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

PLOS ONE, Dec 2019

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.

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

June Earlier Menarche Is Associated with Lower Insulin Sensitivity and Increased Adiposity in Young Adult Women Dyanne A. Wilson 0 1 José G. B. Derraik 0 1 Deborah L. Rowe 0 1 Paul L. Hofman 0 1 Wayne S. Cutfield 0 1 0 Academic Editor: Marià Alemany, Faculty of Biology, SPAIN 1 1 Liggins Institute, University of Auckland , Auckland , New Zealand , 2 School of Nursing, Faculty of Medical and Health Sciences , Auckland , University of Auckland We aimed to assess whether age at menarche was associated with insulin sensitivity in young adult women. 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. 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. - 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. Competing Interests: The authors have declared that no competing interests exist. The onset and timing of puberty in humans are not fully understood, but are dependent on numerous factors, including genetic variability, energy balance, brain structure, multiple neuroendocrine pathways, and hormonal profiles. Nonetheless, it is acknowledged that successful reproduction requires suitable energy stores to support the associated physiological functions [1]. Therefore, puberty is "metabolically gated" to prevent fertility in conditions of energy insufficiency [2], so that metabolic conditions and the amount of energy reserves play an important role modulating puberty timing [1,2]. Peptides from the digestive tract such as ghrelin (i.e. energy intake) and adipose tissue such as leptin (i.e. energy storage) inform the central nervous system about the individual's current metabolic status [1]. These peptides are important modulators of the gonadotropic axis that are capable of disturbing pubertal onset or progression [1]. Leptin has been shown to provide important signals of energy sufficiency, working at the level of the hypothalamus to modulate the function of the gonadotropin-releasing hormone (GnRH) neuronal system [2,3]. There is evidence that insulin, alongside leptin, also plays a role in the modulation of GnRH neurons and reproductive development [4,5]. An experimental model in vivo has shown that increasing insulin concentrations stimulated luteinizing hormone secretion, while an in vitro model showed a direct dose-dependent stimulation of GnRH secretion by insulin [6]. As a result, insulin sensitivity during childhood may also be important in the initiation of and progression through puberty. Adolescents with anorexia nervosa (who are nutritionally deficient) and those with chronic illness (who have a combination of nutritional, inflammatory, and therapeutic compromises) have delayed puberty and enhanced insulin sensitivity [7,8]. Children with constitutional delay of growth and development are also more insulin sensitive, even after controlling for adiposity [9]. In contrast, obese children have an earlier onset of puberty [10] and lower insulin sensitivity [11], while children born prematurely or small-for-gestational-age (SGA) (both associated with decreased insulin sensitivity) have an increased risk of premature adrenarche and early puberty [12]. Insulin sensitivity seems to play an important physiological role during puberty, when a marked reduction in insulin sensitivity occurs coinciding with Tanner 2 stage of development [13]. This reduction in insulin sensitivity is proposed to be important to pubertal development, as it leads to increased circulation of growth factors and promotes protein (muscle) production [14]. We therefore hypothesised that the timing of puberty would affect insulin sensitivity in young adult women; i.e. early puberty would be associated with lower insulin sensitivity and late puberty with increased insulin sensitivity. Thus, we aimed to determine whether age at menarche was associated with insulin sensitivity in early adulthood. This study was approved by the Northern X Region (...truncated)


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Dyanne A. Wilson, José G. B. Derraik, Deborah L. Rowe, Paul L. Hofman, Wayne S. Cutfield. Earlier Menarche Is Associated with Lower Insulin Sensitivity and Increased Adiposity in Young Adult Women, PLOS ONE, 2015, Volume 10, Issue 6, DOI: 10.1371/journal.pone.0128427