Does a ketogenic diet impair metabolic health?

生酮饮食会损害代谢健康吗？

基本信息

批准号：
10751471
负责人：
Molly Rachel Gallop
金额：
$ 6.91万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10751471
关键词：
Acute Adherence Affect Automobile Driving Beta Cell Blood Glucose Body Weight Body Weight decreased Body fat Bolus Infusion Carbohydrates Cell physiology Cholecystokinin Chronic Coupled Data Development Diabetes Mellitus Diet Dietary Intervention Eating Energy Intake Energy Metabolism Epilepsy Equilibrium Fasting Fatty acid glycerol esters Feeling Fellowship Future Genetic Transcription Glucose Glucose Intolerance Glycosylated hemoglobin A Goals Health Heart Diseases High Fat Diet Human Hunger Hyperphagia Impairment Insulin Intervention Ketone Bodies Life Maintenance Mammals Measurement Metabolic Mission Monitor Mus National Institute of Diabetes and Digestive and Kidney Diseases Neurons Obese Mice Obesity Outcome Participant Patients Peptides Persons Plasma Proteins Public Health Reducing diet Regulation Reporting Research Risk Rodent Safety Seizures Syndrome Testing Therapeutic Thinness Weight Weight Gain Weight maintenance regimen Work blood glucose regulation cancer type career design dietary control effective therapy energy balance fasting glucose fat burning feeding ghrelin glucagon-like peptide 1 glucose tolerance improved in vivo innovation insight insulin secretion islet ketogenic diet lipid biosynthesis morphometry obesity treatment prevent reduced food intake response transcriptomics weight gain prevention

项目摘要

Project Summary Since the 1960s, a ketogenic diet (KD) has been touted as a potential treatment for diabetes and obesity. A KD is a very low carbohydrate, high fat, and moderate protein diet that has been used since the 1910s to treat epilepsy and was designed to mimic the benefits that fasting had on seizure control. Noting metabolic similarities between a KD and fasting — namely a switch from burning glucose to burning fat — a KD was hypothesized to lower fasting glucose and insulin, leading to consequent inhibition of lipogenesis, thereby favoring burning rather than storage of fat. However, the efficacy and metabolic effects of a KD have been largely underexplored. As obesity raises the risk for the development of many health conditions, including diabetes, heart disease, and multiple types of cancer, the long-term goal of this work is to develop rigorously tested and efficacious weight control therapeutics. The overall objective of this proposal is to determine whether a KD is a safe and effective treatment to control weight and blood glucose. The driving hypothesis of this proposed work is that a KD suppresses weight gain and causes weight loss but impairs glucose homeostasis. The rationale for carrying out the proposed studies is that the efficacy of a KD as a weight control diet, and the overall effects that KD has on metabolic health are unclear. Since KD is now a commonly used diet, it is critical to understand the effects of a KD on metabolic health so that we do not make health conditions worse by prescribing a KD. In humans who have obesity, some studies report greater weight loss when participants were prescribed a KD versus a control weight loss diet. However, other studies have reported that a KD produces similar effects to other weight loss diets, making the effects of KD on weight regulation unclear and necessitating further study. Conversely, while studies in both rodents and humans have shown that a KD intervention lowered fasting glucose and HbA1c, several studies have suggested that glucose tolerance is impaired on a KD. This proposed work is of crucial importance since a KD is prescribed to people who may already have diabetes or obesity, so it is imperative to understand if a KD worsens blood glucose regulation. Thus, to ascertain whether a KD is a metabolically safe and beneficial intervention for people with diabetes and/or obesity, we will elucidate the mechanisms by which a KD controls body weight (Aim 1) and establish the effects of a KD on beta cell function (Aim 2). The proposed studies are innovative as the mechanistic effects of KD on weight and blood glucose regulation have been largely under-investigated. Ultimately, these studies will determine whether a KD is a safe and effective treatment for weight control and glucose homeostasis. Furthermore, mechanistic insights gained from elucidating the effects of a KD on weight control will pave the way for the development of future weight control therapies.

项目概要自 20 世纪 60 年代以来，生酮饮食 (KD) 一直被誉为治疗糖尿病和肥胖症的潜在疗法。是一种极低碳水化合物、高脂肪和适量蛋白质的饮食，自 1910 年代以来一直用于治疗癫痫，旨在模仿禁食对癫痫发作控制的益处。在 KD 和禁食之间（即从燃烧葡萄糖到燃烧脂肪的转变），KD 被竞相进行降低空腹血糖和胰岛素，从而抑制脂肪生成，从而有利于燃烧而不是然而，生酮饮食的功效和代谢作用尚未得到充分研究。肥胖会增加许多健康状况的风险，包括糖尿病、心脏病和多种类型的癌症，这项工作的长期目标是开发经过严格测试的有效体重该提案的总体目标是确定 KD 是否安全有效。这项研究的驱动假设是 KD。抑制体重增加并导致体重减轻，但会损害葡萄糖稳态。拟议的研究是，生酮饮食作为体重控制饮食的功效，以及生酮饮食对体重的总体影响由于生酮饮食现在是一种常用的饮食方式，因此了解代谢健康的影响至关重要。生酮饮食对代谢健康的影响，这样我们就不会因为给患有生酮饮食的人开处方而使健康状况恶化。患有肥胖症，一些研究报告称，与对照组相比，服用 KD 的参与者体重减轻幅度更大然而，其他研究表明生酮饮食可以产生与其他减肥方法相似的效果。饮食，使得 KD 对体重调节的影响尚不清楚，需要进一步的离线研究。对啮齿动物和人类的研究表明，生酮饮食干预可降低空腹血糖和 HbA1c，多项研究表明生酮饮食会损害葡萄糖耐量，这项工作至关重要。重要性，因为 KD 是为可能已经患有糖尿病或肥胖症的人开的，所以必须生酮饮食是否会使血糖调节恶化因此，要了解生酮饮食是否是代谢安全的。以及对糖尿病和/或肥胖症患者进行有益的干预，我们将阐明其机制 KD 控制体重（目标 1）并确定 KD 对 β 细胞功能的影响（目标 2）。这项研究具有创新性，因为生酮饮食对体重和血糖调节的机制作用已在很大程度上得到了证实。最终，这些研究将确定 KD 是否是一种安全有效的治疗方法。此外，通过阐明影响获得了机制见解。 KD 在体重控制方面的研究将为未来体重控制疗法的发展铺平道路。