Association of Insulin Resistance and FGF21 on Cardiac Function in Pediatric Dilated Cardiomyopathy
Study Details
Study Description
Brief Summary
This study will investigate whether there is an association between insulin resistance and cardiac function in children with dilated or hypertrophic cardiomyopathy. This study will also investigate whether there is an association between FGF21 and cardiac function in children with dilated or hypertrophic cardiomyopathy and whether this is mediated through greater insulin resistance and/or through independent effects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Although pediatric cardiomyopathy is rare, the condition is severe and life-threatening. The main focus of this proposed study will examine whether insulin resistance is correlated with decreased cardiac function which will hopefully pave the way for future clinical trials using medications that sensitize insulin such as metformin or glucagon-like peptide-1 (GLP-1 agonists) as possible therapeutic agents. The exploratory piece of this study will investigate a novel therapeutic target by determining whether FGF21 has any direct effects on cardiac function and whether it interacts with insulin resistance in altering cardiac function. Patients with cardiomyopathy normally undergo ECHO as part of routine evaluation and follow up and is standard of care. At this time, there are no official guidelines for pediatric patients with cardiomyopathy to undergo oral glucose tolerance testing (OGTT) and thus it is not part of the standard of care. Based on findings from this study, the investigators hope to justify performing an OGTT on pediatric patients with dilated or hypertrophic cardiomyopathy and incorporate the procedure in future practice guidelines.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: cardiomyopathy only one arm, all participants undergo oral glucose tolerance testing and results are used to evaluate association with degree of cardiac dysfunction |
Diagnostic Test: Oral glucose tolerance test
measure insulin, glucose and FGF21 levels in response to oral glucose challenge
|
Outcome Measures
Primary Outcome Measures
- Whole body insulin sensitivity index [baseline]
correlate whole body insulin sensitivity index with left ventricular ejection fraction
Secondary Outcome Measures
- FGF21 level [baseline]
correlate FGF21 levels with whole body sensitivity index and left ventricular ejection fraction
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of dilated or hypertrophic cardiomyopathy
-
Pubertal (Tanner 2 breast in females or testicular volume ≥ 4mL in males)
-
Permission by the primary cardiologist of the patient for enrollment in the study
Exclusion Criteria:
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Prior diagnosis of diabetes and treatment with anti-diabetes medication
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Neuromuscular disorder
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Inborn error of metabolism
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Malformation syndrome
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Clinically unstable based on the assessment of the primary cardiologist caring for the patient
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inability of parent/legal guardian to provide informed consent
-
non-English speaking
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Le Bonheur Children's Hospital | Memphis | Tennessee | United States | 38103 |
Sponsors and Collaborators
- Le Bonheur Children's Hospital
Investigators
- Principal Investigator: Daniel Mak, MD, Le Bonheur/UTHSC Pediatric Endocrine fellowship
Study Documents (Full-Text)
None provided.More Information
Publications
- Camporez JP, Jornayvaz FR, Petersen MC, Pesta D, Guigni BA, Serr J, Zhang D, Kahn M, Samuel VT, Jurczak MJ, Shulman GI. Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice. Endocrinology. 2013 Sep;154(9):3099-109. doi: 10.1210/en.2013-1191. Epub 2013 Jun 13.
- Fisher FM, Maratos-Flier E. Understanding the Physiology of FGF21. Annu Rev Physiol. 2016;78:223-41. doi: 10.1146/annurev-physiol-021115-105339. Epub 2015 Nov 19. Review.
- Neglia D, De Caterina A, Marraccini P, Natali A, Ciardetti M, Vecoli C, Gastaldelli A, Ciociaro D, Pellegrini P, Testa R, Menichetti L, L'Abbate A, Stanley WC, Recchia FA. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3270-8. Epub 2007 Oct 5.
- Riehle C, Abel ED. Insulin Signaling and Heart Failure. Circ Res. 2016 Apr 1;118(7):1151-69. doi: 10.1161/CIRCRESAHA.116.306206. Review.
- Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, Messere J, Cox GF, Lurie PR, Hsu D, Canter C, Wilkinson JD, Lipshultz SE. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006 Oct 18;296(15):1867-76.
- 19-06748-FB