Fatty acid supplementation in management of type 2 diabetes

补充脂肪酸治疗 2 型糖尿病

• 批准号: 7643913
• 负责人: MARTHA A BELURY
• 金额: $ 18.01万
• 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 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7643913
• 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; 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; 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; Pharmacologic Substance; Physical activity; Pilot Projects; Pioglitazone; Placebos; Property; Qualifying; Reporting; Role; Safety; Sales; Supplementation; Takeda brand of pioglitazone hydrochloride; Testing; Thiazolidinediones; Tissues; Toxic effect; United States; Weight; Weight Gain; Weight maintenance regimen; Woman; Work; adipocyte differentiation; compliance behavior; dietary supplements; energy balance; fasting glucose; 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2型糖尿病的人，使用MULIT面对面的方法（包括体重控制和药物治疗）改善了高血糖的管理。胰岛素敏化药物噻唑烷二酮（TZDS）的使用提供了改善血糖控制的希望，同时保留β细胞功能。不幸的且可能长期的问题是，大多数患者的TZD治疗会导致体重和脂肪增加。两项大型研究（UKPDS和DCCT）清楚地表明，用于管理Hyerpglycemia的单一疗法在4 - 6年内失去了疗效，需要更改或添加补充疗法。从长远来看，TZD诱导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（商业上作为Tonalin，可以抑制实验动物的体重增加和脂肪的累积，并且在超重或肥胖的人类受试者中具有抑制重量。该R21提案的目的是开发一种严格的实验方法，以了解使用CLA补充TZD以改善2型糖尿病的管理的安全性和功效。我们假设与TZD结合使用，CLA会抑制男性和女性体重增加。这项研究将是一项双掩盖的随机，安慰剂对照研究，其中60名受试者将分为三组之一：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的第32周（低CLA，高CLA与“安慰剂”补充剂）之间的体重变化。次要变量包括脂肪质量，瘦肉，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。由于饮食能量摄入，食欲和体育锻炼可能会影响能量平衡，因此也将测量这些因素。如果有效且安全，将CLA与TZD的组合提供了互补剂的可能性，以抑制体重增加并扩展TZD的功效。此外，这项足够动力和足够的持续时间研究的发现将证实（或驳斥）CLA是体重抑制中有效的饮食补充剂。随着CLA的销售额达到2004年的2.2亿美元，每年增加，CLA的功效和安全性需要进行严格的评估。