A study and the growth and the development of microvascular complications in patients with type 1 diabetes mellitus

1형 당뇨병 환자의 성장과 미세혈관 합병증 발생에 대한 연구

  • Lee, Young Ah (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Yun, Kyong-Ah (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Shin, Choong Ho (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Yang, Sei Won (Department of Pediatrics, Seoul National University College of Medicine)
  • 이영아 (서울대학교 의과대학 소아과학교실) ;
  • 윤경아 (서울대학교 의과대학 소아과학교실) ;
  • 신충호 (서울대학교 의과대학 소아과학교실) ;
  • 양세원 (서울대학교 의과대학 소아과학교실)
  • Received : 2006.09.15
  • Accepted : 2006.12.15
  • Published : 2007.02.15

Abstract

Purpose : Reduced growth and microvascular complications have been recognized as consequences of type 1 diabetes mellitus (T1DM). We assessed the effect of T1DM on growth and factors associated with the development of microvascular complications. Methods : We conducted a retrospective longitudinal evaluation of 154 patients above 16 years of age. We analyzed factors which affect final height standard deviation scores (SDS) and development of microvascular complications. Results : Final height SDS was $-0.11{\pm}1.15$ ($-0.26{\pm}1.33$ in females, $0.04{\pm}0.91$ in males). Final height SDS was significantly lower than midparental height SDS and height SDS at diagnosis. There was no difference in final height SDS according to age at onset, existence or nonexistence of complications, or average $HbA_{1C}$. Height SDS at onset of puberty, midparental height SDS and pubertal growth gain affected final height SDS. The number of patients with complications was 37 (24 percent). Microvascular complications developed at a younger age and after longer duration of diabetes in patients with a prepubertal onset of T1DM compared to patients with pubertal onset. Patients with complications had a higher level of average $HbA_{1C}$ than patients without complications. Patients whose microalbuminuria regressed had lower levels of average $HbA_{1C}$, systolic BP, second 24h urine microalbumin than patients with persistant or progressed microalbuminuria. Conclusion : The results suggest that degrees of glycemic control don't affect final height, but various factors associated with T1DM can impair growth potential. Additionally, the degrees of glycemic control and puberty affect the development of microvascular complications.

목 적: 1형 당뇨병 소아, 청소년에서 혈당 조절이 불량하면 성장 장애와 미세혈관 합병증이 발생할 수 있다. 1형 당뇨병이 성장에 미치는 영향과 미세혈관 합병증(당뇨병성 신병증 또는 망막병증) 발생과 관련된 요인을 파악하고자 하였다. 방 법: 서울대병원에서 추적 중인 16세 이상의 154명 환자들의 의무기록을 후향적으로 분석하였다. 성인키 SDS(standard deviation score)에 영향을 미치는 요인을 분석하였고 합병증 유무, 미세알부민뇨의 경과에 따라 군을 나누어 특징을 비교하였다. 결 과: 성인키 SDS는 $-0.11{\pm}1.15$(여 $-0.26{\pm}1.33$, 남 $0.04{\pm}0.91$)였다. 성인키 SDS는 중간부모키 SDS에 비해 작았고(여 P=0.001, 남 P=0.002), 진단시 키 SDS에 비해서도 유의하게 감소하였다(여 P<0.001, 남 P=0.013). 진단시 사춘기 유무, 합병증 유무, 혈당 조절 정도, 이환 기간은 성인키 SDS에 영향을 미치지 않았다. 사춘기 시작시 키 SDS, 중간부모키 SDS, 사춘기 성장이 성인키 SDS에 영향을 미치는 요인이었다. 합병증이 발생한 37명(24%) 중에서 신병증은 29명, 망막병증은 19명, 동반된 경우는 11명이었다. 사춘기 전에 발병한 환자들은 사춘기에 발병한 환자들에 비해 첫 합병증이 발생한 연령은 더 낮았으나 첫 합병증 발생까지의 유병 기간은 더 길었다. 합병증이 발생한 그룹은 합병증이 없는 그룹보다 평균당화혈색소가 더 높았다. 미세알부민뇨가 소실된 환자들은 미세알부민뇨가 지속되거나 현성 신병증으로 진행한 환자들에 비해 평균당화혈색소, 수축기 혈압, 두 번째 측정한 24시간 소변 미세알부민 수치가 더 낮았다. 결 론: 1형 당뇨병 환자의 성인키는 혈당 조절 정도의 영향을 받지 않았지만, 중간부모키, 진단시 키에 비해 감소하여 당뇨병의 여러 요인에 의해 성장소실이 가능함을 알 수 있었다. 미세혈관 합병증 발생을 예방하기 위해서는 철저한 혈당 조절이 필요하다. 혈당 조절이 불량하거나 사춘기가 시작되면 미세혈관 합병증에 대한 선별검사를 시행해야 한다.

Keywords

References

  1. Boyd JD, Kantrow AH. Retardation of growth in diabetic children. Am J Dis Child 1938;55:460-71
  2. Tattersall RB, Pyke DA. Growth in diabetic children. Studies in identical twins. Lancet 1973;2:1105-93
  3. Wise JE, Kolb EL, Sauder SE. Effect of glycemic control on growth velocity in children with IDDM. Diabetes Care 1992;15:826-30 https://doi.org/10.2337/diacare.15.7.826
  4. Salerno M, Argenziano A, Di Maio S, Gasparini N, Formicola S, De filippo G, et al. Pubertal growth, sexual maturation, and final height in children with IDDM. effects of age at onset and metabolic control. Diabetes care 1997;20:721-4 https://doi.org/10.2337/diacare.20.5.721
  5. Penford J, Chase HP, Marshall G, Walravens CF, Walravens PA, Garg SK. Final adult height and its relationship to blood glucose control and microvascular complications in type 1 diabetes mellitus. Diabet Med 1995;12:129-33 https://doi.org/10.1111/j.1464-5491.1995.tb00443.x
  6. Holl RW, Grabert M, Heinze E, Sorgo W, Debatin KM. Age at onset and long term metabolic control affect height in type 1 diabetes mellitus. Eur J Ped 1998;157:972-7 https://doi.org/10.1007/s004310050980
  7. Salardi S, Tonioli S, Tassoni P, Tellarini M, Mazzanti I, Cacciari E. Growth and growth factors in diabetes mellitus. Arch Dis Child 1987;62:57-62 https://doi.org/10.1136/adc.62.1.57
  8. Lebl J, Schober E, Zidek T, Baldis S, Rami B, Pruhova S, et al. Growth data in large series of 587 children and adolescents with type 1 diabetes mellitus. Endocr Regul 2003; 37:153-61
  9. Min Ho Jung, Pei Tai Wang, Choong Ho Shin, Sei Won Yang. Factors related to the development of microalbuminuria in children and adolescents with type 1 diabetes mellitus. J Korean Pediatr Soc 2001;44:577-86
  10. Donaghue KC, Fairchild JM, Chan A, Hing SJ, Howard NJ, Silink M. Diabetes complication screening in 937 children and adolescents. J Pediatr Endocrinol Metab 1999;12:185-92
  11. The microalbuminuria collaborative study group. Predictors of the development of microalbuminuria in patients with type 1 diabetes mellitus: a seven-year prospective study. Diabetes Med 1999;16:918-25 https://doi.org/10.1046/j.1464-5491.1999.00182.x
  12. Olsen BS, Sjolie AK, Hougaard P, Johannesen J, Marinelli K, Jacobsen BB, et al. The significance of the prepubertal diabetes duration for the development of retinopathy and nephropathy in patients with type 1 diabetes. J Diabetes Complications 2004;18:160-4 https://doi.org/10.1016/S1056-8727(03)00073-4
  13. Holl RW, Lang GE, Grabert M, Heinze E, Lang GK, Debatin KM. Diabetic retinopathy in pediatric patients with type 1 diabetes; effect of diabetes duration, perpubertal and pubertal onset of diabetes, and metabolic control. J pediatr 1998;132: 790-4 https://doi.org/10.1016/S0022-3476(98)70305-1
  14. Haffner SM, Klein R, Moss SE, Klein BE. Sex hormones and the incidence of severe retinopathy in male subjects with type 1 diabetes. Ophthalmology 1993;100:1782-6 https://doi.org/10.1016/S0161-6420(93)31398-9
  15. Rogers DG, White NH, Shalwitz RA, Palmberg P, Smith ME, Santiago JV. The effect of puberty on the development of early diabetic microvascular disease in insulin-dependent diabetes. Diabetes Res Clin Pract 1987;3:39-44 https://doi.org/10.1016/S0168-8227(87)80006-2
  16. Schultz CJ, Konopelska-Bahu T, Dalton RN, Carroll TA, Stratton I, Gale EA, et al. microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Diabetes care 1999;22:495-502 https://doi.org/10.2337/diacare.22.3.495
  17. Danne T, Kordonouri O, Enders I, Weber B. Factors influencing height and weight development in children with diabetes. results of the Berlin Retinopathy Study. Diabetes Care 1997;20:281-5 https://doi.org/10.2337/diacare.20.3.281
  18. Jos J, Meteyer I, Farkas D, Oberkampf B. Growth of children with insulin dependent diabetes. Study of 104 cases. Arch Pediatr 1996;3:218-26 https://doi.org/10.1016/0929-693X(96)81298-X
  19. d'Annunzio G, Cortona L, Vitali L, Pessino P, Lorini R. Final height attainment in girls and boys with insulindependent diabetes mellitus. Diabetes Res Clin Pract 1994; 24:187-93 https://doi.org/10.1016/0168-8227(94)90115-5
  20. Kanumakala S, Dabadghao P, Carlin JB, Vidmar S, Cameron FJ. Linear growth and height outcomes in children with early onset type 1 diabetes mellitus- a 10-yr longitudinal study. Pediatr Diabetes 2002;3:189-93 https://doi.org/10.1034/j.1399-5448.2002.30404.x
  21. Merimee TJ. A follow up study of vascular disease in growth hormone deficient dwarfs with diabetes. N Engl J Med 1978;298:1217-22 https://doi.org/10.1056/NEJM197806012982202
  22. Acerini CL, Williams RM, Dunger DB. Metabolic impact of puberty on the course of type 1 diabetes. Diabetes Metab 2001;27:19-25
  23. Laszlo B, Adrienn T. Alterations in insulin like growth factor binding protein-1 and sex hormone binding globulin levels in type 1 diabetic adolescents with microalbuminuria. Diabetes care 2001;24:605-6 https://doi.org/10.2337/diacare.24.3.605
  24. Cummings EA, Sochett EB, Dekker MG, Lawson ML, Daneman D. Contribution of Growth hormone and IGF-1 to early diabetic nephropathy in type 1 diabetes. Diabetes 1998; 47:1341-6 https://doi.org/10.2337/diabetes.47.8.1341
  25. Williamson JR, Rowold E, Chang K, Marvel J, Tomlinson M, Sherman WR, et al. Sex steroid dependency of diabetesinduced changes in polyol metabolism, vascular permeability, and collagen cross-linking. Diabetes 1986;35:20-7 https://doi.org/10.2337/diabetes.35.1.20
  26. Olsen BS, Sjolie A, Hougaard P, Johannesen J, Borch- Johnsen K, Marinelli K, et al. A 6-year nationwide cohort study of glycaemic control in young people with type 1 diabetes risk markers for the development of retinopathy, nephropathy, and neuropathy. Danish Study Group of Diabetes in Childhood. J Diabetes Complications 2000;14:295-300 https://doi.org/10.1016/S1056-8727(00)00078-7
  27. Peter R, Philip H, Hans-Henrik P. Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients. A 10-year prospective observational study. Diabetes Care 2002;25:859-64 https://doi.org/10.2337/diacare.25.5.859
  28. Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin dependent patients. N Engl J Med 1984; 311:89-93 https://doi.org/10.1056/NEJM198407123110204
  29. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003;348:2285-93 https://doi.org/10.1056/NEJMoa021835
  30. Rudberg S, Dahlquist G. Determinants of progression of microalbuminuria in adolescents with IDDM. Diabetes Care 1996;19:369-71 https://doi.org/10.2337/diacare.19.4.369
  31. Tabaei BP, Al-Kassab AS, Ilag LL, Zawacki CM, Herman WH. Does microalbuminuria predict diabetic nephropathy? Diabetes care 2001; 24:1560-6 https://doi.org/10.2337/diacare.24.9.1560
  32. Remuzzi AE, Ruggenenti P, Benigni A. Understanding the nature of renal disease progression. Kidney Int 1997;51:2-15 https://doi.org/10.1038/ki.1997.2
  33. Raptis AE, Viberti G. Pathogenesis of diabetic nephropathy. Exp Clin Endocrinol Diabetes 2001;109:424-37 https://doi.org/10.1055/s-2001-18600
  34. Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N. Factors associated with progression to macroalbuminuria in microalbuminuric type 1 diabetic patients; the EURODIAB prospective complications study, DiabeLtologiac 2004;47:1020-8
  35. Verrotti A, Catino M, Di Ricco L, Casani A, Chiarelli F. Prevention of microvascular complication in diabetic children and adolescents. Acta Paediatr suppl 1999;88:35-8 https://doi.org/10.1111/j.1651-2227.1999.tb14338.x
  36. Chiarelli F, Casani A, Verrotti A, Morgese G, Pinelli L. Diabetic nephropathy in children and adolescents; a critical review with particular reference to ACE inhibitors. Acta Paediatr 1998;425:42-5
  37. Rudberg J, Aperia A, Freyschuss U, Persson B. Enalapril reduces microalbuminuria in young normotensive type 1 diabetic patients irrespective of its hypotensive effect. Diabetologia 1990;33:470-6 https://doi.org/10.1007/BF00405108
  38. Vilarrasa N. Soler J, Montanya E. Regression of microalbuminuria in type 1 diabetic patients: results of a sequential intervention with improved metabolic control and ACE inhibitors. Acta Diabetol 2005;42:87-94 https://doi.org/10.1007/s00592-005-0184-0