在非重度肥胖糖尿病患者接受Roux-Y胃旁路手术后，亚硝化应激而非血糖参数与神经病变改善相关。
Nitrosative stress but not glycemic parameters correlate with improved neuropathy in nonseverely obese diabetic patients after Roux-Y gastric bypass.
作者信息
Müller-Stich Beat P, Billeter Adrian T, Fleming Thomas, Fischer Lars, Büchler Markus W, Nawroth Peter P
机构信息
Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
出版信息
Surg Obes Relat Dis. 2015 Jul-Aug;11(4):847-54. doi: 10.1016/j.soard.2014.12.007. Epub 2014 Dec 16.
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.
背景
糖尿病神经病变在2型糖尿病患者（T2DM）中很常见，但严格的血糖控制并不能改善症状。相比之下，Roux-Y胃旁路术（RYGB）对活动性神经病变症状有积极影响，且独立于血糖控制。本研究的目的是确定RYGB术后改善糖尿病神经病变症状的潜在机制。
方法
对20例胰岛素依赖型T2DM且BMI<35kg/m²的患者进行前瞻性队列研究，采用RYGB治疗。19例患者完成随访。在12个月内对空腹血糖、糖化血红蛋白（HbA1c）、亚硝化、羰基和氧化应激标志物（硝基酪氨酸、羧化赖氨酸（CML）、甲基乙二醛、氧化型低密度脂蛋白（oxLDL））以及神经肽Y和神经激肽A进行了研究。使用神经病变缺陷评分（NDS）评估神经病变。
结果
术前NDS在12个月内有所改善（5.1±0.6至2.6±0.4，P = 0.010）。与术前值相比，空腹血糖和HbA1c也有所改善（分别为201.1±16.6mg/dL至128±8.7mg/dL，P = 0.004；8.5±0.3%（53±3.3mmol/mol）至7±0.3%（67±3.3mmol/mol），P = 0.001）。术后硝基酪氨酸、CML和甲基乙二醛均下降（1067.3±266.9nM至355.8±36.4nM，P = 0.003；257.1±10.2ng/ml至215.3±18.3ng/ml，P = 0.039；402.3±3.9nM至163.4±10.3nM，P = 0.002）。oxLDL保持不变。空腹血糖和HbA1c与神经病变的改善无关。6个月和12个月后硝基酪氨酸的下降与NDS的改善相关（r = 0.9，P < 0.001和r = 0.68，P = 0.03）。6个月后甲基乙二醛的下降与12个月后NDS的下降相关（r = 0.897，P = 0.003）。
结论
RYGB似乎能改善氧化、亚硝化和羰基应激，已知这些应激在糖尿病神经病变中起因果作用。
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