Billeter Adrian T, Vittas Spiros, Israel Barbara, Scheurlen Katharina M, Hidmark Asa, Fleming Thomas H, Kopf Stefan, Büchler Markus W, Müller-Stich Beat P
From the Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
From the Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
Langenbecks Arch Surg. 2017 Sep;402(6):901-910. doi: 10.1007/s00423-017-1601-x. Epub 2017 Jul 9.
The underlying causes of type 2 diabetes (T2DM) remain poorly understood. Adipose tissue dysfunction with high leptin, inflammation, and increased oxidative stress may play a pivotal role in T2DM development in obese patients. Little is known about the changes in the adipose tissue after Roux-Y gastric bypass (RYGB) in non-severely obese patients (BMI < 35 kg/m) and since these patients have more T2DM-associated complications than obese patients ("obesity paradox"), we investigated changes in adipose tissue function in a cohort of BMI <35 kg/m with insulin-dependent T2DM after RYGB surgery which resolves T2DM.
Twenty patients with insulin-dependent T2DM and BMI <35 kg/m underwent RYGB. Insulin-resistance, leptin, oxidative stress, and cytokines were determined over 24 months. Expression of cytokines and NF-kappaB pathway genes were measured in leukocytes (PBMC). Adipose tissue inflammation was examined histologically preoperatively and 24 months after RGYB in subcutaneous adipose tissue.
Insulin-resistance, leptin, oxidative stress as well as adipose tissue inflammation decreased significantly after RYGB. Similarly, systemic inflammation was reduced and peripheral blood mononuclear cells (PBMCs) were reprogrammed towards an M2-type inflammation. Loss of BMI correlated with leptin levels (r = 0.891, p < 0.0001), insulin resistance (r = 0.527, p = 0.003), and oxidative stress (r = 0.592, p = 0.016). Leptin correlated with improved insulin resistance (r = 0.449, p = 0.032) while reduced leptin showed a strong association with improved oxidative stress (r = 0.809, p = 0.001). Lastly, reduced oxidative stress correlated strongly with improved insulin-resistance (r = 0.776, p = 0.001).
RYGB improves adipose tissue function and inflammation. Leptin as marker for adipose tissue dysfunction may be the mediating factor between insulin resistance and oxidative stress and thereby likely improving T2DM.
2型糖尿病（T2DM）的潜在病因仍未完全明确。脂肪组织功能障碍，伴有高瘦素、炎症及氧化应激增加，可能在肥胖患者T2DM的发生发展中起关键作用。对于非重度肥胖患者（体重指数<35kg/m²）接受Roux-Y胃旁路术（RYGB）后脂肪组织的变化知之甚少，且由于这些患者比肥胖患者有更多与T2DM相关的并发症（“肥胖悖论”），我们调查了一组体重指数<35kg/m²且患有胰岛素依赖型T2DM的患者在接受RYGB手术（该手术可缓解T2DM）后脂肪组织功能的变化。
20例体重指数<35kg/m²的胰岛素依赖型T2DM患者接受了RYGB手术。在24个月内测定胰岛素抵抗、瘦素、氧化应激和细胞因子水平。检测白细胞（外周血单个核细胞）中细胞因子和核因子κB信号通路基因的表达。术前及RYGB术后24个月对皮下脂肪组织进行组织学检查，观察脂肪组织炎症情况。
RYGB术后胰岛素抵抗、瘦素、氧化应激以及脂肪组织炎症均显著降低。同样，全身炎症减轻，外周血单个核细胞（PBMCs）向M2型炎症方向重编程。体重指数的降低与瘦素水平（r = 0.891，p < 0.0001）、胰岛素抵抗（r = 0.527，p = 0.003）及氧化应激（r = 0.592，p = 0.016）相关。瘦素与胰岛素抵抗改善相关（r = 0.449，p = 0.032），而瘦素降低与氧化应激改善密切相关（r = 0.809，p = 0.001）。最后，氧化应激降低与胰岛素抵抗改善密切相关（r = 0.776，p = 0.001）。
RYGB可改善脂肪组织功能及炎症。瘦素作为脂肪组织功能障碍的标志物，可能是胰岛素抵抗和氧化应激之间的介导因素，从而可能改善T2DM。
