Early MRI Detection of Myocardial Deterioration as a Preventive, Disease Staging, and Prognostic Biomarker in Insulin Resistance
Condition: Cardiomyopathies; Insulin Resistance; Non-ischemic Cardiomyopathy; Cardiac Fibrosis; Diabetes
MeSH terms: Cardiomyopathies; Insulin Resistance; Fibrosis
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        South Asians between the age of 20 and 60 who have no active coronary heart disease or
        other non-ischemic cardiomyopathies
      
Biospecimen description: 
      The investigators will probe individual patient risk based on initial cardiac fibrosis
      measurements. In insulin resistance, the degree of fibrosis may be out of proportion to
      disease severity, pointing to a genetic predisposition for increased cardiac cell dropout
      (i.e. apoptosis) and replacement fibrosis. To address this idea, the investigators will
      collect and store peripheral blood samples from every patient, identify those with high and
      low fibrosis levels, and then select patients with disproportionately high fibrosis levels
      given their disease burden. Induced pluripotent stem cell-derived cardiomyocytes (iPSC- CMs)
      will then be generated. The iPSC-CMs will be tested, in vitro, for drug sensitivity,
      susceptibility to apoptotic stimuli, and the propensity to produce pro-fibrotic cytokine
      activation. In this manner, the investigators will study the individual patient's myocardial
      cell features that increase the risk of cardiac fibrosis and the subsequent adverse outcomes
      that ensue.
    
Keywords: South Asian; Insulin Resistance; Cardiac Fibrosis; MRI; Diabetes; Cardiomyopathy