What is metabolic syndrome, and why are children getting it?

Abstract

Metabolic syndrome comprises a cluster of cardiovascular risk factors (hypertension, altered glucose metabolism, dyslipidemia, and abdominal obesity) that occur in obese children. However, metabolic syndrome can also occur in lean individuals, suggesting that obesity is a marker for the syndrome, not a cause. Metabolic syndrome is difficult to define, due to its nonuniform classification and reliance on hard cutoffs in the evaluation of disorders with non‐Gaussian distributions. Defining the syndrome is even more difficult in children, owing to racial and pubertal differences and lack of cardiovascular events. Lipid partitioning among specific fat depots is associated with insulin resistance, which can lead to mitochondrial overload and dysfunctional subcellular energy use and drive the various elements of metabolic syndrome. Multiple environmental factors, in particular a typical Western diet, drive mitochondrial overload, while other changes in Western society, such as stress and sleep deprivation, increase insulin resistance and the propensity for food intake. These culminate in an adverse biochemical phenotype, including development of altered glucose metabolism and early atherogenesis during childhood and early adulthood.

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     Kirk S, Brehm B, Saelens BE, et al. Role of carbohydrate modification in weight management among obese children: a randomized clinical trial. J. Pediatr. 2012;161:320-327.

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     Bremer AA, Stanhope KL, Graham JL, et al. Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes. Clin. Transl. Sci. 2011;4:243-252.

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     Le KA, Tappy L. Metabolic effects of fructose. Curr. Opin. Nutr. Metab. Care. 2006;9:469-475.

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     Lim JS, Mietus-Snyder M, Valente A, et al. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat. Rev. Gastroenterol. Hepatol. 2010;7:251-264.

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     Tuncman G, Hirosumi J, Solinas G, et al. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc. Natl. Acad. Sci. USA. 2006;103:10741-10746.

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     Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose-, not glucose-sweetened beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J. Clin. Invest. 2009;119:1322-1334.

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     Pickens MK, Yan JS, Ng RK, et al. Dietary sucrose is essential to the development of liver injury in the MCD model of steatohepatitis. J. Lipid Res. 2009;50:2072-2082.

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     Layman DK, Walker DA. Potential importance of leucine in treatment of obesity and the metabolic syndrome. J. Nutr. 2006;136(Suppl):319S-323S.

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     Tai ES, Tan ML, Stevens RD, et al. Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia. 2010;53:757-787.

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     Schneider J, Tesdorfpf M, Kaffarnik H, et al. Alteration of plasma lipids and intermediates of lipid metabolism in healthy fasting volunteers by ethanol and fructose. Res. Exp. Med. 1976;167:159-170.

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     Sozio M, Crabb DW. Alcohol and lipid metabolism. Am. J. Physiol. Endocrinol. Metab. 2008;295:E10-E16.

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     Yokoyama H, Hiroshi H, Ohgo H, et al. Effects of excessive ethanol consumption on the diagnosis of the metabolic syndrome using its clinical diagnostic criteria. Intern. Med. 2007;46:1345-1352.

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     Gupta N, Goel K, Bhatt SP, Misra A. Childhood obesity in developing countries: epidemiology, determinants, and prevention. Endocr. Rev. 2012;33:48-70.

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     Lustig RH, Weiss R, Sperling MA. Disorders of energy balance. Textbook of Pediatric Endocrinology. 2008;688-713.

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     Lustig RH. Fructose: metabolic, hedonic, and societal parallels with ethanol. J. Am. Diet. Assoc. 2010;110:1307-1321.

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• Effects of Polyphenol Intake on Metabolic Syndrome: Current Evidences from Human Trials · 2017
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• A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals · 2013
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