Glycemic Index Variations In the Early Period Following Bariatric Surgery
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Changes in intestinal microbiota composition prior and following bariatric surgery
研究概览
简要总结
The diverse community of gut microbes commonly referred to as the 'gut microbiome', is increasingly suggested to play significant roles in health and disease, and to affect even distant non-GI organs by metabolite signaling. Type 2 diabetes mellitus (T2DM) patients feature a distinct gut microbiome signature4, while modulating the gut microbiome by either antibiotics or fecal microbial transplantation (FMT) is suggested to impact insulin sensitivity. Originally designed to treat obesity, bariatric surgeries often induce a robust and rapid weight-independent improvement in glucose homeostasis within days. Early diabetes remission following bariatric surgery is hypothesized to be mediated by rapid alterations in the gut microbiome and bile acids composition, however, the exact mechanism is yet to be uncovered. Elucidating this mechanism is important as it may form the basis of a new therapeutic modality in diabetes. The investigators intend to deeply characterize early post-bariatric changes in the gut microbiome of diabetic patients, as well as their gut mucosal transcriptome and metabolome, by using state-of-the-art experimental and computational pipelines. Additionally, The investigators will utilize a unique mouse model of bariatric surgery under germ-free conditions, developed at the Elinav lab, that allows us to dissect the role of microbes in post-operative metabolic improvements.
详细描述
Type 2 diabetes mellitus (T2DM) is one of the most prevalent and deadly conditions in the 21st century. T2DM is characterized by obesity and insulin resistance that leads to chronic hyperglycemia, which even with best medical care is often uncontrolled, resulting in life-threatening micro- and macrovascular complications.
The gut microbiota (i.e. the microbial population inhabiting the gut) has been extensively linked to blood glucose levels and was shown to mediate insulin response in various settings, including anti-diabetic pharmacotherapy. Moreover, fecal microbial transplantation (FMT) from lean healthy donors improved insulin resistance in humans suffering from metabolic syndrome. These pre-clinical and clinical evidence suggest that the gut microbiota has a mechanistic role in insulin-resistance.
Bariatric surgeries were originally designed to treat obesity but were also retrospectively found to ameliorate T2DM among other metabolic and non-metabolic disorders. Since obesity is a significant risk factor for T2DM, it is not surprising that surgically-induced weight loss which occurs within several months after surgery also improves insulin sensitivity. However, a substantial share of patients experience an improvement in insulin resistance within days after bariatric surgery, which clinically presents as normal glycemic values despite decreased dosage of anti-diabetic medications in the first post-operative days. This phenomenon of early diabetes remission after surgery precedes any weight-loss, therefore it is weight-independent and it is far from being understood.
Several explanations were suggested to explain early post-bariatric surgery diabetes remission, among which are acute caloric restriction, amplified incretins response, and rapid alterations in bile acids composition; however, none of them accounts for such a drastic improvement in glycemic control within such a short time frame.
Bariatric surgery rapidly alters the gut microbiome in a conserved fashion in both humans and rodents. Although descriptive studies demonstrated a change in microbiome composition within a few months after surgery, most studies didn't analyze microbiome in the first post-operative weeks in which the improvement in diabetes takes place, and data so far remains associative at best. Two independent studies exhibited improved metabolism following FMT from post-bariatric surgery humans and mice donors
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult Population (> 18 years old)
- •Diabetic Patients (Type 2)
- •Bariatric surgery candidates for two types of bariatric surgery, i.e. sleeve gastrectomy and Roux-en-Y gastric bypass
- •Laparoscopic Cholecystectomy candidates
排除标准
- •Pregnant Women
- •< 18 years old
结局指标
主要结局
Changes in intestinal microbiota composition prior and following bariatric surgery
时间窗: two weeks
Changes in intestinal microbiota composition following bariatric surgery measured with RNA sequencing
Changes in glycemic index prior and following bariatric surgery
时间窗: two weeks
Changes in glycemic index prior and following bariatric surgery measured with continues glucose monitoring system (FreeStyle Libre)
次要结局
未报告次要终点
研究者
Dr. Nir Horesh resident Department of Surgery and Transplant
Principal Investigator
Sheba Medical Center