Tag Archives: insulin resistance

Pediatric NAFLD: You Don’t Have to be Obese/Overweight to Have Fatty Liver Disease (but it helps)

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A recent study (P Kumar et al. JPGN 2018; 67: 75-9) examined suspected NAFLD in 12 to 18 year olds using data from NHANES. In the analysed cohort, there were 124 suspected NAFLD and 1385 without suspicion of NAFLD.  This subset was weight to represent a U.S. population of over 18 million.

Key definitions:

  • Suspected NAFLD was defined by abnormal ALT (>25.8 U/L for boys and >22.1 U/L for girls) who did not have another explanation (eg. viral hepatitis, medication)
  • Lean BMI was defined by BMI less than 85th% for age
  • Hypertriglyceridemia ≥ 150
  • Low HDL ≤ 40 mg/dL
  • HOMA-IR =fasting glucose x insulin (microU/mL) divided by 405. Insulin resistance was defined as HOMA-IR ≥ 3

Key findings:

  • Suspected NAFLD affects ~8% of lean adolescents in the U.S.
  • Hypertriglyceridemia was noted in 10 of 124 suspected NAFLD and was a risk factor (P=0.028) as was Low HDL which occurred in 15 (P=0.016) and IR which occurred in 43 (P=0.053)

My take: Elevated ALT, a marker for fatty liver disease, is common even in adolescents without obesity. Elevated triglycerides, low HDL, and insulin resistance are all risk factors for suspected NAFLD in non-overweight/non-obese teens.

Related blog posts:

Cumberland Island 2018

Lower leptin with physical activity

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Leptin is a cytokine expressed primarily by adipose tissue and helps regulate energy homeostasis in the body.  Higher leptin levels are found in obesity and associated with an increase risk of cardiovascular disease, insulin resistance, and type 2 diabetes.  In a recent study, physical activity, especially vigorous physical activity, has been shown to be negatively associated with leptin levels (J Pediatr 2012; 160: 598-603).

This study was conducted in school settings in 10 European cities from 9 countries (n=902) with ages 12-18 years.  Several fitness tests including handgrip, long jump, and shuttle runs were measured along with serum fasting leptin, insulin, and glucose.

Vigorous activity and fitness test results were associated with lower leptin levels; these findings were maintained when controlling for confounders.  It is not known the exact mechanisms whereby physical activity can lower leptin levels as this finding is independent of total body fat.  The authors note that previous studies have shown some contradictory results; the authors note that this could be related to drawbacks in how some studies measured physical activity.

This study’s information, when combined with previous studies (see below) on hormonal adaptations with weight loss, suggest a reason why exercise is important to maintain weight loss.  Losing weight without exercise could result in increased appetite and make it more difficult to achieve long-term results.  In contrast, physical activity may help maintain weight loss by improving hormonal adaptation.

Additional references:

  • -NEJM 2011; 365: 1597.  Persistence of hormonal adaptations with weight loss.  Due to persistent changes in hormones like leptin & peptide YY, hard to keep wt off -result is increased appetite.
  • -NEJM 2009; 360: 859.  Obesity-wt loss: composition of diet does not seem to be important.  Total calories important.
  • -NEJM 2007; 356: 237.  Leptin receptor deficiency present in 3% of 300 patients with early-onset obesity and hyperphagia.
  • -Pediatrics 2007; 120: suppl 4: S164-S287.
  • -NEJM 2007; 357: 370.  Obestiy spread in social network.
  • -Gastroenterology 2007; 132: 2085-2276.  Special issue on obesity issues.
  • -NEJM 2006; 355: 1593.  Case review on obesity c DDx and mgt.