ferdousi, M., Liu, Y. et al. Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity. Int J Obes 45, 631–638 (2021).

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