Seminars in Pediatric Neurology
Volume 12, Issue 3 , Pages 178-186 , September 2005

Complications of Diabetes Mellitus in Childhood

  • Sarah J. Glastras, MBBS (Hons), BSc Psychol (Hons)

      Affiliations

    • Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia.
  • ,
  • Fauzia Mohsin, MBBS (FCPS)

      Affiliations

    • Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia.
  • ,
  • Kim C. Donaghue, MBBS, PhD (FRACP)

      Affiliations

    • Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia.
    • Department of Medicine, University of Sydney, NSW 2006, Sydney, Australia.
    • Corresponding Author InformationCorresponding author. Kim C. Donaghue, Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia.

References 

  1. Nishikawa T , Edelstein D , Brownlee M . The missing link (a single unifying mechanism for diabetic complications) . Kidney Int . 2000;77:S26–S30
  2. Gabbay KH . Hyperglycemia, polyol metabolism, and complications of diabetes mellitus . Annu Rev Med . 1975;26:521–536
  3. Giugliano D , Ceriello A , Paolisso G . Oxidative stress and diabetic vascular complications . Diabetes Care . 1996;19:257–267
  4. DCCT Research Group . 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 . 1993;329:977–986
  5. Klein R , Klein BE , Moss SE , et al.   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 . 1998;105:1801–1815
  6. DCCT Research Group . 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 . 1994;125:177–188
  7. White NH , Cleary PA , Dahms W , et al.   Beneficial effects of intensive therapy of diabetes during adolescence (outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT)) . J Pediatr . 2001;139:804–812
  8. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group . Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus . JAMA . 2002;287:2563–2569
  9. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group . Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy (the Epidemiology of Diabetes Interventions and Complications (EDIC) study) . JAMA . 2003;290:2159–2167
  10. DCCT/Epidemiology of Diabetes Interventions and Complications Research Group . Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy . N Engl J Med . 2000;342:381–389
  11. Rossing P , Hougaard P , Parving HH . Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients (a 10-year prospective observational study) . Diabetes Care . 2002;25:859–864
  12. Kostraba JN , Dorman JS , Orchard TJ , et al.   Contribution of diabetes duration before puberty to development of microvascular complications in IDDM subjects . Diabetes Care . 1989;12:686–693
  13. Donaghue KC , Fairchild JM , Craig ME , et al.   Do all prepubertal years of diabetes duration contribute equally to diabetes complications? . Diabetes Care . 2003;26:1224–1229
  14. Chaturvedi N , Sjoelie AK , Porta M , et al.   Markers of insulin resistance are strong risk factors for retinopathy incidence in type 1 diabetes . Diabetes Care . 2001;24:284–289
  15. Chew EY , Klein ML , Ferris FL , et al.   Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy (Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22) . Arch Ophthalmol . 1996;114:1079–1084
  16. Kordonouri O , Danne T , Hopfenmuller W , et al.   Lipid profiles and blood pressure (are they risk factors for the development of early background retinopathy and incipient nephropathy in children with insulin-dependent diabetes mellitus?) . Acta Paediatr . 1996;85:43–48
  17. Lloyd CE , Klein R , Maser RE , et al.   The progression of retinopathy over 2 years (the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study) . J Diabetes Complications . 1995;9:140–148
  18. Rossing P , Rossing K , Jacobsen P , et al.   Unchanged incidence of diabetic nephropathy in IDDM patients . Diabetes . 1995;44:739–743
  19. Couper JJ , Staples AJ , Cocciolone R , et al.   Relationship of smoking and albuminuria in children with insulin-dependent diabetes . Diabet Med . 1994;11:666–669
  20. Chase HP , Garg SK , Marshall G , et al.   Cigarette smoking increases the risk of albuminuria among subjects with type 1 diabetes . JAMA . 1991;265:614–617
  21. Scott LJ , Warram JH , Hanna LS , et al.   A nonlinear effect of hyperglycemia and current cigarette smoking are major determinants of the onset of microalbuminuria in type 1 diabetes . Diabetes . 2001;50:2842–2849
  22. Diabetes Drafting Group . Prevalence of small vessel and large vessel disease in diabetic patients from 14 centres (the World Health Organisation multinational study of vascular disease in diabetics) . Diabetologia . 1985;28:615–640
  23. West KM , Ahuja MM , Bennett PH , et al.   Interrelationships of microangiopathy, plasma glucose and other risk factors in 3583 diabetic patients (a multinational study) . Diabetologia . 1982;22:412–420
  24. Moss SE , Klein R , Klein BE . Cigarette smoking and ten-year progression of diabetic retinopathy . Ophthalmology . 1996;103:1438–1442
  25. Klein R , Klein BE , Moss SE , et al.   The Wisconsin Epidemiologic Study of Diabetic Retinopathy. IX, Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years . Arch Ophthalmol . 1989;107:237–243
  26. Kohner EM , Dollery CT . The rate of formation and disappearance of microaneurysms in diabetic retinopathy . Trans Ophthalmol Soc U K . 1970;90:369–374
  27. Diabetic Retinopathy Study . Photocoagulation treatment of proliferative diabetic retinopathy (the second report of diabetic retinopathy study findings) . Ophthalmology . 1978;85:82–106
  28. Klein R , Klein BE , Moss SE , et al.   The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years . Arch Ophthalmol . 1984;102:520–526
  29. Fairchild JM , Hing SJ , Donaghue KC , et al.   Prevalence and risk factors for retinopathy in adolescents with type 1 diabetes . Med J Aust . 1994;160:757–762
  30. Maguire A , Chan A , Cusumano J , et al.   The case for biennial retinopathy screening in children and adolescents . Diabetes Care . 2005;28:509–513
  31. Nordwall M , Bojestig M , Arnqvist HJ , et al.   Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of type 1 diabetes (-the Linkoping Diabetes Complications Study) . Diabetologia . 2004;47:1266–1272
  32. Moss SE , Klein R , Kessler SD , et al.   Comparison between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy . Ophthalmology . 1985;92:62–67
  33. The Kroc Collaborative Study Group . Blood glucose control and the evolution of diabetic retinopathy and albuminuria (a preliminary multicenter trial) . N Engl J Med . 1984;311:365–372
  34. Group DR . Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial . Arch Ophthalmol . 1998;116:874–886
  35. Chaturvedi N , Sjolie AK , Stephenson JM , et al.   Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes: the EUCLID study group. EURODIAB controlled trial of lisinopril in insulin-dependent diabetes mellitus . Lancet . 1998;351:28–31
  36. Bailey CC , Sparrow JM , Grey RH , et al.   The National Diabetic Retinopathy Laser Treatment Audit. III. Clinical outcomes . Eye . 1999;13:151–159
  37. Ferris F . Early photocoagulation in patients with either type I or type II diabetes . Trans Am Ophthalmol Soc . 1996;94:505–537
  38. Mogensen CE , Poulsen PL . Microalbuminuria, glycemic control, and blood pressure predicting outcome in diabetes type 1 and type 2 . Kidney Int Suppl . 2004;66:S40–S41
  39. Brink SJ . Complications of pediatric and adolescent type 1 diabetes mellitus . Curr Diab Rep . 2001;1:47–55
  40. Borch-Johnsen K , Kreiner S . Proteinuria (value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus) . Br Med J (Clin Res Ed) . 1987;294:1651–1654
  41. Valdorf-Hansen F , Jensen T , Borch-Johnsen K , et al.   Cardiovascular risk factors in type I (insulin-dependent) diabetic patients with and without proteinuria . Acta Med Scand . 1987;222:439–444
  42. Bognetti E , Calori G , Meschi F , et al.   Prevalence and correlations of early microvascular complications in young type I diabetic patients (role of puberty) . J Pediatr Endocrinol . 1997;10:587–592
  43. Olsen BS , Johannesen J , Sjolie AK , et al.   Metabolic control and prevalence of microvascular complications in young Danish patients with type 1 diabetes mellitus (Danish Study Group of Diabetes in Childhood) . Diabet Med . 1999;16:79–85
  44. Roe TF , Costin G , Kaufman FR , et al.   Blood glucose control and albuminuria in type 1 diabetes mellitus . J Pediatr . 1991;119:178–182
  45. Mortensen HB , Marinelli K , Norgaard K , et al.   A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus (Danish Study Group of Diabetes in Childhood) . Diabet Med . 1990;7:887–897
  46. Dahlquist G , Rudberg S . The prevalence of microalbuminuria in diabetic children and adolescents and its relation to puberty . Acta Paediatr Scand . 1987;76:795–800
  47. Svensson M , Sundkvist G , Amqvist HJ , et al.   Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management (results from the nation-wide population-based Diabetes Incidence Study in Sweden (DISS)) . Diabetes Care . 2003;26:2903–2909
  48. Bryden KS , Dunger DB , Mayou RA , et al.   Poor prognosis of young adults with type 1 diabetes (a longitudinal study) . Diabetes Care . 2003;26:1052–1057
  49. Harvey JN , Allagoa B . The long-term renal and retinal outcome of childhood-onset type 1 diabetes . Diabet Med . 2004;21:26–31
  50. Lurbe E , Redon J , Kesani A , et al.   Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes . N Engl J Med . 2002;347:797–805
  51. Lafferty AR , Werther GA , Clarke CF . Ambulatory blood pressure, microalbuminuria, and autonomic neuropathy in adolescents with type 1 diabetes . Diabetes Care . 2000;23:533–538
  52. Poulsen PL , Hansen KW , Mogensen CE . Ambulatory blood pressure in the transition from normo- to microalbuminuria (a longitudinal study in IDDM patients) . Diabetes . 1994;43:1248–1253
  53. Schultz CJ , Neil HA , Dalton RN , et al.   Oxfom Regional Prospective Study G (risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes) . Diabetes Care . 2000;23:1811–1815
  54. Hovind P , Tarnow L , Rossing P , et al.   Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes (inception cohort study) . BMJ . 2004;328:1105–1109
  55. Rudberg S , Dahlquist G . Determinants of progression of microalbuminuria in adolescents with IDDM . Diabetes Care . 1996;19:369–371
  56. Couper JJ , Clarke CF , Byrne GC , et al.   Progression of borderline increases in albuminuria in adolescents with insulin-dependent diabetes mellitus . Diabet Med . 1997;14:766–771
  57. Bojestig M , Arnqvist HJ , Karlberg BE , et al.   Glycemic control and prognosis in type I diabetic patients with microalbuminuria . Diabetes Care . 1996;19:313–317
  58. Perkins BA , Ficociello LH , Silva KH , et al.   Regression of microalbuminuria in type I diabetes . N Engl J Med . 2003;348:2285–2293
  59. ACE Inhibitors in Diabetic Nephropathy Trialist Group . Should all patients with type I diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors?. A meta-analysis of individual patient data . Ann Intern Med . 2001;134:370–379
  60. Makino H , Nakamura Y , Wada J . Remission and regression of diabetic nephropathy . Hypertens Res . 2003;26:515–519
  61. Kofoed-Enevoldsen A , Borch-Johnsen K , Kreiner S , et al.   Declining incidence of persistent proteinuria in type I (insulin-dependent) diabetic patients in Denmark . Diabetes . 1987;36:205–209
  62. Donaghue KC , Fairchild JM , Chan A , et al.   Diabetes complication screening in 937 children and adolescents . J Pediatr Endocrinol Metab . 1999;12:185–192
  63. Mogensen CE . Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes . J Intern Med . 2003;254:45–66
  64. Meinhardt U , Ammann RA , Fluck C , et al.   Microalbuminuria in diabetes mellitus (efficacy of a new screening method in comparison with timed overnight urine collection) . J Diabetes Complications . 2003;17:254–257
  65. Cook J , Daneman D , Spino M , et al.   Angiotensin converting enzyme inhibitor therapy to decrease microalbuminuria in normotensive children with insulin-dependent diabetes mellitus . J Pediatr . 1990;117:39–45
  66. Kasiske BL , Kalil RS , Ma JZ , et al.   Effect of antihypertensive therapy on the kidney in patients with diabetes (a meta-regression analysis) . Ann Intern Med . 1993;118:129–138
  67. Lewis EJ , Hunsicker LG , et al.   The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy (the Collaborative Study Group) . N Engl J Med . 1993;329:1456–1462
  68. The EUCLID Study Group . Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria . Lancet . 1997;349:1787–1792
  69. Mathiesen ER , Hommel E , Hansen HP , et al.   Randomised controlled trial of long term efficacy of captopril on preservation of kidney function in normotensive patients with insulin dependent diabetes and microalbuminuria . BMJ . 1999;319:24–25
  70. The Microalbuminuria Captopril Study Group . Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria . Diabetologia . 1996;39:587–593
  71. Viberti G , Mogensen CE , Groop LC , et al.   Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria (European Microalbuminuria Captopril Study Group) . JAMA . 1994;271:275–279
  72. O’Hare P , Bilbous R , Mitchell T , et al.  ACE-Inhibitor Trial to Lower Albuminuria in Normotensive Insulin-Dependent Subjects Study Group   Low-dose ramipril reduces microalbuminuria in type 1 diabetic patients without hypertension (results of a randomized controlled trial) . Diabetes Care . 2000;23:1823–1829
  73. Rudberg S , Osterby R , Bangstad HJ , et al.   Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with type I (insulin-dependent) diabetes mellitus . Diabetologia . 1999;42:589–595
  74. Chiarelli F , Casani A , Verrotti A , et al.   Diabetic nephropathy in children and adolescents (a critical review with particular reference to angiotensin-converting enzyme inhibitors) . Acta Paediatr Suppl . 1998;425:42–45
  75. White NH , Waltman SR , Krupin T , et al.   Reversal of neuropathic and gastrointestinal complications related to diabetes mellitus in adolescents with improved metabolic control . J Pediatr . 1981;99:41–45
  76. Pirart J . Diabetes mellitus and its degenerative complications (a prospective study of 4,400 patients observed between 1947 and 1973) . Diabet Metab . 1977;3:173–182
  77. Hyllienmark L , Brismar T , Ludvigsson J . Subclinical nerve dysfunction in children and adolescents with IDDM . Diabetologia . 1995;38:685–692
  78. Maser RE , Becker DJ , Drash AL , et al.   Pittsburgh Epidemiology of Diabetes Complications Study (measuring diabetic neuropathy follow-up study results) . Diabetes Care . 1992;15:525–527
  79. Ewing DJ . The natural history of diabetic autonomic neuropathy . Q J Med . 1980;49:95–108
  80. Maser RE , Mitchell BD , Vinik AI , et al.   The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes (a meta-analysis) . Diabetes Care . 2003;26:1895–1901
  81. Ewing DJ , Boland O , Neilson JM , et al.   Autonomic neuropathy, QT interval lengthening, and unexpected deaths in male diabetic patients . Diabetologia . 1991;34:182–185
  82. Watkins PJ , Campbell IW , Clarke BF , et al.   Clinical observations and experiments in diabetic neuropathy . Diabetologia . 1992;35:2–11
  83. Sindrup SH , Ejlertsen B , Gjessing H , et al.   Peripheral nerve function during hyperglycemic clamping in healthy subjects . Acta Neurol Scand . 1988;78:141–145
  84. DCCT Research Group . Effect of intensive diabetes treatment on nerve conduction in the Diabetes Control and Complications Trial . Ann Neurol . 1995;38:869–880
  85. DCCT Research Group . The effect of intensive diabetes therapy on the development and progression of neuropathy . Ann Intern Med . 1995;122:561–568
  86. Davis EA , Jones TW , Walsh P , et al.   The use of biothesiometry to detect neuropathy in children and adolescents with IDDM . Diabetes Care . 1997;20:1448–1453
  87. Donaghue KC , Bonney M , Simpson JM , et al.   Autonomic and peripheral nerve function in adolescents with and without diabetes . Diabet Med . 1993;10:664–671
  88. Sosenko JM , Kato M , Soto R , et al.   Comparison of quantitative sensory-threshold measures for their association with foot ulceration in diabetic patients . Diabetes Care . 1990;13:1057–1061
  89. Coppini DV , Young PJ , Weng C , et al.   Outcome on diabetic foot complications in relation to clinical examination and quantitative sensory testing (a case-control study) . Diabet Med . 1998;15:765–771
  90. Veves A , Murray HJ , Young MJ , et al.   The risk of foot ulceration in diabetic patients with high foot pressure (a prospective study) . Diabetologia . 1992;35:660–663
  91. Duffin AC , Donaghue KC , Potter M , et al.   Limited joint mobility in the hands and feet of adolescents with type 1 diabetes mellitus . Diabet Med . 1999;16:125–130
  92. Duffin AC , Kidd R , Chan A , et al.   High plantar pressure and callus in diabetic adolescents (incidence and treatment) . J Am Podiatr Med Assoc . 2003;93:214–220
  93. Steel JM , Young RJ , Lloyd GG , et al.   Clinically apparent eating disorders in young diabetic women (associations with painful neuropathy and other complications) . Br Med J (Clin Res Ed) . 1987;294:859–862
  94. Nakayama M , Nakamura J , Hamada Y , et al.   Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy . Diabetes Care . 2001;24:1093–1098
  95. Sosenko JM , Breslow JL , Miettinen OS , et al.   Hyperglycemia and plasma lipid levels (a prospective study of young insulin-dependent diabetic patients) . N Engl J Med . 1980;302:650–654
  96. Lopes-Virella MF , Wohltmann HJ , Loadholt CB , et al.   Plasma lipids and lipoproteins in young insulin-dependent diabetic patients (relationship with control) . Diabetologia . 1981;21:216–223
  97. Lyons TJ , Jenkins AJ . Lipoprotein glycation and its metabolic consequences . Curr Opin Lipidol . 1997;8:174–180
  98. Jenkins AJ , Best JD , Klein RL , et al.   Lipoproteins, glycoxidation and diabetic angiopathy . Diabetes Metab Res Rev . 2004;20:349–368
  99. de Jongh S , Ose L , Szamosi T , et al.   Efficacy and safety of statin therapy in children with familial hypercholesterolemia (a randomized, double-blind, placebo-controlled trial with simvastatin) . Circulation . 2002;106:2231–2237
  100. Larsen J , Brekke M , Sandvik L , et al.   Silent coronary atheromatosis in type 1 diabetic patients and its relation to long-term glycemic control . Diabetes . 2002;51:2637–2641
  101. Wiltshire EJ , Gent R , Hirte C , et al.   Endothelial dysfunction relates to folate status in children and adolescents with type 1 diabetes . Diabetes . 2002;51:2282–2286
  102. Jarvisalo MJ , Raitakari M , Toikka JO , et al.   Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes . Circulation . 2004;109:1750–1755
  103. Hanukoglu A , Mizrachi A , Dalal I , et al.   Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first-degree relatives (a multicenter study) . Diabetes Care . 2003;26:1235–1240
  104. Glastras SJ , Craig ME , Verge CF , et al.   The role of autoimmunity at diagnosis of type 1 diabetes in the development of thyroid and celiac disease and microvascular complications . Diabetes Care . 2005;
  105. International Society for Pediatric and Adolescent Diabetes . Consensus guidelines for the management of type 1 diabetes mellitus in children and adolescents . Zeist, The Netherlands: Medical Forum International; 2000;
  106. Dorman JS , Laporte RE , Kuller LH , et al.   The Pittsburgh insulin-dependent diabetes mellitus (IDDM) morbidity and mortality study (mortality results) . Diabetes . 1984;33:271–276
  107. American Diabetes Association . Management of dyslipidemia in children and adolescents with diabetes . Diabetes Care . 2003;26:2194–2197
  108. Australasian Paediatric Endocrine Group . Clinical practice guidelines (type 1 diabetes in children and adolescents) . 2005; Available at: http://www.nhmrc.gov.au/publications/pdf/cp102.pdf. Accessed March 15, 2005.
  109. National Institute for Clinical Excellence . Type 1 diabetes (childhood) (diagnosis and management of type 1 diabetes in children and young people) . London: RCOG Press; 2005;

 This article is reprinted from Pediatr Clin N Am 52 (2005) 1735-1753.

PII: S1071-9091(06)00006-4

doi: 10.1016/j.spen.2006.01.002

Seminars in Pediatric Neurology
Volume 12, Issue 3 , Pages 178-186 , September 2005