Nonalcoholic Fatty Liver Disease in Hispanic Youth With Dysglycemia

Risk for Subclinical Atherosclerosis?

Fida Bacha; Anca Tomsa; Sara K. Bartz; Sarah E. Barlow; Zili David Chu; Ramkumar Krishnamurthy; Rajesh Krishnamurthy; E. O'Brian Smith

Disclosures

J Endo Soc. 2017;1(8):1029-1040. 

In This Article

Abstract and Introduction

Abstract

Context: Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden.

Objective: To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth.

Design: Cross-sectional study.

Setting: Academic institution.

Participants: Thirty-six OHAs (15.3±0.4 years), 20 with prediabetes and 16 with type 2 diabetes, with and without NAFLD.

Intervention: Evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) by peripheral arterial tonometry; muscle, hepatic, and adipose tissue insulin sensitivity (IS; hyperinsulinemic-euglycemic clamp 80 mu/m2/min, with [6,6 2H2]glucose and [2H5] glycerol); body composition; and abdominal and hepatic fat by magnetic resonance imaging/spectroscopy.

Outcome Measures: RHI and AIx.

Hypothesis: OHAs with dysglycemia and NAFLD have worse RHI and AIx vs those without NAFLD.

Results: 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 (1.4±0.05 vs 1.7±0.09, P = 0.002), greater AIx (–6.0±1.6 vs –12.0±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).

Conclusion: 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.

Introduction

Nonalcoholic fatty liver disease (NAFLD), comprising a spectrum of conditions ranging from steatosis to steatohepatitis and cirrhosis, represents the most common cause of chronic liver disease. The prevalence has increased significantly with the current obesity epidemic and is estimated to be between 20% and 30% in the general adult population[1] and ~10% in children.[2,3] The prevalence varies among ethnic groups. In the Dallas Heart Study, fatty liver disease was most common in Hispanics and lowest in African Americans.[4] Also, the prevalence is higher in individuals with type 2 diabetes mellitus (T2DM; 70% to 80%) compared with the general population (~30%).[1,5] Hispanic children are disproportionately affected by the obesity epidemic with 38.1% of Hispanic children and adolescents 12 to 19 years of age found to be overweight/obese according to the 2011–2012 National Health and Nutrition Examination data.[6] They are also known to be at high risk for T2DM[7] and NAFLD.[2,8]

In population studies, NAFLD was found to be independently associated with increased risk of cardiovascular disease (CVD).[9] In adults with T2DM, elevated liver enzymes were associated with abnormal brachial flow-mediated dilation, independent of whole body insulin sensitivity (IS) and other prognostic factors, suggestive of an increased CVD risk in adults with T2DM and liver disease.[10] In diet controlled adults with T2DM, those with NAFLD (by ultrasound) had greater carotid intima-media thickness (c-IMT) explained by insulin resistance index rather than liver fat.[11] Other studies questioned the added risk related to NAFLD in the setting of diabetes. c-IMT was not found to be higher in individuals with T2DM with vs without NAFLD, but hepatic steatosis was not associated with c-IMT.[12] Another study concluded that hepatic fat may be protective against atherosclerosis in 60-year-old adults with T2DM.[13] In children, increased hepatic fat has been associated with insulin resistance,[14–16] prediabetes phenotype,[17] higher inflammatory markers,[17] and lower adiponectin.[18] Children with biopsyproven NAFLD have significantly higher fasting insulin, triglycerides, cholesterol, blood pressure, and lower high-density lipoprotein (HDL) compared with obese peers with no NAFLD.[19]

The role of NAFLD as an added risk for subclinical atherosclerosis in obese youth with altered glucose metabolism, beyond the effect of hyperglycemia is not clear. This study aimed to investigate whether the presence of NAFLD has an additive effect on subclinical endothelial dysfunction, an early biomarker of atherosclerosis, in obese Hispanic adolescents (OHAs) with prediabetes and T2DM. We hypothesized that (1) Hispanic youth with dysglycemia and NAFLD have worse endothelial function compared with those without NAFLD and (2) this endothelial dysfunction is related to insulin resistance and inflammation.

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