Fatty acid supplementation in management of type 2 diabetes

描述(由申请人提供)：对于大多数2型糖尿病患者，采用多方面的方法改善高血糖的管理，包括体重控制和药物治疗。胰岛素增敏药物噻唑烷二酮(TZDS)的使用为改善血糖控制，同时保护胰岛细胞功能提供了希望。一个不幸的和潜在的长期问题是，TZD治疗会导致大多数患者的体重和脂肪增加。两项大型研究(UKPDS和DCCT)清楚地表明，控制血糖的单一疗法在4-6年内失效，需要改变或增加补充疗法。长期来看，TZD导致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(商业名称为妥纳林)，可抑制实验动物的体重增加和脂肪堆积，并对超重或肥胖的人类受试者具有减肥效果。这项R21提案的目标是开发一种严格的实验方法，以了解使用CLA补充TZD改善2型糖尿病管理的安全性和有效性。我们假设，当与TZD联合使用时，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，60名受试者将被分成三组：A组，TZD安慰剂油组；B组，TZD低剂量CLA组；C组，TZD高剂量CLA组。主要变量是从基线到第32周干预期间不同组(低CLA组、高CLA组和安慰剂补充组)体重的变化。次要变量包括脂肪质量、瘦质量、胰岛素敏感指数、肝酶水平、浮肿、不良反应和脂肪细胞因子水平的变化。由于饮食能量摄入量、食欲和体力活动可能会影响能量平衡，因此也将对这些因素进行测量。如果有效和安全，CLA和TZD的联合使用为抑制体重增加和延长TZD的疗效提供了补充药物的可能性。此外，这项有足够能量和足够持续时间的研究结果将证实(或驳斥)共轭亚油酸是一种有效的减肥膳食补充剂的说法。随着CLA的销售额在2004年达到2.2亿美元，而且每年都在增加，CLA的有效性和安全性需要严格的评估。

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.