NONALCOHOLIC FATTY LIVER DISEASE IN TYPE 2 DIABETES MELLITUS

2 型糖尿病中的非酒精性脂肪肝

• 批准号: 7718702
• 负责人: KENNETH CUSI
• 金额: $ 0.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718702
• 关键词: African American; Area; Caring; Caucasians; Caucasoid Race; Chronic; Communities; Computer Retrieval of Information on Scientific Projects Database; Condition; Diagnosis; Dietary Intervention; Disease; Early Intervention; Enzymes; Epidemic; Fatty Liver; Fatty acid glycerol esters; Fibrosis; Funding; Glucose Intolerance; Gold; Grant; Hepatic; Hispanics; Image; Incidence; Institution; Insulin Resistance; Intervention; Knowledge; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Spectroscopy; Measures; Natural History; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Obesity; Patient Agents; Patients; Pioglitazone; Prevention; Protocols documentation; Public Health; Range; Research; Research Personnel; Resources; Risk; Screening procedure; Source; Standards of Weights and Measures; Steatohepatitis; Symptoms; Techniques; United States National Institutes of Health; base; clinically relevant; experience; insulin sensitizing drugs; liver biopsy; non-alcoholic fatty liver; nonalcoholic steatohepatitis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The objectives are to establish the magnitude of the epidemic of NAFLD in T2DM (protocol #1 or "Screening Study") and to compare the current standard of care (dietary intervention alone) vs. the insulin-sensitizer pioglitazone (protocol #2 or "Treatment of NAFLD Study"). We want to establish if pioglitazone is a disease-modifying agent for patients with T2DM and NAFLD/NASH. RESEARCH PLAN: Type 2 diabetes mellitus (T2DM) is a major public health problem, but less well recognized is that obesity and T2DM are fueling another "silent epidemic": nonalcoholic fatty liver disease (NAFLD). NAFLD is a chronic liver condition associated with insulin resistance, impaired glucose intolerance or frank type 2 diabetes (T2DM) and hepatic fat accumulation, ranging from simple steatosis to severe steatohepatitis with necroinflammation (NASH) and eventually fibrosis. The diagnosis of NAFLD and NASH is difficult as it gives few symptoms, the most common being vague right upper quadrant discomfort, and while liver enzymes may be elevated (ALTAST) in NAFLD, the real problem is that they are normal in ~2/3 of patients. Therefore, a large number of patients are undiagnosed and undergoing chronic liver damage. METHODS: There are two steps in this proposal. The first is to establish the magnitude of the epidemic of NAFLD in T2DM (protocol #1 or "Screening Study"). To this end, we plan to screen 250 unselected patients with T2DM for NAFLD from the San Antonio area non-invasively by magnetic resonance spectroscopy (MRS) which is the gold-standard technique. The second aim as outlined in protocol #2 ("Treatment of NAFLD Study") will be to estimate the incidence of NASH (hepatic fat accumulation plus necroinflammation and/or fibrosis by liver biopsy - the only way to establish this diagnosis as it cannot be done by imaging) and compare two treatments: the current standard of care (the empiric approach based on dietary intervention alone) vs. the insulin-sensitizer pioglitazone. This will allow us to establish if pioglitazone is a disease-modifying agent during long-term treatment, capable of changing the natural history of NAFLD/NASH in patients with T2DM. CLINICAL RELEVANCE: There are no large studies to date as the one proposed here to bridge the gap in our knowledge about the real magnitude of the epidemic of fatty liver disease in T2DM. The greater availability of MRS has allowed a fast and highly reproducible way to measure liver fat. In our experience with MRS over the past five years, we have established that ~80% of patients with T2DM have NAFLD and Hispanics had a greater hepatic fat content when matched for major pertinent variables (unpublished). Recent studies have confirmed that Hispanics are at much greater risk of NAFLD than Caucasians or African-Americans, making this proposal particularly relevant for the San Antonio community in order to develop new prevention and early intervention strategies.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：建立2型糖尿病患者非酒精性脂肪肝(NAFLD)流行的严重程度(方案1或“筛查研究”)，并比较目前的护理标准(仅限饮食干预)和胰岛素增敏剂吡格列酮(方案2或“NAFLD治疗研究”)。我们想要确定吡格列酮是否是T2 DM和NAFLD/NASH患者的疾病改良剂。 研究计划：2型糖尿病(T2 DM)是一个主要的公共健康问题，但人们不太清楚的是，肥胖和T2 DM正在助长另一种“沉默的流行病”：非酒精性脂肪性肝病(NAFLD)。NAFLD是一种慢性肝病，与胰岛素抵抗、糖耐量受损或坦率的2型糖尿病(T2 DM)和肝脏脂肪堆积有关，范围从简单的脂肪变性到严重的脂肪性肝炎伴坏死性炎症(NASH)，最后是纤维化。NAFLD和NASH的诊断很困难，因为它几乎没有症状，最常见的是模糊的右上腹不适，尽管NAFLD的肝酶可能升高(ALTAST)，但真正的问题是~2/3的患者肝酶正常。因此，大量患者没有得到诊断，正在遭受慢性肝损伤。 方法：本方案分为两个步骤。第一个是确定T2 DM中NAFLD的流行程度(方案1或“筛查研究”)。为此，我们计划通过磁共振波谱(MRS)这项金标准技术，从圣安东尼奥地区非侵入性地筛查250名未被选中的T2 DM患者的NAFLD。方案2(“NAFLD研究的治疗”)概述的第二个目标将是评估NASH(肝脏脂肪堆积加上坏死性炎症和/或肝纤维化--这是唯一确定这种诊断的方法，因为它不能通过成像)的发生率，并比较两种治疗方法：目前的护理标准(仅基于饮食干预的经验性方法)与胰岛素增敏剂吡格列酮。这将使我们能够确定在长期治疗期间，吡格列酮是否是一种疾病改良剂，能够改变T2 DM患者NAFLD/NASH的自然病史。 临床相关性：到目前为止，还没有像这里提议的那样的大型研究来弥合我们对T2 DM中脂肪肝流行的真实规模的认识差距。MRS的更广泛的可用性使得一种快速和高度重复性的方法能够测量肝脏脂肪。在我们过去五年的MRS治疗经验中，我们已经确定，大约80%的T2 DM患者患有NAFLD，当与主要相关变量匹配时，拉美裔人的肝脏脂肪含量更高(未发表)。最近的研究证实，拉美裔人患NAFLD的风险比高加索人或非裔美国人高得多，这使得这项建议特别适用于圣安东尼奥社区，以便制定新的预防和早期干预战略。