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.
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.
Study Type
OBSERVATIONAL
Enrollment
39
Stanford University
Stanford, California, United States
Identifying patients with high fibrosis levels using peripheral blood samples
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.
Time frame: Blood samples drawn once at baseline visit
Insulin Sensitivity measured by OGTT
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.
Time frame: OGTT done at baseline/ first visit
Insulin Sensitivity measured by Fasting Lipid Panel
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.
Time frame: Lipid Panel done at baseline/ first visit
Left ventricular volume
Cardiac MRI/ CMR done to noninvasively image heart and determine volume of left ventricle
Time frame: CMR done at baseline visit
Left ventricular mass
Cardiac MRI/ CMR done to noninvasively image heart and determine mass of left ventricle
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Time frame: CMR done at baseline visit
Ejection fraction %
Cardiac MRI/ CMR done to noninvasively image heart and determine ejection fraction
Time frame: CMR done at baseline visit
Myocardial tagging for strain analysis
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
Time frame: CMR done at baseline visit
Assessing diffuse fibrosis via T1 mapping
A CMR technique called T1 mapping will be performed to calculate level of extracellular volume (ECV), which helps with the quantification of diffuse fibrosis
Time frame: CMR done at baseline visit
Assessing level of edema via T2 mapping
A CMR technique called T1 mapping will be performed assess amount of edema in the heart
Time frame: CMR done at baseline visit
Collagen turnover assessment
Patients will have blood drawn for serum measurement of propeptides of several procollagens to determine the level of collagen turnover
Time frame: Blood drawn at baseline visit
Endothelial Function
The investigators will also measure endothelial function using the endoPAT device, which employs noninvasive measurement of finger arterial pulsatile volume changes as a measure of endothelial function. This test takes approximately 15 minutes and is noninvasive.
Time frame: 15 minute procedure done at baseline visit
Urine test for albumin levels
24 Hour urine test for assessment of albumin levels
Time frame: One urine test done at baseline visit
Urine test for creatinine levels
24 Hour urine test for assessment of creatinine levels
Time frame: One urine test done at baseline visit