Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, 56100 Pisa, Italy.
J Clin Endocrinol Metab. 2013 Jul;98(7):2765-73. doi: 10.1210/jc.2013-1476. Epub 2013 May 10.
Diabetes remission is frequent after biliopancreatic diversion (BPD) in morbidly obese patients with type 2 diabetes (T2D). Data, mechanisms, and clinical indications in nonobese T2D patients are scanty.
The objective of the study was to assess remission and investigate insulin sensitivity and β-cell function after BPD in nonobese patients with long-standing T2D.
DESIGN, SETTING, AND PATIENTS: This was a clinical research study comparing 15 T2D patients (aged 55 ± 1 years, duration of 16 ± 2 years, body mass index of 28.3 ± 0.6 kg/m², glycosylated hemoglobin 8.6% ± 1.3%) with 15 gender-, age-, and body mass index-matched nondiabetic controls. Before surgery and 2 months and 1 year later, a 3-hour oral glucose tolerance test, a 5-hour mixed-meal test, and a 3-hour euglycemic clamp were performed.
The intervention included a BPD (distal gastrectomy, proximal ileum anastomosed to remaining stomach, biliopancreatic limb anastomosed to ileum 50 cm from the ileocecal valve).
Glycemia improved in all patients, but remission (glycosylated hemoglobin < 6.5% and normal oral glucose tolerance test) occurred in 6 of 15 patients. Insulin resistance (19.8 ± 0.8 μmol · min⁻¹ · kg(ffm)⁻¹, P < .001 vs 40.9 ± 5.3 of controls) resolved already at 2 months (34.2 ± 2.8) and was sustained at 1 year (34.7 ± 1.6), although insulin-mediated suppression of endogenous glucose production remained impaired. In contrast, β-cell glucose sensitivity (19 [12] pmol · min⁻¹ · m⁻² · mM⁻¹ vs 96 [73] of controls, P < .0001) rose (P = .02) only to 31 [26] at 1 year and was lower in nonremitters (16 [18]) than remitters (46 [33]).
In nonobese patients with long-standing T2D, BPD improves metabolic control but induces remission in only approximately 40% of patients. Peripheral insulin sensitivity is restored early after surgery and similarly in remitters and nonremitters, indicating a weight-independent effect of the operation. The initial extent of β-cell incompetence is the main predictor of the metabolic outcome.
在患有 2 型糖尿病(T2D)的病态肥胖患者中,胆胰分流术(BPD)后常出现糖尿病缓解。非肥胖 T2D 患者的数据、机制和临床适应证很少。
本研究旨在评估非肥胖、长期 T2D 患者接受 BPD 后的缓解情况,并探讨胰岛素敏感性和β细胞功能。
设计、地点和患者:这是一项临床研究,比较了 15 名 T2D 患者(年龄 55 ± 1 岁,病程 16 ± 2 年,体重指数 28.3 ± 0.6 kg/m²,糖化血红蛋白 8.6% ± 1.3%)和 15 名性别、年龄和体重指数匹配的非糖尿病对照者。手术前、术后 2 个月和 1 年后,进行 3 小时口服葡萄糖耐量试验、5 小时混合餐试验和 3 小时正葡萄糖钳夹试验。
干预措施包括 BPD(胃远端切除术,剩余胃与近端空肠吻合,胆胰支与回肠距回盲瓣 50cm 吻合)。
所有患者的血糖均有所改善,但仅 6 名患者(6/15)达到缓解(糖化血红蛋白<6.5%,口服糖耐量正常)。胰岛素抵抗(19.8 ± 0.8 μmol·min⁻¹·kg(ffm)⁻¹,P<0.001 与对照组 40.9 ± 5.3 相比)在术后 2 个月(34.2 ± 2.8)就已得到改善,在 1 年时仍保持(34.7 ± 1.6),尽管胰岛素介导的内源性葡萄糖产生抑制仍受损。相比之下,β细胞葡萄糖敏感性(19[12]pmol·min⁻¹·m⁻²·mM⁻¹与对照组 96[73]相比,P<0.0001)仅在术后 1 年升高(P=0.02)至 31[26],且在未缓解者(16[18])中低于缓解者(46[33])。
在非肥胖、长期患有 T2D 的患者中,BPD 可改善代谢控制,但仅约 40%的患者能获得缓解。术后外周胰岛素敏感性早期恢复,缓解者和未缓解者相似,提示手术有体重独立的作用。β细胞功能不全的初始程度是代谢结果的主要预测因素。