The Association Between Hepatic Fat Content and Liver Injury in Obese Children and Adolescents: Effects of ethnicity, insulin resistance, and common gene variants

Background: Obesity is the main risk factor for essential hypertension (EH) in childhood. The O.Si.Me. study (Obesity and Metabolic Syndrome in children and adolescents) evaluated the prevalence of metabolic syndrome (MetS) and its constitutive traits in a sample of obese children and adolescents living in Campania, southern Italy. Patients and methods: Four hundred and fifteen children and adolescents consecutively referred to the National Health Service participating Outpatient Clinics for minor health problems and found to have a Body Mass Index (BMI) Z-score > 2.0 were enrolled in the study. The entire sample was screened for MetS, which was defined as the presence of at least 2 of the following alterations in addition to obesity: fasting hyperglycemia, low levels of high-density lipoproteins cholesterol, hypertriglyceridemia, and EH. The present analysis evaluated the clinical characteristics of the O.Si.Me subgroup of EH participants (systolic and/or diastolic BP ≥ 95 th percentile for age, gender and height) as compared with normotensive participants. Results: The prevalence of EH in the O.Si.Me population was 23.6 % (98/415, 48M and 50F.) and two-thirds of the EH participants met the MetS diagnostic criteria. The EH participants featured serum insulin and HOMA-IR levels significantly higher compared with normotensive ones (11.6±0.6 vs. 9.5±0.4 μIU/ml, p = 0.014; 2.6±0.1 vs. 2.2±0.1, p = 0.028 for insulin and HOMA-IR, respectively). These differences were common to boys and girls and remained significant after correction for age, pubertal stage, body weight, length, BMI, gestational age at birth, duration of breastfeeding and anthropometric parental parameters. Accordingly, children and adolescents with EH had a a relative risk of being insulin resistant (defined as a HOMA-IR ≥2.5) significantly greater compared to those without. Moreover, they exhibited higher serum creatinine levels (53.8±7.1 vs. 35.4±6.8 μmol/l, p=0.025) accounting for gender and body weight. Conclusions: More than a quarter of obese children and adolescents meet the diagnostic criteria for EH in the Campania region in southern Italy. These obese boys and girls have an increased prevalence of insulin resistance and apparently an initial reduction in renal function compared with obese children and adolescents with normal BP.

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Acanthosis nigricans, vitamin D, and insulin resistance in obese children and adolescents

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2013-0465 ◽

2014 ◽

Vol 0 (0) ◽

Author(s):

Arnold H. Slyper ◽

Laurissa Kashmer ◽

Wei-Min Huang ◽

Yochai Re’em

Keyword(s):

Insulin Resistance ◽

Vitamin D ◽

Children And Adolescents ◽

Acanthosis Nigricans ◽

Obese Children

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Gender-Specific Prevalences of Fatty Liver in Obese Children and Adolescents: Roles of Body Fat Distribution, Sex Steroids, and Insulin Resistance

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1125 ◽

2009 ◽

Vol 94 (10) ◽

pp. 3872-3881 ◽

Cited By ~ 75

Author(s):

Christian Denzer ◽

Dorothee Thiere ◽

Rainer Muche ◽

Wolfgang Koenig ◽

Hermann Mayer ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Liver ◽

Children And Adolescents ◽

Body Fat ◽

Sex Steroids ◽

Fat Distribution ◽

Body Fat Distribution ◽

Obese Children ◽

Gender Specific

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Dietary determinants of hepatic fat content and insulin resistance in overweight/obese children: a cross-sectional analysis of the Prevention of Diabetes in Kids (PREDIKID) study

British Journal Of Nutrition ◽

10.1017/s0007114519000436 ◽

2019 ◽

Vol 121 (10) ◽

pp. 1158-1165 ◽

Cited By ~ 5

Author(s):

Lide Arenaza ◽

María Medrano ◽

Maddi Oses ◽

Inge Huybrechts ◽

Ignacio Díez ◽

...

Keyword(s):

Insulin Resistance ◽

Dietary Intake ◽

Dietary Habits ◽

Sugar Content ◽

Model Assessment ◽

Obese Children ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Sugar Intake ◽

Hepatic Fat

AbstractPaediatric non-alcoholic fatty liver disease has increased in parallel with childhood obesity. Dietary habits, particularly products rich in sugars, may influence both hepatic fat and insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR)). The aim of the study was to examine the association of the consumption of foods and food components, dairy desserts and substitutes (DDS), sugar-sweetened beverages (SSB), as well as total and added sugars, with hepatic fat and HOMA-IR. Dietary intake (two non-consecutive 24 h-recalls), hepatic fat (MRI) and HOMA-IR were assessed in 110 overweight/obese children (10·6 (sd 1·1) years old). Linear regression analyses were used to examine the association of dietary intake with hepatic fat and HOMA-IR adjusted for potential confounders (sex, age, energy intake, maternal educational level, total and abdominal adiposity and sugar intake). The results showed that there was a negative association between cereal intake and hepatic fat (β=–0·197, P<0·05). In contrast, both SSB consumption (β=0·217; P=0·028) and sugar in SSB (β=0·210, P=0·035), but not DDS or sugar in DDS or other dietary components, were positively associated with hepatic fat regardless of potential confounders including total sugar intake. In conclusion, cereal intake might decrease hepatic fat, whereas SSB consumption and its sugar content may increase the likelihood of having hepatic steatosis. Although these observations need to be confirmed using experimental evidence, these results suggest that healthy lifestyle intervention programs are needed to improve dietary habits as well as to increase the awareness of the detrimental effects of SSB consumption early in life.

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Metabolic Profiles in Obese Children and Adolescents with Insulin Resistance

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.097 ◽

2018 ◽

Vol 6 (3) ◽

pp. 511-518 ◽

Cited By ~ 2

Author(s):

Marko Kostovski ◽

Viktor Simeonovski ◽

Kristina Mironska ◽

Velibor Tasic ◽

Zoran Gucev

Keyword(s):

Insulin Resistance ◽

Children And Adolescents ◽

Plasma Glucose ◽

Metabolic Profile ◽

Total Serum ◽

Model Assessment ◽

Fasting Insulin ◽

Obese Children ◽

Insulin Resistant ◽

Study Results

BACKGROUND: In the past several decades, the increasing frequency of overweight and obese children and adolescents in the world has become a public health problem. It has contributed significantly to the already high tide of diabetes, cardiovascular and cerebrovascular diseases.AIM: To investigate the frequency of insulin resistance and to evaluate the metabolic profile of insulin resistant and non-insulin resistant obese children and adolescents.SUBJECTS AND METHODS: The study included 96 (45 boys, 51 girls) obese children and adolescents aged 4-17 years old (10.50 ± 2.87 years). Only participants with Body Mass Index ≥ 95 percentile were included. We analysed sera for fasting insulin levels (FI), fasting serum triglycerides (TG), total serum cholesterol (TC), fasting plasma glucose (FPG) and plasma glucose 2 hours after the performance of the oral glucose tolerance test (2-h G). Homeostatic model assessment for insulin resistance (HOMA-IR) index was calculated as fasting insulin concentration (microunits per millilitre) x fasting glucose concentration (millimolar)/22.5. The value of HOMA-IR above 3.16 was used as a cut-off value for both genders.RESULTS: Insulin resistance was determined in 58.33% of study participants. Insulin resistant participants had significantly higher level of 2-h G (p = 0.02), FI level (p = 0.000) as well as TG levels (p = 0.01), compared to non-insulin resistant group. Strikingly, 70.73% of the pubertal adolescents were insulin resistant in comparison to 49.09% of the preadolescents (p = 0.03). Significantly higher percentage of insulin-resistant participants were girls (p = 0.009). Moreover, a higher percentage of the girls (70.59%) than boys (44.44%) had HOMA-IR above 3.16 and had elevated FI levels (70.59% vs 48.89%). The difference in the frequency of insulin resistance among obese versus severely obese children and adolescents was not significant (p = 0.73, p > 0.05). Our study results also showed positive, but weak, correlation of HOMA-IR with age, FPG, TG and BMI of the participants (p < 0.05).CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.

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Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle

BMC Pediatrics ◽

10.1186/s12887-015-0513-6 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 21

Author(s):

Cilius Esmann Fonvig ◽

Elizaveta Chabanova ◽

Johanne Dam Ohrt ◽

Louise Aas Nielsen ◽

Oluf Pedersen ◽

...

Keyword(s):

Skeletal Muscle ◽

Children And Adolescents ◽

Multidisciplinary Care ◽

Fat Content ◽

Ectopic Fat ◽

Obese Children ◽

One Year

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Plasma Adiponectin in Nonalcoholic Fatty Liver Is Related to Hepatic Insulin Resistance and Hepatic Fat Content, Not to Liver Disease Severity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-2240 ◽

2005 ◽

Vol 90 (6) ◽

pp. 3498-3504 ◽

Cited By ~ 265

Author(s):

Elisabetta Bugianesi ◽

Uberto Pagotto ◽

Rita Manini ◽

Ester Vanni ◽

Amalia Gastaldelli ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Female Gender ◽

Fat Content ◽

Hepatic Insulin Resistance ◽

Nonalcoholic Fatty Liver ◽

Plasma Adiponectin ◽

Histological Features ◽

The Metabolic Syndrome ◽

Hepatic Fat

Plasma levels of adiponectin are decreased in patients with nonalcoholic fatty liver disease (NAFLD), but the relationship among plasma adiponectin, insulin sensitivity, and histological features is unclear. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentrations in relation to 1) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); 2) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and 3) histological features at liver biopsy (n = 116). When the data from all subjects were combined, plasma adiponectin levels were positively associated with increased age, female gender, and plasma high-density lipoprotein levels, and negatively associated with waist circumference, body mass index, triglycerides, indices of insulin resistance, and aminotransferase levels, and also predicted the presence of the metabolic syndrome. In step-wise regression, increased age, female gender, waist circumference, triglyceride levels, and homeostasis model assessment independently associated with adiponectin (adjusted R2, 0.329). In NAFLD, adiponectin was only associated with increased age, female gender, and triglycerides (adjusted R2, 0.245). When the measured histological parameters were included in the model, plasma adiponectin levels were also inversely proportional to the percentage of hepatic fat content (adjusted R2, 0.221), whereas necroinflammation and fibrosis did not fit in the model. Adiponectin was negatively correlated with insulin-suppressed endogenous glucose production during the clamp (P = 0.011). The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinemia in NAFLD is part of a metabolic disturbance characterized by ectopic fat accumulation in the central compartment.

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