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

Murphy, Michael J.; Metcalf, Brad; Voss, Linda D; Jeffery, Alison N.; Kirkby, Joanne; Mallam, Katie M; Wilkin, Terence J.

doi:10.1542/peds.113.1.82

Cited by 133 publications

(123 citation statements)

References 30 publications

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“…25 Crucially, the sex difference in insulin resistance remains after adjustment for a wide range of variables with which insulin resistance correlates ( Table 1), suggesting that the difference is intrinsic. 24 Fathers in the same study were, as expected, more insulin resistant than the mothers, 24 but this apparent switch in sex difference from childhood to adulthood reversed after adjustment for waist circumference (Table 2). 26 Waist circumference is a surrogate for visceral fat which is believed to underlie acquired insulin resistance.…”

Section: Introductionsupporting

confidence: 57%

“…[15][16][17][18][19][20][21][22][23] This sex difference in insulin resistance has usually been attributed to differences in adiposity or pubertal stage, but in studies which have adjusted for these factors 15,18 a residual difference remains which has not been explained. We have shown that girls are substantially (B33%) more insulin resistant than boys at 5 years 24 and in the years leading up to puberty. 25 Crucially, the sex difference in insulin resistance remains after adjustment for a wide range of variables with which insulin resistance correlates ( Table 1), suggesting that the difference is intrinsic.…”

Section: Introductionmentioning

confidence: 77%

“…26 Waist circumference is a surrogate for visceral fat which is believed to underlie acquired insulin resistance. Following adjustment, The adjustments are first made separately for each factor, and all together in the final row (data from Murphy et al 24 ). a Mean of five sites.…”

Section: Introductionmentioning

confidence: 99%

“…Abbreviations: BMI, body mass index; VF, visceral fat. Table 2 Mean insulin resistance (back-transformed log, where the data are first converted to logarithms, the mean established and the anti-log of the mean reported) in girls and boys at 5 years, and in their mothers and fathers, before and after adjustment for waist circumference (data from Murphy et al 24 Why girls are born lighter than boys TJ Wilkin and MJ Murphy the mothers were 25% more insulin resistant than the fathers. This finding is all the more significant given that mothers as a group will exclude those women with the highest insulin resistance who for that reason are unable to ovulate.…”

Section: Introductionmentioning

confidence: 99%

“…A recent population study in Mauritius confirms that women are more insulin resistant than men despite smaller waist circumference. 27 Regressions describing the relationship between (log) insulin resistance and waist circumference in men and women should have similar gradients, but different constants Figure 1 compares the relationship in women and men between (log) insulin resistance and waist circumference (data from Murphy et al 24 ). The gradient describes how insulin resistance changes with waist circumference, and the constant (intercept on the y axis) insulin resistance that is independent of waist circumference, that is, intrinsic.…”

Section: Introductionmentioning

confidence: 99%

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The gender insulin hypothesis: why girls are born lighter than boys, and the implications for insulin resistance

Wilkin

Murphy

2006

Int J Obes

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Girls are born lighter than boys. The consistency of this observation across different populations is striking, suggesting that it may have fundamental significance for those conditions linked with lower birth weight, such as diabetes. Previous hypotheses relating low birth weight to subsequent diabetes have addressed differences in insulin resistance within the sexes, not between them. Here, we propose that gender-specific genes affecting insulin sensitivity are responsible for the gender difference in birth weight -the genetically more insulin resistant female fetus is less responsive to the trophic effects of insulin and is therefore smaller. These genes also render female subjects more susceptible to diabetes, explaining why reports of type 2 diabetes (T2D) in younger populations show a female preponderance. Consistent with our proposal, concentrations of insulin and/or its propeptides are higher at birth in female populations and they are intrinsically more insulin resistant throughout life, with attendant impact on their metabolism, and the regressions describing the relationship between insulin resistance and adiposity in female and male subjects have similar gradients, but different constants. These gender-specific genes have a demonstrable impact on fetal growth and insulin resistance. Diabetes and cardiovascular disease are thought to be driven by insulin resistance, and the observations reported here may help to focus the search for genes that control it.

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Section: Introductionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The gender insulin hypothesis: why girls are born lighter than boys, and the implications for insulin resistance

Wilkin

Murphy

2006

Int J Obes

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Physical activity is related to insulin sensitivity in children and adolescents, independent of adiposity: a review of the literature

Berman

Weigensberg

Spruijt‐Metz

2012

Diabetes Metabolism Res

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In adults, there is evidence that physical activity effectively improves insulin sensitivity regardless of adiposity. Whether this is also the case in children and adolescents has been less clear. Whether this is also the case in children and adolescents is less clear. Clarifying this matter may help to identify the best outcomes to target in exercise programs for these age groups, where changes in adiposity may not always be desirable or realistic. A review of the literature was conducted on studies that examined the relationships of physical activity, cardiorespiratory fitness and strength with insulin sensitivity independent of adiposity in children and adolescents. Experimental (intervention) and correlational (longitudinal and cross-sectional) studies on participants ages 18 and younger were identified. A total of 42 studies were included in this review. Sample sizes in the studies ranged from 14 to 4,955 participants, with individual ages ranging from 5 to 19 years. A significant relationship with SI existed in 78% of studies on physical activity, 69% of studies on cardiorespiratory fitness and 66% of studies on strength. In studies that examined both physical activity and cardiorespiratory fitness concurrently, evidence suggests that they are both correlated with insulin sensitivity independent of adiposity, especially when physical activity is at higher intensities. However the strength of this relationship might be influenced by study design, measurement techniques and participant characteristics. This is the first review of its type to take research design into account, and to examine study outcomes according to participant ethnicity, gender, age, pubertal status and weight status.

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Determinants of birth weight in boys and girls

et al. 2009

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

Cited by 133 publications

References 30 publications

The gender insulin hypothesis: why girls are born lighter than boys, and the implications for insulin resistance

The gender insulin hypothesis: why girls are born lighter than boys, and the implications for insulin resistance

Physical activity is related to insulin sensitivity in children and adolescents, independent of adiposity: a review of the literature

Determinants of birth weight in boys and girls

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