INSULIN RESISTANCE IN CHILDHOOD

Summary

Principal Investigator: Silva A Arslanian
Affiliation: Children's Hospital of Pittsburgh
Country: USA
Abstract: This is a competing renewal application for a K24 in patient-oriented research (POR) for Silva Arslanian, M.D. of the Children's Hospital University of Pittsburgh, School of Medicine. The applicant's original award provided support for POR for investigating insulin resistance during childhood growth and development, mentoring of junior faculty and fellows, advancing the research in new directions, and leadership in POR locally, nationally, and internationally. All of these aims have been executed with outstanding rigor, and the candidate has been successful in accomplishing the following: 1) Competitively renewed her R01 (2R01 HD027503); 2) Obtained new independent NIH funding as PI (1U01 DK063704), and funding for several pharmaceutical trials; 3) Advanced her mentoring commitment by obtaining new funding as PI for a fellow training grant (T32 DK63686) and junior faculty development grant (K12 DK63704), both in pediatric diabetes; 4) Established new collaborations in POR at her own institution (1R01- HD38425, and 5U01 DK061230; PI, Marsha Marcus, Ph.D.) and with other academic institutions (1R01 DK071485; PI, Shumei Sun, Ph.D., Wright State University); 5) Competitively renewed the GCRC grant (5M01RR00084), with an outstanding score, at Children's Hospital of Pittsburgh, where she is director; 6) Became a board member of the Endocrine Fellows Foundation, a national organization whose primary and sole mission is the education and research support of endocrine fellows nationally; 7) Increased the pool of pediatrician investigators in POR by attracting and mentoring new fellows/faculty from within and outside the institution; 9) Assumed a leadership role in directing the newly founded Weight Management & Wellness Center (WMWC) at Children's Hospital of Pittsburgh; and, last but not least, received the inaugural University of Pittsburgh Medical Center Richard L. Day Endowed Chair in Pediatrics. This renewal application proposes to: 1) Continue the leadership of the PI in POR in the area of childhood obesity, insulin resistance, type 2 diabetes, and cardiovascular disease, major public health problems of this millennium; 2) Provide ongoing mentoring to junior faculty, fellows, and medical students; and 3) To conduct innovative research in childhood insulin resistance, its causes, complications and control strategies. Support for these activities will enable Dr. Arslanian to further strengthen and expand the research scope of childhood obesity and insulin resistance but, more importantly, contribute to the academic development of young and upcoming clinician-investigators who will contribute to the global childhood obesity control by developing new paradigms of intervention, prevention and treatment.
Funding Period: 2000-05-01 - 2011-11-30
more information: NIH RePORT

Top Publications

  1. ncbi Family history of type 2 diabetes is associated with decreased insulin sensitivity and an impaired balance between insulin sensitivity and insulin secretion in white youth
    Silva A Arslanian
    Division of Pediatric Endocrinology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Diabetes Care 28:115-9. 2005
  2. ncbi Type 2 diabetes in children and adolescents: a review for the primary care provider
    Tamara S Hannon
    Department of Pediatrics, Children's Hospital, University of Pittsburgh Medical Center, PA 15213, USA
    Pediatr Ann 35:880-7. 2006
  3. ncbi Insulin resistance: link to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth
    SoJung Lee
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213, USA
    Diabetes Care 30:2091-7. 2007
  4. ncbi Growth hormone treatment in adolescent males with idiopathic short stature: changes in body composition, protein, fat, and glucose metabolism
    Tamara S Hannon
    Division of Pediatric Endocrinology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Clin Endocrinol Metab 92:3033-9. 2007
  5. ncbi Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin, and inflammatory biomarkers
    SoJung Lee
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    J Pediatr 152:177-84. 2008
  6. ncbi Race and gender differences in the relationships between anthropometrics and abdominal fat in youth
    SoJung Lee
    Children s Hospital of Pittsburgh, Division of Weight Management and Wellness, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Obesity (Silver Spring) 16:1066-71. 2008
  7. ncbi Measures of beta-cell function during the oral glucose tolerance test, liquid mixed-meal test, and hyperglycemic clamp test
    Fida Bacha
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    J Pediatr 152:618-21. 2008
  8. ncbi Hyperinsulinemia in African-American adolescents compared with their American white peers despite similar insulin sensitivity: a reflection of upregulated beta-cell function?
    Tamara S Hannon
    Division of Pediatric Endocrinology, Metabolism, and Diabetes, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Diabetes Care 31:1445-7. 2008
  9. ncbi Menstrual health and the metabolic syndrome in adolescents
    Hala Tfayli
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Ann N Y Acad Sci 1135:85-94. 2008
  10. ncbi Reproducibility of the oral glucose tolerance test in overweight children
    I M Libman
    Children s Hospital of Pittsburgh, and Department of Epidemiology, Graduate School of Public Health, Center for Exercise and Health Fitness Research, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Clin Endocrinol Metab 93:4231-7. 2008

Scientific Experts

Detail Information

Publications34

  1. ncbi Family history of type 2 diabetes is associated with decreased insulin sensitivity and an impaired balance between insulin sensitivity and insulin secretion in white youth
    Silva A Arslanian
    Division of Pediatric Endocrinology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Diabetes Care 28:115-9. 2005
    ..beta-Cell compensation for insulin sensitivity was calculated as the product of insulin sensitivity x first-phase insulin secretion, termed glucose disposition index (GDI)...
  2. ncbi Type 2 diabetes in children and adolescents: a review for the primary care provider
    Tamara S Hannon
    Department of Pediatrics, Children's Hospital, University of Pittsburgh Medical Center, PA 15213, USA
    Pediatr Ann 35:880-7. 2006
  3. ncbi Insulin resistance: link to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth
    SoJung Lee
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213, USA
    Diabetes Care 30:2091-7. 2007
    ..We examined the relationship of in vivo insulin sensitivity to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth...
  4. ncbi Growth hormone treatment in adolescent males with idiopathic short stature: changes in body composition, protein, fat, and glucose metabolism
    Tamara S Hannon
    Division of Pediatric Endocrinology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Clin Endocrinol Metab 92:3033-9. 2007
    ..Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH...
  5. ncbi Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin, and inflammatory biomarkers
    SoJung Lee
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    J Pediatr 152:177-84. 2008
    ....
  6. ncbi Race and gender differences in the relationships between anthropometrics and abdominal fat in youth
    SoJung Lee
    Children s Hospital of Pittsburgh, Division of Weight Management and Wellness, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Obesity (Silver Spring) 16:1066-71. 2008
    ..We examined the influence of race and gender on abdominal adipose tissue (AT) distribution for a given anthropometric measure including waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height (W/Ht) in youth...
  7. ncbi Measures of beta-cell function during the oral glucose tolerance test, liquid mixed-meal test, and hyperglycemic clamp test
    Fida Bacha
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    J Pediatr 152:618-21. 2008
    ....
  8. ncbi Hyperinsulinemia in African-American adolescents compared with their American white peers despite similar insulin sensitivity: a reflection of upregulated beta-cell function?
    Tamara S Hannon
    Division of Pediatric Endocrinology, Metabolism, and Diabetes, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Diabetes Care 31:1445-7. 2008
    ..The aim of the present investigation was to assess whether glucose-stimulated insulin response is higher in AA versus AW adolescents who have comparable in vivo insulin sensitivity...
  9. ncbi Menstrual health and the metabolic syndrome in adolescents
    Hala Tfayli
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Ann N Y Acad Sci 1135:85-94. 2008
    ..Careful assessment of menstrual history and appropriate laboratory work-up could reveal the presence of PCOS in obese at-risk adolescent girls with a family history of the metabolic syndrome...
  10. ncbi Reproducibility of the oral glucose tolerance test in overweight children
    I M Libman
    Children s Hospital of Pittsburgh, and Department of Epidemiology, Graduate School of Public Health, Center for Exercise and Health Fitness Research, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Clin Endocrinol Metab 93:4231-7. 2008
    ..We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results...
  11. ncbi Fat oxidation in black and white youth: a metabolic phenotype potentially predisposing black girls to obesity
    SoJung Lee
    University of Pittsburgh, School of Medicine, Weight Management and Wellness Center, Pediatric Clinical and Translational Research Center, Children s Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA
    J Clin Endocrinol Metab 93:4547-51. 2008
    ..Thus, we examined the relationships between race, pubertal development, and postabsorptive fat oxidation in youth...
  12. ncbi In vivo insulin sensitivity and secretion in obese youth: what are the differences between normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes?
    Fida Bacha
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Diabetes Care 32:100-5. 2009
    ..The aim of this study was to investigate the differences in insulin sensitivity (IS) and secretion in obese adolescents with IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes...
  13. ncbi Effects of an intravenous lipid challenge and free fatty acid elevation on in vivo insulin sensitivity in African American versus Caucasian adolescents
    Stephen F Burns
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Diabetes Care 32:355-60. 2009
    ..The present investigation determined whether elevating FFA is more deleterious to insulin sensitivity in African American than in Caucasian adolescents...
  14. ncbi Phenotypic type 2 diabetes in obese youth: insulin sensitivity and secretion in islet cell antibody-negative versus -positive patients
    Hala Tfayli
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Diabetes 58:738-44. 2009
    ..In this study, we investigated the differences in insulin sensitivity and secretion between autoantibody-negative (Ab-) and -positive (Ab+) youth with clinically diagnosed type 2 diabetes in comparison with control subjects...
  15. ncbi Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon
    Hala Tfayli
    Division of Weight Management and Wellness from Center, Children s Hospital of Pittsburgh, University of Pittsburgh Medical Center, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA
    Arq Bras Endocrinol Metabol 53:165-74. 2009
    ..These challenges combined with the evolving picture of youth T2DM and its future complications provide unending opportunities for acquisition of new knowledge in the field of childhood diabetes...
  16. ncbi In vivo insulin sensitivity and lipoprotein particle size and concentration in black and white children
    Stephen F Burns
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Diabetes Care 32:2087-93. 2009
    ..To examine sex-specific black/white differences in lipoprotein profile and the role of visceral adiposity and to assess the relationship between insulin sensitivity and lipoprotein profiles in each group...
  17. ncbi Waist circumference, blood pressure, and lipid components of the metabolic syndrome
    SoJung Lee
    Weight Management and Wellness Center and Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    J Pediatr 149:809-16. 2006
    ..This observation supports the notion that WC should be included in the evaluation of childhood obesity along with BMI percentile to identify those at increased health risks due to excess abdominal fat...
  18. ncbi Longitudinal study of physiologic insulin resistance and metabolic changes of puberty
    Tamara S Hannon
    Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus and Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Pediatr Res 60:759-63. 2006
    ..These metabolic changes are proposed to be partially mediated by increased GH secretion and are consistent with the Randle cycle of competition between glucose and fat oxidation...
  19. ncbi Youth type 2 diabetes: insulin resistance, beta-cell failure, or both?
    Neslihan Gungor
    Division of Pediatric Endocrinology, Children s Hospital of Pittsburgh, 3705 Fifth Ave at DeSoto St, Pittsburgh, PA 15213, USA
    Diabetes Care 28:638-44. 2005
    ..This study evaluates insulin sensitivity, pancreatic beta-cell function (BCF), and the balance between the two in youth with type 2 diabetes and assesses the relationship of diabetes duration and HbA(1c) to insulin sensitivity and BCF...
  20. ncbi Early signs of cardiovascular disease in youth with obesity and type 2 diabetes
    Neslihan Gungor
    Division of Endocrinology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto Street, Pittsburgh, PA 15213, USA
    Diabetes Care 28:1219-21. 2005
  21. ncbi Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates
    Rola Saad
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children's Hospital of Pittsburgh, PA 15213, USA
    Pediatr Diabetes 6:95-9. 2005
    ....
  22. ncbi Does adiponectin explain the lower insulin sensitivity and hyperinsulinemia of African-American children?
    Fida Bacha
    Division of Endocrinology, Metabolism and Diabetes Mellitus, Children s Hospital of Pittsburgh, PA 15213, USA
    Pediatr Diabetes 6:100-2. 2005
    ..Lower adiponectin does not seem to explain the racial differences in insulin sensitivity. The relationship of hyperinsulinemia and hypoadiponectinemia needs to be further explored...
  23. ncbi Childhood obesity and type 2 diabetes mellitus
    Tamara S Hannon
    Division of Weight Management and Wellness, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Pediatrics 116:473-80. 2005
    ..Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease...
  24. ncbi Comparison of maximal oxygen consumption between obese black and white adolescents
    Joseph L Andreacci
    Department of Exercise, Bloomsburg University, Bloomsburg, PA 17815, USA
    Pediatr Res 58:478-82. 2005
    ..Further investigations should study Hb flow rate (a function of [Hb] . maximal cardiac output) and physical activity/inactivity patterns in obese black and white children as it relates to VO2max...
  25. ncbi Type 2 diabetes mellitus in youth: the complete picture to date
    Neslihan Gungor
    Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA
    Pediatr Clin North Am 52:1579-609. 2005
    ..This article discusses the amassed information in type 2 diabetes mellitus of youth to date with respect to the epidemiology, pathophysiology, risk factors, clinical presentation, screening, and management strategies...
  26. ncbi Racial differences in adiponectin in youth: relationship to visceral fat and insulin sensitivity
    SoJung Lee
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Weight Management and Wellness Center, Children s Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto St, Pittsburgh, Pennsylvania 15213, USA
    Diabetes Care 29:51-6. 2006
    ....
  27. ncbi Clamp techniques in paediatrics: what have we learned?
    Silva A Arslanian
    Children s Hospital of Pittsburgh, Weight Management and Wellness Center, and Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Pittsburgh, PA 15213, USA
    Horm Res 64:16-24. 2005
    ..This article will delineate our paediatric experience with the clamp technique, the hyperinsulinaemic-euglycaemic clamp in assessing in vivo insulin sensitivity, and the hyperglycaemic clamp in assessing insulin secretion...
  28. ncbi Waist circumference is an independent predictor of insulin resistance in black and white youths
    SoJung Lee
    Children's Hospital of Pittsburgh, Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, Weight Management and Wellness Center, 3705 Fifth Avenue at DeSoto Street, Pittsburgh, PA 15213, USA
    J Pediatr 148:188-94. 2006
    ..Such observations would reinforce the importance of including WC in the assessment of childhood obesity to identify those at increased metabolic risk due to excess abdominal fat...
  29. ncbi Treatment of PCOS in adolescence
    Julia Warren-Ulanch
    Division of Endocrinology, University of Pittsburgh Medical Center, Children s Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213 2583, USA
    Best Pract Res Clin Endocrinol Metab 20:311-30. 2006
    ..Long-term follow-up is needed to determine the effectiveness of these approaches in changing the natural history of the reproductive and metabolic outcomes without causing undue harm...
  30. ncbi Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents?
    Fida Bacha
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus and the Weight Management and Wellness Center, Children s Hospital of Pittsburgh, Pennsylvania 15213, USA
    Diabetes Care 29:1599-604. 2006
    ..However, wide variations in insulin sensitivity are noted in obese youth. It is not clear if greater insulin resistance confers a higher risk of cardiovascular comorbidities and risk for type 2 diabetes...
  31. ncbi Cardiorespiratory fitness and abdominal adiposity in youth
    S J Lee
    Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Weight Management and Wellness Center, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Eur J Clin Nutr 61:561-5. 2007
    ....
  32. ncbi Cardiorespiratory fitness in youth: relationship to insulin sensitivity and beta-cell function
    SoJung Lee
    Children's Hospital of Pittsburgh, Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, Weight Management and Wellness Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Obesity (Silver Spring) 14:1579-85. 2006
    ..However, this relationship disappears after adjusting for differences in adiposity, suggesting that the association between fitness and IS is mediated, at least in part, through fatness...
  33. ncbi Use of markers of dyslipidemia to identify overweight youth with insulin resistance
    Tamara S Hannon
    Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Pediatr Diabetes 7:260-6. 2006
    ..Markers to identify overweight youth with insulin resistance are of clinical importance...
  34. ncbi Waist circumference, atherogenic lipoproteins, and vascular smooth muscle biomarkers in children
    Stephen F Burns
    Division of Weight Management and Wellness, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    J Clin Endocrinol Metab 94:4914-22. 2009
    ..The present study determined differences in lipoprotein particle size and subclass concentration and markers of vascular smooth muscle function in children using WC percentile cutoffs...