Aims/hypothesis

Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes.

Methods

In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body [¹⁸F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change.

Results

One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (−26.3% [95% CI −49.5, −3.0], p=0.009) and non-significantly following LCD (−20.9% [95% CI −58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected.

Conclusions/interpretation

The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks.

Trial registration

ClinicalTrials.gov NCT02988011

Funding

This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union’s Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants

Graphical Abstract

中文翻译：

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肥胖手术与低能量饮食对身体成分和组织特异性葡萄糖摄取的短期影响：一项使用全身集成 18F-FDG-PET/MRI 的随机临床研究

目标/假设

肥胖手术（OS）和饮食诱导的减肥可迅速改善胰岛素抵抗。我们的目的是研究与低能量饮食（低热量饮食；LCD）相比，Roux-en-Y 胃绕道手术 (RYGB) 或袖状胃切除术 (SG) 手术对身体成分、血糖控制和胰岛素敏感性的影响，对肥胖但非糖尿病个体的整体和组织特异性水平进行评估。

方法

在这项平行组随机对照试验中，OS 等待名单上的患者被随机（无盲法、密封信封）直接接受手术或在手术前接受 LCD 检查。在基线和手术后 4 周（n = 15、11 RYGB 和 4 SG）或 LCD 开始后 4 周（n = 9）进行了研究，包括 OGTT 和高胰岛素-正常血糖钳夹，在此期间同时进行整体检查。进行身体[ ¹⁸ F]氟脱氧葡萄糖-正电子发射断层扫描(PET)/MRI。主要结果是 HOMA-IR 变化。

结果

减肥手术和开始 LCD 1 个月后，两种治疗均导致体重（平均值±标准差：分别为 -7.7±1.4 kg 和 -7.4±2.2 kg）、脂肪组织体积（7%）和肝脏脂肪含量（ 2% 单位）。主要终点 HOMA-IR 在 OS 后显着降低（−26.3% [95% CI -49.5, -3.0], p =0.009），在 LCD 后不显着降低（−20.9% [95% CI -58.2, 16.5] ）。两组的甘油三酯和低密度脂蛋白胆固醇都有类似的降低。仅在 OS 后空腹血糖和胰岛素也显着降低。 OS 组中 OGTT 导致葡萄糖 AUC 增加（增加 20%），但 LCD 组则没有增加。在高胰岛素血症期间，仅 OS 组显示骨骼肌中 PET 衍生的葡萄糖摄取率显着增加，但心脏和腹部脂肪组织的摄取率降低。手术或 LCD 后，肝脏和大脑的葡萄糖摄取率均未变化。全身葡萄糖的处理和内源性葡萄糖的产生没有受到显着影响。

结论/解释

OS 后 4 周出现的短期代谢影响并不能仅用体脂减少来解释。因此，OS（而非 LCD）导致空腹血糖和胰岛素抵抗降低，以及胰岛素刺激的葡萄糖流向不同组织的明显变化。这些作用可能有助于预防或逆转 OS 后的 2 型糖尿病。此外，对全身胰岛素抵抗和血糖的全面影响需要超过 4 周的时间。

试用注册

临床试验.gov NCT02988011

资金

这项工作得到了阿斯利康研发部、瑞典糖尿病基金会、欧盟 Horizo​​n Europe 研究项目 PAS GRAS、欧盟委员会通过 Marie Sklodowska Curie 创新培训网络 TREATMENT、EXODIAB、Family Ernfors 基金会、PO Zetterling 基金会、诺和诺德的支持基金会、艾格尼丝和麦克鲁德伯格基金会以及乌普萨拉大学医院 ALF 赠款

图形概要