Age Before Stage: Insulin Resistance Rises Before the Onset of Puberty

Abstract

OBJECTIVEInsulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1.RESEARCH DESIGN AND METHODSThe EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5–14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L).RESULTSIR rose progressively from age 7 years, 3–4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P < 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels.CONCLUSIONSIR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important.

Physical activity attenuates the mid-adolescent peak in insulin resistance but by late adolescence the effect is lost: a longitudinal study with annual measures from 9–16 years (EarlyBird 66)

“…Our own (EarlyBird) data show no association between activity and IR in pre-adolescence (age 8 years) [10]. The higher levels of IR in the adolescent age group that we and others have reported [11][12][13] may explain the emergence of an association with physical activity around that time.…”

“…In such circumstances, the biological control loop would be expected to oscillate spontaneously between tissue function and diminishing beta cell reserve in order to defend blood glucose [38]. These oscillations could be more closely related to age than to puberty itself, as we have suggested previously [11], explaining the link to adolescence and limited interaction with pubertal stage. The higher insulin levels in the less active children during mid-adolescence will have put a greater demand on the beta cells over that period.…”

Concentración de insulina e índices de insulinosensibilidad en niños y adolescentes sanos

“…Jeffery y col., observaron un incremento de insulina alrededor de los 7 años, antes del aumento de la hormona luteinizante (luteinizing hormone; LH, por sus siglas en inglés) y aparición de signos clínicos puberales. 28 El aumento de la adiposidad, de los andrógenos adrenales y del IGF-I explicarían la menor insulinosensibilidad antes del inicio puberal. Apoyando estas hipótesis, nuestro grupo de trabajo observó que la concentración de 17-hidroxiprogesterona (precursor de andrógenos) y de los niveles de IGF-I en niños sanos a edades peripuberales fueron significativamente mayores comparados con prepúberes de menor edad.…”

Insulin level and insulin sensitivity indices among healthy children and adolescents

“…Differences during prepuberty and puberty had been previously reported. 8,[26][27][28] Based on our results, a HOMA-IR higher than 1.4, 2.0, and 2.6 in prepubertal children younger and older than 7.5 years old and pubertal children, respectively, and a G/ Ins ratio value below 10 suggest certain level of insulin resistance in children and adolescents. Our study proposes a RI for simplified glycemia and insulinemia indices obtained in fasting conditions; however, there are other indices that reflect insulin sensitivity in baseline conditions and in the post-absorption phase.…”

“…Jeffery et al observed that insulin increased around 7 years old, before the increase in luteinizing hormone (LH) and the onset of clinical signs of puberty. 28 Increases in adiposity, adrenal androgens, and IGF-1 might explain the lower insulin sensitivity observed before the onset of puberty. In support of these hypotheses, our task force observed that 17-hydroxyprogesterone (an androgen precursor) and IGF-1 levels in healthy peripubertal children were significantly higher than those in younger prepubertal children.…”