ORIGINAL ARTICLE Early-life factors are associated with nocturnal cortisol and glucose effectiveness in Afro–Caribbean young adults Debbie S. Thompson*, Trevor S. Ferguson*, Rainford J. Wilks*, David I. Phillips†, Clive Osmond†, Maureen Samms-Vaughan‡, Terrence E. Forrester* and Michael S. Boyne* *Tropical Medicine Research Institute, The University of the West Indies, Kingston, Jamaica, †MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK and ‡Department of Child Health, The University of the West Indies, Kingston, Jamaica Summary Context Early-life factors (including intrauterine growth retar- dation) may influence the development of type 2 diabetes. We postulated that birth size is associated with cortisol levels, which itself could alter serum adipomyokines (i.e. adiponectin, IGF-I, myostatin) and glucose metabolism. Design An observational study with 60 Afro-Caribbean young adults from a birth cohort. Measurements Fasting blood was drawn for serum adiponectin, IGF-I and myostatin. A frequently sampled intravenous glucose tolerance test measured insulin sensitivity (SI), acute insulin response (AIRg), disposition index (DI) and glucose effectiveness (Sg). Body composition was assessed by dual-energy X-ray absorp- tiometry. Salivary cortisol was collected at home at 0800 and 2300 h. Sex-adjusted correlations were used to explore the rela- tionships between birth size, cortisol and the metabolic variables. Results The participants were 55% male, mean age 23Á1 Æ 0Á5 years. Birth weight correlated positively with 2300-h cortisol (P = 0Á04), although not after adjusting for gestational age. Gestational age was correlated with 2300 h cortisol (r = 0Á38, P = 0Á03), even after adjusting for birth weight (P = 0Á02). 2300 h cortisol was not associated with adiponectin, IGF-I, myo- statin, SI, AIRg or DI, but was negatively correlated with Sg (r = À0Á30, P = 0Á05) even after adjusting for birth and adult anthropometry. Adiponectin, IGF-I and myostatin were unre- lated to glucose metabolism. Conclusions Gestational age is associated with higher nocturnal cortisol, which in turn is associated with lower glucose effective- ness in adulthood. Higher glucose effectiveness could therefore be a compensatory mechanism to improve glucose uptake. (Received 18 February 2014; returned for revision 30 March 2014; finally revised 29 May 2014; accepted 26 June 2014) Introduction Early-life events (such as foetal growth, infant size, prematurity and postnatal growth) may influence the later development of obesity, insulin resistance and type 2 diabetes. 1 This relationship may not be linear but rather quadratic, i.e. J-shaped or U-shaped. Consequently, children who either have intrauterine growth retardation or who are large for gestational age are at increased risk. The actual mechanisms underlying these associa- tions are unclear. One potential pathway is altered activity of the hypothalamo– pituitary–adrenal axis (HPAA). Children with small birth size have up-regulated HPAA activity, so they have increased basal and stress-induced levels of ACTH and cortisol as adults. 2 The association between birth weight and cortisol may involve pla- cental 11 b-hydroxysteroid dehydrogenase (11 b-HSD-2), which converts cortisol to inert 11-keto products. In turn, increased HPAA activity, as seen in low birth weight individuals, is associ- ated with glucose intolerance. 2 It is not clear if this is a direct effect on glucose metabolism 2 or an effect mediated by other intermediary hormones such as adipomyokines. Adipomyokines such as adiponectin, IGF-1 and myostatin have a demonstrated association with birth weight. Adiponectin is the most abundant adipocytokine in serum. In cross-sectional studies, small for gestational age children have lower serum adiponectin concentrations in young adulthood. 3 Also, maternal IGF-I at 35 weeks and foetal IGF-I by cord blood were signifi- cantly correlated with birth weight in pregnant women of Afri- can origin. 4 Additionally, myostatin, a transforming growth factor, which negatively regulates skeletal muscle mass, has greater mRNA expression in lower birth weight pigs. 5 However, we are unaware of any data that demonstrate an association between birth size and myostatin in humans. Hypothetically, cortisol itself can affect the expression of these adipomyokines as there are glucocorticoid response elements in their promoter regions. Glucocorticoids reduce adiponectin tran- scription in tissue cultures 6 and could therefore mediate the Correspondence: Michael S. Boyne, Tropical Metabolism Research Unit, Tropical Medicine Research Institute, The University of the West Indies, Mona, Kingston 7, Jamaica. Tel.: 876-977-6251; Fax: 876-977-0632; E-mail: michael.boyne@uwimona.edu.jm 352 © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2015) 82, 352–358 doi: 10.1111/cen.12537