Mutation in Ret Proto - Oncogene in Medullary Thyroid Cancer and Multiple Endocrine Neoplasia Type 2A ( Men 2A ) and Men 2B with Hirschcprung`s Disease

유순집(Soon Jib Yoo),이희진(Hee Jin Lee),안유배(Yu Bae Ahn),한제호(Je Ho Han),윤건호(Kun Ho Yoon),강무일(Moo Il Kang),차봉연(Bong Yun Cha),이광우(Kwang Woo Lee),손호영(Ho Young Son),강성구(Sung Koo Kang),김영실(Young Sill Kim),김병기(By 대한내과학회 1998 대한내과학회 추계학술대회 Vol.55 No.-

당뇨환자에서 당화혈색소와 관련된 우울, 불안, 감정표현불능, 스트레스반응 - 예비적 연구 -

정종현,고승현,홍승철,한진희,이성필,안유배,송기호,Jeong, Jong-Hyun,Ko, Seung-Hyun,Hong, Seung-Chul,Han, Jin-Hee,Lee, Sung-Pil,Ahn, Yoo-Bae,Song, Ki-Ho 한국정신신체의학회 2004 정신신체의학 Vol.12 No.2

서론: 최근 경제수준의 향상과 사회구조의 변화 등으로 신생활이 서구화되고 노령화 사회가 되어가면서 만성질환 및 성인병 등의 박병률이 급격히 증가하고 있다. 특히 당뇨병은 전 세계적으로 및 유병율이 계속 증가하고 있으면, 만성질환 중 주요사망 원인인 뇌혈관 질환과 심혈관계 질환의 중요한 위험요인으로 잘 알려져 있다. 그러나 당뇨병은 고혈당 자체보다는 여러 장기에 복합적으로 침범하는 합병증으로 인하여 환자자신은 물론 가족과 사회에 심각한 건강 문제와 사회, 경제적 문제를 초래하게 되는 질환이다. 그러므로 당뇨병의 치료에 있어 엄격한 혈당의 조절과 함께 정서적 스트레스에 대한 배려가 필요할 것이다. 이에 저자들은 당뇨병 환자의 과거 3개월간의 혈당조절의 지표로 알려진 당화혈색소를 기준으로 당뇨조절과 관련된 정신병리를 확인해보고자 하였다. 방법: 2004년 3월부터 2004년 8월까지 가톨릭대학교 성빈센트병원 내분비내과에서 치료 중인 환자 55명을 대상으로 하였으며, 이 중 당화혈색소가 7%이하인군을 혈당조절 양호군으로 하였다. 이들에 대하여 사회 인구학적인 변인에 대한 문항, Beck의 Beck Depression Inventory(BDI), Spielberger의 State-Trait Anxiety Inventory (STAI), Taylor의 Tronto Alexithymia Scale (TAS), 고경봉의 스트레스반응척도(SRI)를 사용하여, 혈당조절 양호군과 불량군간의 차이를 비교하였다. 결과: 1) 대상군 55명의 평균나이는 $49.9{\pm}9.9$세(연령분포 : $24{\sim}67$세)였으며, 이 중 남자가 49.1%(27명), 여자가 50.9% (28명)이었고, 평균 유병기간은 $47.6{\pm}62.6$개월, 평균 신체질량지수는 $25.3{\pm}4.2$로 측정되었다. 총 55명중에서 혈당조절 양호군은 10명(평균나이 $47.2{\pm}12.3$세, 남자 60%, 여자 40%)이었고, 혈당조절 불량군은 45명 (평균나이 $50.5{\pm}9.4$세, 남자 46.7%, 여자 53.3%)이었다. 2) 두 군간에서 나이, 성별, 신체질량지수 등의 인구학적 변인에서 유의한 차이는 없었으나, 당뇨병 유병기간에서 혈당조절 양호군이 $12.2{\pm}55.4$개월, 혈당조절 불량군이 $55.4{\pm}66.6$개월로 혈당조절 양호군이 유의하게 짧은 유병기간을 보이고 있었다(p=0.000). 3) 혈당조절 양호군과 불량군의 상태불안의 평균점수는 각각, $38.7{\pm}3.8$점, $43.7{\pm}6.7$점이었고, 특성불안의 평균점수는 각각, $36.9{\pm}5.7$점, $41.5{\pm}6.4$점으로 두군 모두에서 상태불안(p=0.029)과 특성불안(p=0.043)에 있어서 유의한 차이를 보이고 있었다. 4) 우울증상척도, 감정표현불능척도, 스트레스반응척도에서는 혈당조절 양호군과 불량군 모두에서 유의한 차이가 없었다. 결론: 이상의 결과에서 당뇨조절에 문제가 있는 군은 그렇지 않은 군보다 높은 상태불안 및 특성불안을 겪고 있는 것으로 확인되었다. 당뇨환자의 치료에 있어서 환자들이 느끼는 불안에 대한 통합적인 접근이 필요할 것으로 사료된다. Objectives : This study was designed to investigate depression, anxiety, alexithymia, stress responses between well-controlled and poorly-controlled diabetic patients by glycated hemoglobin levels. Methods : The subjects were 55 diabetic patients(mean age : $49.9{\pm}9.9$, 27 men and 28 women) who were confirmed to have diabetes depending on the laboratory findings as well as clinical symptoms at the St. Vincent Hospital Diabetes Clinic, from Mar. 2004 to Aug. 2004. Korean version of Beck Depression Inventory(BDI), State and Trait Anxiety Inventory(STAI), Toronto Alexithymia Scale(TAS) and Stress Response Inventory(SRI) were used for assessment. Based on glycated hemoglobin levels, the patients were divided into 10 well-controlled group(below 7%) and 45 poorly-controlled group(above 7%). We compared BDI, STAI, TAS and SRI scores between two groups by independent t-test. Results 1) Well-controlled diabetics, compared with poorly controlled group, manifested decreased illness duration($12.2{\pm}55.4$months vs. $55.4{\pm}66.6 months)(p=0.000), but other demographic data showed no difference between two groups. 2) The STAI scores of poorly-controlled group were significantly higher in both state anxiety sores $(38.7{\pm}3.8 \;vs.\;43.7{\pm}6.7)(p=0.29)$ and trait anxiety scores$(36.9{\pm}5.7\;vs.\;41.5{\pm}6.4)(p=0.43)$ than well-controlled groups. 3) No significant differences were found in the score of BDI, TAS, SRI between well and poorly-controlled diabetic groups. Conclusion : The above results suggest that poorly-controlled diabetic patients are more likely to have higher anxiety level than well-controlled diabetic patients. However, there were no differences in depression, alexithymia, stress responses between two group. We suggest that physicians should consider integrated approaches for psychiatric problems in the management of diabetic patients.

당뇨병 환자에서의 우울 및 관련증상에 관한 예비적 연구

고승현,정종현,홍승철,한진희,이성필,안유배,송기호,Ko, Seung-Hyun,Jeong, Jong-Hyun,Hong, Seung-Chul,Han, Jin-Hee,Lee, Seung-Pil,Ahn, Yoo-Bae,Song, Ki-Ho 한국정신신체의학회 2004 정신신체의학 Vol.12 No.2

목적 : 당뇨병은 인단 발생하면 질병 경과의 조절은 어느 정도 가능하나 대부분 완치가 어렵고 평생동안 치료와 자기관리론 요하는 만성질환으로, 이러한 합병증은 혈당을 가능한 정상인에 가깝도록 유지함으로서 합병증의 발생 및 진행을 억제할 수 있다. 당뇨병 진단이후 만성질환에 대한 합병증 발생에 따른 두려움, 혈당을 정상화시키기 위한 생활습관의 갑작스런 개선, 당뇨병 치료를 위한 약물 복용 및 인슐린 주사, 당뇨병성 합병증의 발생 등은 정서적 스트레스로 작용할 가능성이 크다. 이에 저자들은 자가보고식 우울증 척도를 기준으로 당뇨조절과 관련된 요인들을 확인해보고자 하였다. 방법: 2004년 3월부터 2004년 9월까지 가톨릭대학교 성빈센트병원 내분비내과에서 치료 중인 환자 60명을 대강으로 하였으며, 이 중 Beck의 우울척도(Beck Depression Inventory, BDI)점수를 기준으로 20점 이하인 군을 비우울군, 21점 이상인 군을 우울군으로 하였다. 이들에 대하여 사회 인구학적인 변인, 혈액화학 검사, 단백뇨검사, 당화혈색소검사 및 Spielberger의 상태-특성불안 척도(State-Trait Anxiety Inventory, STAI), Bagby의 감정표현불능척도(Tronto Alexithymia Scale), 고경봉의 스트레스반응척도(Stress Response Inventory)를 사용하여, 우울군과 비우울군 간의 차이론 비교하였다. 결과: 1) 대상군 60명의 평균나이는 $50.3{\pm}9.7$세(연령분포 : $24{\sim}67$세)였으며, 이중 남자가 51.7%(31명), 여자가 48.3%(29명)이었고, 평균 유병기간은 $47.1{\pm}61.5$개월, 평균 신체질량지수는 $25.2{\pm}4.3$으로 측정되었다. 총 60명중에서 비우울군은 47명(평균나이 $48.9{\pm}9.8$세, 남자 51.1%(24명), 여자 48.9%(23명))이었고, 우울군은 13명(평균나이 $55.4{\pm}7.2$세, 남자 53.8%(7명), 여자 46.2%(6명))이었다. 2) 두군 간에서 평균연령이 우울군에서 유의하게 높았으나($55.4{\pm}7.2$세 vs. $48.9{\pm}9.8$세)(p=0.031), 성별, 신체질량지수, 당뇨병 유병기간, 교육정도, 직업 등의 인구학적 변인에서 유의한 차이는 없었다. 또한 혈중 크레아틴 농도가 우울군에서 유의하게 높게 측정되었으나$(0.91{\pm}0.14\;vs.\;0.8{\pm}0.14)(p=0.26)$, 공복 시 혈당, 식후 혈당, 당화혈색소 및 단백뇨검사 등의 검사에서는 유의한 차이가 없었다. 3) 우울군과 비우울군의 스트레스 반응척도의 평균점수는 각각 $59.7{\pm}24.9,\;31.5{\pm}22.0$으로 두군 간의 유의한 차이를 보이고 있었다(p=0.000). 4) 상태불안 및 특성불안, 감정표현불능척도에서는 우울군과 비우울군 간의 유의한 차이가 없었다. 결론: 이상의 결과에서 우울증상이 있는 당뇨환자에 있어서 당조절의 지표라고 여겨지는 혈당 및 당화혈색소 등은 악화되어있지 않았으나, 당뇨병의 장기적인 합병증과 관련되어있을 것으로 생각되는 혈중 크레아틴의 농도가 증가되어있고, 스트레스에 매우 취약한 상태라는 점이 확인되었다. 우울증이 있는 당뇨환자의 치료에 있어서 이에 대한 통합적인 접근이 필요할 것이며, 추가적인 연구가 필요할 것으로 생각된다. Objectives: Diabetes mellitus is a heterogeneous, chronic, progressive disease characterized by hyperglycemia and abnormality in protein, carbohydrate, fat metabolism. Recent studies have reorted two times prevalence of depression in individuals with diabetes compared to individuals without diabetics. This study was designed to investigate glycemic controls, anxiety, alexithymia, stress responses between depressed diabetic patients and non-depressed diabetic patients. Methods The subjects were 60 diabetic patients(mean age : $50.3{\pm}9.7$ years, 31 men and 29 women) who were confirmed to have diabetes depending on the laboratory findings as welt as clinical symptoms at the St. Vincent Hospital Diabetes Clinic, from Mar. 2004 to Sep. 2004. Laboratory test including, blood chemistry. glycated hemoglobin, urinalysis for proteinuria and Korean version of Beck Depression Inventory(BDI), State and Trait Anxiety Inventory(STAI), Toronto Alexithymia Scale(TAS) and Stress Response Inventory(SRI) were used for assessment. Based on BDI scores, all diabetics were divided into 13 depressed-diabetics group(above 20 point) and 47 non-depressed group(below 20 point). We compared demographic data. glycemic controls, STAI, TAS and SRI scores between two groups by independent t-test. Results : 1) Depressed diabetic groups were 13(mean age : $55.4{\pm}7.2$ years, 7 men and 6 women) and non depressed groups were 47(mean age $48.9{\pm}9.8$ years, 24 men and 23 women). In depressed diabetics, compared with non-depressed group, manifested aged(p=0.031), but other demographic data showed no difference between two groups. 2) No significant differences were noted in FBS, PP2h, Hb A1C, total cholesterol, HDL-cholesterol, SGOT/SGPT, BUN levels between depressed and non-depressed groups. But, blood creatine levels of depressed group were significantly increased than non-depressed group(p=0.026). 3) No significant differences were found in the score of STAI, STAI-S, STAI-T, TAS between depressed and non-depressed groups. 4) The SRI scores of depressed groups were significantly higher than non-depressed groups$(59.7{\pm}24.9\;vs.\;31.5{\pm}22.0)(p=0.000)$. Conclusion : The above results suggest that depressed diabetic patients are have more stress responses and higher blood creatine levels. However, there were no differences in laboratory data related to glycemic controls, and anxiety. alexithymia levels between two groups. We suggest that physicians should consider integrated approaches for psychiatric problems in the management of diabetes.

수술적 치료를 받은 갑상선질환의 임상적 고찰 - 1988 년부터 1992 년까지 갑상선 수술의 경향 -

김형근(Hyung Keun Kim),문성대(Sung Dae Moon),장상아(Sang Ah Chang),안유배(Yoo Bae Ahn),송기호(Ki Ho Song),한제호(Je Ho Han),유순집(Soon Jip Yoo),이종민(Jong Min Lee),손현식(Hyun Sik Son),윤건호(Kun Ho Yoon),강무일(Moo Il Kang),차봉연(Bo 대한내과학회 1998 대한내과학회지 Vol.55 No.6

N/A Objectives: The thyroid disease is the common form of endocrine diseases, which often requires surgical management. Recently, fine needle aspiration biopsy is widely used preoperatively. As a result, some studies show that numbers of thyroid operation have decreased significantly. We performed this study to analyze the clinical features of thyroid diseases and the trend of thyroid operation in Korea. Methods: We reviewed medical records of 1787 cases with thyroid diseases who were managed surgically in Catholic Medical Center, Korea from 1988 to 1992. Results: 1) The percentage of thyroid diseases in total cases undergoing operation in Department of General Surgery was 3%, which tended to decrease with time. 2) 72.9% of thyroid diseases was benign. Among them, the frequency of nodular hyperplasia and follicular adenoma were 67.5% and 18.4%, respectively. 3) The percentage of thyroid cancers in thyroid diseases was 27.1%, which tended to increase with time. The frequency of papillary adenocarcinoma was 78.6%, follicular adenocarcinoma 18.2% and medullary carcinoma 1.5%. 4) Thyroid cancers were most commonly found in the forty and sixty decades. Male: female ratio was 1:8.5. 5) 7.6% of thyroid cancers was accompanied by benign thyroid diseases which were mostly nodular hyperplasia and follicular adenoma. 6) The most common type of operation was lobectomy(82.5%) in benign thyroid diseases, and total thyroidectomy(47.1%) and lobectomy(41.1%) in thyroid cancers. 7) Fine needle aspiration biopsy was performed in 51.7% of thyroid nodules, the frequency of which tended to increase with time. The sensitivity, specificity, false negative rate and false positive rate of this test were 78.3%, 89.4%, 13.7% and 17.2%, respectively. Conclusion: With the use of fine needle aspiration biopsy, numbers of thyroid operation decreased and the percentage of thyroid cancers in thyroid operation increased.

그레이브스 병에서 항갑상성제 투여중 발생한 갑상성기능저하증의 치료

송기호(Ki Ho Song),김병수(Byung Su Kim),장상아(Sang A Jang),안유배(Yu Bae Ahn),한제호(Je Ho Han),유순집(Soon Jip Yoo),이종민(Jong Min Lee),손현식(Hyun Sik Son),윤건호(Kun Ho Yoon),감무일(Moo Il Kang),차봉연(Bong Yun Cha),이광우(Kwang Wo 대한내과학회 1996 대한내과학회지 Vol.51 No.3

N/A Objectives : Antithyroid drug is highly effective and safe in the treatment of Graves` disease. However, some patients may be rendered hypothyroid by large dosage of andithyroid drug : at this point reduction of dosage is common but often difficult to quantitate. Alternatively, combination therapy of antithyroid drug with L-thyroxine is often used, but there are few reports on its long-term effectiveness. Methods : 43 patients with Graves` disease who developed hypothyroidism during methimazole treatment were studied. They received combination therapy of 100mg methimazole with 50 ㎍(group 1, n=16) or 100 ㎍(group 2, n=27) L-thyroxine per day. Hypothyroidism was defined as elevation of seruum thyroid-stimulating hormone (TSH) concentrations above normal ranges. Results : 1) Hypothyroidism occurred within 5.8±3.7(mean ± SD) months after methimazole treatment and mean doses of methimazole were 22,1±8.4mg per day. 2) Serum total thyroxine concentrations increased significantly from 3.7±2,4㎍/dl in the hypothyroid stage to 9.4+3.0 ㎍/dl after 2 months of combination therapy(p<0.0001). 3) Serum TSH concentrations decreased significantly from 34.1+30.6μU/ml in the hypothyroid stage to 3.4+5.2 μU/ml after 2 months of combination therapy(p<0.0001). 4) After 6 months of combination therapy, 74.2Yo of patients became euthyroid. 5) There was no significant difference in the frequency of euthyroid patients after combination therapy betwen group 1 and group 2. Conclusion: These results suggest that long- term combination therapy of antithyroid drug with L-thyroxine in small fixed doses could be effective and convenient to maintain euthyroidism in patients with Graves' disease who developed hypothyroidism during antithyroid drug treatment.

정상한국인에서 혈중 호모시스테인과 엽산 농도 및 Methylenetetrahydrofolate Reductase 유전자 다형성

오기원(Ki Won oh),이원영(Won Young Lee),안유배(Yoo Bae Ahn),송기호(Ki Ho Song),유순집(Soon Jib Yoo),윤건호(Kun Ho Yoon),강무일(Moo Il Kang),차봉연(Bong Youn Cha),이광우(Kwang Woo Lee),손호영(Ho Young Son),강성구(Sung Ku Kang) 대한내과학회 1999 대한내과학회지 Vol.57 No.6

N/A Background : Hyperhomocysteinemia is an independent risk factor for cardiovascualr disease. Recently, a mutation (677C→T) was identified in the methylenetetrahydrofolate reductase gene leading to the substitution of valine(V) for alanine(A). This mutation causes a reduced folate-dependent enzyme activity which leads to increased homocysteine. In this study, we examined the association between the V allele of the methylenetetrahydrofolate reductase gene and serum total homocysteine and folate concentrations in Korean healthy subjects. Methods : In 198 healthy subjects, the methylenetetrahydrofolate reductase genotypes were analyzed by polymerase chain reaction followed by HinfI digestion. Serum total homocysteine and folate concentrations were measured in age- and sex-matched 14 healthy subjects in each of three methylenetetrahydrofolate reductase genotypes. Results : Homozygosity for 677C→T mutation in the methylenetetrahydrofolate reductase gene was found in 31 (15.7%) of 198 healthy subjects. In healthy subjects, those bearing the VV genotype tend to have higher serum total homocysteine concentrations 1.5 μmol/L(18.6%) than AA genotype but this was not statistically significant. Correlation between serum total homocysteine concentrations and other clinical variables showed that serum folate and creatinine were significant. Conclusion : We conclude that although the frequency of VV genotype in Korean healthy subjects is higher than that of other reports, this mutation is not associated with increased serum total homocysteine concentrations in Korean healthy subjects. (Korean J Med 57:1030-1036, 1999)

소의 대동맥 내피세포에서 산화저밀도 지단백에 의한 아포프토시스에 백일해 독소 및 콜레라 독소가 미치는 영향

손호영(Ho Young Son),강성구(Sung Ku Kang),강무일(Moo Il Kang),차봉연(Bong Youn Cha),이광우(Kwang Woo Lee),장상아(Sang Ah Chang),최윤희(Yoon Hee Choi),문성대(Sung Dae Moon),안유배(Yoo Bae Ahn),손현식(Hyun Sik Son),윤건호(Kun Ho Yoon) 대한내과학회 1999 대한내과학회지 Vol.56 No.5

N/A Objectives : Oxidized LDL is thought to play a key role in atherogenesis. Among their wide variety of biological properties, oxidized LDL injures the endothelium as an early event of atherogenesis. However, the mechanisms by which oxidized LDL injures endothelial cells are not definitely known. In order to evaluate the involvement of GTP-binding protein on the mechanism of apoptosis, we studied the effects of pertussis and cholera toxin on oxidized LDL-induced apoptosis in bovine aortic endothelial cells(BAECs). Methods : Oxidized LDL elicited apoptosis in cultured BAECs as shown by characteristic morphological and biochemical changes. Chromatin condensation and nucleus fragmentation were visualized by using fluorescence microscopy of intact cells staining by acridine orange/ ethidium bromide. DNA fragmentation was quantified by an ELISA with specific antibody for bromodeoxyuridine- labelled DNA fragments and confirmed with DNA ladder formation. Results : Studies using a combination of bacterial toxins which change the function of GTP-binding protein suggest that oxidized LDL-induced apoptosis was regulated by GTP-binding protein. Oxidized LDL-induced apoptosis was not changed by pretreatment of BAECs with pertussis toxin. In contrast, pretreatment with cholera toxin completely prevented the oxidized LDL- induced apoptosis. Conclusion : These results show that oxidized LDL induces apoptosis of BAECs and suggest that cholera toxin-sensitive G-proteins are involved in signal transduction of oxidized LDL-induced apoptosis of BAEC.

심근염과 완전 방실차단 및 췌장염이 합병된 장티푸스 1예

안유배,김양리,유진홍,신완식,강문원 대한감염학회 1993 감염 Vol.25 No.3

The report of completer atrioventricular (AV) block wit myocarditis complicating typhoid fever is a rare occurrence. The patient was a 30-year-old woman and experienced fever, chill and abdominal pain two weeks earlier followed by mental confusion. Typhoid fever was confirmed by islolation of S. typhi in blood and stool. Laboratory examination showed the elevation of cardiac enzymes and serum amylase level. On the fifth hospital day, complete AV block developed transiently and disappeared without any intervention. The patient was treated with dexamethasone and a two-week course of chloramphenicol. We report a case of typhoid fever complicated by complete AV block, myocarditis and pancreatitis.

부신부전을 동반한 원발성 양측성 부신 림프종 1 예

이성구,유진영,김정아,최윤석,유수은,임현미,안유배,강진형 대한내과학회 2001 대한내과학회지 Vol.61 No.2

Adrenal gland is an uncommon primary site in non-Hodgkin's malignant lymphoma and reports of primary bilateral adrenal lymphoma with its functional impairment are extremely rare. Only 15 cases were reported during past 50 years, and 11 of them expired within 6 months after diagnosis. A woman came to emergency room with lethargy, abdominal pain and diarrhea. Bilateral adrenal enlargement was found on a previous abdominal sonogram. Under the impression of acute adrenal insufficiency, intravenous hydrocortisone and vigorous saline infusion were given immediately. Later, the endocrine function tests revealed primary hypoadrenalism. The 1st CHOP chemotherapy was administered after tissue diagnosis. This report describes the clinical, radiologic, and pathologic findings in a 58-year-old woman with adrenal insufficiency due to primary bilateral adrenal lymphoma with the review of previous literatures.(Korean J Med 61:184-189, 2001)

제2형 당뇨병 동물모델인 OLETF 쥐에서 장기간 라미프릴 투여가 내당능 및 췌도 베타세포에 미치는 효과

고승현,윤건호,김명미,안유배,송기호,유순집,손현식,차봉연,이광우,손호영,강성구 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:최근 소개된 HOPE(Heart Outcomes Prevention Evaluation)study의 결과에 의하면, 심혈관질환이나 이에 대한 위험인자가 1가지 이상인 9,541명을 대상으로 안지오텐신 전환효소 억제제의 일종인 라미프릴을 투여하여 사망율과 뇌졸증, 심부전, 당뇨병 합병증이 개선되었을 뿐 아니라 다른 항고혈압제에 비해 새롭게 당뇨병으로 진단되는 환자가 줄었음을 보고한바 있다. 이에 저자들은 라미프릴(ramipril)을 제2형 당뇨병 동물모델에 장기간 투여함으로써 당뇨병을 예방하거나 고혈당 상태 또는 인슐린 감수성을 개선시킬수 있는지를 알아보고자 하였다. 방법:생후 24주된 체중 400∼450g의 OLETF와 LETO 쥐를 대상으로 6개월간 라미프릴 경구투여 하였고 혈압, 24시간 단백뇨 및 인슐린 내성검사를 시행하였다. 6개월 이후로는 8주간 투여군과 대조군의 체중을 비슷하게 맞추어 내당능 상태를 평가하였고 이후 다시 8주간 고농도 포도당을 투여하였다. 경구당부하검사를 시행한 후 희생시켜 조직표본을 만들어 guinea pig anti­human insulin 항체로 염색후 DAB로 발색하여 point count 법으로 베타세포를 정량하였고, 면역염색으로 췌도의 변화와 섬유화의 정도를 관찰하였다. 결과:라미프릴을 6개월간 투여하였을 때 OLETF 쥐에서 1)체중 증가가 적었으며 2)경구 당부하검사시 포도당하 면적은 의미있게 감소하였고 3)인슐린 내성검사상 Kitt가 증가되는 경향을 보였으며 4)수축기, 이완기 혈압과 24시간 단백뇨양이 의미있게 감소하였고 5)체중을 맞추면 내당능 상태가 비슷해졌다가 고농도 포도당 주입시 다시 포도당하 면적이 대조군에서 더 증가되었다. 라미프릴 투여군에서 췌도변형 및 파괴와 탈과립, 췌도내 섬유화가 감소하였다. 결론:본 실험에서는 인슐린 비의존성 당뇨병 동물 모델인 OLETF 쥐에서 당뇨병 발생 이전 단계부터 장기간 라미프릴을 투여할 경우 체중증가가 적었고, 투여군과 대조군의 체중을 맞추었을 때는 내당능상태의 차이가 없아가 고혈당 투여시 다시 투여군과 대조군에서 의미있는 차이를 보였다. 라미프릴 투여가 베타세포의 기능면에서 이로운 효과를 보일 것으로 생각되었다. 따라서 비만한 환자에서 안지오텐신 전환효소 억제제의 장기투여는 단백뇨 감소, 혈압강하 효과 이외에 체중증가의 억제 및 당뇨병 발생을 억제할 가능성을 시사한다. Background : In a Heart Outcomes Prevention Evaluation HOPE study, ramipril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, significantly reduced the death rates the number of myocardial infarctions, strokes, heart failure as well as the risk of complications related to diabetes and of diabetes itself. However, it is known that ACE inhibitors improve glucose tolerance or insulin sensitivity or reduce the incidence of diabetes. Methods : 24 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 400 ~ 450 g were used in this study. 4 groups of rats were examined in parallel for 40 weeks. The OLETF rats were randomized for treatment with an aqueous solution of ramipril (5 mg/Kg) daily [OL (RMP), n=10)] and with saline [OL (CON), n=10)]. The LETO rats were also randomized in the same was as the OLETF rats (LT(RMP), n=10, LT (CON), n=10). The blood glucose level, body weight, systolic and diastolic blood pressure was assessed every month. At 3 and 6 months, the 24hrs urinary protein concentration was measured, and as insulin tolerance test and oral glucose tolerance test were conducted in all experimental groups. After 6 months, the body·weight was matched for 2 months in each corresponding group. Subsequently, a 15% sucrose loading was done for 2 months. After the glucose tolerance test, the pancreas was excised and immuno histochemical staining was conducted for insulin to quantify the beta cell mass by a point-counting method. In addition, the islet morphology was evaluated in the pancreas. Results : Ramipril treatment for a period of 6 months improved the 2hr blood glucose level, the area under the glucose curve in the oral glucose tolerance test, insulin sensitivity in addition to lowering significantly systolic and diastolic blood pressure and 24hrs urinary protein level significantly in OLETF rats. Of note, a lower weight gain was observed in both the ramipril-treated animals at 6 months. After weight matching, the AUC g and 2hr blood glucose level values were similar between the corresponding groups, but a 15% sucrose loading worsened the AUC g value. Histologically, the islets were less disorganized and the extent of fibrosis was lower in the ramipril-treated OLETF rats in the trichrome stain. Conclusion : Long-term treatment of ramipril, a long acting angiotensin-converting enzyme inhibitor may be useful for suppressing weight gain and proteinuria in addition to having a protective effect on the islet to harmful stimuli such as hyperglycemia (J Kor Diabetes Asso 25:469~482, 2001).