Fatty acid supplementation in management of type 2 diabetes

补充脂肪酸治疗 2 型糖尿病

• 批准号: 7314641
• 负责人: MARTHA A BELURY
• 金额: $ 22.16万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7314641
• 关键词: 2,4-thiazolidinedione; Acute; Address; Adipocytes; Adipose tissue; Adult; Adverse effects; Adverse event; Affect; Affinity; Agonist; Animals; Attenuated; Beta Cell; Body Weight; Body Weight decreased; Body fat; Cause of Death; Cell physiology; Class; Clinical; Clinical Data; Clinical Research; Complement; Complementary therapies; Conjugated Linoleic Acids; Data; Desire for food; Diabetes Mellitus; Dietary Oils; Dose; Double-Blind Method; Drug Delivery Systems; Edema; Endocrinologist; Energy Intake; Enzymes; Epidemiologic Studies; Evaluation; Family; Fasting; Fatty Acids; Fatty acid glycerol esters; Generations; Glucose; Glycosylated Hemoglobin; Goals; Hepatic; Human; Hyperglycemia; Insulin; Intervention; Isomerism; Ligands; Link; Longevity; Marketing; Masks; Measures; Mediating; Medical center; Molecular Target; Motivation; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oils; Oral; Overweight; PPAR gamma; Pan Genus; Patients; Peripheral; Peroxisome Proliferator-Activated Receptors; Personal Satisfaction; Pharmacologic Substance; Physical activity; Pilot Projects; Pioglitazone; Placebos; Property; Qualifying; Range; Rate; Reporting; Role; Safety; Sales; Supplementation; Testing; Thiazolidinediones; Tissues; Toxic effect; United States; Week; Weight; Weight Gain; Weight maintenance regimen; Woman; Work; adipocyte differentiation; compliance behavior; dietary supplements; energy balance; glucose uptake; glycemic control; human subject; improved; indexing; insulin sensitivity; insulin sensitizing drugs; lipid metabolism; member; men; pre-clinical; prevent; randomized placebo controlled trial; rosiglitazone; statistics; transcription factor

DESCRIPTION (provided by applicant): For the majority of people with type 2 diabetes mellitus, management of hyperglycemia is improved using a mulit-faceted approach including of weight control and pharmaceutical therapy. The usage of insulin sensitizing drugs thiazolidinediones (TZDs) offers the hope of improving glycemic control while preserving beta cell function. An unfortunate and potentially long term problem is that TZD therapy causes weight and adipose gain in most patients. Two large studies (UKPDS and DCCT) have clearly shown that monotherapies for managing hyerpglycemia lose efficacy within 4-6 years and require change or addition of complementary therapies. Weight gain induced by TZD could further compromise insulin sensitivity in the long term. Conjugated linoleic acid is a naturally occurring oil (commercially available as Tonalin), that inhibits weight gain and adipose accumulation in experimental animals and has weight suppressive effects in human subjects who are overweight or obese. The goal of this R21 proposal is to develop a rigorous experimental approach for understanding the safety and efficacy for using CLA to complement TZD for improved management of type 2 diabetes. We hypothesize that when combined with TZD, CLA suppresses weight gain in men and women. This study will be a double-masked randomized, placebo-controlled study where 60 subjects will be divided into one of three groups: A, TZD + Placebo Oil; B TZD + low dose CLA; C, TZD + high dose CLA. The primary variable is the change in body weights compared between groups (low CLA, high CLA vs. 'placebo' supplement) from baseline to Week 32 of intervention. Secondary variables include changes in fat mass, lean mass, insulin sensitivity index, hepatic enzyme levels, edema, adverse effects, and levels of adipocytokines. Because dietary energy intake, appetite and physical activity may influence energy balance, each of these factors will also be measured. If effective and safe, the combination of CLA with TZD offers the possibility of a complementary agent to suppress weight gain and extend the efficacy of TZD. Furthermore, findings from this adequately powered and sufficient duration study will substantiate (or refute) claims that CLA is an effective dietary supplement in weight suppression. With sales of CLA reaching $ 220 million for 2004 and increasing each year, efficacy and safety of CLA require rigorous evaluation.

描述（由申请人提供）：对于大多数患有 2 型糖尿病的人来说，使用包括体重控制和药物治疗在内的多方面方法可以改善高血糖的管理。胰岛素增敏药物噻唑烷二酮类药物 (TZD) 的使用有望改善血糖控制，同时保留 β 细胞功能。一个不幸且潜在的长期问题是 TZD 治疗会导致大多数患者体重和脂肪增加。两项大型研究（UKPDS 和 DCCT）明确表明，治疗高血糖的单一疗法会在 4-6 年内失效，需要改变或添加补充疗法。从长远来看，TZD 引起的体重增加可能会进一步损害胰岛素敏感性。共轭亚油酸是一种天然存在的油（市售品为 Tonalin），可抑制实验动物的体重增加和脂肪积累，并对超重或肥胖的人类受试者具有体重抑制作用。该 R21 提案的目标是开发严格的实验方法，以了解使用 CLA 补充 TZD 以改善 2 型糖尿病管理的安全性和有效性。我们假设，当与 TZD 结合时，CLA 可以抑制男性和女性的体重增加。这项研究将是一项双盲随机、安慰剂对照研究，其中 60 名受试者将被分为三组之一：A、TZD + 安慰剂油； B TZD+低剂量CLA； C、TZD+高剂量CLA。主要变量是从基线到干预第 32 周，各组之间的体重变化（低 CLA、高 CLA 与“安慰剂”补充剂）。次要变量包括脂肪量、瘦体重、胰岛素敏感性指数、肝酶水平、水肿、不良反应和脂肪细胞因子水平的变化。由于膳食能量摄入、食欲和体力活动可能会影响能量平衡，因此还将测量这些因素中的每一个。如果有效且安全，CLA 与 TZD 的组合提供了一种补充药物来抑制体重增加并延长 TZD 疗效的可能性。此外，这项充分有力且持续时间足够长的研究结果将证实（或反驳）CLA 是一种有效抑制体重的膳食补充剂的说法。 2004 年 CLA 销售额达到 2.2 亿美元，并且逐年增加，CLA 的功效和安全性需要严格的评估。