Earlier Menarche Is Associated with Lower Insulin Sensitivity and Increased Adiposity in Young Adult Women.

OBJECTIVE: We aimed to assess whether age at menarche was associated with insulin sensitivity in young adult women. METHODS: We studied 54 healthy young women aged 20-30 years. Participants were grouped according to age at menarche: Early (≤11.0 years; n=13), Average (>12.0 and ≤13.0 years; n=28), and Late (≥14.0 years, n=13). Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman's minimal model. Body composition was assessed using whole-body dual-energy X-ray absorptiometry. RESULTS: Earlier menarche was associated with lower insulin sensitivity (p=0.015). There was also a continuous increase in adiposity with younger age at menarche, which was associated with increased weight (p=0.001), BMI (p=0.002), total body fat (p=0.049), and truncal fat (p=0.020). Stratified analyses showed that insulin sensitivity in Early women (5.5 x10-4·min-1(mU/l)) was lower than in Average (8.0 x10-4·min-1(mU/l), p=0.021) and Late (8.6 x10-4·min-1(mU/l), p=0.033) groups. Early women (weight=66.1 kg; BMI=24.1 kg/m2) were considerably heavier and fatter than Average (59.0 kg, p=0.004; 21.4 kg/m2, p=0.002) and Late (57.0 kg, p=0.001; 20.8 kg/m2, p=0.0009) women. CONCLUSIONS: Early menarche is associated with lower insulin sensitivity and increased adiposity in young adulthood, potentially increasing the risk of type 2 diabetes and the metabolic syndrome later in life.

Decreasing birth weight is associated with adverse metabolic profile and lower stature in childhood and adolescence.

OBJECTIVE: We aimed to evaluate the association of birth weight SDS with insulin resistance, blood pressure, and auxology in children and adolescents born 23-42 weeks of gestation. METHODS: We studied 143 singleton children and adolescents aged 9.3 ± 3.3 years (range 2.0-17.9 years). Clinical assessments included insulin resistance measured by HOMA2-IR, auxology, and blood pressure from sphygmomanometer measurements. Continuous associations were examined, and stratified analyses carried out. For the latter, participants were divided into those of below-average birth weight (BABW, <0 SDS) and above-average birth weight (AABW, ≥0 SDS). RESULTS: Irrespective of gestational age, lower birth weight SDS was associated with progressively greater HOMA2-IR (p<0.0001) and higher fasting insulin concentrations (p<0.0001). Decreasing birth weight SDS was associated with higher systolic (p = 0.011) and diastolic (p = 0.006) blood pressure. Lower birth weight SDS was also associated with decreasing stature (p<0.010). The BABW group was ~40% more insulin resistant than AABW participants (p = 0.004), with the former also displaying fasting insulin concentrations 37% higher (p = 0.004). BABW participants were 0.54 SDS shorter than those of higher birth weight (p = 0.002). On average, BABW participants had not met their genetic potential, tending to be shorter than their parents (p = 0.065). As a result, when corrected for parents' heights, BABW participants were 0.62 SDS shorter than those born of higher birth weight (p = 0.001). Sub-group analyses on participants born appropriate-for-gestational-age (n = 128) showed that associations of birth weight SDS with both insulin resistance and stature remained (although attenuated). CONCLUSION: Decreasing birth weight SDS (even within the normal range) is associated with adverse metabolic profile and lower stature in children and adolescents.

Cortisol response to synacthen stimulation is attenuated following abusive head trauma.

BACKGROUND: Child abuse and other early-life environmental stressors are known to affect the hypothalamic-pituitary-adrenal axis. We sought to compare synacthen-stimulated cortisol responses in children who suffered inflicted or accidental traumatic brain injury (TBI). METHODS: Children with a history of early-childhood TBI were recruited from the Starship Children's Hospital database (Auckland, New Zealand, 1992-2010). All underwent a low-dose ACTH(1-24) (synacthen 1 µg IV) test, and serum cortisol response was compared between inflicted (TBI(I) ) and accidental (TBI(A) ) groups. RESULTS: We assessed 64 children with TBI(I) and 134 with TBI(A) . Boys were more likely than girls to suffer accidental (P < 0·001), but not inflicted TBI. TBI(I) children displayed a 14% reduction in peak stimulated cortisol in comparison with the TBI(A) group (P < 0·001), as well as reduced cortisol responses at + 30 (P < 0·01) and + 60 min (P < 0·001). Importantly, these differences were not associated with severity of injury. The odds ratio of TBI(I) children having a mother who suffered domestic violence during pregnancy was 6·2 times that of the TBI(A) group (P < 0·001). However, reported domestic violence during pregnancy or placement of child in foster care did not appear to affect cortisol responses. CONCLUSION: Synacthen-stimulated cortisol response is attenuated following inflicted TBI in early childhood. This may reflect chronic exposure to environmental stress as opposed to pituitary injury or early-life programming.

Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood.

BACKGROUND: We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). METHODS: We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 µg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. RESULTS: We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 ± 1.5 yr) 6.5 ± 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. CONCLUSION: Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population.

Preterm birth and the endocrine regulation of growth in childhood and adolescence.

OBJECTIVE: Poor growth during childhood is a common problem associated with preterm birth, but few studies have examined the associations between linear growth, weight and body composition with the postnatal hormonal milieu in preterm children. We aimed to define the IGF-IGFBP axis in preterm children and its association with growth. DESIGN AND PATIENTS: A cohort of healthy 2- to 20-year-old subjects who were born prematurely (<37 weeks gestation) and experienced normal neurological development were recruited. In total, 54 premature and 82 control subjects were included in this study. RESULTS: Preterm subjects were relatively shorter (P < 0·001) and leaner (P < 0·05) than their parents in contrast to the term cohort. Preterm children also appeared to fail to reach their genetic height potential (prepuberty: P < 0·01; puberty: P < 0·05). Only IGFBP-2 differed between preterm and term cohorts, with higher levels observed in prepubertal preterm subjects (P < 0·01). In the term group, height SDS was positively associated with IGF-I (P < 0·01) and IGFBP-3 (P < 0·001) concentrations, but no such associations were observed for preterm subjects. CONCLUSION: Preterm children are shorter and lighter than controls throughout childhood, remaining below their genetic height potential. Preterm birth appears to alter the endocrine regulation of postnatal growth in childhood and adolescence, so growth is no longer associated with its normal endocrine regulators.