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Regulation of ghrelin is related to estimated insulin sensitivity in obese children

International Journal of Obesity volume 30, pages 1482–1487 (2006)Cite this article

Abstract

Objective:

To investigate whether ghrelin concentrations and their changes during weight loss in obese children are associated with parameters of glucose and insulin metabolism.

Design:

Total plasma ghrelin, insulin and glucose were measured during oral glucose tolerance testing before and after diet-induced weight loss over 6 weeks.

Setting:

In-patient rehabilitation program in a pediatric hospital.

Participants:

Twenty-three obese children (age 10–16 years) and 11 normal weight controls (age 10–15 years).

Outcome measures:

Changes in ghrelin concentrations during weight loss and correlation analysis of changes in ghrelin and changes in parameters of glucose and insulin metabolism. After data collection, subgroup analysis of obese patients with high, medium and low estimated insulin sensitivity whole-body insulin sensitivity index (WBISI) was performed.

Results:

Weight loss increased the area under the curve (AUC) of ghrelin by 26% (P<0.001). The increase in ghrelin AUC correlated significantly with improved estimated insulin sensitivity (WBISI) (r=0.69, P<0.001). The independent predicting effect of WBISI was confirmed in multivariate analysis. In children with low WBISI, ghrelin reached the level of control values after weight loss. In children with high WBISI, ghrelin increased markedly above control levels.

Conclusions:

Changes in ghrelin are independently associated with changes in glucose and insulin metabolism. The increase in plasma ghrelin above control levels was limited to obese children with high WBISI.

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References

  1. Koletzko B, Girardet JP, Klish W, Tabacco O . Obesity in children and adolescents worldwide: current views and future directions – working group report of the first world congress of pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr 2002; 35 (Suppl 2): S205–S212.

    Article  PubMed  Google Scholar 

  2. Fisberg M, Baur L, Chen W, Hoppin A, Koletzko B, Lau D et al. Obesity in children and adolescents: working group report of the second world congress of pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr 2004; 39 (Suppl 2): S678–S687.

    Article  PubMed  Google Scholar 

  3. Rocchini AP, Katch V, Schork A, Kelch RP . Insulin and blood pressure during weight loss in obese adolescents. Hypertension 1987; 10: 267–273.

    Article  CAS  PubMed  Google Scholar 

  4. Gower BA, Nagy TR, Goran MI . Visceral fat, insulin sensitivity, and lipids in prepubertal children. Diabetes 1999; 48: 1515–1521.

    Article  CAS  PubMed  Google Scholar 

  5. Sinaiko AR, Donahue RP, Jacobs Jr DR, Prineas RJ . Relation of weight and rate of increase in weight during childhood and adolescence to body size, blood pressure, fasting insulin, and lipids in young adults. The Minneapolis Children's Blood Pressure Study. Circulation 1999; 99: 1471–1476.

    Article  CAS  PubMed  Google Scholar 

  6. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML . Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707–709.

    Article  CAS  PubMed  Google Scholar 

  7. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002; 87: 240–244.

    Article  CAS  PubMed  Google Scholar 

  8. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346: 1623–1630.

    Article  PubMed  Google Scholar 

  9. Soriano-Guillen L, Barrios V, Campos-Barros A, Argente J . Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation. J Pediatr 2004; 144: 36–42.

    Article  CAS  PubMed  Google Scholar 

  10. Ikezaki A, Hosoda H, Ito K, Iwama S, Miura N, Matsuoka H et al. Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes 2002; 51: 3408–3411.

    Article  CAS  PubMed  Google Scholar 

  11. Purnell JQ, Weigle DS, Breen P, Cummings DE . Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 2003; 88: 5747–5752.

    Article  CAS  PubMed  Google Scholar 

  12. Saad MF, Bernaba B, Hwu CM, Jinagouda S, Fahmi S, Kogosov E et al. Insulin regulates plasma ghrelin concentration. J Clin Endocrinol Metab 2002; 87: 3997–4000.

    Article  CAS  PubMed  Google Scholar 

  13. Briatore L, Andraghetti G, Cordera R . Acute plasma glucose increase, but not early insulin response, regulates plasma ghrelin. Eur J Endocrinol 2003; 149: 403–406.

    Article  CAS  PubMed  Google Scholar 

  14. Caixas A, Bashore C, Nash W, Pi-Sunyer F, Laferrere B . Insulin, unlike food intake, does not suppress ghrelin in human subjects. J Clin Endocrinol Metab 2002; 87: 1902.

    Article  CAS  PubMed  Google Scholar 

  15. McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE . Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 2004; 89: 1630–1635.

    Article  CAS  PubMed  Google Scholar 

  16. Matsuda M, DeFronzo RA . Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462–1470.

    Article  CAS  PubMed  Google Scholar 

  17. Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, Burgert TS et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab 2004; 89: 1096–1101.

    Article  CAS  PubMed  Google Scholar 

  18. Cole TJ, Rolland-Cachera MF . Measurement and definition. In: Burniat W, Cole TJ, Lissau I, Poskitt EME (eds). Child and Adolescent Obesity. University Press: Cambridge, 2002. pp 3–27.

    Chapter  Google Scholar 

  19. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH . Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000; 320: 1240–1243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Radikova Z . Assessment of insulin sensitivity/resistance in epidemiological studies. Endocr Regul 2003; 37: 189–194.

    PubMed  Google Scholar 

  21. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1999; 22 (Suppl 1): S5–S19.

  22. Whatmore AJ, Hall CM, Jones J, Westwood M, Clayton PE . Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol (Oxford) 2003; 59: 649–654.

    Article  CAS  Google Scholar 

  23. Soriano-Guillen L, Barrios V, Martos G, Chowen JA, Campos-Barros A, Argente J . Effect of oral glucose administration on ghrelin levels in obese children. Eur J Endocrinol 2004; 151: 119–121.

    Article  CAS  PubMed  Google Scholar 

  24. Nakagawa E, Nagaya N, Okumura H, Enomoto M, Oya H, Ono F et al. Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose. Clin Sci (London) 2002; 103: 325–328.

    Article  CAS  Google Scholar 

  25. Soriano-Guillen L, Barrios V, Chowen JA, Sanchez I, Vila S, Quero J et al. Ghrelin levels from fetal life through early adulthood: relationship with endocrine and metabolic and anthropometric measures. J Pediatr 2004; 144: 30–35.

    Article  CAS  PubMed  Google Scholar 

  26. Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL et al. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 2001; 145: 669–673.

    Article  CAS  PubMed  Google Scholar 

  27. Ball GD, Huang TT, Gower BA, Cruz ML, Shaibi GQ, Weigensberg MJ et al. Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty. J Pediatr 2006; 148: 16–22.

    Article  CAS  PubMed  Google Scholar 

  28. Goran MI, Gower BA . Longitudinal study on pubertal insulin resistance. Diabetes 2001; 50: 2444–2450.

    Article  CAS  PubMed  Google Scholar 

  29. Eckel RH . Insulin resistance: an adaptation for weight maintenance. Lancet 1992; 340: 1452–1453.

    Article  CAS  PubMed  Google Scholar 

  30. Gould AJ, Williams DE, Byrne CD, Hales CN, Wareham NJ . Prospective cohort study of the relationship of markers of insulin resistance and secretion with weight gain and changes in regional adiposity. Int J Obes Relat Metab Disord 1999; 23: 1256–1261.

    Article  CAS  PubMed  Google Scholar 

  31. Hoag S, Marshall JA, Jones RH, Hamman RF . High fasting insulin levels associated with lower rates of weight gain in persons with normal glucose tolerance: the San Luis Valley Diabetes Study. Int J Obes Relat Metab Disord 1995; 19: 175–180.

    CAS  PubMed  Google Scholar 

  32. Hodge AM, Dowse GK, Alberti KG, Tuomilehto J, Gareeboo H, Zimmet PZ . Relationship of insulin resistance to weight gain in nondiabetic Asian Indian, creole, and Chinese Mauritians. Mauritius non-communicable disease study group. Metabolism 1996; 45: 627–633.

    Article  CAS  PubMed  Google Scholar 

  33. Schwartz MW, Boyko EJ, Kahn SE, Ravussin E, Bogardus C . Reduced insulin secretion: an independent predictor of body weight gain. J Clin Endocrinol Metab 1995; 80: 1571–1576.

    CAS  PubMed  Google Scholar 

  34. Swinburn BA, Nyomba BL, Saad MF, Zurlo F, Raz I, Knowler WC et al. Insulin resistance associated with lower rates of weight gain in Pima Indians. J Clin Invest 1991; 88: 168–173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Valdez R, Mitchell BD, Haffner SM, Hazuda HP, Morales PA, Monterrosa A et al. Predictors of weight change in a bi-ethnic population. The San Antonio Heart Study. Int J Obes Relat Metab Disord 1994; 18: 85–91.

    CAS  PubMed  Google Scholar 

  36. Johnson MS, Figueroa-Colon R, Huang TT, Dwyer JH, Goran MI . Longitudinal changes in body fat in African American and Caucasian children: influence of fasting insulin and insulin sensitivity. J Clin Endocrinol Metab 2001; 86: 3182–3187.

    CAS  PubMed  Google Scholar 

  37. Odeleye OE, de Court, Pettitt DJ, Ravussin E . Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children. Diabetes 1997; 46: 1341–1345.

    Article  CAS  PubMed  Google Scholar 

  38. Maffeis C, Moghetti P, Grezzani A, Clementi M, Gaudino R, Tato L . Insulin resistance and the persistence of obesity from childhood into adulthood. J Clin Endocrinol Metab 2002; 87: 71–76.

    Article  CAS  PubMed  Google Scholar 

  39. Travers SH, Jeffers BW, Eckel RH . Insulin resistance during puberty and future fat accumulation. J Clin Endocrinol Metab 2002; 87: 3814–3818.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank D Hölzel for assistance with the statistical analysis. We thank all children who participated in the study. Kathrin Krohn was financially supported in part by an unconditional grant from the Schweisfurth Foundation, Munich, Germany.

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Authors and Affiliations

  1. Division of Metabolic Diseases and Nutritional Medicine, Dr von Hauner Children's Hospital, University of Munich, Germany

    K Krohn, C Boczan & B Koletzko

  2. Department of Medicine, University of Munich, Germany

    B Otto, W Heldwein & R Landgraf

  3. Paediatric Rehabilitation Center Gaissach, LVA Oberbayern, Germany

    C P Bauer

Authors
  1. K Krohn
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  2. C Boczan
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Correspondence to B Koletzko.

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Krohn, K., Boczan, C., Otto, B. et al. Regulation of ghrelin is related to estimated insulin sensitivity in obese children. Int J Obes 30, 1482–1487 (2006). https://doi.org/10.1038/sj.ijo.0803399

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  • DOI: https://doi.org/10.1038/sj.ijo.0803399

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