Department of Internal Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy.
Diabetologia. 2011 Aug;54(8):2093-102. doi: 10.1007/s00125-011-2193-6. Epub 2011 May 26.
AIMS/HYPOTHESIS: Bariatric surgery consistently induces remission of type 2 diabetes. We tested whether there are diabetes-specific mechanisms in addition to weight loss.
We studied 25 morbidly obese patients (BMI 51.7 ± 1.5 kg/m(2) [mean ± SEM]), 13 with non-insulin-treated type 2 diabetes (HbA(1c) 7.1 ± 0.5% [54 ± 5 mmol/mol]), before and at 2 weeks and 1 year after Roux-en-Y gastric bypass (RYGB). Lean (n = 8, BMI 23.0 ± 0.5 kg/m(2)) and obese (n = 14) volunteers who were BMI-matched (36.0 ± 1.2) to RYGB patients at 1 year after surgery served as controls. We measured insulin-stimulated glucose disposal (M) and substrate utilisation (euglycaemic clamp/indirect calorimetry), endogenous glucose production (EGP) by 6,6-[(2)H(2)]glucose, lipolysis (rate of appearance of [(2)H(5)]glycerol) and beta cell function (acute insulin response to i.v. glucose [AIR] as determined by C-peptide deconvolution).
At baseline, all obese groups showed typical metabolic abnormalities, with M, glucose oxidation and non-oxidative disposal impaired, and EGP, lipolysis, lipid oxidation and energy expenditure increased. Early after RYGB plasma glucose and insulin levels, and energy expenditure had decreased, while lipid oxidation increased, with M, EGP and AIR unchanged. At 1 year post-RYGB (BMI 34.4 ± 1.1 kg/m(2)), all diabetic patients were off glucose-lowering treatment and mean HbA(1c) was 5.4 ± 0.14% (36 ± 2 mmol/mol) (p = 0.03 vs baseline); AIR also improved significantly. In all RYGB patients, M, substrate oxidation, EGP, energy expenditure and lipolysis improved in proportion to weight loss, and were therefore similar to values in obese controls, but still different from those in lean controls.
CONCLUSIONS/INTERPRETATION: In morbidly obese patients, RYGB has metabolic effects on liver, adipose tissue, muscle insulin sensitivity and pattern of substrate utilisation; these effects can be explained by energy intake restriction and weight loss, the former prevailing early after surgery, the latter being dominant in the longer term.
目的/假设：减重手术能持续缓解 2 型糖尿病。我们检测了除了体重减轻之外是否还有糖尿病特异性机制。
我们研究了 25 名病态肥胖患者（BMI 51.7±1.5 kg/m²[平均值±SEM]），其中 13 名患者患有未经胰岛素治疗的 2 型糖尿病（HbA1c 7.1±0.5%[54±5 mmol/mol]），在 Roux-en-Y 胃旁路手术（RYGB）前、术后 2 周和 1 年后进行了检测。在 RYGB 术后 1 年，与 RYGB 患者 BMI 匹配的瘦（n=8，BMI 23.0±0.5 kg/m²）和肥胖（n=14）志愿者作为对照组。我们通过胰岛素刺激葡萄糖处置（M）和底物利用（正葡萄糖钳夹/间接测热法）、6,6-[(2)H(2)]葡萄糖内源性葡萄糖生成（EGP）、脂肪分解（[(2)H(5)]甘油出现率）和β细胞功能（通过 C 肽反卷积确定的静脉内葡萄糖急性胰岛素反应[AIR]）来测量胰岛素刺激的葡萄糖处置（M）和底物利用（正葡萄糖钳夹/间接测热法）。
基线时，所有肥胖组均表现出典型的代谢异常，M、葡萄糖氧化和非氧化处置受损，EGP、脂肪分解、脂质氧化和能量消耗增加。RYGB 术后早期，血糖和胰岛素水平降低，脂类氧化增加，而能量消耗增加，M、EGP 和 AIR 不变。RYGB 术后 1 年（BMI 34.4±1.1 kg/m²）时，所有糖尿病患者均停止降糖治疗，平均 HbA1c 为 5.4±0.14%（36±2 mmol/mol）（p=0.03 与基线相比）；AIR 也显著改善。在所有 RYGB 患者中，M、底物氧化、EGP、能量消耗和脂肪分解与体重减轻成比例改善，因此与肥胖对照组相似，但仍与瘦对照组不同。
结论/解释：在病态肥胖患者中，RYGB 对肝脏、脂肪组织、肌肉胰岛素敏感性和底物利用模式有代谢作用；这些作用可以通过能量摄入限制和体重减轻来解释，前者在手术后早期起主导作用，后者在长期起主导作用。
