Comparison of leptin levels, body composition and insulin sensitivity and secretion by OGTT in healthy, early pubertal girls born at either appropriate- or small-for-gestational age
A. Martínez-Aguayo
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorT. Capurro
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorV. Peña
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorG. Iñiguez
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorM. I. Hernández
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorA. Avila
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorT. Salazar
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorS. Asenjo
Pediatric Department, Faculty of Medicine, University of Concepción, Concepción, Chile
Search for more papers by this authorV. Mericq
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorA. Martínez-Aguayo
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorT. Capurro
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorV. Peña
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorG. Iñiguez
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorM. I. Hernández
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorA. Avila
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorT. Salazar
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorS. Asenjo
Pediatric Department, Faculty of Medicine, University of Concepción, Concepción, Chile
Search for more papers by this authorV. Mericq
Institute of Maternal and Child Research (IDIMI), Faculty of Medicine, University of Chile, Santiago, Chile,
Search for more papers by this authorSummary
Background Small for gestational age (SGA) has been associated with decreased insulin sensitivity (IS). A possible mechanism is the postnatal development of a metabolically disadvantageous body composition (BC).
Aim To determine whether there are differences between IS and BC in girls in early puberty who were SGA (birth weight < 10th percentile) or appropriate for gestational age (AGA, 10th–90th percentile).
Methods Age-matched (SGA/AGA) early pubertal girls (Tanner II) were recruited from local schools. We determined waist circumference (WC), the sum of four skinfolds (S4S), and per cent fat mass (fat %) by impedanciometry. Leptin and OGTT assays were performed. The insulinogenic index (I-In), HOMA-IR (homeostasis model assessment of insulin resistance) and WBISI (whole body insulin sensitivity) were calculated.
Results Median age (interquartile range) for 30 SGA and 35 AGA girls was 10·2 (1·1) vs. 9·8 (0·9), respectively (P = NS). BMI percentiles were 62·6 (56) vs. 67·4 (39); WC 60·5 (9·5) vs. 62·2 (6·5) cm; S4S 52 (30) vs. 52·2 (29·5) cm, and fat %[26·2 (6·7) vs. 28·5 (6·3)] was similar in both groups. SGA girls had higher leptin levels [15·4 (9·7) vs. 9·6 (11) ng/ml; P = 0·01] and I-In [2·05 (1·86) vs. 1·47 (1·27) µU/ml* mg/dl; P = 0·02]. No differences between HOMA-IR [2·07 (1·26) vs. 2·04 (1·4)] and WBISI [5·3 (3·3) vs. 5·1 (3·1)] were found between groups.
Conclusion The higher leptin level and I-In in girls born SGA at the beginning of puberty may be early indicators of an underlying subtle degree of insulin resistance, despite similar BMI and BC to AGA girls.
References
- 1 Hales, C. N. & Barker, D. (2001) The thrifty phenotype hypothesis, type 2 diabetes. British Medical Bulletin, 60, 5–20.
- 2 Bateson, P., Barker, D., Clutton-Brock, T., Deb, D., D’Udine, B., Foley, R.A., Gluckman, P., Godfrey, K., Kirkwood, T., Lahr, M.M., McNamara, J., Metcalfe, N.B., Monaghan, P., Spencer, H.G. & Sultan, S.E. (2004) Developmental plasticity and human health. Nature, 22, 419–421.
- 3 Garnett, S.P., Cowell, C.T., Baur, L.A., Fay, R.A., Lee, J., Coakley, J., Peat, J.K. & Boulton, T.J. (2001) Abdominal fat and birth size in healthy prepubertal children. International Journal of Obesity and Related Metabolic Disorders, 25, 1667–1673.
- 4 Ravelli, G.P., Stein, Z.A. & Susser, M.W. (1976) Obesity in young men after famine exposure in utero and early infancy. New England Journal of Medicine, 295, 349–353.
- 5 Ong, K.K., Ahmed, M.L., Emmett, P.M., Preece, M.A. & Dunger, D.B. (2000) Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. British Medical Journal, 320, 967–971.
- 6 Leger, J., Limoni, C., Collin, D. & Czernichow, P. (1998) Prediction factors in the determination of final height in subjects born small for gestational age. Pediatric Research, 43, 808–812.
- 7 Jaquet, D., Leger, J., Tabone, M.D., Czernichow, P. & Levy-Marchal, C. (1999) High serum leptin concentrations during catch-up growth of children born with intrauterine growth retardation. Journal of Clinical Endocrinology and Metabolism, 84, 1949–1953.
- 8 Bazaes, R.A., Alegria, A., Pittaluga, E., Avila, A., Iniguez, G. & Mericq, V. (2004) Determinants of insulin sensitivity and secretion in very-low-birth-weight children. Journal of Clinical Endocrinology and Metabolism, 89, 1267–1272.
- 9 Soto, N., Bazaes, R.A., Pena, V., Salazar, T., Avila, A., Iniguez, G., Ong, K.K., Dunger, D.B. & Mericq, M.V. (2003) 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. Journal of Clinical Endocrinology and Metabolism, 88, 3645–3650.
- 10 Ibanez, L., Potau, N., Francois, I. & De Zegher, F. (1998) Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. Journal of Clinical Endocrinology and Metabolism, 83, 3558–3562.
- 11 Ibanez, L., Ong, K., Potau, N., Marcos, M.V., De Zegher, F. & Dunger, D. (2001) Insulin gene variable number of tandem repeat genotype and the low birth weight, precocious pubarche, and hyperinsulinism sequence. Journal of Clinical Endocrinology and Metabolism, 86, 5788–5793.
- 12 Ibanez, L., Valls, C., Marcos, M.V., Ong, K., Dunger, D.B. & De Zegher, F. (2004) Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome: effects of prepubertal initiation and postpubertal discontinuation of metformin treatment. Journal of Clinical Endocrinology and Metabolism, 89, 4331–4337.
- 13 Ibanez, L., Ong, K., De Zegher, F., Marcos, M.V., Del Rio, L. & Dunger, D.B. (2003) Fat distribution in non-obese girls with and without precocious pubarche: central adiposity related to insulinaemia and androgenaemia from prepuberty to postmenarche. Clinical Endocrinology, 58, 372–379.
- 14 Tanner, J.M. (1981) Growth and maturation during adolescence. Nutrition Reviews, 39, 43–55.
- 15 Juez, G. (1989) Intrauterine growth curve for the appropriate diagnosis of intrauterine growth retardation. Revista Médica de Chile, 117, 1311.
- 16 Kuczmarski, R.J., Ogden, C.L., Grummer-Strawn, L.M., Flegal, K.M., Guo, S.S., Wei, R., Mei, Z., Curtin, L.R., Roche, A.F. & Johnson, C.L.(2000) CDC growth charts: United States. Advance Data from Vital and Health Statistics, No. 314. National Center for Health Statistics, Hyattsville, MD.
- 17 Hernández, M.I., Martínez, A., Capurro, T., Peña, V., Trejo, L., Avila, A., Salazar, T., Asenjo, S., Iñiguez, G. & Mericq, V. (2006) Comparison of clinical, ultrasonographic and biochemical differences at the beginning of puberty in healthy girls born either small for gestational age (SGA) or appropriate for gestational age (AGA): preliminary results. Journal of Clinical Endocrinology and Metabolism, 91, 3377–3381.
- 18 Greulich, W.W. & Pyle, S.I. (1959) Radiographics Atlas of Skeletal Development of the Hand and Wrist, 2nd edn. Stanford University Press, Stanford, CA.
- 19 Lee, S., Bacha, F., Gungor, N. & Arslanian, S.A. (2006) Waist circumference is an independent predictor of insulin resistance in black and white youths. Journal of Pediatrics, 148, 188–194.
- 20 Youlton, R. & Valenzuela, C. (1990) Growth patterns in height and weight in children aged 0–17 years and cranial circumference in children aged 0–2 years from medium-high and high socioeconomic status in Santiago. Comparison with growth in children from medium-low and low status in the Northern area of Santiago. Revista Chilena de Pediatría, 1–22.
- 21 Gungor, N., Saad, R., Janosky, J. & Arslanian, S. (2004) Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. Journal of Pediatrics, 144, 47–55.
- 22 Yeckel, C.W., Weiss, R., Dziura, J., Taksali, S.E., Dufour, S., Burgert, T.S., Tamborlane, W.V. & Caprio, S. (2004) Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. Journal of Clinical Endocrinology and Metabolism, 89, 1096–1101.
- 23 Phillips, D.I., Clark, P.M., Hales, C.N. & Osmond, C. (1994) Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabetic Medicine, 11, 286–292.
- 24 Hanson, R.L., Pratley, R.E., Bogardus, C., Narayan, K.M., Roumain, J.M., Imperatore, G., Fagot-Campagna, A., Pettitt, D.J., Bennett, P.H. & Knowler, W.C. (2000) Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. American Journal of Epidemiology, 151, 190–198.
- 25 Hofman, P.L., Cutfield, W.S., Robinson, E.M., Bergman, R.N., Menon, R.K., Sperling, M.A. & Gluckman, P.D. (1997) Insulin resistance in short children with intrauterine growth retardation. Journal of Clinical Endocrinology and Metabolism, 82, 402–406.
- 26 Potau, N., Gussinye, M., Sanchez Ufarte, C., Rique, S., Vicens-Calvet, E. & Carrascosa, A. (2001) Hyperinsulinemia in pre- and post-pubertal children born small for gestational age. Hormone Research, 56, 146–150.
- 27 Law, C.M., Gordon, G.S., Shiell, A.W., Barker, D.J. & Hales, C.N. (1995) Thinness at birth and glucose tolerance in seven-year-old children. Diabetic Medicine, 12, 24–29.
- 28 Whincup, P.H., Cook, D.G., Adshead, F., Taylor, S.J., Walker, M., Papacosta, O. & Alberti, K.G. (1997) Childhood size is more strongly related than size at birth to glucose and insulin levels in 10–11-year-old children. Diabetologia, 40, 319–326.
- 29 Caprio, S., Bronson, M., Sherwin, R.S., Rife, F. & Tamborlane, W.V. (1996) Co-existence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children. Diabetologia, 39, 1489–1497.
- 30 Kahn, S.E., Prigeon, R.L., McCulloch, D.K., Boyko, E.J., Bergman, R.N., Schwartz, M.W., Neifing, J.L., Ward, W.K., Beard, J.C., Palmer, J.P. & Porte, D. Jr (1993) Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes, 42, 1663–1672.
- 31 Weiss, R., Dziura, J., Burgert, T.S., Tamborlane, W.V., Taksali, S.E., Yeckel, C.W., Allen, K., Lopes, M., Savoye, M., Morrison, J., Sherwin, R.S. & Caprio, S. (2004) Obesity and the metabolic syndrome in children and adolescents. New England Journal of Medicine, 350, 2362–2374.
- 32 Le Stunff, C. & Bougneres, P. (1994) Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity. Diabetes, 43, 696–702.
- 33 Ong, K.K. & Dunger, D.B. (2002) Perinatal growth failure: the road to obesity, insulin-resistance and cardio-vascular disease in adults. Best Practice & Research: Clinical Endocrinology & Metabolism, 6, 191–207.
- 34 Ong, K.K., Petry, C.J., Emmett, P.M., Sandhu, M.S., Kiess, W., Hales, C.N., Ness, A.R., Dunger, D.B. & ALSPAC study team. (2004) Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels. Diabetologia, 47, 1064–1070.
- 35 Veening, M.A., Van Weissenbruch, M.M. & Delemarre-Van De Waal, H.A. (2002) Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age. Journal of Clinical Endocrinology and Metabolism, 87, 4657–4661.
- 36 Hyppönen, E., Power, C. & Davey Smith, G. (2003) Prenatal growth, BMI, and risk of type 2 diabetes by early midlife. Diabetes Care, 26, 2512–2517.
- 37 Hales, C.N. & Barker, D.J. (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia, 35, 595–601.
- 38 McKeigue, P.M., Lithell, H.O. & Leon, D.A. (1998) Glucose tolerance and resistance to insulin-stimulated glucose uptake in men aged 70 years in relation to size at birth. Diabetologia, 41, 1133–1138.
- 39 Caprio, S., Bronson, M., Sherwin, R.S., Rife, F. & Tamborlane, W.V. (1996) Co-existence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children. Diabetologia, 39, 1489–1497.
- 40 Pulzer, F., Haase, U., Knupfer, M., Kratzsch, J., Richter, V., Rassoul, F., Kiess, W. & Keller, E. (2001) Serum leptin in formerly small-for-gestational-age children during adolescence: relationship to gender, puberty, body composition, insulin sensitivity, creatinine, and serum uric acid. Metabolism, 50, 1141–1146.
- 41 Marchini, G., Fried, G., Ostlund, E. & Hagenas, L. (1998) Plasma leptin in infants: relations to birth weight and weight loss. Pediatrics, 101, 429–432.
- 42 Skurk, T., Alberti-Huber, C., Herder, C. & Hauner, H. (2007) Relationship between adipocyte size and adipokine expression and secretion. Journal of Clinical Endocrinology and Metabolism, 92, 1023–1033.
- 43 Ishida, K., Murakami, T., Mizuno, A., Iida, M., Kuwajima, M. & Shima, K. (1997) Leptin suppresses basal insulin secretion from rat pancreatic islets. Regulatory Peptides, 70, 179–182.
- 44 Hunziker, E. & Stein, M. (2000) Nestin-expressing cells in the pancreatic islets of Langerhans. Biochemistry and Biophysics Research Communications, 271, 116–119.
- 45 Scarpace, P.J., Matheny, M., Tumer, N., Cheng, K.Y. & Zhang, Y. (2005) Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats. Diabetologia, 48, 1075–1083.
- 46 Boguszewski, M., Dahlgren, J., Bjarnason, R., Rosberg, S., Carlsson, L.M., Carlsson, B. & Albertsson-Wikland, K. (1997) Serum leptin in short children born small for gestational age: relationship with the growth response to growth hormone treatment. The Swedish Study Group for Growth Hormone Treatment. European Journal of Endocrinology, 137, 387–395.
- 47 Tenhola, S., Halonen, P., Jaaskelainen, J. & Voutilainen, R. (2005) Serum markers of GH and insulin action in 12-year-old children born small for gestational age. European Journal of Endocrinology, 152, 335–340.
- 48 Ibanez, L., Ong, K., Dunger, D.B. & De Zegher, F. (2006) Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. Journal of Clinical Endocrinology and Metabolism, 91, 2153–2158.
- 49 Jayagopal, V., Kilpatrick, E.S., Jennings, P.E., Hepburn, D.A. & Atkin, S.L. (2003) The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance. Journal of Clinical Endocrinology and Metabolism, 88, 1528–1533.
- 50 Pugeat, M., Crave, J.C., Tourniaire, J. & Forest, M.G. (1996) Clinical utility of sex hormone-binding globulin measurement. Hormone Research, 45, 148–155.
- 51 Kistner, A., Jacobson, S.H., Celsi, G., Vanpee, M. & Brismar, K. (2004) IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMI. Journal of Internal Medicine, 255, 82–88.
Citing Literature
