Early MRI Detection of Myocardial Deterioration as a Preventive, Disease Staging, and Prognostic Biomarker in Insulin Resistance

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.

Study Overview

• Status: Completed
• Conditions: Diabetes; Insulin Resistance; Cardiomyopathies; Cardiac Fibrosis; Non-ischemic Cardiomyopathy

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.

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

• Study Contact: Name: Esha Roy, BS; Phone Number: 408-313-7538; Email: esharoy@stanford.edu
• Study Contact Backup: Name: Rajesh Dash, MD, PhD; Phone Number: 650-723-8138; Email: rhombus@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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

Description

Inclusion Criteria:

- South Asian

Exclusion Criteria:

• Pregnant women
• Patients with prior diagnoses of diabetes
• Patients on insulin therapy
• Patients with known coronary heart disease or other non-ischemic cardiomyopathies

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
South Asians with Insulin Resistance; 125 patients (anticipated)
South Asians without Insulin Resistance; 125 patients (anticipated)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Lipid Panel done at baseline/ first visit
Left ventricular volume	Cardiac MRI/ CMR done to noninvasively image heart and determine volume of left ventricle	CMR done at baseline visit
Left ventricular mass	Cardiac MRI/ CMR done to noninvasively image heart and determine mass of left ventricle	CMR done at baseline visit
Ejection fraction %	Cardiac MRI/ CMR done to noninvasively image heart and determine ejection fraction	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	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	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	CMR done at baseline visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collagen turnover assessment	Patients will have blood drawn for serum measurement of propeptides of several procollagens to determine the level of collagen turnover	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.	15 minute procedure done at baseline visit
Urine test for albumin levels	24 Hour urine test for assessment of albumin levels	One urine test done at baseline visit
Urine test for creatinine levels	24 Hour urine test for assessment of creatinine levels	One urine test done at baseline visit

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Study Director: Abha Khandelwal, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2015
• Primary Completion (Actual): September 11, 2019
• Study Completion (Actual): November 11, 2019

Study Registration Dates

• First Submitted: May 8, 2017
• First Submitted That Met QC Criteria: April 25, 2018
• First Posted (Actual): April 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Diabetes; Insulin Resistance; Cardiomyopathy; South Asian; Cardiac Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Fibrosis; Insulin Resistance; Cardiomyopathies
• Other Study ID Numbers: 31279

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No