title: Nitrosative stress but not glycemic parameters correlate with improved neuropathy in nonseverely obese diabetic patients after Roux-Y gastric bypass.
abstract: 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).
  
  
  CONCLUSIONS
  RYGB seems to improve oxidative, nitrosative and carbonyl stress, known to have a causal role in diabetic neuropathy.
authors: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: beat.mueller@med.uni-heidelberg.de.
authors: Beat P
authors: BP
authors: Müller-Stich
authors: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors: Adrian T
authors: AT
authors: Billeter
authors: Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
authors: Thomas
authors: T
authors: Fleming
authors: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors: Lars
authors: L
authors: Fischer
authors: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors: Markus W
authors: MW
authors: Büchler
authors: Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
authors: Peter P
authors: PP
authors: Nawroth
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003929:Diabetic Neuropathies / Q000097:blood* / Q000150:complications; D018450:Disease Progression; D005215:Fasting / Q000097:blood; D005260:Female; D015390:Gastric Bypass / Q000379:methods*; D006801:Humans; D010535:Laparoscopy / Q000379:methods; D008297:Male; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D018384:Oxidative Stress; D011184:Postoperative Period; D011446:Prospective Studies; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood; D015431:Weight Loss / Q000502:physiology*
chemical_list: D001786:Blood Glucose; C002744:3-nitrotyrosine; D014443:Tyrosine
keywords: Carbonyl stress; Diabetes; Gastric bypass; Metabolic surgery; Neuropathy; Oxidative stress; RYGB