Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지
DOI QR코드

DOI QR Code

소아청소년기에 1형 당뇨병으로 진단된 젊은 성인에서 대혈관 합병증의 발생과 이에 연관된 인자에 대한 연구

A study of the development of macrovascular complications and factors related to these complications in young adults with childhood/adolescence-onset type 1 diabetes mellitus

  • 강민재 (서울대학교 의과대학 소아과학교실) ;
  • 김주화 (서울대학교 의과대학 소아과학교실) ;
  • 정혜림 (서울대학교 의과대학 소아과학교실) ;
  • 이영아 (서울대학교 의과대학 소아과학교실) ;
  • 신충호 (서울대학교 의과대학 소아과학교실) ;
  • 양세원 (서울대학교 의과대학 소아과학교실) ;
  • 김유예 (서울대학교 의과대학 소아과학교실) ;
  • 진선미 (을지대학교 의과대학 소아과학교실) ;
  • 노정일 (서울대학교 의과대학 소아과학교실)
  • Kang, Min Jae (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Kim, Joo Hwa (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Chung, Hye Rim (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Lee, Young Ah (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Shin, Choong Ho (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Yang, Sei Won (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Kim, You Yeh (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Jin, Seon Mi (Department of Pediatrics, Eulji University School of Medicine) ;
  • Noh, Chung Il (Department of Pediatrics, College of Medicine, Seoul National University)
  • 투고 : 2008.07.30
  • 심사 : 2008.11.16
  • 발행 : 2009.02.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목 적 : 대혈관 합병증은 1형 당뇨병에서 주된 사망 원인으로 합병증을 예방하고 조기에 발견하는 것은 중요하므로, 저자들은 소아-청소년기에 1형 당뇨병으로 진단된 젊은 성인에서 대혈관 합병증의 발생 여부를 알아보고자 혈관초음파 검사를 통해 동맥경화의 초기 변화를 측정하였고, 이 변화와 관련된 위험인자를 분석하기 위해 본 연구를 시행하였다. 방 법 : 서울대학교병원에서 18세 이전에 1형 당뇨병으로 진단받고 추적 관찰 중인 20대의 72명의 환자들과 건강한 20명의 대조군을 대상으로 하였다. 환자들에서 고혈압과 고지혈증의 빈도 및 관련 인자를 알아보았으며, 환자군과 대조군 간에 혈관 초음파 검사를 통해 측정한 FMD, mean IMT를 비교하였고, 위험인자와의 상관성을 분석하였다. 결 과 : 72명의 대상 환자 중 32명(44.4%)에서 고혈압이 있었고, 고혈압군은 정상 혈압군 보다 남자의 빈도(P=0.03)와 평균 체질량지수(P=0.04)가 더 높았다. LDLc이 100 mg/dL 이상으로 측정된 환자는 31명(N=69, 44.9%)이었고, 전체 환자군의 LDLc은 평균 당화혈색소(r=0.32, P=0.008), 하루 총 인슐린 사용량(r=0.27, P=0.02)과 양의 상관관계를 보였다. Mean IMT는 환자군이 대조군 보다 유의하게 더 두꺼웠고($0.43{\pm}0.06$ mm vs $0.39{\pm}0.06$ mm, P=0.03), FMD는 두 군 사이의 통계적 유의성은 없었으나, 환자군 내에서 사춘기발현 이후의 유병기간이 길수록 FMD는 감소하는 경향을 보였다(r=-0.34, P=0.01). 결 론 : 20대의 1형 당뇨병 환자에서도 동맥경화가 진행되고 있으므로 대혈관 합병증의 위험인자에 대한 선별검사 및 이의 조절이 필요하며, 1형 당뇨병이 있는 젊은 성인뿐만 아니라 청소년기의 환자에서도 대혈관 합병증의 위험인자에 대한 주기적인 평가가 필요할 것으로 생각된다.

Purpose : Macrovascular complications are the main cause of mortality in type 1 diabetes mellitus (T1DM). The purpose of this study was to clarify the presence of early vascular changes and to assess the risk factors of macrovascular complications in young adults with T1DM diagnosed in childhood and adolescence. Methods : Seventy-two patients ($23.9{\pm}2.4$ years) with T1DM diagnosed before 18 years of age and twenty normal controls were included. The incidence of hypertension, dyslipidemia, and other risk factors of macrovascular complication were reviewed. Flow-mediated vasodilation (FMD) and mean intima-media thickness (IMT) measured by ultrasound were compared between patients and control subjects, and their correlations with macrovascular risk factors were analyzed. Results : Of the 72 patients, 32 (44.4%) had hypertension. The proportions of maleness (P=0.03) and mean body mass index (P=0.04) were higher in the hypertensive patients than in normotensive patients. Thirty-one (N=69, 44.9%) patients had dyslipidemia and LDL-cholesterol was positively correlated with mean HbA1c (r=0.32, P=0.008) and total daily insulin dose (r=0.27, P=0.02). The mean IMT was significantly higher in patients than in control subjects ($0.43{\pm}0.06$ mm vs $0.39{\pm}0.06$ mm, P=0.03). There was no difference in the value of FMD between patients and controls, but the duration of the disease after pubertal onset was negatively correlated with FMD (r=-0.34, P=0.01). Conclusion : Hypertension, dyslipidemia and atherosclerotic vascular change were observed in young adults with T1DM diagnosed during childhood and adolescence; this strongly suggests that meticulous screening of macrovascular complications and control of their risk factors should be conducted.

키워드

참고문헌

  1. Daneman D. Type 1 diabetes. Lancet 2006;367:847-58 https://doi.org/10.1016/S0140-6736(06)68341-4
  2. Gallego PH, Wiltshire E, Donaghue KC. Identifying children at particular risk of long-term diabetes complications. Pediatr Diabetes 2007;8 Suppl 6:S40-8 https://doi.org/10.1111/j.1399-5448.2007.00298.x
  3. Arauz-Pacheco C, Parrott MA, Raskin P. The treatment of hypertension in adult patients with diabetes. Diabetes Care 2002;25:134-47 https://doi.org/10.2337/diacare.25.1.134
  4. Wadwa RP. Cardiovascular disease risk in youth with diabetes mellitus. Rev Endocr Metab Disord 2006;7:197-204 https://doi.org/10.1007/s11154-006-9016-y
  5. Dalla Pozza R, Bechtold S, Bonfig W, Putzker S, Kozlik- Feldmann R, Netz H, et al. Age of onset of type 1 diabetes in children and carotid intima medial thickness. J Clin Endocrinol Metab 2007;92:2053-7 https://doi.org/10.1210/jc.2006-2868
  6. Jarvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation 2004;109:1750-5 https://doi.org/10.1161/01.CIR.0000124725.46165.2C
  7. Schwab KO, Doerfer J, Krebs A, Krebs K, Schorb E, Hallermann K, et al. Early atherosclerosis in childhood type 1 diabetes: role of raised systolic blood pressure in the absence of dyslipidaemia. Eur J Pediatr 2007;166:541-8 https://doi.org/10.1007/s00431-007-0440-0
  8. Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T, Cerami A, et al. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Natl Acad Sci U S A 1994;91:9441-5 https://doi.org/10.1073/pnas.91.20.9441
  9. American Diabetes Association. Standards of medical care in diabetes 2008. Diabetes Care 2008;31 Suppl 1:S12-54
  10. Airaksinen KE, Salmela PI, Linnaluoto MK, Ikaheimo MJ, Ahola K, Ryhanen LJ. Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen. Cardiovasc Res 1993;27:942-5 https://doi.org/10.1093/cvr/27.6.942
  11. Jarvisalo MJ, Putto-Laurila A, Jartti L, Lehtimaki T, Solakivi T, Ronnemaa T, et al. Carotid artery intima-media thickness in children with type 1 diabetes. Diabetes 2002;51:493-8 https://doi.org/10.2337/diabetes.51.2.493
  12. Jacobs DR Jr, Crow RS. Subclinical cardiovascular disease markers applicable to studies of oral health: multiethnic study of atherosclerosis. Ann N Y Acad Sci 2007;1098:269-87 https://doi.org/10.1196/annals.1384.029
  13. McGill HC Jr, McMahan CA, Zieske AW, Sloop GD, Walcott JV, Troxclair DA, et al. Associations of coronary heart disease risk factors with the intermediate lesion of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol 2000;20:1998-2004
  14. Wissler RW, Strong JP. Risk factors and progression of atherosclerosis in youth. PDAY Research Group. Pathological Determinants of Atherosclerosis in Youth. Am J Pathol 1998;153:1023-33
  15. Jarvisalo MJ, Jartti L, Nanto-Salonen K, Irjala K, Ronnemaa T, Hartiala JJ, et al. Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children. Circulation 2001;104:2943-7 https://doi.org/10.1161/hc4901.100522
  16. Sankatsing RR, de Groot E, Jukema JW, de Feyter PJ, Pennell DJ, Schoenhagen P, et al. Surrogate markers for atherosclerotic disease. Curr Opin Lipidol 2005;16:434-41 https://doi.org/10.1097/01.mol.0000174400.68938.f6
  17. Ter Avest E, Stalenhoef AF, de Graaf J. What is the role of non-invasive measurements of atherosclerosis in individual cardiovascular risk prediction? Clin Sci (Lond) 2007;112: 507-16 https://doi.org/10.1042/CS20060228
  18. Bennett PH. Impact of the new WHO classification and diagnostic criteria. Diabetes Obes Metab 1999;1 Suppl 2:S1-6
  19. Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, et al. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 2003;46:760-5 https://doi.org/10.1007/s00125-003-1116-6
  20. Rodriguez BL, Fujimoto WY, Mayer-Davis EJ, Imperatore G, Williams DE, Bell RA, et al. Prevalence of cardiovascular disease risk factors in U.S. children and adolescents with diabetes: the SEARCH for diabetes in youth study. Diabetes Care 2006;29:1891-6 https://doi.org/10.2337/dc06-0310
  21. Williams MR, Westerman RA, Kingwell BA, Paige J, Blombery PA, Sudhir K, et al. Variations in endothelial function and arterial compliance during the menstrual cycle. J Clin Endocrinol Metab 2001;86:5389-95 https://doi.org/10.1210/jc.86.11.5389
  22. Raitakari OT, Juonala M, Kahonen M, Taittonen L, Laitinen T, Maki-Torkko N, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA 2003;290:2277-83 https://doi.org/10.1001/jama.290.17.2277
  23. Stabouli S, Kotsis V, Papamichael C, Constantopoulos A, Zakopoulos N. Adolescent obesity is associated with high ambulatory blood pressure and increased carotid intimal- medial thickness. J Pediatr 2005;147:651-6 https://doi.org/10.1016/j.jpeds.2005.06.008
  24. Best JD, O'Neal DN. Diabetic dyslipidaemia: current treatment recommendations. Drugs 2000;59:1101-11 https://doi.org/10.2165/00003495-200059050-00006
  25. Li S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, et al. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study. JAMA 2003;290:2271-6 https://doi.org/10.1001/jama.290.17.2271
  26. Siraj ES, Seyoum B, Saenz C, Abdulkadir J. Lipid and lipoprotein profiles in Ethiopian patients with diabetes mellitus. Metabolism 2006;55:706-10 https://doi.org/10.1016/j.metabol.2005.08.002
  27. Varvarovska J, Racek J, Stetina R, Sykora J, Pomahacova R, Rusavy Z, et al. Aspects of oxidative stress in children with type 1 diabetes mellitus. Biomed Pharmacother 2004;58: 539-45 https://doi.org/10.1016/j.biopha.2004.09.011
  28. Shamir R, Kassis H, Kaplan M, Naveh T, Shehadeh N. Glycemic control in adolescents with type 1 diabetes mellitus improves lipid serum levels and oxidative stress. Pediatr Diabetes 2008;9:104-9 https://doi.org/10.1111/j.1399-5448.2007.00313.x
  29. Jarvisalo MJ, Lehtimaki T, Raitakari OT. Determinants of arterial nitrate-mediated dilatation in children: role of oxidized low-density lipoprotein, endothelial function, and carotid intima-media thickness. Circulation 2004;109:2885-9 https://doi.org/10.1161/01.CIR.0000129304.98566.D8
  30. Clarkson P, Celermajer DS, Donald AE, Sampson M, Sorensen KE, Adams M, et al. Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. J Am Coll Cardiol 1996;28:573-9
  31. Acerini CL, Williams RM, Dunger DB. Metabolic impact of puberty on the course of type 1 diabetes. Diabetes Metab 2001;27:19-25
  32. 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
  33. Lee YA, Yun KA, Shin CH, Yang SW. A study and the growth and the development of microvascular complications in patients with type 1 diabetes mellitus. Korean J Pediatr 2007;50:190-7 https://doi.org/10.3345/kjp.2007.50.2.190
  34. Atabek ME, Pirgon O, Kurtoglu S, Imamoglu H. Evidence for an association between type 1 diabetes and premature carotid atherosclerosis in childhood. Pediatr Cardiol 2006;27: 428-33 https://doi.org/10.1007/s00246-006-1199-1
  35. Celermajer DS, Ayer JG. Childhood risk factors for adult cardiovascular disease and primary prevention in childhood. Heart 2006;92:1701-6 https://doi.org/10.1136/hrt.2005.081760
  36. Shivalkar B, Dhondt D, Goovaerts I, Van Gaal L, Bartunek J, Van Crombrugge P, et al. Flow mediated dilatation and cardiac function in type 1 diabetes mellitus. Am J Cardiol 2006;97:77-82 https://doi.org/10.1016/j.amjcard.2005.07.111

피인용 문헌

  1. 생마늘 및 흑마늘 추출분말이 Streptozotocin 유발 당뇨 흰쥐의 혈청 및 장기 내 주요성분에 미치는 영향 vol.23, pp.3, 2009, https://doi.org/10.5352/jls.2013.23.3.432