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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 3 757-760
Copyright © 1998 by The Endocrine Society

Original Studies

Elevated Plasma Cortisol Concentrations: A Link between Low Birth Weight and the Insulin Resistance Syndrome?1

D. I. W. Phillips, D. J. P. Barker, C. H. D. Fall, J. R. Seckl, C. B. Whorwood, P. J. Wood and B. R. Walker

Medical Research Council Environmental Epidemiology Unit, University of Southampton (D.I.W.P., D.J.P.B., C.H.D.F, C.B.W.), and the Regional Endocrine Unit, Southampton General Hospital (P.W.), Southampton, United Kingdom; and the Department of Medicine, University of Edinburgh, Western General Hospital (J.R.S., B.R.W.), Edinburgh, Scotland

Address all correspondence and requests for reprints to: Dr. D. I. W. Phillips, Medical Research Council Unit, Southampton General Hospital, Tremona Road, Southampton, United Kingdom SO16 6YD. E-mail: diwp{at}mrc.soton.ac.uk

Recent studies have shown that reduced fetal growth is associated with the development of the insulin resistance syndrome in adult life. The mechanisms are not known. However increased activity of the hypothalamic-pituitary-adrenal axis (HPAA) may underlie this association; the axis is known to be reset by fetal growth retardation in animals, and there is evidence in humans of an association between raised HPAA activity and the insulin resistance syndrome. We have, therefore, examined the relations among size at birth, plasma cortisol concentrations, and components of the insulin resistance syndrome in a sample of healthy men. We measured 0900 h fasting plasma cortisol and corticosteroid-binding globulin levels in 370 men who were born in Hertfordshire, UK, between 1920–1930 and whose birth weights were recorded. Fasting plasma cortisol concentrations varied from 112–702 nmol/L and were related to systolic blood pressure (P = 0.02), fasting and 2-h plasma glucose concentrations after an oral glucose tolerance test (P = 0.0002 and P = 0.04), plasma triglyceride levels (P = 0.009), and insulin resistance (P = 0.006). Plasma cortisol concentrations fell progressively (P = 0.007) from 408 nmol/L in men whose birth weights were 5.5 lb (2.50 kg) or less to 309 nmol/L among those who weighed 9.5 lb (4.31 kg) or more at birth, a trend independent of age and body mass index. These findings suggest that plasma concentrations of cortisol within the normal range could have an important effect on blood pressure and glucose tolerance. Moreover, this study provides the first evidence that intrauterine programming of the HPAA may be a mechanism underlying the association between low birth weight and the insulin resistance syndrome in adult life.




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 EndocrinologyHome page
M. Manikkam, E. J. Crespi, D. D. Doop, C. Herkimer, J. S. Lee, S. Yu, M. B. Brown, D. L. Foster, and V. Padmanabhan
Fetal Programming: Prenatal Testosterone Excess Leads to Fetal Growth Retardation and Postnatal Catch-Up Growth in Sheep
Endocrinology, February 1, 2004; 145(2): 790 - 798.
[Abstract] [Full Text] [PDF]

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 Recent Prog Horm ResHome page
J. R. Seckl, N. M. Morton, K. E. Chapman, and B. R. Walker
Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue
Recent Prog. Horm. Res., January 1, 2004; 59(1): 359 - 393.
[Abstract] [Full Text]

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 Arch. Dis. Child. Fetal Neonatal Ed.Home page
J A Jackson, M P Wailoo, J R Thompson, and S A Petersen
Early physiological development of infants with intrauterine growth retardation
Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2004; 89(1): F46 - F50.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
K. Herrick, D. I. W. Phillips, S. Haselden, A. W. Shiell, M. Campbell-Brown, and K. M. Godfrey
Maternal Consumption of a High-Meat, Low-Carbohydrate Diet in Late Pregnancy: Relation to Adult Cortisol Concentrations in the Offspring
J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3554 - 3560.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. Soto, R. A. Bazaes, V. Pena, T. Salazar, A. Avila, G. Iniguez, K. K. Ong, D. B. Dunger, and M. V. Mericq
Insulin Sensitivity and Secretion Are Related to Catch-Up Growth in Small-for-Gestational-Age Infants at Age 1 Year: Results from a Prospective Cohort
J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3645 - 3650.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
F. H. Bloomfield, M. H. Oliver, C. D. Giannoulias, P. D. Gluckman, J. E. Harding, and J. R. G. Challis
Brief Undernutrition in Late-Gestation Sheep Programs the Hypothalamic-Pituitary-Adrenal Axis in Adult Offspring
Endocrinology, July 1, 2003; 144(7): 2933 - 2940.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. S. Lindsay, D. J. Wake, S. Nair, J. Bunt, D. E. W. Livingstone, P. A. Permana, P. A. Tataranni, and B. R. Walker
Subcutaneous Adipose 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity and Messenger Ribonucleic Acid Levels Are Associated with Adiposity and Insulinemia in Pima Indians and Caucasians
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2738 - 2744.
[Abstract] [Full Text] [PDF]

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 PediatricsHome page
R. A. Bazaes, T. E. Salazar, E. Pittaluga, V. Pena, A. Alegria, G. Iniguez, K. K. Ong, D. B. Dunger, and M. V. Mericq
Glucose and Lipid Metabolism in Small For Gestational Age Infants at 48 Hours of Age
Pediatrics, April 1, 2003; 111(4): 804 - 809.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Tenhola, E. Rahiala, A. Martikainen, P. Halonen, and R. Voutilainen
Blood Pressure, Serum Lipids, Fasting Insulin, and Adrenal Hormones in 12-Year-Old Children Born with Maternal Preeclampsia
J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1217 - 1222.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
H. Olausson, K. Uvnas-Moberg, and A. Sohlstrom
Postnatal oxytocin alleviates adverse effects in adult rat offspring caused by maternal malnutrition
Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E475 - E480.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
K R Poore and A L Fowden
The effect of birth weight on hypothalamo-pituitary-adrenal axis function in juvenile and adult pigs
J. Physiol., February 15, 2003; 547(1): 107 - 116.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
M. Leonhardt, J. Lesage, D. Croix, I. Dutriez-Casteloot, J. C. Beauvillain, and J. P. Dupouy
Effects of Perinatal Maternal Food Restriction on Pituitary-Gonadal Axis and Plasma Leptin Level in Rat Pup at Birth and Weaning and on Timing of Puberty
Biol Reprod, February 1, 2003; 68(2): 390 - 400.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. C. Andrews, O. Herlihy, D. E. W. Livingstone, R. Andrew, and B. R. Walker
Abnormal Cortisol Metabolism and Tissue Sensitivity to Cortisol in Patients with Glucose Intolerance
J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5587 - 5593.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
E.J. Brunner, H. Hemingway, B.R. Walker, M. Page, P. Clarke, M. Juneja, M.J. Shipley, M. Kumari, R. Andrew, J.R. Seckl, et al.
Adrenocortical, Autonomic, and Inflammatory Causes of the Metabolic Syndrome: Nested Case-Control Study
Circulation, November 19, 2002; 106(21): 2659 - 2665.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
E. Rask, B. R. Walker, S. Soderberg, D. E. W. Livingstone, M. Eliasson, O. Johnson, R. Andrew, and T. Olsson
Tissue-Specific Changes in Peripheral Cortisol Metabolism in Obese Women: Increased Adipose 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3330 - 3336.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. H. D. Fall, E. Dennison, C. Cooper, J. Pringle, S. D. Kellingray, and P. Hindmarsh
Does Birth Weight Predict Adult Serum Cortisol Concentrations? Twenty-Four-Hour Profiles in the United Kingdom 1920-1930 Hertfordshire Birth Cohort
J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2001 - 2007.
[Abstract] [Full Text] [PDF]

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 Am J EpidemiolHome page
V. Grill, B. Dinesen, S. Carlsson, S. Efendic, O. Pedersen, and C.-G. Ostenson
Hyperproinsulinemia and Proinsulin-to-Insulin Ratios in Swedish Middle-aged Men: Association with Glycemia and Insulin Resistance but Not with Family History of Diabetes
Am. J. Epidemiol., May 1, 2002; 155(9): 834 - 841.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
C. B. Whorwood, S. J. Donovan, D. Flanagan, D. I.W. Phillips, and C. D. Byrne
Increased Glucocorticoid Receptor Expression in Human Skeletal Muscle Cells May Contribute to the Pathogenesis of the Metabolic Syndrome
Diabetes, April 1, 2002; 51(4): 1066 - 1075.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. L. Coe, M. Kramer, C. Kirschbaum, P. Netter, and E. Fuchs
Prenatal Stress Diminishes the Cytokine Response of Leukocytes to Endotoxin Stimulation in Juvenile Rhesus Monkeys
J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 675 - 681.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
D. T. Lackland, B. M. Egan, H. E. Syddall, and D. J.P. Barker
Associations Between Birth Weight and Antihypertensive Medication in Black and White Medicaid Recipients
Hypertension, January 1, 2002; 39(1): 179 - 183.
[Abstract] [Full Text] [PDF]

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 Diabetes CareHome page
C. Li, M. S. Johnson, and M. I. Goran
Effects of Low Birth Weight on Insulin Resistance Syndrome in Caucasian and African-American Children
Diabetes Care, December 1, 2001; 24(12): 2035 - 2042.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Sarkar, S.-W. Tsai, T. T. Nguyen, M. Plevyak, J. F. Padbury, and L. P. Rubin
Inhibition of placental 11beta -hydroxysteroid dehydrogenase type 2 by catecholamines via alpha -adrenergic signaling
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2001; 281(6): R1966 - R1974.
[Abstract] [Full Text] [PDF]

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 Br Med BullHome page
A. M Prentice
Obesity and its potential mechanistic basis: Type 2 diabetes
Br. Med. Bull., November 1, 2001; 60(1): 51 - 67.
[Abstract] [Full Text] [PDF]

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 Br Med BullHome page
C. E Bertram and M. A Hanson
Animal models and programming of the metabolic syndrome: Type 2 diabetes
Br. Med. Bull., November 1, 2001; 60(1): 103 - 121.
[Abstract] [Full Text] [PDF]

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 Br Med BullHome page
C. D Byrne
Programming other hormones that affect insulin: Type 2 diabetes
Br. Med. Bull., November 1, 2001; 60(1): 153 - 171.
[Abstract] [Full Text] [PDF]

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 Br. J. PsychiatryHome page
C. THOMPSON, H. SYDDALL, I. RODIN, C. OSMOND, and D. J. P. BARKER
Birth weight and the risk of depressive disorder in late life
The British Journal of Psychiatry, November 1, 2001; 179(5): 450 - 455.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
B. Blondeau, J. Lesage, P. Czernichow, J. P. Dupouy, and B. Breant
Glucocorticoids impair fetal {beta}-cell development in rats
Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E592 - E599.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Bertram, A. R. Trowern, N. Copin, A. A. Jackson, and C. B. Whorwood
The Maternal Diet during Pregnancy Programs Altered Expression of the Glucocorticoid Receptor and Type 2 11{beta}-Hydroxysteroid Dehydrogenase: Potential Molecular Mechanisms Underlying the Programming of Hypertension in Utero
Endocrinology, July 1, 2001; 142(7): 2841 - 2853.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
L. A. Nolan, E. J. Hart, R. J. Windle, S. A. Wood, X. W. Hu, A. J. Levi, C. D. Ingram, and A. Levy
Lack of Effect of Protein Deprivation-Induced Intrauterine Growth Retardation on Behavior and Corticosterone and Growth Hormone Secretion in Adult Male Rats: A Long-Term Follow-Up Study
Endocrinology, July 1, 2001; 142(7): 2996 - 3005.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Nilsson, B.-M. Larsson, E. Jennische, E. Eriksson, P. Bjorntorp, D. A. York, and A. Holmang
Maternal Endotoxemia Results in Obesity and Insulin Resistance in Adult Male Offspring
Endocrinology, June 1, 2001; 142(6): 2622 - 2630.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. B. Whorwood, S. J. Donovan, P. J. Wood, and D. I. W. Phillips
Regulation of Glucocorticoid Receptor {{alpha}} and {beta} Isoforms and Type I 11{beta}-Hydroxysteroid Dehydrogenase Expression in Human Skeletal Muscle Cells: A Key Role in the Pathogenesis of Insulin Resistance?
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2296 - 2308.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
R. M. Reynolds, B. R. Walker, H. E. Syddall, C. B. Whorwood, P. J. Wood, and D. I. W. Phillips
Elevated Plasma Cortisol in Glucose-Intolerant Men: Differences in Responses to Glucose and Habituation to Venepuncture
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1149 - 1153.
[Abstract] [Full Text]

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 EndocrinologyHome page
D. S. Gardner, A. J. W. Fletcher, A. L. Fowden, and D. A. Giussani
Plasma Adrenocorticotropin and Cortisol Concentrations during Acute Hypoxemia after a Reversible Period of Adverse Intrauterine Conditions in the Ovine Fetus During Late Gestation
Endocrinology, February 1, 2001; 142(2): 589 - 598.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. M. Reynolds, B. R. Walker, H. E. Syddall, R. Andrew, P. J. Wood, C. B. Whorwood, and D. I. W. Phillips
Altered Control of Cortisol Secretion in Adult Men with Low Birth Weight and Cardiovascular Risk Factors
J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 245 - 250.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
N. S. Levitt, E. V. Lambert, D. Woods, C. N. Hales, R. Andrew, and J. R. Seckl
Impaired Glucose Tolerance and Elevated Blood Pressure in Low Birth Weight, Nonobese, Young South African Adults: Early Programming of Cortisol Axis
J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4611 - 4618.
[Abstract] [Full Text]

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 Rheumatology (Oxford)Home page
C. Cooper, K. Walker-Bone, N. Arden, and E. Dennison
Novel insights into the pathogenesis of osteoporosis: the role of intrauterine programming
Rheumatology, December 1, 2000; 39(12): 1312 - 1315.
[Full Text] [PDF]


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