Mari A, Manco M, Guidone C, Nanni G, Castagneto M, Mingrone G, Ferrannini E
CNR Institute of Biomedical Engineering, Corso Stati Uniti 4, 35127, Padua, Italy.
Diabetologia. 2006 Sep;49(9):2136-43. doi: 10.1007/s00125-006-0337-x. Epub 2006 Jul 4.
AIMS/HYPOTHESIS: The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing bilio-pancreatic diversion (BPD).
We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic-hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52+/-7 kg/m(2), mean+/-SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery.
BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre-BPD 341+/-79 ml min(-1) m(-2), post-BPD 511+/-57 ml min(-1) m(-2), lean 478+/-49 ml min(-1) m(-2)). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min(-1) m(-2) l mmol(-1), median [interquartile range]) compared with lean subjects (82 [98]; p</=0.05). After BPD, beta cell glucose sensitivity showed a tendency towards improvement but remained impaired in diabetic subjects (30 [62]; p<0.01 vs lean). Total insulin output decreased in parallel with the insulin sensitivity increase in all groups. In the whole patient group, mean OGTT glucose levels were inversely related to both insulin sensitivity and beta cell glucose sensitivity (r (2)=0.67, partial r=-0.76 and -0.41, respectively). NEFAs, leptin and adiponectin were related to insulin sensitivity but could not explain the early improvement.
CONCLUSIONS/INTERPRETATION: Following BPD, glucose tolerance was restored mainly as a result of a rapid and large improvement in insulin sensitivity.
目的/假设：本研究旨在分析病态肥胖患者接受胆胰转流术（BPD）后糖耐量改善的潜在机制。
我们评估了32例病态肥胖（BMI = 52±7 kg/m²，均值±标准差）患者（12例糖耐量正常、9例糖耐量受损、11例2型糖尿病）在BPD前后以及22例体重正常对照者的糖耐量（通过口服葡萄糖耐量试验[OGTT]）、胰岛素敏感性（正常血糖高胰岛素钳夹试验及OGTT指数OGIS）和β细胞功能（OGTT模型分析）。在手术前以及术后7天至60个月对患者进行研究。
BPD改善了所有受试者的糖耐量，术后所有受试者糖耐量均正常。所有受试者的胰岛素敏感性均恢复至正常水平（BPD术前341±79 ml·min⁻¹·m⁻²，BPD术后511±57 ml·min⁻¹·m⁻²，体重正常者478±49 ml·min⁻¹·m⁻²）。BPD术后10天内即可检测到胰岛素敏感性的变化。基线时，糖尿病受试者的β细胞对葡萄糖的敏感性受损（25 [18] pmol·min⁻¹·m⁻²·l·mmol⁻¹，中位数[四分位间距]），而体重正常者为82 [98]；p≤0.05）。BPD术后，β细胞对葡萄糖的敏感性有改善趋势，但糖尿病受试者仍受损（30 [62]；与体重正常者相比p<0.01）。所有组的总胰岛素分泌量均随胰岛素敏感性增加而平行下降。在整个患者组中，平均OGTT血糖水平与胰岛素敏感性和β细胞对葡萄糖的敏感性均呈负相关（r² = 0.67，偏相关系数分别为-0.76和-0.41）。非酯化脂肪酸、瘦素和脂联素与胰岛素敏感性有关，但无法解释早期的改善情况。
结论/解读：BPD术后，糖耐量恢复主要是由于胰岛素敏感性迅速大幅改善。
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