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Associations of Insulin Resistance and Glycemia With Liver Enzymes in Hispanic/Latino Youths

Results From the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth)

Parrinello, Christina M., PhD, MPH*; Rudolph, Bryan J., MD; Lazo, Mariana, MD, PhD, ScM; Gallo, Linda C., PhD§; Thyagarajan, Bharat, MD, PhD; Cotler, Scott J., MD; Qi, Qibin, PhD*; Seeherunvong, Tossaporn, MD#; Vidot, Denise C., PhD**; Strickler, Howard D., MD, MPH*; Kaplan, Robert C., PhD*; Isasi, Carmen R., MD, PhD*

Journal of Clinical Gastroenterology: February 2019 - Volume 53 - Issue 2 - p e46–e53
doi: 10.1097/MCG.0000000000000946
ONLINE ARTICLES: Original Articles

Background: Associations of insulin resistance and hyperglycemia with a panel of liver enzymes have not been well studied in a young, heterogenous Hispanic/Latino population. We aimed to assess the associations of insulin resistance and glycemia with nonalcoholic fatty liver disease (NAFLD), as measured by liver enzymes and the pediatric NAFLD fibrosis index (PNFI), and whether these associations are modified by body mass index and mediated by inflammation or endothelial dysfunction.

Materials and Methods: We conducted a cross-sectional study of 1317 boys and girls aged 8 to 16 years from the Hispanic Community Children’s Health Study/Study of Latino Youth. We used Poisson regression to assess the associations of fasting glucose, hemoglobin A1c, and homeostasis model assessment of insulin resistance (HOMA-IR) with elevated alanine aminotransferase (ALT) (>25 U/L in boys, >22 U/L in girls), aspartate aminotransferase (AST) (≥37 U/L), gamma-glutamyl transpeptidase (GGT) (≥17 U/L), and PNFI (≥9; a function of age, waist circumference, and triglyceride level).

Results: HOMA-IR was associated with elevated ALT, AST, GGT, and PNFI [prevalence ratios (95% confidence intervals) for each 1-unit increase in the natural log of HOMA-IR: 1.99 (1.40-2.81), 2.15 (1.12-4.12), 1.70 (1.26-2.30), and 1.98 (1.43-2.74), respectively]. Associations were observed in overweight/obese children, but not in normal weight children (P-interaction=0.04 for AST and P-interaction=0.07 for GGT). After further adjustment for adiponectin, high-sensitivity C-reactive protein, e-selectin, and PAI-1, associations of HOMA-IR with liver enzymes and PNFI were attenuated, but remained statistically significant for AST and PNFI.

Conclusion: Insulin resistance was associated with NAFLD in overweight/obese Hispanic/Latino youth, and this association may be partially mediated by inflammation and endothelial dysfunction.

*Department of Epidemiology and Population Health

Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY

Johns Hopkins School of Medicine and the Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, MD

§Department of Psychology, San Diego State University, San Diego, CA

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN

The Program for Experimental and Theoretical Modeling, Department of Medicine, Division of Hepatology, Loyola University Chicago Medical Center, Maywood, IL

#Division of Pediatric Endocrinology, University of Miami Leonard M. Miller School of Medicine, Miami

**Department of Psychology, University of Miami, Coral Gables, FL

C.M.P.: designed the study, conducted the analysis, interpreted the data, and drafted the manuscript. B.J.R., M.L., L.C.G., B.T., S.J.C., Q.Q., T.S., D.C.V., H.D.S., and R.C.K.: interpreted the data and critically revised the manuscript. C.R.I.: designed the study, acquired the data, interpreted the data, and critically revised the manuscript.

SOL Youth was supported by grant number R01HL102130 from the National Heart, Lung, and Blood Institute. The children in SOL Youth are drawn from the study of adults: The Hispanic Community Health Study/Study of Latinos, which was supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to NHLBI: National Center on Minority Health and Health Disparities, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. R.C.K. is supported by R01 HL136266 and 1R01MD011389-01. Q.Q. is supported by a Scientist Development Award (K01HL129892) from the NHLBI.

The authors declare that they have nothing to disclose.

Address correspondence to: Carmen R. Isasi, MD, PhD, 1300 Morris Park Avenue, Belfer 1308D, Bronx, NY 10461 (e-mail: carmen.isasi@einstein.yu.edu).

Received August 25, 2016

Accepted July 18, 2017

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