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PEDIATRICS Vol. 113 No. 1 January 2004, pp. 82-86

Girls at Five Are Intrinsically More Insulin Resistant Than Boys: The Programming Hypotheses Revisited—The EarlyBird Study (EarlyBird 6)

Michael J. Murphy, MRCPath*, Brad S. Metcalf, BSc{ddagger}, Linda D. Voss, PhD{ddagger}, Alison N. Jeffery, RGN{ddagger}, Joanne Kirkby, BSc{ddagger}, Katie M. Mallam, MRCPCH{ddagger} and Terence J. Wilkin, MD{ddagger}

* Department of Molecular and Cellular Pathology, University of Dundee, Dundee, United Kingdom
{ddagger} Peninsula Medical School, Plymouth, United Kingdom

Objective. Recent studies of type 2 diabetes in young populations consistently show a predominance of affected girls over boys. Girls are more insulin resistant than boys. We aimed in the present report to establish how much of the sex difference in insulin resistance is intrinsic.

Methods. EarlyBird is a community-based, nonintervention cohort study of 307 healthy children from school entry at age 5 years. It asks the question: which children are insulin resistant and why? Anthropometric measures, physical activity, resting energy expenditure, and insulin resistance and its metabolic correlates were measured.

Results. At 5 years, insulin resistance was 35% higher in girls than in boys. Girls carried 26% more subcutaneous fat despite similar body weights. However, after correcting for anthropometric variables and physical activity, girls remained 33% more insulin resistant than boys. Triglycerides were significantly higher in girls, and high-density lipoprotein cholesterol and sex hormone-binding globulin were significantly lower.

Conclusions. Sex-linked genes may account for the intrinsic sex difference observed. These genes may have an important impact on the development of insulin resistance and the metabolic syndrome and may help to explain the female preponderance of type 2 diabetes in children. Their identification may also help in understanding the pathogenesis of insulin resistance.

Key Words: type 2 diabetes • insulin resistance • sex difference • programming • sex-linked genes

Abbreviations: BMI, body mass index • SD, standard deviation • REE, resting energy expenditure • HOMA-IR, homeostasis model assessment, insulin resistance • SHBG, sex hormone-binding globulin • HDL, high-density lipoprotein

Received for publication Dec 4, 2002; Accepted Mar 24, 2003.


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