Nitrosative stress but not glycemic parameters correlate with improved neuropathy in nonseverely obese diabetic patients after Roux-Y gastric bypass

Background: Diabetic neuropathy is common in type 2 diabetic patients (T2DM) but tight glycemic control does not improve the symptoms. In contrast, Roux-Y gastric bypass (RYGB) has a positive effect on active neuropathic symptoms, independent from glycemic control. The purpose of the present study was to identify potential mechanisms of improved diabetic neuropathic symptoms after RYGB. Methods: A prospective cohort of 20 patients with insulin-dependent T2DM and BMI <35 kg/m(2) were treated with RYGB. Nineteen patients had complete follow-up. Fasting glucose, HbA1c (glycated hemoglobin), markers for nitrosative, carbonyl, and oxidative stress (nitrotyrosine, carboxylated-lysine (CML), methylglyoxal, oxidized low-density-lipoprotein (oxLDL)) as well as Neuropeptid Y and Neurokinin A were investigated over 12 months. Neuropathy was assessed using the Neuropathy Deficit Score (NDS). Results: The preoperative NDS improved within twelve months (5.1 +/- 0.6 to 2.6 +/- 0.4, P = .010). Fasting glucose and HbA1c also improved compared to preoperative values (201.1 +/- 16.6 mg/dL to 128 +/- 8.7 mg/dL, P = .004 and 8.5 +/- 0.3% (53 +/- 3.3 mmol/mol) to 7 +/- 0.3% (67 +/- 3.3 mmol/mol), P = .001, respectively). Nitrotyrosine, CML, and methylglyoxal all 3 decreased postoperatively (1067.3 +/- 266.9 nM to 355.8 +/- 36.4 nM, P = .003; 257.1 +/- 10.2 ng/ml to 215.3 +/- 18.3 ng/ml, P = .039; 402.3 +/- 3.9 nM to 163.4 +/- 10.3 nM, P = .002). OxLDL remained unchanged. Fasting glucose and HbA1c did not correlate with improved neuropathy. The decrease in nitrotyrosine correlated with improvement in the NDS after 6 and twelve months (r = .9, P < .001 and r = .68, P = .03). The decrease in methylglyoxal after 6 months correlated with decrease in NDS after twelve months (r = 0.897, P = .003). Conclusion: RYGB seems to improve oxidative, nitrosative and carbonyl stress, known to have a causal role in diabetic neuropathy. (C) 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved.