Pediatric Nephrology

, Volume 26, Issue 3, pp 365–375 | Cite as

Microvascular disease in children and adolescents with type 1 diabetes and obesity

Educational Review


The incidence of type 1 diabetes (T1D) is increasing worldwide and is associated with a significant burden, mainly related to the development of vascular complications. Over the last decades, concomitant with the epidemic of childhood obesity, there has been an increasing number of cases of type 2 diabetes (T2D) among children and adolescents. Microvascular complications of diabetes, which include nephropathy, retinopathy and neuropathy, are characterized by damage to the microvasculature of the kidney, retina and neurons. Although clinically evident microvascular complications are rarely seen among children and adolescents with diabetes, there is clear evidence that their pathogenesis and early signs develop during childhood and accelerate during puberty. Diabetic vascular complications are often asymptomatic during their early stages, and once symptoms develop, there is little to be done to cure them. Therefore, screening needs to be started early during adolescence and, in the case of T2D, already at diagnosis. Identification of risk factors and subclinical signs of complications is essential for the early implementation of preventive and therapeutic strategies, which could change the course of vascular complications and improve the prognosis of children, adolescents and young adults with diabetes.


Microvascular complications Type 1 diabetes Type 2 diabetes Children Adolescents 


  1. 1.
    Daneman D (2006) Type 1 diabetes. Lancet 367:847–858PubMedCrossRefGoogle Scholar
  2. 2.
    Gungor N, Hannon T, Libman I, Bacha F, Arslanian S (2005) Type 2 diabetes mellitus in youth: the complete picture to date. Pediatr Clin North Am 52:1579–1609PubMedCrossRefGoogle Scholar
  3. 3.
    Orchard TJ (1994) From diagnosis and classification to complications and therapy. DCCT. Part II? Diabetes Control and Complications Trial. Diabetes Care 17:326–338Google Scholar
  4. 4.
    Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF (2003) Lifetime risk for diabetes mellitus in the United States. JAMA 290:1884–1890PubMedCrossRefGoogle Scholar
  5. 5.
    International Diabetes Federation (2007) International Diabetes Federation diabetes atlas. Available at:
  6. 6.
    Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G (2009) Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet 373:2027–2033PubMedCrossRefGoogle Scholar
  7. 7.
    Daneman D (2005) Early diabetes-related complications in adolescents: risk factors and screening. Horm Res 63:75–85PubMedCrossRefGoogle Scholar
  8. 8.
    Rossing P (2006) Prediction, progression and prevention of diabetic nephropathy. The Minkowski Lecture 2005. Diabetologia 49:11–19PubMedCrossRefGoogle Scholar
  9. 9.
    US Renal Data System (2005) US Renal system: annual data report 2005. Available at
  10. 10.
    Tuomilehto J, Borch-Johnsen K, Molarius A, Forsen T, Rastenyte D, Sarti C, Reunanen A (1998) Incidence of cardiovascular disease in Type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland. Diabetologia 41:784–790PubMedCrossRefGoogle Scholar
  11. 11.
    Rossing P, Hougaard P, Borch-Johnsen K, Parving HH (1996) Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study. Br Med J 313:779–784Google Scholar
  12. 12.
    Viberti GC, Jarrett RJ, Keen H (1982) Microalbuminuria as prediction of nephropathy in diabetics. Lancet 2:611PubMedCrossRefGoogle Scholar
  13. 13.
    Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93PubMedCrossRefGoogle Scholar
  14. 14.
    Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS (2003) Regression of microalbuminuria in type 1 diabetes. N Engl J Med 348:2285–2293PubMedCrossRefGoogle Scholar
  15. 15.
    Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH (2004) Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. Br Med J 328:1105CrossRefGoogle Scholar
  16. 16.
    The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986Google Scholar
  17. 17.
    Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462PubMedCrossRefGoogle Scholar
  18. 18.
    Nordwall M, Bojestig M, Arnqvist HJ, Ludvigsson J (2004) Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes-the Linkoping Diabetes Complications Study. Diabetologia 47:1266–1272PubMedCrossRefGoogle Scholar
  19. 19.
    Mohsin F, Craig ME, Cusumano J, Chan AK, Hing S, Lee JW, Silink M, Howard NJ, Donaghue KC (2005) Discordant trends in microvascular complications in adolescents with type 1 diabetes from 1990 to 2002. Diabetes Care 28:1974–1980CrossRefGoogle Scholar
  20. 20.
    Tryggvason G, Indridason OS, Thorsson AV, Hreidarsson AB, Palsson R (2005) Unchanged incidence of diabetic nephropathy in Type 1 diabetes: a nation-wide study in Iceland. Diabet Med 22:182–187PubMedCrossRefGoogle Scholar
  21. 21.
    Amin R, Widmer B, Dalton RN, Dunger DB (2009) Unchanged incidence of microalbuminuria in children with type 1 diabetes since 1986: a UK based inception cohort. Arch Dis Child 94:258–262PubMedCrossRefGoogle Scholar
  22. 22.
    Nordwall M, Arnqvist HJ, Bojestig M, Ludvigsson J (2009) Good glycemic control remains crucial in prevention of late diabetic complications–the Linkoping Diabetes Complications Study. Pediatr Diabetes 10:168–176PubMedCrossRefGoogle Scholar
  23. 23.
    Mogensen CE (1999) Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia 42:263–285PubMedCrossRefGoogle Scholar
  24. 24.
    Jones CA, Leese GP, Kerr S, Bestwick K, Isherwood DI, Vora JP, Hughes DA, Smith C (1998) Development and progression of microalbuminuria in a clinic sample of patients with insulin dependent diabetes mellitus. Arch Dis Child 78:518–523PubMedCrossRefGoogle Scholar
  25. 25.
    Gorman D, Sochett E, Daneman D (1999) The natural history of microalbuminuria in adolescents with type 1 diabetes. J Pediatr 134:333–337PubMedCrossRefGoogle Scholar
  26. 26.
    Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, Marcovecchio L, Neil A, Dalton RN, Dunger DB (2008) Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ 336:697–701CrossRefGoogle Scholar
  27. 27.
    Schultz CJ, Neil HA, Dalton RN, Dunger DB (2000) Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes. Diabetes Care 23:1811–1815CrossRefGoogle Scholar
  28. 28.
    Gilbert RE, Tsalamandris C, Bach LA, Panagiotopoulos S, O'Brien RC, Allen TJ, Goodall I, Young V, Seeman E, Murray RM, Cooper ME, Jerums G (1993) Long-term glycemic control and the rate of progression of early diabetic kidney disease. Kidney Int 44:855–859PubMedCrossRefGoogle Scholar
  29. 29.
    Ciulla TA, Amador AG, Zinman B (2003) Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care 26:2653–2664CrossRefGoogle Scholar
  30. 30.
    Klein R, Klein BE, Moss SE, Cruickshanks KJ (1998) The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 105:1801–1815PubMedCrossRefGoogle Scholar
  31. 31.
    Donaghue KC, Craig ME, Chan AK, Fairchild JM, Cusumano JM, Verge CF, Crock PA, Hing SJ, Howard NJ, Silink M (2005) Prevalence of diabetes complications 6 years after diagnosis in an incident cohort of childhood diabetes. Diabet Med 22:711–718PubMedCrossRefGoogle Scholar
  32. 32.
    Nordwall M, Hyllienmark L, Ludvigsson J (2006) Early diabetic complications in a population of young patients with type 1 diabetes mellitus despite intensive treatment. J Pediatr Endocrinol Metab 19:45–54PubMedGoogle Scholar
  33. 33.
    Maguire A, Chan A, Cusumano J, Hing S, Craig M, Silink M, Howard N, Donaghue K (2005) The case for biennial retinopathy screening in children and adolescents. Diabetes Care 28:509–513CrossRefGoogle Scholar
  34. 34.
    Trotta D, Verrotti A, Salladini C, Chiarelli F (2004) Diabetic neuropathy in children and adolescents. Pediatr Diabetes 5:44–57PubMedCrossRefGoogle Scholar
  35. 35.
    Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D (2005) Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28:956–962CrossRefGoogle Scholar
  36. 36.
    Marshall SM (2004) Recent advances in diabetic nephropathy. Clin Med (London, England) 4:277–282Google Scholar
  37. 37.
    Girach A, Vignati L (2006) Diabetic microvascular complications—can the presence of one predict the development of another? J Diabetes Complications 20:228–237PubMedCrossRefGoogle Scholar
  38. 38.
    Schalkwijk CG, Stehouwer CD (2005) Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond) 109:143–159CrossRefGoogle Scholar
  39. 39.
    Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32:219–226PubMedCrossRefGoogle Scholar
  40. 40.
    Stehouwer CD, Lambert J, Donker AJ, van Hinsbergh VW (1997) Endothelial dysfunction and pathogenesis of diabetic angiopathy. Cardiovasc Res 34:55–68PubMedCrossRefGoogle Scholar
  41. 41.
    Satchell SC, Tooke JE (2008) What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia 51:714–725PubMedCrossRefGoogle Scholar
  42. 42.
    Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH (2003) Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia 46:1402–1407PubMedCrossRefGoogle Scholar
  43. 43.
    Marcovecchio ML, Giannini C, Widmer B, Dalton RN, Martinotti S, Chiarelli F, Dunger DB (2008) C-reactive protein in relation to the development of microalbuminuria in type 1 diabetes: the Oxford Regional Prospective Study. Diabetes Care 31:974–976CrossRefGoogle Scholar
  44. 44.
    Diabetes Control and Complications Trial Research Group (1994) Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. J Pediatr 125:177–188Google Scholar
  45. 45.
    The Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2002) Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 287:2563–2569Google Scholar
  46. 46.
    White NH, Sun W, Cleary PA, Tamborlane WV, Danis RP, Hainsworth DP, Davis MD (2010) Effect of prior intensive therapy in type 1 diabetes on 10-year progression of retinopathy in the DCCT/EDIC: comparison of adults and adolescents. Diabetes 59:1244–1253PubMedCrossRefGoogle Scholar
  47. 47.
    Marcovecchio ML, Dalton RN, Schwarze CP, Prevost AT, Neil HA, Acerini CL, Barrett T, Cooper JD, Edge J, Shield J, Widmer B, Todd JA, Dunger DB (2009) Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes. Diabetologia 52:1173–1181PubMedCrossRefGoogle Scholar
  48. 48.
    Gallego PH, Craig ME, Hing S, Donaghue KC (2008) Role of blood pressure in development of early retinopathy in adolescents with type 1 diabetes: prospective cohort study. Br Med J (Clinical research edn) 337:a918CrossRefGoogle Scholar
  49. 49.
    Tesfaye S, Stevens LK, Stephenson JM, Fuller JH, Plater M, Ionescu-Tirgoviste C, Nuber A, Pozza G, Ward JD (1996) Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia 39:1377–1384PubMedCrossRefGoogle Scholar
  50. 50.
    Abraha A, Schultz C, Konopelska-Bahu T, James T, Watts A, Stratton IM, Matthews DR, Dunger DB (1999) Glycaemic control and familial factors determine hyperlipidaemia in early childhood diabetes. Oxford Regional Prospective Study of Childhood Diabetes. Diabet Med 16:598-604Google Scholar
  51. 51.
    Bonnet F, Cooper ME (2000) Potential influence of lipids in diabetic nephropathy: insights from experimental data and clinical studies. Diabetes Metab 26:254–264PubMedGoogle Scholar
  52. 52.
    Marcovecchio ML, Dalton RN, Prevost AT, Acerini CL, Barrett TG, Cooper JD, Edge J, Neil A, Shield J, Widmer B, Todd JA, Dunger DB (2009) Prevalence of abnormal lipid profiles and the relationship with the development of microalbuminuria in adolescents with type 1 diabetes. Diab Care 32:658–663CrossRefGoogle Scholar
  53. 53.
    Caprio S, Plewe G, Diamond MP, Simonson DC, Boulware SD, Sherwin RS, Tamborlane WV (1989) Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J Pediatr 114:963–967PubMedCrossRefGoogle Scholar
  54. 54.
    Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV (1986) Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 315:215–219PubMedCrossRefGoogle Scholar
  55. 55.
    Holl RW, Swift PG, Mortensen HB, Lynggaard H, Hougaard P, Aanstoot HJ, Chiarelli F, Daneman D, Danne T, Dorchy H, Garandeau P, Greene S, Hoey HM, Kaprio EA, Kocova M, Martul P, Matsuura N, Robertson KJ, Schoenle EJ, Sovik O, Tsou RM, Vanelli M, Aman J (2003) Insulin injection regimens and metabolic control in an international survey of adolescents with type 1 diabetes over 3 years: results from the Hvidore study group. Eur J Pediatr 162:22–29PubMedCrossRefGoogle Scholar
  56. 56.
    Orchard TJ, Dorman JS, Maser RE, Becker DJ, Drash AL, Ellis D, LaPorte RE, Kuller LH (1990) Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes 39:1116–1124PubMedCrossRefGoogle Scholar
  57. 57.
    Coonrod BA, Ellis D, Becker DJ, Bunker CH, Kelsey SF, Lloyd CE, Drash AL, Kuller LH, Orchard TJ (1993) Predictors of microalbuminuria in individuals with IDDM. Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 16:1376–1383CrossRefGoogle Scholar
  58. 58.
    Donaghue KC, Fairchild JM, Craig ME, Chan AK, Hing S, Cutler LR, Howard NJ, Silink M (2003) Do all prepubertal years of diabetes duration contribute equally to diabetes complications? Diabetes Care 26:1224–1229CrossRefGoogle Scholar
  59. 59.
    Hietala K, Harjutsalo V, Forsblom C, Summanen P, Groop PH (2010) Age at onset and the risk of proliferative retinopathy in type 1 diabetes. Diabetes Care 33:1315–1319CrossRefGoogle Scholar
  60. 60.
    Schultz CJ, Konopelska-Bahu T, Dalton RN, Carroll TA, Stratton I, Gale EA, Neil A, Dunger DB (1999) Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group. Diabetes Care 22:495–502CrossRefGoogle Scholar
  61. 61.
    The Diabetes Control and Complications Trial Research Group (1997) Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. Diabetes 46:1829-1839Google Scholar
  62. 62.
    Seaquist ER, Goetz FC, Rich S, Barbosa J (1989) Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 320:1161–1165PubMedCrossRefGoogle Scholar
  63. 63.
    Marcovecchio ML, Tossavainen PH, Acerini CL, Barrett TG, Edge J, Neil A, Shield J, Widmer B, Dalton RN, Dunger DB (2010) Maternal but not paternal association of ambulatory blood pressure with albumin excretion in young offspring with type 1 diabetes. Diabetes Care 33:366–371CrossRefGoogle Scholar
  64. 64.
    Chase HP, Garg SK, Marshall G, Berg CL, Harris S, Jackson WE, Hamman RE (1991) Cigarette smoking increases the risk of albuminuria among subjects with type I diabetes. JAMA 265:614–617PubMedCrossRefGoogle Scholar
  65. 65.
    Mohamed Q, Gillies MC, Wong TY (2007) Management of diabetic retinopathy: a systematic review. JAMA 298:902–916PubMedCrossRefGoogle Scholar
  66. 66.
    Waden J, Forsblom C, Thorn LM, Saraheimo M, Rosengard-Barlund M, Heikkila O, Hietala K, Ong K, Wareham N, Groop PH (2009) Adult stature and diabetic complications in patients with type 1 diabetes. Diabetes 58:1914–1920PubMedCrossRefGoogle Scholar
  67. 67.
    Donaghue KC, Chiarelli F, Trotta D, Allgrove J, Dahl-Jorgensen K (2007) ISPAD clinical practice consensus guidelines 2006-2007. Microvascular and macrovascular complications. Pediatr Diabetes 8:163–170PubMedCrossRefGoogle Scholar
  68. 68.
    Almerie MQ, Williams RM, Acerini CL (2008) Should Angiotensin converting enzyme inhibitors be used in children with type 1 diabetes and microalbuminuria? Arch Dis Child 93:633–635PubMedCrossRefGoogle Scholar
  69. 69.
    Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM (2010) Prevalence of high body mass index in US children and adolescents, 2007–2008. JAMA 303:242–249PubMedCrossRefGoogle Scholar
  70. 70.
    Wang Y, Lobstein T (2006) Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 1:11–25PubMedCrossRefGoogle Scholar
  71. 71.
    Cali AM, Caprio S (2008) Obesity in children and adolescents. J Clin Endocrinol Metab 93:S31–S36PubMedCrossRefGoogle Scholar
  72. 72.
    Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA (1998) Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl Med 338:1650–1656PubMedCrossRefGoogle Scholar
  73. 73.
    Alberti G, Zimmet P, Shaw J, Bloomgarden Z, Kaufman F, Silink M (2004) Type 2 diabetes in the young: the evolving epidemic: the international diabetes federation consensus workshop. Diabetes Care 27:1798–1811CrossRefGoogle Scholar
  74. 74.
    Savino A, Pelliccia P, Chiarelli F, Mohn A (2010) Obesity-related renal injury in childhood. Horm Res Paediatr 73:303–311PubMedCrossRefGoogle Scholar
  75. 75.
    Cheung N, Wong TY (2007) Obesity and eye diseases. Surv Ophthalmol 52:180–195PubMedCrossRefGoogle Scholar
  76. 76.
    Grassi G, Dell'Oro R, Facchini A, Quarti Trevano F, Bolla GB, Mancia G (2004) Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. J Hypertens 22:2363–2369PubMedCrossRefGoogle Scholar
  77. 77.
    Rabbia F, Silke B, Conterno A, Grosso T, De Vito B, Rabbone I, Chiandussi L, Veglio F (2003) Assessment of cardiac autonomic modulation during adolescent obesity. Obes Res 11:541–548PubMedCrossRefGoogle Scholar
  78. 78.
    Riva P, Martini G, Rabbia F, Milan A, Paglieri C, Chiandussi L, Veglio F (2001) Obesity and autonomic function in adolescence. Clin Exp Hypertens 23:57–67PubMedCrossRefGoogle Scholar
  79. 79.
    Pinhas-Hamiel O, Zeitler P (2007) Acute and chronic complications of type 2 diabetes mellitus in children and adolescents. Lancet 369:1823–1831PubMedCrossRefGoogle Scholar
  80. 80.
    Dean HJ, Sellers EA (2007) Comorbidities and microvascular complications of type 2 diabetes in children and adolescents. Pediatr Diabetes 8[Suppl 9]:35–41PubMedCrossRefGoogle Scholar
  81. 81.
    Yokoyama H, Okudaira M, Otani T, Sato A, Miura J, Takaike H, Yamada H, Muto K, Uchigata Y, Ohashi Y, Iwamoto Y (2000) Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan. Kidney Int 58:302–311PubMedCrossRefGoogle Scholar
  82. 82.
    Ettinger LM, Freeman K, DiMartino-Nardi JR, Flynn JT (2005) Microalbuminuria and abnormal ambulatory blood pressure in adolescents with type 2 diabetes mellitus. J Pediatr 147:67–73PubMedCrossRefGoogle Scholar
  83. 83.
    Eppens MC, Craig ME, Cusumano J, Hing S, Chan AK, Howard NJ, Silink M, Donaghue KC (2006) Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes. Diab Care 29:1300–1306Google Scholar
  84. 84.
    Pavkov ME, Bennett PH, Knowler WC, Krakoff J, Sievers ML, Nelson RG (2006) Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. JAMA 296:421–426Google Scholar
  85. 85.
    Krakoff J, Lindsay RS, Looker HC, Nelson RG, Hanson RL, Knowler WC (2003) Incidence of retinopathy and nephropathy in youth-onset compared with adult-onset type 2 diabetes. Diabetes Care 26:76–81Google Scholar

Copyright information

© IPNA 2010

Authors and Affiliations

  • M. Loredana Marcovecchio
    • 1
  • Francesco Chiarelli
    • 1
  1. 1.Department of PaediatricsUniversity of ChietiChietiItaly

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