Early MRI Detection of Myocardial Deterioration as a Preventive, Disease Staging, and Prognostic Biomarker in Insulin Resistance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Identifying patients with high fibrosis levels using peripheral blood samples
研究概览
简要总结
The purpose of this study is to evaluate the relationship between insulin resistance (IR) and myocardial tissue abnormalities. The study will focus on a patient population, South Asians, with a high prevalence of IR.
详细描述
Cardiac fibrosis has been linked to adverse outcomes in non-ischemic cardiomyopathy. Fibrosis is also detectable in diabetic patients, but does not appear to closely track with insulin sensitivity. Hence, fibrosis may be an independent risk factor for adverse outcomes in IR and diabetic patients. As a result, a critical need exists to develop a non-invasive tool to identify and treat the highest-risk patients. Early detection of cardiac fibrosis and other CMR- detectable abnormalities in IR patients may help to 'stage' a patient's disease process and future risk of events, ultimately leading to an adjustment in the aggressiveness of their medical management and long-term monitoring accordingly. This project is aimed at reducing the mortality and morbidity associated with insulin resistance and diabetes, and the investigators believe this project could have a transformative impact on long-term diabetic care and shed new light upon the biology of diffuse cardiac fibrosis in insulin resistance and diabetes and its role in shaping the long-term cardiovascular risk for these patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •South Asian
排除标准
- •Pregnant women
- •Patients with prior diagnoses of diabetes
- •Patients on insulin therapy
- •Patients with known coronary heart disease or other non-ischemic cardiomyopathies
结局指标
主要结局
Identifying patients with high fibrosis levels using peripheral blood samples
时间窗: Blood samples drawn once at baseline visit
The investigators will collect and store peripheral blood samples from every patient, identify those with high and low fibrosis levels using our described protocol, and then select patients with disproportionately high fibrosis levels given their disease burden. The investigators can test for the level of fibrosis by generating induced pluripotent stem cell-derived cardiomyocytes (iPSC- CMs) from these collected blood samples. These iPSC-CMs will be tested, in vitro, for drug sensitivity, susceptibility to apoptotic stimuli, and the propensity to produce pro-fibrotic cytokine activation- all factors which will help the investigators determine fibrosis levels.
Left ventricular volume
时间窗: CMR done at baseline visit
Cardiac MRI/ CMR done to noninvasively image heart and determine volume of left ventricle
Insulin Sensitivity measured by OGTT
时间窗: OGTT done at baseline/ first visit
An oral glucose tolerance test with insulin measurement (OGTT) will be performed for all the patients. The investigators will draw blood to determine a fasting glucose measurement, and then the patients will be given a 75 g glucose solution to drink. Blood samples will be collected at serial time points (30 minutes, 60 minutes, 120 minutes) after ingestion of this liquid to determine blood glucose and insulin levels. The OGTT will help investigators determine the patient's degree of insulin sensitivity.
Insulin Sensitivity measured by Fasting Lipid Panel
时间窗: Lipid Panel done at baseline/ first visit
Baseline fasting lipids will be assessed to calculate a TG/HDL-C ratio, which also correlates with the degree of insulin sensitivity or lack thereof. These results will be correlated to the insulin sensitivity assessment performed by the OGTT.
Left ventricular mass
时间窗: CMR done at baseline visit
Cardiac MRI/ CMR done to noninvasively image heart and determine mass of left ventricle
Ejection fraction %
时间窗: CMR done at baseline visit
Cardiac MRI/ CMR done to noninvasively image heart and determine ejection fraction
Myocardial tagging for strain analysis
时间窗: CMR done at baseline visit
Cardiac MRI/ CMR done to noninvasively image heart and assess ventricular function through myocardial tagging. By modulating the magnetization gradient of the MRI prior to acquiring images, any parts of the heart which are not contracting can be identified. These images will be analyzed via strain analysis for such abnormalities in function
Assessing diffuse fibrosis via T1 mapping
时间窗: CMR done at baseline visit
A CMR technique called T1 mapping will be performed to calculate level of extracellular volume (ECV), which helps with the quantification of diffuse fibrosis
Assessing level of edema via T2 mapping
时间窗: CMR done at baseline visit
A CMR technique called T1 mapping will be performed assess amount of edema in the heart
次要结局
- Collagen turnover assessment(Blood drawn at baseline visit)
- Endothelial Function(15 minute procedure done at baseline visit)
- Urine test for albumin levels(One urine test done at baseline visit)
- Urine test for creatinine levels(One urine test done at baseline visit)
研究者
Rajesh Dash, MD PHD
Asst Prof-Med Ctr Line
Stanford University