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Exp Clin Endocrinol Diabetes 2015; 123(04): 252-259
DOI: 10.1055/s-0034-1398503
Article
© Georg Thieme Verlag KG Stuttgart · New York

Expression of the Central Obesity and Type 2 Diabetes Mellitus Genes is Associated with Insulin Resistance in Young Obese Children

S. Skoczen
1   Department of Clinical Immunology, Chair of Clinical Immunology and Transplantology, Jagiellonian University Medical College, Krakow, Poland
2   Transplantation Centre, University Children’s Hospital, Krakow, Poland
,
M. Wojcik
3   Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
,
K. Fijorek
4   Department of Statistics, Cracow University of Economics, Krakow, Poland
,
M. Siedlar
1   Department of Clinical Immunology, Chair of Clinical Immunology and Transplantology, Jagiellonian University Medical College, Krakow, Poland
,
J. B. Starzyk
3   Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
› Author Affiliations
Further Information

Publication History

received 12 September 2014
first decision 15 November 2014

accepted 17 December 2014

Publication Date:
13 April 2015 (online)

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Abstract

Objectives: The assessment of the health consequences associated with obesity in young children is challenging. The aims of this study were: (1) to compare insulin resistance indices derived from OGTT in obese patients and healthy control (2) to analyze central obesity and Type 2 Diabetes genes expression in obese children, with special attention to the youngest group (< 10 years old).

Patients and methods: The study included 49 children with obesity (median age 13.5 years old), and 25 healthy peers. Biochemical blood tests and expression of 11 central obesity and 33 Type 2 Diabetes genes was assessed.

Results: A significant difference in insulin resistance between obese and non-obese adolescents was observed in all studied indices (mean values of the insulin levels: 24.9 vs. 9.71 mIU/L in T0, 128 vs. 54.7 mIU/L in T60 and 98.7 vs. 41.1 mIU/L in T120 respectively; AUC: 217 vs. 77.2 ng/ml*h, mean values of B% (state beta cell function), S% (insulin sensitivity), and IR were 255 (±97) vs. 135 (±37.8), 46.6 (±37.3) vs. 84.2 (±29.6) and 3 (±1.55) vs. 1.36 (±0,56); HIS, WBIS and ISIBel median 3.89, 44.7, 0.73 vs. 8.57, 110, 2.25. All comparisons differed significantly p<0.001). Moreover, insulin sensitivity was significantly better in the older obese group (>10 years old): median AUC 239 vs. 104 ng/ml*h, and HIS, WBIS and ISIBel 3.57, 38, 0.67 vs. 6.23, 75.6, 1.87 respectively in the obese older compared to the obese younger subgroup, p<0.05. The expression of 64% of the central obesity genes and 70% of Type 2 Diabetes genes was higher in the obese compared to control groups. The differences were more pronounced in the younger obese group.

Conclusion: Insulin resistance may develop in early stage of childhood obesity and in very young children may be associated with higher expression of the central obesity and Type 2 Diabetes genes.

Key words

microarrays - metabolic syndrome - adolescents
 

  • References

  • 1 Ferrannini E, Galvan AQ, Gastaldelli A et al. Insulin: new roles for an ancient hormone. Eur J Clin Invest 1999; 29: 842-852
    CrossrefPubMedGoogle Scholar
  • 2 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607
    CrossrefPubMedGoogle Scholar
  • 3 Zimmet P, Alberti KG, Kaufman F et al. The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatr Diabetes 2007; 8: 299-306
    CrossrefPubMedGoogle Scholar
  • 4 Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab 2004; 89: 2526-2539
    CrossrefPubMedGoogle Scholar
  • 5 Sinaiko AR, Steinberger J, Moran A et al. Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence. Circulation 2005; 111: 1985-1991
    CrossrefPubMedGoogle Scholar
  • 6 Levy-Marchal C, Arslanian S, Cutfield W et al. Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab 2010; 95: 5189-5198
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 Weghuber D, Mangge H, Hochbrugger E et al. Impact of age and metabolic syndrome on the adipokine profile in childhood and adult obesity. Exp Clin Endocrinol Diabetes 2014; 122: 363-367
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Ballesteros-Pomar MD, Calleja S, Díez-Rodríguez R et al. Inflammatory Status is Different in Relationship to Insulin Resistance in Severely Obese People and Changes after Bariatric Surgery or Diet-induced Weight Loss. Exp Clin Endocrinol Diabetes 2014; 122: 592-596
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Bouglé D, Morello R, Brouard J. Thyroid Function and Metabolic Risk Factors in Obese Youth. Changes during Follow-up: A Preventive Mechanism?. Exp Clin Endocrinol Diabetes 2014; 22: 548-552
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Frayling TM. Are the causes of obesity primarily environmental? No. BMJ 2012; 11 345e5844
    PubMedGoogle Scholar
  • 12 Speliotes EK, Willer CJ, Berndt SI et al. Association analyses of 249 796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937-948
    CrossrefPubMedGoogle Scholar
  • 13 Ingelsson E, Langenberg C, Hivert MF et al. Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. Diabetes 2010; 59: 1266-1275
    CrossrefPubMedGoogle Scholar
  • 14 Dupuis J, Langenberg C, Prokopenko I et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 2010; 42: 105-116
    CrossrefPubMedGoogle Scholar
  • 15 Strawbridge RJ, Dupuis J, Prokopenko I et al. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes 2011; 60: 2624-2634
    CrossrefPubMedGoogle Scholar
  • 16 WHO Anthro (version 3.2.2, January 2011) and macros www.who.int/childgrowth/software/en/
    PubMed
  • 17 Child of Cracovia region 2000. Biological development of children and adolescents in Krakow city. Poziom rozwoju biologicznego dzieci i młodzieży miasta Krakowa. Studia i Monografie AWF w Krakowie Nr 19, Maria Chrzanowska, Stanisław Gołąb (editor)
    PubMed
  • 18 Barlow SE. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007; 120: 164-192
    PubMedGoogle Scholar
  • 19 Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in girls. Arch Dis Child 1969; 44: 291-303
    CrossrefPubMedGoogle Scholar
  • 20 Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970; 45: 13-23
    CrossrefPubMedGoogle Scholar
  • 21 Cook S, Auinger P, Huang TT. Growth curves for cardio-metabolic risk factors in children and adolescents. J Pediatr 2009; 155: S6.e15-S6.e26
    PubMedGoogle Scholar
  • 22 Lurbe E, Cifkova R, Cruickshank JK et al. European Society of Hypertension: Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens 2009; 27: 1719-1742
    CrossrefPubMedGoogle Scholar
  • 23 Xi 1 B, Cheng H, Shen Y et al. Study of 11 BMI-associated loci identified in GWAS for associations with central obesity in the Chinese children. PLoS One 2013; 8: e56472
    CrossrefPubMedGoogle Scholar
  • 24 Levine R, Haft D. Carbohydrate homeostasis. N Engl J Med 1970; 283: 237-246
    CrossrefPubMedGoogle Scholar
  • 25 Myllynen P, Koivisto V, Nikkila E. Glucose intolerance and insulin resistance accompany immobilization. Acta Med Scand 1987; 222: 75-81
    PubMedGoogle Scholar
  • 26 Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998; 21: 2191-2192
    CrossrefPubMedGoogle Scholar
  • 27 Turner R, Holman R, Matthews D et al. Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism 1979; 28: 1086-1096
    CrossrefPubMedGoogle Scholar
  • 28 Matthews D, Hosker J, Rudenski A et al. Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
    Google Scholar
  • 29 Hosker J, Matthews D, Rudenski A et al. Continuous infusion of glucose with model assessment: measurement of insulin resistance and b-cell function in man. Diabetologia 1985; 28: 401-411
    CrossrefPubMedGoogle Scholar
  • 30 https://www.dtu.ox.ac.uk/homacalculator/index.php
    PubMed
  • 31 Belfiore F, Iannello S, Volpicelli G. Insulin sensitivity indices calculated from basal and OGTT-induced insulin, glucose, and FFA levels. Mol Gen Metab 1998; 63: 134-141
    CrossrefPubMedGoogle Scholar
  • 32 Fridley BL, Jenkins GD, Biernacka JM et al. Self-Contained Gene-Set Analysis of Expression Data: An Evaluation of Existing and Novel Methods. PLoS ONE 2010; 5: e12693
    CrossrefPubMedGoogle Scholar
  • 33 Bacha F, Gungor N, Lee S et al. In vivo insulin sensitivity and secretion in obese youth: what are the differences between normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes?. Diabetes Care 2009; 32: 100-105
    CrossrefPubMedGoogle Scholar
  • 34 Weiss R, Caprio S, Trombetta M et al. β-Cell function across the spectrum of glucose tolerance in obese youth. Diabetes 2005; 54: 1735-1743
    CrossrefPubMedGoogle Scholar
  • 35 Weigensberg MJ, Ball GD, Shaibi GQ et al. Decreased β-cell function in overweight Latino children with impaired fasting glucose. Diabetes Care 2005; 28: 2519-2524
    CrossrefPubMedGoogle Scholar
  • 36 Cali AM, Man CD, Cobelli C et al. Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents. Diabetes Care 2009; 32: 456-461
    CrossrefPubMedGoogle Scholar
  • 37 Lee S, Bacha F, Gungor N et al. Comparison of different definitions of pediatric metabolic syndrome: relation to central adiposity, insulin resistance, adiponectin, and inflammatory biomarkers. J Pediatr 2008; 152: 177-184
    CrossrefPubMedGoogle Scholar
  • 38 Ramachandran A, Snehalatha C, Yamuna A et al. Insulin resistance and clustering of cardiometabolic risk factors in urban teenagers in southern India. Diabetes Care 2007; 30: 1828-1833
    CrossrefPubMedGoogle Scholar
  • 39 Sinaiko AR, Steinberger J, Moran A et al. Influence of insulin resistance and body mass index at age 13 on systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol at age 19. Hypertension 2006; 48: 730-736
    CrossrefPubMedGoogle Scholar
  • 40 Schwartz B, Jacobs Jr DR, Moran A et al. Measurement of insulin sensitivity in children: comparison between the euglycemic-hyperinsulinemic clamp and surrogate measures. Diabetes Care 2008; 31: 783-788
    CrossrefPubMedGoogle Scholar
  • 41 Stumvoll M, Mitrakou A, Pimenta W et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2008; 23: 295-301
    PubMedGoogle Scholar
  • 42 Yeckel CW, Weiss R, Dziura J 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
    CrossrefPubMedGoogle Scholar