Beat P Müller-Stich1, Adrian T Billeter2, Thomas Fleming3, Lars Fischer2, Markus W Büchler2, Peter P Nawroth3. 1. Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: beat.mueller@med.uni-heidelberg.de. 2. Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. 3. Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
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). CONCLUSION: RYGB seems to improve oxidative, nitrosative and carbonyl stress, known to have a causal role in diabetic neuropathy.
BACKGROUND:Diabetic neuropathy is common in type 2 diabeticpatients (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.
Authors: Adrian T Billeter; Stefan Kopf; Martin Zeier; Katharina Scheurlen; Lars Fischer; Thilo M Schulte; Hannes G Kenngott; Barbara Israel; Philipp Knefeli; Markus W Büchler; Peter P Nawroth; Beat P Müller-Stich Journal: Dtsch Arztebl Int Date: 2016-12-09 Impact factor: 5.594
Authors: Adrian T Billeter; Spiros Vittas; Barbara Israel; Katharina M Scheurlen; Asa Hidmark; Thomas H Fleming; Stefan Kopf; Markus W Büchler; Beat P Müller-Stich Journal: Langenbecks Arch Surg Date: 2017-07-09 Impact factor: 3.445
Authors: Adrian T Billeter; Jonas Senft; Daniel Gotthardt; Philipp Knefeli; Felix Nickel; Thilo Schulte; Lars Fischer; Peter P Nawroth; Markus W Büchler; Beat P Müller-Stich Journal: Obes Surg Date: 2016-08 Impact factor: 4.129
Authors: Adrian T Billeter; Katharina M Scheurlen; Barbara Israel; Beate K Straub; Peter Schirmacher; Stefan Kopf; Peter P Nawroth; Beat P Müller-Stich Journal: Ann Surg Date: 2022-07-26 Impact factor: 13.787