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

다국어 초록 (Multilingual Abstract)

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±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±0.06 mm vs 0.39±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.

국문 초록 (Abstract)

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±0.06 mm vs 0.39±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.

참고문헌 (Reference)

• 1 Ter Avest E, "What is the role of non-invasive measurements of atherosclerosis in individual cardiovascular risk prediction?" 112 : 507-516, 2007
• 2 Williams MR, "Variations in endothelial function and arterial compliance during the menstrual cycle" 86 : 5389-5395, 2001
• 3 Daneman D, "Type 1 diabetes" 367 : 847-858, 2006
• 4 Arauz-Pacheco C, "The treatment of hypertension in adult patients with diabetes" 25 : 134-147, 2002
• 5 Rogers DG, "The effect of puberty on the development of early diabetic microvascular disease in insulin-dependent diabetes" 3 : 39-44, 1987
• 6 Sankatsing RR, "Surrogate markers for atherosclerotic disease" 16 : 434-441, 2005
• 7 Jacobs DR Jr, "Subclinical cardiovascular disease markers applicable to studies of oral health: multiethnic study of atherosclerosis" 1098 : 269-287, 2007
• 8 American Diabetes Association, "Standards of medical care in diabetes 2008" 31 (31): S12-S54, 2008
• 9 Wissler RW, "Risk factors and progression of atherosclerosis in youth. PDAY Research Group. Pathological Determinants of Atherosclerosis in Youth" 153 : 1023-1033, 1998
• 10 Rodriguez BL, "Prevalence of cardiovascular disease risk factors in U.S. children and adolescents with diabetes: the SEARCH for diabetes in youth study" 29 : 1891-1896, 2006
• 11 Laing SP, "Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes" 46 : 760-765, 2003
• 12 Bucala R, "Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency" 91 : 9441-9445, 1994
• 13 Acerini CL, "Metabolic impact of puberty on the course of type 1 diabetes" 27 : 19-25, 2001
• 14 Raitakari OT, "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" 290 : 2277-2283, 2003
• 15 Siraj ES, "Lipid and lipoprotein profiles in Ethiopian patients with diabetes mellitus" 55 : 706-710, 2006
• 16 Jarvisalo MJ, "Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children" 104 : 2943-2947, 2001
• 17 Clarkson P, "Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels" 28 : 573-579, 1996
• 18 Bennett PH, "Impact of the new WHO classification and diagnostic criteria" 1 (1): S1-S6, 1999
• 19 Gallego PH, "Identifying children at particular risk of long-term diabetes complications" 8 (8): S40-S48, 2007
• 20 Shamir R, "Glycemic control in adolescents with type 1 diabetes mellitus improves lipid serum levels and oxidative stress" 9 : 104-109, 2008
• 21 Shivalkar B, "Flow mediated dilatation and cardiac function in type 1 diabetes mellitus" 97 : 77-82, 2006
• 22 Atabek ME, "Evidence for an association between type 1 diabetes and premature carotid atherosclerosis in childhood" 27 : 428-433, 2006
• 23 Jarvisalo MJ, "Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes" 109 : 1750-1755, 2004
• 24 Schwab KO, "Early atherosclerosis in childhood type 1 diabetes: role of raised systolic blood pressure in the absence of dyslipidaemia" 166 : 541-548, 2007
• 25 Airaksinen KE, "Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen" 27 : 942-945, 1993
• 26 Best JD, "Diabetic dyslipidaemia: current treatment recommendations" 59 : 1101-1111, 2000
• 27 Jarvisalo MJ, "Determinants of arterial nitrate-mediated dilatation in children: role of oxidized low-density lipoprotein, endothelial function, and carotid intima-media thickness" 109 : 2885-2889, 2004
• 28 Celermajer DS, "Childhood risk factors for adult cardiovascular disease and primary prevention in childhood" 92 : 1701-1706, 2006
• 29 Li S, "Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study" 290 : 2271-2276, 2003
• 30 Jarvisalo MJ, "Carotid artery intima-media thickness in children with type 1 diabetes" 51 : 493-498, 2002
• 31 Wadwa RP, "Cardiovascular disease risk in youth with diabetes mellitus" 7 : 197-204, 2006
• 32 McGill HC Jr, "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" 20 : 1998-2004, 2000
• 33 Varvarovska J, "Aspects of oxidative stress in children with type 1 diabetes mellitus" 58 : 539-545, 2004
• 34 Dalla Pozza R, "Age of onset of type 1 diabetes in children and carotid intima medial thickness" 92 : 2053-2057, 2007
• 35 Stabouli S, "Adolescent obesity is associated with high ambulatory blood pressure and increased carotid intimal- medial thickness" 147 : 651-656, 2005
• 36 이영아, "1형 당뇨병 환자의 성장과 미세혈관 합병증 발생에 대한 연구" 대한소아과학회 50 (50): 190-197, 2007