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Insulin Resistance Syndrome in Children

Pediatric Endocrinology Department, Maimonides Medical Center (S.T.) Brooklyn, New York 11219; Diabetes Program, Weill-Cornell Medical School and New York-Presbyterian Hospital (N.M.), New York, New York 10021; and BioSeek Endocrine Clinics (N.M.), New York, New York 10022

Address all correspondence and requests for reprints to: Dr. Noel Maclaren, BioSeek Endocrine Clinics, 5 East 57th Street, 16th Floor, New York, New York 10022. E-mail: maclaren{at}endoclinics.com.

The insulin resistance syndrome (syndrome X, metabolic syndrome) has become the major health problem of our times. Associated obesity, dyslipidemia, atherosclerosis, hypertension, and type 2 diabetes conspire to shorten life spans, while hyperandrogenism with polycystic ovarian syndrome affect the quality of life and fertility of increasing numbers of women. Whereas a growing number of single genetic diseases affecting satiety or energy metabolism have been found to produce the clinical phenotype, strong familial occurrences, especially in racially prone groups such as those from the Indian subcontinent, or individuals of African, Hispanic, and American Indian descents, together with emerging genetic findings, are revealing the polygenetic nature of the syndrome. However, the strong lifestyle factors of excessive carbohydrate and fat consumption and lack of exercise are important keys to the phenotypic expression of the syndrome. The natural history includes small for gestational age birth weight, excessive weight gains during childhood, premature pubarche, an allergic diathesis, acanthosis nigricans, striae compounded by gynecomastia, hypertriglyceridemia, hepatic steatosis, premature atherosclerosis, hypertension, polycystic ovarian syndrome, and focal glomerulonephritis appearing increasingly through adolescence into adulthood. Type 2 diabetes, which develops because of an inherent and/or an acquired failure of an insulin compensatory response, is increasingly seen from early puberty onward, as is atheromatous disease leading to coronary heart disease and stroke. A predisposition to certain cancers and Alzheimer’s disease is also now recognized. The looming tragedy from growing numbers of individuals affected by obesity/insulin resistance syndrome requires urgent public health approaches directed at their early identification and intervention during childhood. Such measures include educating the public on the topic, limiting the consumption of sucrose-containing drinks and foods with high carbohydrate and fat contents, and promoting exercise programs in our nation’s homes and schools.

Abbreviations: AGRP, Agouti-related peptide; AIR, acute insulin response; ALT, alanine aminotransferase; AN, acanthosis nigricans; BMI, body mass index; CBG, corticosteroid-binding globulin; CHD, coronary heart disease; CoA, coenzyme A; CRP, C-reactive protein; DI, disposition index; FA, fatty acid; FFA, free fatty acid; FSIVGTT, frequently sampled iv glucose tolerance test; GLUT4, glucose transporter 4; HDL, high-density lipoprotein; 11ßHSD1, 11ß-hydroxysteroid dehydrogenase type 1; IFN, interferon-; IGFBP-1, IGF-binding protein-1; IGT, impaired glucose tolerance; IR, insulin resistant, insulin resistance; IRS, insulin resistance syndrome; LDL, low-density lipoprotein; MC4R, melanocortin 4 receptor; NPY, neuropeptide Y; OGTT, oral glucose tolerance test; PAI-1, plasminogen activator inhibitor-1; PCOS, polycystic ovarian syndrome; POMC, proopiomelanocortin; PPAR, peroxisomal proliferator-activated receptor; SERPINS, serine protease inhibitors; SGA, small for gestational age; Si, insulin sensitivity; TG, triglycerides; Th1, T helper cell type 1; Vit-BP, vitamin D-binding protein; VLDL, very LDL.

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