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Title: Nonalcoholic fatty liver disease in hispanic youth with dysglycemia: Risk for subclinical atherosclerosis?

Author
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item TOMSA, ANCA - Children'S Nutrition Research Center (CNRC)
item BARTZ, SARA - Children'S Nutrition Research Center (CNRC)
item BARLOW, SARAH - Texas Children'S Hospital
item CHU, ZILI DAVID - Texas Children'S Hospital
item KRISHNAMURTHY, RAMKUMAR - Texas Children'S Hospital
item KRISHNAMURTHY, RAJESH - Texas Children'S Hospital
item SMITH, E. O'BRIAN - Children'S Nutrition Research Center (CNRC)

Submitted to: Endocrine Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/22/2017
Publication Date: 6/27/2017
Citation: Bacha, F., Tomsa, A., Bartz, S.K., Barlow, S.E., Chu, Z., Krishnamurthy, R., Krishnamurthy, R., Smith, E. 2017. Nonalcoholic fatty Liver disease in Hispanic youth with dysglycemia: Risk for subclinical atherosclerosis? Endocrine Journal. 1(8):1029-1040.

Interpretive Summary: Obese Hispanic adolescents are known to be at higher risk of type 2 diabetes and fatty liver disease. It is not known if having fatty liver disease (increased deposition of fat in the liver) will increase the risk for cardiovascular disease in Hispanic youth who have glucose regulation abnormalities (prediabetes and type 2 diabetes). We investigated measures of vascular health in obese Hispanic adolescents with abnormalities in glucose metabolism with and without fatty liver disease (determined by magnetic resonance imaging [MRI] and liver enzyme elevation], to understand if those with fatty liver have added cardiovascular disease risk. We measured vascular reactivity and stiffness of the small blood vessels. These measures have been found to predict adverse outcomes in adults. We also measured insulin sensitivity and body fat distribution to understand the factors that may be responsible for the increased vascular risk. We found that the presence of fatty liver disease in these youth was associated with adverse vascular measures including lower reactivity and greater stiffness of the small blood vessels. The vascular dysfunction was directly related to the fat content in the liver and related to insulin resistance which is also increased in those with fatty liver disease. These findings indicate that obese Hispanic youth with altered glucose metabolism are at greater risk of cardiovascular disease if they also have fatty liver disease.

Technical Abstract: Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden. To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth. Cross-sectional study. Academic institution. Thirty-six OHAs (15.360.4 years), 20 with prediabetes and 16 with type 2 diabetes, with and without NAFLD. Evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) by peripheral arterial tonometry; muscle, hepatic, and adipose tissue insulin sensitivity (IS; hyperinsulinemiceuglycemic clamp 80 mu/m2/min, with [6, 6 2H2] glucose and [2H5] glycerol); body composition; and abdominal and hepatic fat by magnetic resonance maging/spectroscopy. RHI and AIx. OHAs with dysglycemia and NAFLD have worse RHI and AIx vs those without NAFLD. The NAFLD (n = 23) and non-NAFLD (n = 13) groups were of similar age, sex, glycemic status, body mass index, % body fat and abdominal fat. The NAFLD group had higher hepatic fat (P, 0.001) lower skeletal muscle IS (P = 0.01), hepatic IS (P = 0.01), and adipose tissue IS (P = 0.04). The NAFLD vs non-NAFLD group had lower RHI (1.460.05 vs 1.760.09, P = 0.002), greater AIx (–6.061.6 vs –12.06 2.1, P = 0.03). Hepatic fat was inversely related to RHI (r = –0.49, P = 0.002) and positively related to Aix (r = 0.45, P = 0.006). Hepatic IS (r = –0.42, P = 0.01) and adipose IS (r = –.54, P = 0.001) correlated with arterial stiffness (AIx). In OHAs with dysglycemia, NAFLD is associated with worse endothelial function. RHI and AIx were related to hepatic fat content. Vascular stiffness was related to hepatic and adipose tissue insulin resistance.