Pediatric Nephrology

, Volume 27, Issue 4, pp 627–635 | Cite as

Glucose intolerance: is it a risk factor for cardiovascular disease in children with chronic kidney disease?

  • Nur CanpolatEmail author
  • Salim Caliskan
  • Lale Sever
  • Alper Guzeltas
  • Fatih Kantarci
  • Cengiz Candan
  • Mahmut Civilibal
  • Ozgur Kasapcopur
  • Nil Arisoy
Original Article


A total of 66 children and adolescents with chronic kidney disease (CKD) (20 pre-dialysis patients and 46 chronic dialysis patients) were evaluated to address the prevalence of abnormalities in glucose and insulin metabolism and their association with cardiovascular disease. Glucose intolerance was assessed using an oral glucose tolerance test; insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). Carotid artery intima-media thickness (IMT) and left ventricular hypertrophy (LVH) were examined as early markers of cardiovascular disease. Thirty-four patients (7 pre-dialysis, 27 dialysis) exhibited an abnormal glucose tolerance; however, ten patients (7 pre-dialysis, 3 dialysis) were insulin-resistant. Height-specific standard deviation scores of carotid artery IMT were above normal in three of the pre-dialysis patients (15%) and in 34 of the dialysis patients (74%). LVH was present in seven pre-dialysis (35%) and 34 dialysis patients (74%). In addition, two of the pre-dialysis patients (10%) and 18 of the dialysis patients (39%) had severe LVH. The prevalence of both increased carotid artery IMT and LVH were similar in patients with or without glucose intolerance in both groups, but severe LVH was more prevalent in pre-dialysis patients with glucose intolerance (p = 0.042). The multivariate analyses showed that neither carotid artery IMT nor LVM index was predicted by serum glucose levels or HOMA-IR. In conclusion, children with CKD are at a high risk of glucose intolerance and also have a greater risk of subclinical cardiovascular disease (CVD). However, the presence of glucose intolerance does not appear to be an independent risk factor for increased carotid artery IMT or LVH.


Cardiovascular disease Childhood Chronic kidney disease Glucose intolerance Insulin resistance 



We are grateful to our dialysis specialist nurses, Gulseren Pehlivan, Didem Cakır, and Sennur Erkut, for their help.


All authors declare that there is no conflict of interest.


  1. 1.
    Groothoff JW, Gruppen MP, Offringa HJ, Lillien MR, Van De Kar NJ, Wolff ED, Davin JC, Heymans HS (2002) Mortality and causes of death of end-stage renal disease in children: a Dutch cohort study. Kidney Int 61:621–629PubMedCrossRefGoogle Scholar
  2. 2.
    Parekh RS, Carrol CE, Wolfe RA, Port FK (2002) Cardiovascular mortality in children and young adults with end-stage kidney disease. J Pediatr 141:191–197PubMedCrossRefGoogle Scholar
  3. 3.
    Mitsnefes MM (2008) Cardiovascular complications of pediatric chronic kidney disease. Pediatr Nephrol 23:27–39PubMedCrossRefGoogle Scholar
  4. 4.
    Lillien MR, Groothoff JW (2009) Cardiovascular disease in children with CKD or ESRD. Nat Rev Nephrol 10:229–235CrossRefGoogle Scholar
  5. 5.
    Shroff R, Quinlan C, Mitsnefes M (2011) Ureamic vasculopathy in children with chronic kidney disease: prevention or damage limitation? Pediatr Nephrol 26:853–865PubMedCrossRefGoogle Scholar
  6. 6.
    Wilson AC, Mitsnefes MM (2009) Cardiovascular disease in CKD in children: update on risk factors, risk assessment, and management. Am J Kidney Dis 54:345–360PubMedCrossRefGoogle Scholar
  7. 7.
    Ekundayo OJ, Muchimba M, Aban IB, Ritchie C, Campbell RC, Ahmed A (2009) Multimorbidity due to diabetes mellitus and chronic kidney disease and outcomes in chronic heart failure. Am J Cardiol 103:88–92PubMedCrossRefGoogle Scholar
  8. 8.
    Menon V, Greene T, Pereira AA, Wang X, Beck GJ, Kusek JW, Collins AJ, Levey AS, Samak MJ (2005) Glycosylated hemoglobin and mortality in patients with nondiabetic chronic kidney disease. J Am Soc Nephrol 16:3411–3417PubMedCrossRefGoogle Scholar
  9. 9.
    Shinohara K, Shoji T, Emoto M, Tahara H, Koyama H, Ishimura E, Miki T, Tabata T, Nıshizawa Y (2002) Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J Am Soc Nephrol 13:1894–1900PubMedCrossRefGoogle Scholar
  10. 10.
    Lai HL, Kartal J, Mitsnefes MM (2007) Hyperinsulinemia in pediatric patients with chronic kidney disease: the role of tumor necrosis factor-α. Pediatr Nephrol 22:1751–1756PubMedCrossRefGoogle Scholar
  11. 11.
    Lidbland YT, Axelsson J, Barany P, Celsi G, Lindholm B, Qureshi AR, Carrea A, Canepa A (2008) Hyperinsulinemia and insulin resistance, early cardiovascular risk factors in children with chronic kidney disease. Blood Purif 26:518–525CrossRefGoogle Scholar
  12. 12.
    Mak RH (1998) Insulin, branched-chain amino acids, and growth failure in uremia. Pediatr Nephrol 12:637–642PubMedCrossRefGoogle Scholar
  13. 13.
    Shishido S, Sato H, Asanuma H, Shindo M, Hataya H, Ishikura K, Hamasaki Y, Goto M, Ikeda M, Honda M (2006) Unexpectedly high prevalence of pretransplant abnormal glucose tolerance in pediatric kidney transplant recipients. Pediatr Transplant 10:67–73PubMedCrossRefGoogle Scholar
  14. 14.
    Mak RH, Haycock GB, Chantler C (1983) Glucose intolerance in children with chronic renal failure. Kidney Int 15[Suppl 1]:S22–S26Google Scholar
  15. 15.
    Greenspan LC, Gitelman SE, Leung MA, Glidden DV, Mathias RS (2002) Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis. Pediatr Nephrol 17:1–5PubMedCrossRefGoogle Scholar
  16. 16.
    Prokai A, Fekete A, Kis E, Reusz GS, Sallay P, Korner A, Wagner L, Tulassay T, Szabo AJ (2008) Post-transplant diabetes mellitus in children following renal transplantation. Pediatr Transplant 12:643–649PubMedCrossRefGoogle Scholar
  17. 17.
    Schwartz GJ, Gauthier B (1985) A simple estimate of glomerular filtration rate in adolescent boys. J Pediatr 106:522–526PubMedCrossRefGoogle Scholar
  18. 18.
    Neyzi O, And Rzej F, Bundak R, Gunoz H, Darendeliler F, Bas F (2006) Growth references for Turkish children aged 6 to 18 years. Acta Pediatr 95:1635–1641CrossRefGoogle Scholar
  19. 19.
    Bundak R, Furman A, Gunoz H, Darendeliler F, Bas F, Neyzi O (2006) Body mass index references for Turkish children. Acta Pediatr 95:194–198CrossRefGoogle Scholar
  20. 20.
    American Diabetes Association (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33[Suppl 1]:62–69CrossRefGoogle Scholar
  21. 21.
    Matsumoto K, Miyake S, Yano M, Ueki Y, Yamaguchi Y, Akazawa S, Tominaga Y (1997) Glucose tolerance, insulin secretion, and insulin sensitivity in nonobese and obese Japanese subjects. Diabetes Care 20:1562–1568PubMedCrossRefGoogle Scholar
  22. 22.
    D’Annunzio G, Vanelli M, Pistorio A, Minuto N, Bergamino L, Iafusco D, Lorini R, Diabetes Study Group of the Italian Society for Pediatric Endocrinology and Diabetes (ISPED) (2009) Insulin resistance and secretion indexes in healthy Italian children and adolescents: a multicenter study. Acta Biomed 80:21–28PubMedGoogle Scholar
  23. 23.
    National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRefGoogle Scholar
  24. 24.
    Sahn DJ, De Maria A, Kisslo J, Weyman A (1978) Recommendations regarding quantification in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 58:1072–1083PubMedGoogle Scholar
  25. 25.
    Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. J Am Coll Cardiol 57:450–458Google Scholar
  26. 26.
    De Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Diviitis O, Alderman MH (1992) Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol 20:1251–1260PubMedCrossRefGoogle Scholar
  27. 27.
    De Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH (1995) Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol 25:1056–1062PubMedCrossRefGoogle Scholar
  28. 28.
    Jourdan C, Wühl E, Litwin M, Fahr K, Trelewicz J, Jobs K, Schenk JP, Grenda R, Mehls O, Tröger J, Schaefer F (2005) Normative values for intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens 23:1707–1715PubMedCrossRefGoogle Scholar
  29. 29.
    Amendt P, Filler G (2000) Glucose metabolism in children with renal failure: oral or intravenous glucose tolerance. Exp Clin Endocrinol Diabetes 108:253–258PubMedCrossRefGoogle Scholar
  30. 30.
    Mak RH (2008) Insulin and its role in chronic kidney disease. Pediatr Nephrol 23:355–362PubMedCrossRefGoogle Scholar
  31. 31.
    Mak RH, Ikizler AT, Kovesdy CP, Raj DS, Stenvinkel P, Kalantar-Zadeh K (2011) Wasting in chronic kidney disease. J Cachexia Sarcopenia Muscle 2:9–25PubMedCrossRefGoogle Scholar
  32. 32.
    Siew ED, Pupim LB, Majchrzak KM, Shintani A, Flakol PJ, Ikizler TA (2007) Insulin resistance is associated with skeletal muscle protein breakdown in non-diabetic chronic hemodialysis patients. Kidney Int 71:146–152PubMedCrossRefGoogle Scholar
  33. 33.
    Alvestrand A, Mujagic M, Wajngot A (1989) Glucose intolerance in uremic patients: the relative contributions of impaired beta-cell function and insulin resistance. Clin Nephrol 31:175–183PubMedGoogle Scholar
  34. 34.
    Buyan N, Bideci A, Ozkaya O, Ortac E, Bakkaloglu S, Gonen S, Peru H, Soylemezoglu O, Cinaz P (2006) Leptin and resistin levels and their relationships with glucose metabolism in children with chronic renal insufficiency and undergoing dialysis. Nephrology 11:192–196PubMedCrossRefGoogle Scholar
  35. 35.
    Mak RH (1985) The influence of hyperparathyroidism on glucose metabolism in uremia. J Clin Endocrinol Metab 60:229–233PubMedCrossRefGoogle Scholar
  36. 36.
    Mak RH (1998) 1,25-Dihydroxyvitamin D3 corrects insulin and lipid abnormalities in uremia. Kidney Int 53:1353–1357PubMedCrossRefGoogle Scholar
  37. 37.
    Mak RH (1998) Effect of metabolic acidosis on insulin action and secretion in uremia. Kidney Int 54:603–607PubMedCrossRefGoogle Scholar
  38. 38.
    Mak RH (1996) Correction of anemia by erthyropoietin reverses insulin resistance and hyperinsulinemia in uremia. Am J Physiol 270:F839–F894PubMedGoogle Scholar
  39. 39.
    Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, Cameron AJ, Dwyer T, Taylor HR, Tonkin AM, Wong TY, McNeil J, Shaw JE (2007) Risk of cardiovascular and all-cause mortality in individuals with diabetes-mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation 116:151–157PubMedCrossRefGoogle Scholar
  40. 40.
    Brohall G, Oden A, Fogerberg B (2006) Carotid artery intima-media thickness in patients with Type 2 diabetes mellitus and impaired glucose intolerance: a systematic review. Diabet Med 23:609–616PubMedCrossRefGoogle Scholar
  41. 41.
    Hanefeld M, Temelkova-Kurktschiev T, Schaper F, Henkel E, Siegert G, Koehler C (1999) Impaired fasting glucose is not a risk factor for atherosclerosis. Diabet Med 16:212–218PubMedCrossRefGoogle Scholar
  42. 42.
    Oh J, Wunsch W, Turzer M, Bahner M, Raggi P, Querfeld U, Mehls O, Schaefer F (2002) Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 106:100–105PubMedCrossRefGoogle Scholar
  43. 43.
    Litwin M, Wühl E, Jourdan C, Trelewicz J, Niemiska A, Fahr K, Jobs K, Grenda R, Wawer ZT, Rajszys P, Tröger J, Mehls O, Schaefer F (2005) Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation. J Am Soc Nephrol 16:1494–1500PubMedCrossRefGoogle Scholar
  44. 44.
    Civilibal M, Caliskan S, Adaletli I, Oflaz H, Sever L, Candan C, Canpolat N, Kasapcopur O, Kuruoglu S, Arisoy N (2006) Coronary artery calcifications in children with end-stage renal disease. Pediatr Nephrol 21:1426–1433PubMedCrossRefGoogle Scholar
  45. 45.
    Drüeke T, Witko-Sarsat V, Massy Z, Descamps-Latcha B, Guerin AP, Marchais SJ, Gausson V, London GM (2002) Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation 106:2212–2217PubMedCrossRefGoogle Scholar
  46. 46.
    Kalantar-Zadeh K, Rodriguez RA, Humphreys MH (2004) Association between serum ferritin and measures of inflammation, nutrition and iron in hemodialysis patients. Nephrol Dial Transplant 19:141–149PubMedCrossRefGoogle Scholar
  47. 47.
    Stenvinkel P, Heimburger O, Paultre F, Dıczfalusy U, Wang T, Berglund L, Jogestrand T (1999) Strong association between malnutrition, inflammation and atherosclerosis in chronic renal failure. Kidney Int 55:648–658CrossRefGoogle Scholar
  48. 48.
    Mitsnefes MM, Daniels SR, Schwartz SM, Meyer RA, Khoury P, Strife CF (2000) Severe left ventricular hypertrophy in pediatric dialysis: prevalence and predictors. Pediatr Nephrol 14:898–902PubMedCrossRefGoogle Scholar
  49. 49.
    Mitsnefes M, Flynn J, Cohn S, Samuels J, Blydt-Hansen T, Saland J, Kimball T, Furth S, Warady B, for the CKiD study group (2010) Masked hypertension associates with left ventricular hypertrophy in children with CKD. J Am Soc Nephrol 21:137–144PubMedCrossRefGoogle Scholar
  50. 50.
    Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2005) Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism. J Am Soc Nephrol 16:2796–2803PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2011

Authors and Affiliations

  • Nur Canpolat
    • 1
    Email author
  • Salim Caliskan
    • 1
  • Lale Sever
    • 1
  • Alper Guzeltas
    • 2
  • Fatih Kantarci
    • 3
  • Cengiz Candan
    • 1
  • Mahmut Civilibal
    • 1
  • Ozgur Kasapcopur
    • 1
  • Nil Arisoy
    • 1
  1. 1.Department of Pediatric Nephrology, Cerrahpasa Faculty of MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Department of Pediatric Cardiology, Cerrahpasa Faculty of MedicineIstanbul UniversityIstanbulTurkey
  3. 3.Department of Radiology, Cerrahpasa Faculty of MedicineIstanbul UniversityIstanbulTurkey

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