Distal Corneal Small Nerve Fibre Damage in Subjects With Obesity

Abstract Background: We have previously shown that subjects with obesity have elevated vibration and thermal perception thresholds and central corneal nerve loss and patients with diabetic neuropathy have greater corneal nerve loss at the inferior whorl compared to the central cornea. In the current study, we assessed whether there is evidence for a dying-back neuropathy in subjects with obesity with and without diabetes. Methods: 57 obese subjects, with and without diabetes (DM+, n=30; DM-, n=27 respectively) and age- and sex‑matched controls (n=21) underwent venous blood sampling and assessment of the neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration, cold and warm threshold testing, cardiac autonomic function, and corneal confocal microscopy (CCM).Results: NSP and NDS were significantly elevated in obese DM+ (p<0.0001; p=0.001) and DM- (p<0.0001; p=0.001) subjects compared to controls. Vibration perception threshold was significantly higher in DM+ (p=0.001), but not in DM- (p=0.06), compared to controls, whilst cold (p = 0.87) and warm (p = 0.52) perception thresholds did not differ between groups. Deep breathing heart rate variability was significantly lower in DM+ (p=0.01), but not DM- (p=0.9) subjects compared to controls. Corneal nerve fibre density [26.8 ±6.22 vs 26.8 ±6.01 vs 35.3 ±7.41, p<0.0001], branch density [55.4 ±28.2 vs 58.4 ±28.5 vs 88.2 ±31.1, p<0.001], fibre length (CNFL) [17.6 ±4.43 vs 19.9 ±5.43 vs 26.7 ±5.31, p <0.0001], inferior whorl length (IWL) [17.9 ±6.10 vs 18.6 ±7.42 vs 35.3 ±9.70, p<0.0001] and total nerve fibre length (TNFL) [35.5 ±9.58 vs 38.5 ±11.0 vs 62.0 ±12.3, p<0.0001] were significantly lower in obese subjects without and with diabetes compared to controls. In comparison to controls, there was a greater relative reduction in IWL compared to CNFL in DM+ (47.3% vs 25.5%) and DM- (49.3% vs 34.1%).Conclusion: We demonstrate evidence of peripheral neuropathy characterised by neuropathic symptoms, neurological deficits, elevated vibration perception and autonomic dysfunction with a dying-back neuropathy affecting the corneal nerves in obese subjects with and without type 2 diabetes.