Diabetes & Metabolism Journal

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Comparison of Operational Definition of Type 2 Diabetes Mellitus Based on Data from Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey: Jong Ha Baek, Yong-Moon Park, Kyung Do Han, Min Kyong Moon, Jong Han Choi, Seung-Hyun Ko; Diabetes Metab J. 2023;47(2):201-210. Published online February 8, 2023; DOI: https://doi.org/10.4093/dmj.2022.0375

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Background
We evaluated the validity and reliability of the operational definition of type 2 diabetes mellitus (T2DM) based on the Korean National Health Insurance Service (NHIS) database.
Methods
Adult subjects (≥40 years old) included in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2017 were merged with those from the NHIS health check-up database, producing a cross-sectional dataset. We evaluated the sensitivity, specificity, accuracy, and agreement of the NHIS criteria for defining T2DM by comparing them with the KNHANES criteria as a standard reference.
Results
In the study population (n=13,006), two algorithms were devised to determine from the NHIS dataset whether the diagnostic claim codes for T2DM were accompanied by prescription codes for anti-diabetic drugs (algorithm 1) or not (algorithm 2). Using these algorithms, the prevalence of T2DM was 14.9% (n=1,942; algorithm 1) and 20.8% (n=2,707; algorithm 2). Good reliability in defining T2DM was observed for both algorithms (Kappa index, 0.73 [algorithm 1], 0.63 [algorithm 2]). However, the accuracy (0.93 vs. 0.89) and specificity (0.96 vs. 0.90) tended to be higher for algorithm 1 than for algorithm 2. The validity (accuracy, ranging from 0.91 to 0.95) and reliability (Kappa index, ranging from 0.68 to 0.78) of defining T2DM by NHIS criteria were independent of age, sex, socioeconomic status, and accompanied hypertension or dyslipidemia.
Conclusion
The operational definition of T2DM based on population-based NHIS claims data, including diagnostic codes and prescription codes, could be a valid tool to identify individuals with T2DM in the Korean population.

Citations

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Effect of Treadmill Exercise on Interleukin-15 Expression and Glucose Tolerance in Zucker Diabetic Fatty Rats: Hee-Jae Kim, Jae Young Park, Seung Lyul Oh, Yong-An Kim, Byunghun So, Je Kyung Seong, Wook Song; Diabetes Metab J. 2013;37(5):358-364. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.358

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Background

Interleukin-15 (IL-15), a well-known myokine, is highly expressed in skeletal muscle and is involved in muscle-fat crosstalk. Recently, a role of skeletal muscle-derived IL-15 in the improvement of glucose homeostasis and insulin sensitivity has been proposed. However, little is known regarding the influence of endurance training on IL-15 expression in type 2 diabetic skeletal muscles. We investigated the effect of endurance exercise training on glucose tolerance and IL-15 expression in skeletal muscles using type 2 diabetic animal models.

Methods

Male Zucker diabetic fatty (ZDF) and ZDF lean control (ZLC) rats were randomly divided into three groups: sedentary ZLC, sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). The ZDF-Ex rats were forced to run a motor-driven treadmill for 60 minutes once a day 5 times per week for 12 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed after 12 weeks. Expression of IL-15 was measured using ELISA in extracted soleus (SOL) and gastrocnemius medial muscles.

Results

After 12 weeks of treadmill training, reduction of body weight was observed in ZDF-Ex compared to ZDF-Con rats. Glucose tolerance using IPGTT in diabetic rats was significantly improved in ZDF-Ex rats. Furthermore, the expression of IL-15 was significantly increased (P<0.01) only in the SOL of ZDF-Ex rats compared to ZDF-Con. Additionally, IL-15 expression in SOL muscles was negatively correlated with change of body weight (R=-0.424, P=0.04).

Conclusion

The present study results suggest that 12 weeks of progressive endurance training significantly improved glucose tolerance with concomitant increase of IL-15 expression in SOL muscles of type 2 diabetic rats.

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Exercise Treadmill Test in Detecting Asymptomatic Coronary Artery Disease in Type 2 Diabetes Mellitus: Mee Kyoung Kim, Ki Hyun Baek, Ki Ho Song, Hyuk Sang Kwon, Jung Min Lee, Moo Il Kang, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Kwang Woo Lee; Diabetes Metab J. 2011;35(1):34-40. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.34

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Background

The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD).

Methods

A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT).

Results

Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years, P=0.008) and duration of diabetes (16.0±7.5 vs. 5.5±5.7 years, P<0.001). The positive predictive value (PPV) of the ETT was calculated to be 47.8%. The PPV of the ETT increased to 87.5% in elderly patients (≥60 years) with a long duration of diabetes (≥10 years). The latter value is similar to that of patients with T2DM who presented with chest discomfort or exertional dyspnea. The PPV of the ETT in symptomatic patients was 76.9%.

Conclusion

In the interest of cost-effectiveness, screening for asymptomatic CAD could be limited to elderly patients with a duration of diabetes ≥10 years.

Citations

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Obese sedentary patients with dyspnoea on exertion who are at low risk for coronary artery disease by clinical criteria have a very low prevalence of coronary artery disease
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Potential association between coronary artery disease and the inflammatory biomarker YKL-40 in asymptomatic patients with type 2 diabetes mellitus
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The Classification of Diabetic Patients Presenting Diabetic Ketoacidosis: The Characteristics of Fulminant Type 1 Diabetes.: Eun Hee Jang, Jeong Eun Yi, Seung Jae Lee, Sang Hoon Chun, Ki Hyun Baek, Ki Ho Song, Soon Jib Yoo, Jong Min Lee, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Mee Kyung Kim; Korean Diabetes J. 2008;32(5):428-434. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.428

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Abstract PDF

BACKGROUND
The aim of the study was to classify newly diagnosed diabetic patients who initially presented with diabetic ketoacidosis (DKA) into specific types of diabetes and to describe the clinical and biochemical characteristics of patients with fulminant type 1 DM in Korea. METHODS: Using data from 4 hospitals of CMC from 1 January 1999 to 1 March 2008, we identified all patients who manifested DKA when they were first diagnosed as diabetes. Clinical and laboratory data were reviewed from medical records. RESULTS: We identified 51 newly diagnosed diabetic patients manifested DKA. Among them, 14 (27.4%) patients were classified as autoimmune type 1 DM, 8 (15.7%) as antibody negative type 1 DM, 5 (9.8%) as fulminant type 1, 16 (31.4%) as type 2 DM and 8 (15.7%) as secondary DM. Five patients who fulfilled the criteria of fulminant type 1 DM were older (32.2 +/- 10.7 vs. 15.7 +/- 4.4 years, P = 0.010), had shorter duration of symptoms (4.2 +/- 2.7 vs.16.7 +/- 15.2 days, P = 0.014) and lower stimulated C-peptide levels (0.1 +/- 0.0 vs. 0.7 +/- 0.6 ng/mL, P = 0.050) compared with patients with autoimmune type 1 DM. CONCLUSION Newly diagnosed diabetic patients presenting with DKA composed of heterogenous types of diabetes. The prevalence of fulminant type 1 diabetes among them was 9.8% and the clinical and biochemical characteristics of these patients were different from those of autoimmune type 1 DM.

Citations

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A Case of Severe Diabetic Ketoacidosis in a Child with Type 2 Diabetes
Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
Journal of Korean Society of Pediatric Endocrinology.2011; 16(1): 46. CrossRef
A Case of Fulminant Type 1 Diabetes Mellitus Complicated with Ischemic Ileitis
Se-Won Oh, Ju-Ri Park, Yun-Jeong Lee, Hee-Yeong Kim, Ji-A Seo, Nan-Hee Kim, Kyung-Mook Choi, Sei-Hyun Baik, Dong-Seop Choi, Sin-Gon Kim
Journal of Korean Endocrine Society.2009; 24(2): 116. CrossRef

Case Report

A Case of Diabetic Ketoacidosis in Gestational Diabetes Mellitus.: Myung Hwan Kim, Eui Dal Jung, Seung Pyo Hong, Gyu Hwan Bae, Sun Young Ahn, Eon Ju Jeon, Seong Yeon Hong, Ji Hyun Lee, Ho Sang Son; Korean Diabetes J. 2007;31(4):368-371. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.368

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Abstract PDF: Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variant severity with onset or first recognition during present pregnancy. Recently the prevalence of GDM in Korean has reported as 1.7~4.0%. Diabetic ketoacidosis is a serious metabolic complication of diabetes with high mortality if undetected. Its occurrence is very rare in gestational diabetes patients, but is harmful to fetal and maternal health. A 26 years-old pregnant woman was admitted at 37 weeks gestation because of progressive generalized weakness, anorexia and weight loss. Initial physical examination reveals that she had been dehydrated, and blood pressure 130/80 mmHg, pulse rate 100/min, respiratory rate 20/min, and body temperature was 36.9 degrees C. Serum glucose was 545 mg/dL, pH 7.282, HCO3- 10.5 mmol/L, urine ketone 3+, urine glucose 2+ when initial laboratory work was done. She was treated with intravenous fluid and insulin under the impression of diabetic ketoacidosis. Her delivery was performed after 24 hours from admission because of suggestive fetal distress. After recovery, she is being treated with insulin at outpatient department. We experienced a appropriately treated case of diabetic ketoacidosis in pregnant woman with GDM, and report it with a literature review.

Original Article

Prevalence of Metabolic Syndrome in Type 2 DM Patients with Non-alcoholic Fatty Liver.: Ji Min Kim, Ja Young Park, Hyn Kyung Nam, Ja Won Kim, Su Kyung Park, Kyung Jin Nam, Mi Kyoung Park, Hye Jeong Lee, Duk Kyu Kim; Korean Diabetes J. 2006;30(6):442-449. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.442

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Abstract PDF

BACKGROUND
Non-alcoholic fatty liver is rendered as one component of metabolic syndrome (MS). We evaluated the prevalence of MS as well as clinical and laboratory characteristics of Type 2 DM patients with non-alcoholic fatty liver. METHODS: Fatty liver group (n = 71) who showed significant fatty change by ultrasonography and age, sex matched control group (n = 40) were studied retrospectively. We compared demographic and laboratory findings and prevalence of MS by modified WHO criteria and new IDF criteria between both groups. RESULTS: There were no significant difference in age, DM duration, BMI, prevalence of hypertension, coronary artery disease, CVA, diabetic retinopathy, neuropathy, nephropathy between both groups. In fatty liver group, the plasma level of FBS, TG, ALT, total protein, albumin and GGT were significantly higher than those of control group (P = 0.033, P = 0.000, P = 0.002, P = 0.008, P = 0.003, P = 0.001). The plasma levels of HDL-C in fatty liver group were significantly lower than those of control group (P = 0.013). The plasma level of FBS, FFA, TG, total protein, albumin, ALT, HOMA(IR) and BMI were significantly related to the severity of fatty liver. The prevalence of MS in fatty liver group was significantly higher than that of control group by modified WHO criteria (P = 0.001) or new IDF criteria (P = 0.036). CONCLUSION: Type 2 DM patients with nonalcoholic fatty liver frequently accompanied the metabolic syndrome. They showed nonspecific changes in the liver function tests.

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Cardio-Metabolic Features of Type 2 Diabetes Subjects Discordant in the Diagnosis of Metabolic Syndrome
Sa Rah Lee, Ying Han, Ja Won Kim, Ja Young Park, Ji Min Kim, Sunghwan Suh, Mi-Kyoung Park, Hye-Jeong Lee, Duk Kyu Kim
Diabetes & Metabolism Journal.2012; 36(5): 357. CrossRef
Metabolic Syndrome and Serum Alanine Aminotransferase Levels in Korean Adults : The Third Korea National Health and Nutrition Examination Survey (KNHANES III), 2005.
Mi Ah Han, So Yeon Ryu, Jong Park, Myung Geun Kang, Ki Soon Kim
Korean Journal of Epidemiology.2008; 30(1): 25. CrossRef

Case Report

A Case of Chronic Inflammatory Demyelinating Polyneuropathy in a Girl with Type 1 DM .: Yi Sun Jang, Hye Soo Kim, Jong Min Lee; Korean Diabetes J. 2006;30(2):130-135. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.130

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Abstract PDF: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disorder characterized by the symmetrical weakness in both proximal and distal muscles for at least 2 months, hyporeflexia or areflexia, nerve conduction abnormalities, and high CSF protein level. Diabetes mellitus, monoclonal gammopathy, hepatitis C infection, HIV infection, SLE, Sjogren syndrome and lymphoma have been associated with CIDP. The incidence of CIDP in diabetes is not known exactly, but occur more common among diabetic than nondiabetic patients. There is sometimes a difficulty in distinguishing between diabetic polyneuropathy and CIDP, but differential diagnosis is important because CIDP is treatable with immune-modulating therapy. We report a case of CIDP in 22-year-old girl with type 1 DM who presented with generalized motor weakness and walking disturbance which were treated with iv immunoglobulin

Original Articles

The Influence of Metabolic Syndrome on the Intima-Medial Thickness and Cardiovascular Risk Factors in Type 2 Diabetes.: Kwang Pyo Son, Young Je Chae, Tae Yu Lee, In Kyung Jeong, Mina Hur, Gu Young Jo, Young Lee, Seong Jin Lee, Chul Young Park, Ki Won Oh, Eon Kyung Hong, Hyun Kyu Kim, Jae Myoung Yu, Doo Man Kim, Sung Hee Lim, Moon Ki Choi, Hyung Jun Yoo, Sung Woo Park; Korean Diabetes J. 2004;28(5):392-406. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Metabolic syndrome (MS) is usually present in type 2 DM (T2DM), and it is associated with atherosclerosis. The aim of this study is to exam the influence of MS on the intima-medial thickness(IMT) and the cardiovascular risk factors for type 2 diabetic patients. SUBJECTS AND METHODS: A cross sectional study was performed on 82 patients with Type 2 diabetes mellitus (DM) and 84 healthy controls. MS was defined according to the NCEP-ATP III criteria. Those subjects with any history of cerebro vascular accident, ischemic heart disease or acute inflammation were excluded. The cardiovascular risk factors (hsCRP, lipid profile, homocysteine, and uric acid), the status of glucose metabolism (HbA1c, fasting glucose, insulin, and HOMA-IR), the diabetic microvascular complications and the IMT at both common carotid arteries were measured. RESULTS: 1) For patients with T2DM, the levels of waist circumference, blood pressure, TG (1.7+/-1.4 vs 2.2+/-1.4 mmol/L), HDL-C (1.5+/-0.4 vs. 1.3+/-0.3 mmol/L), LDL-C (2.7+/-0.7 vs 3.1+/-0.9 mmol/L), TC/HDL-C (3.5 vs. 41), log of (hsCRP) (-0.11+/-0.4 vs 0.17+/-0.4), mean carotid IMT (0.63+/-0.12 vs. 0.74+/-0.12 mm) and max IMT (0.68+/-0.14 vs. 0.86+/-0.15 mm) were significantly different from the healthy control group. 2) The prevalence of MS in the T2DM groups was 64%. However, a decrease of the waist circumference, as measured by the modified Asian criteria, increased the crude prevalence of MS by up to 75%. 3) Diabetic patients with MS had a higher incidence of hypertension, a lower level of HDL-C, and higher levels of waist circumference, HOMA-IR, TG, and TC/HDL-C, a greater extent of microvasculopathy, an increased log (hsCRP), homocysteine, and carotid IMT than did diabetic patients without MS. 4) Among the component of MS, the presence of hypertriglyceridemia had an influence on the IMT mean and max. 5) The carotid IMT of patients with DM correlated with age, homocysteine, log (hsCRP), and uric acid on univariate analysis, and age and homocysteine we found to be independent risk factors of carotid IMT on multivariated analysis. CONCLUSION: Metabolic syndrome in subjects with glucose intolerance increases the risk of atherosclerosis.

Evaluation of Glycemic Control in Type 2 Diabetic Patients have been Treated in General Hospital.: Joung Ho Park, Kwan Woo Kim, Eun Jin Kang, Tak Young Kim, Sa Ra Lee, Su Chan Bae, Mi Kyung Kim, Sin Yeong Choi, Jeong Hyun Park; Korean Diabetes J. 2004;28(3):208-218. Published online June 1, 2004

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Abstract PDF: BACKGROUND
Good metabolic control is one of the most important parts of managing diabetes. Several studies in western countries have shown glycemic control in type 2 diabetic patients to be poorer than expected. Similar reports in Korea are very limited. Therefore, this study was performed to estimate the degree in glycemic control of type 2 diabetic patients that have been treated in general hospitals in Korea. METHODS: This was a cross-sectional retrospective study conducted on 1012 type 2 diabetic patients treated at the Maryknoll Hospital. Subjects with type 1 diabetes or a treatment duration of less than 6 month were excluded. The glycemic control was estimated by HbA1c and the clinical characteristics, including duration of diabetes, age, height and body weight, checked. The treatment methods were divided into four groups, namely diet, oral hypoglycemic agent, insulin alone, and insulin and oral hypoglycemic agent combination. Data were analyzedsed by SPSS version 11.0. RESULTS: The mean age, BMI, duration of diabetes and HbA1c of the subjects were 61.6+/-9.8 years, 24.6+/-3.2kg/m(2), 12.1+/-6.5 year and 7.6+/-1.3%, respectively, and the percentage of those achieving the goal of glycemic control(HbA1c<7%) was 35.7%. Those who achieved glycemic control were older than those who could not and also had a shorter duration of diabetes(p<0.001). There were no significant differences in the BMI, gender and HbA1c levels before treatment between the four groups. The subjects on diet treatment had a lower mean HbA1c level than those on insulin alone or combined therapy(p<0.05) CONCLUSION: The percentage of type 2 diabetic patients in good glycemic control in our general hospital was less than 40%, which was similar to previous western data. It is our suggestion that a large nationwide study is required to more accurately evaluate the state of glycemic control and find the reasons why certain patients could not reach this goal.

Plasma and urinary Vascular Endothelial Growth Factor and Diabetic Nephropathy in Type 2 Diabetes Mellitus.: Jeong Heon Oh, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dae Ryong Cha, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(2):111-121. Published online April 1, 2004

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Abstract PDF: BACKGROUND
VEGF(vascular endothelial growth factor) has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes mellitus. However, its precise role in diabetic nephropathy is still unknown. Our aims were to determine whether alterations of plasma and urinary VEGF levels were related to diabetic microvascular complications, especially nephropathy in type 2 diabetic patients. METHODS: 107 type 2 diabetic patients, without non-diabetic kidney diseases, and 47 healthy control subjects were studied. The urinary albumin excretion was defined as the albumin-to-creatinine ratio(ACR) in 24 hour urine samples. The study subjects were divided into four groups: a nondiabetic healthy control group(n=47), a normoalbuminuric diabetic group(ACR <30mug/mg, n=37), a microalbuminuric diabetic group(ACR 30~299mug/mg, n=37) and an overt proteinuric diabetic group(ACR=300mug/mg, n=33). The plasma and urinary VEGF levels were measured in these subjects by enzyme-linked immunosorbent assays. RESULTS: 1) The urinary VEGF concentrations were significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage(log VEGF/Cr, normoalbuminuria; 4.33+/-1.06 vs. control; 3.53+/-0.79, p=0.009). The levels of urinary VEGF excretions increased with advancing diabetic nephropathy stage. 2) The plasma and urinary VEGF levels were higher in the hypertensive diabetic than the normotensive diabetic patients. 3) In the diabetic patients, the level of plasma VEGF was positively correlated with the BUN(r=0.398, p=0.039) and urinary ACR (r=0.251, p=0.044). The level of urinary VEGF was positively correlated with the urinary ACR(r=0.645, p<0.001), and creatinine(r=0.336, p=0.009), but negatively correlated with the level of serum albumin(r=-0.557, p<0.001). Both the levels of urinary VEGF and serum creatinine were independently correlated with the urinary ACR. CONCLUSIONS: The excretion of urinary VEGF increased at a relatively earlier stage in diabetic nephropathy and was significantly correlated with the excretion of urinary albumin. These results suggested the possibility of urinary VEGF as a sensitive marker or the detection of diabetic nephropathy and in predicting disease progression.

Change of Cardiac Function and NT-proBNP According to Degree of Albuminuria in Type 2 Diabetic Patients.: Bon Jeong Ku, Jeong Hee Kim, Jin Ok Jeong, Eun Seok Jeon, Dong Hyun Seo, Jae Min Lee, Si Wan Choi, In Whan Seong, Young Kun Kim; Korean Diabetes J. 2004;28(1):28-35. Published online February 1, 2004

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Abstract PDF: BACKGROUND
The prevalence of diabetes mellitus has increased recently. The morbidity and mortality of diabetic patients are mainly caused by chronic complications, especially cardiovascular events. N-terminal proB-type natriuretic peptide(NT-proBNP) is a neurohormone that is secreted from ventricular myocardium due to myocardial dilatation or pressure overload. NT-proBNP has prognostic value, and reflects cardiac function in patients with myocardial infarction or heart failure. This study was performed to evaluate functional changes of the heart, according to the degree of albuminuria and the prognostic value of NT-proBNP in type 2 diabetic patients. METHODS: 57 patients with type 2 diabetes were divided into three groups according to their degree of albuminuria, these being normal(below 30mg/day), microalbuminuria(30 between 300mg/day) and overt proteinuria(over 300mg/ day). The clinical parameters in each of the patients were evaluated, echocardiography performed and the levels of NT-proBNP checked, and compared between the three groups. RESULTS: Of the 57 patients with type 2 diabetes the male:female ratio of 32:25, with mean age, duration of diabetes and BMI of 55.8+/-10.1 and 11.3+/-8.2 years, and 23.2+/-4.0kg/m2, respectively. Twenty-eight patients showed normal(49.1%), 15 microalbuminuria(26.3%) and 14 overt proteinuria(24.6%). The age, BMI, diastolic BP and glycosylated hemoglobin showed no significant difference between the three groups. The duration of diagnosed diabetes was significantly longer, the systolic blood pressure and serum creatinine levels significantly higher and the serum hemoglobin significantly lower (p<0.05) in the overt proteinuria compared to the normal group. The duration of diabetes was significantly longer and serum creatinine levels significantly higher in the overt proteinuria than the microalbuminuria group(p<0.05). The echocardiographic data showed no difference among the groups. The NT-proBNP levels also showed no significant difference, but tended to be elevated toward albuminuria. CONCLUSION: The cardiac function and NT-proBNP levels showed no significant difference between each of the albuminuric groups. This study suggests that the degree of albuminuria is not a predictive factor for changes of the cardiac function and NT-proBNP levels

The Effect of Alpha-lipoic Acid on Endothelial Dysfunction in Postmenopausal Uncomplicated Type 2 Diabetes.: Ho Chan Cho, Sang Jun Lee, Mi Jung Kim, Hye Sun Kim, Tae Sung Yun, Sung Jae Kim, Sang Hyon Kim, Seung Ho Hur, Kyo Chul Moon, Jae Hoon Bae, In Kyu Lee; Korean Diabetes J. 2002;26(4):242-252. Published online August 1, 2002

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Abstract PDF: BACKGROUND
Recently, increased oxidative stress has been proposed as a major cause of vascular complications of patients with diabetes mellitus. Increased generation of oxygen free radicals in patients with diabetes mellitus could deplete cellular antioxidants and inactivate endothelial dependent vasodilating factor (EDRF), such as nitric oxide (NO). The purpose of this study was to evaluate whether the antioxidant alpha-lipoic acid (ALA) is effective in endothelial dysfunction of brachial artery, which induced by increased oxidative stress in postmenopausal diabetic women using high resolution ultrasound technique and initial reaction time (IRT) measurement. METHODS: We enrolled 11 menopausal women (mean age, 56.5+/-5.1 years) with uncomplicated type 2 diabetes. All patients were taking 1200 mg of ALA (Thioctacid(R), Bukwang, Korea). We measured of superoxide anion (O2-) in neutrophils as a marker of oxidative stress. Flow-mediated dilation (FMD) was measured using a high-resolution ultrasound. RESULTS: After treatment of ALA, fasting blood glucose was decreased significantly, the endothelium-dependent vasodilation of the brachial artery was increased, and O2- production was also decreased significantly. CONCLUSION: These results show that short term ALA treatment could improve the endothelial dysfunction in patients with type 2 diabetes mellitus. This improvement might be related with the antioxidants effect of ALA.

The Prevalence of Chronic Complications in Non-Insulin Dependent Diabetic Patients.: Jick Hwa Nam, Soon Hee Lee, Hyun Jeong Lee, Jeung Hun Han, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 1999;23(5):702-714. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The chronic complications of diabetes mellitus are important prognostic factors of diabetics. The pathogenic mechanisms have not been known exactly and the prevalence is different according to the race and the reporter. In general, the development of diabetic microangiopathy depends on the duration and the severity of disease, while that of macroangiopathy does not. This study was undertaken to investigate the prevalence of diabetic chronic complications according to age and duration of diabetes and to elucidate associated factors and correlation of chronic complications. METHODS: We studied 1,270 patients with non- insulin dependent diabetes mellitus (NIDDM) who visited the Endocrine-metabolism clinic at Kyungpook National University during the period from February 1992 to September 1996. We investigated prevalence, severity, associated factors and correlation of chronic vascular complications, including micro- and macroangiopathy. RESULT: 1) The ratio of male to female was similar and the average duration was 7.8 years. Diabetes mellitus was most prevalent in the 6th decade and the 1-5 years of diabetes duration. 2) The prevalences of retinopathy, nephropathy and peripheral polyneuropathy were 47.8%, 31.9% and 41.0%, respectively. Macrovascular complications were found in 6.2% of patients and the prevalences of coronary artery disease, cerebrovas-cular disease and peripheral artery disease were 2.4%, 3.4%, 0.4%, respectively. Prevalence of diabetic foot was 4.4%. 3) The prevalence and severity of microvascular complications increased as the age and diabetic duration of patients increased. In the group of same age, the prevalence of microvascular complications increased as the duration of diabetes increased. However, prevalence of macrovascular complica-tions especially coronary artery disease depended on the age, but not the duration of diabetes (p<0.05). 4) In the group over 10 years of diabetes, the fasting blood glucose, age and serum creatinine levels were increased, while hemoglobin and total protein levels were decreased than other groups (p<0.05). 5) The development of diabetic retinopathy was related to the duration, fasting blood glucose, albumine excretion rate and serum creatinine. The nephropathy was related to the duration and systolic blood pressure. The peripheral polyneuropathy was related to the duration, fasting blood glucose and body mass index. Macrovascular complications-particularly, coronary artery disease-were related to the age of diabeties (p<0.05). 6) There was significant relation between development of retinopathy, nephropathy and neuropathy but no relation between development of micro and macrovascular complications (p<0.05). CONCLUSION : The prevalence of microvascular complications in non-insulin dependent diabetics increased as the duration and the age of diabetics increased. The development of microvascular complications was related to the duration of disease and the glycemic control. There was relation between development of retinopathy, nephropathy and neuropathy. The development of macrovascular complications, however, was related to the age of diabetics but not to the microvascular complications. Our results suggest that different pathogenic mechanisms may be involved in the development of micro- and macrovaseular complications of diabetes mellitus.

The Comparison between Doppler Ultrasonography and Digital Infrared Thermographic Imaging (DITI) in Detecting the Diabetic Peripheral Angiopathy.: Yoon Sang Choi, Hyun Ju Um, Seung Oh Song, Si Yong Kim, Byong Ik Kim, Young Uk Lee, Seok Won Park, Yoo Lee Kim, Hwa Young Lee, Yong Wook Cho, Sang Jong Lee; Korean Diabetes J. 1999;23(5):686-694. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The frequency of nontraumatic lower extremities amputation has significantly increased in patients with type 2 diabetes (DM). Digital Infrared Thermographic (DITI) has been used to demonstrate the skin temperature and its change. mellitus Imaging regional Doppler ultrasonography was developed to show excellent images of superficial arteries. In this study, we observed the relationship between DITI and doppler ultrasonography for detection or evaluation of diabetic peripheral angiopathy. METHODS: 71 patients with type 2 DM were divided to groups with and without peripheral arterial obliteration (PAO) by ankle pressure index (API). For all patients, doppler ultrasonography of lower extremities was performed in measuring inner diameter, wall thickness and calcification of femoral, popliteal and dorsalis pedis artery. DITI was done also. We analized the result of doppler ultrasono-graphy and DITI findings. RESULT: 1) In clinical characteristics of patients between nonperipheral arterial obliteration (NPAO) and PAO : there was no significant differences between two groups with respect to age, sex, smoking, BMI (body mass index), FPG (fasting plasma glucose)/2HPG (2 hour plasma glucose), HbA(1C), serum lipid profile and/or the frequency of NPDR (nonproliferative diabetic retinopathy). However, the number of patients with hypertension and 24hr urine total protein amount were significantly increased in PAO group. 2) The results of doppler ultrasonographic imaging of lower extremities: In PAO group, inner diameters of common femoral artery and dorsalis pedis artery were significantly narrower than in those of NPAO group. However, no difference was detected in respect to vessel wall thickness. The numbers of calcified vessel wall have significantly increased in all vessels in PAO group 3) The results of DITI patterns of big toes after cold stimulus: (1) In 49 patients with NPAO: 11 showed as normal, 14 an increased, 15 a decreased, and 9 flat patterns, respectively. (2) All of 22 patients with PAO showed abnormal patterns. Among them, 2 showed a decreased, but 20 a flat pattern. 4) The comparison between the results of doppler ultrasonography and DITI: In all groups, inner diameter of common femoral artery, which was measured by doppler ultrasonography, were narrow in the flat pattern. Also, the number of calcified vessel walls in common femoral artery and dorsalis pedis artery increased more in the same patterns. No significant difference of vessel wall thickness was found between both groups. CONCLUSION : Vasoreaction of lower extremities after cold stimulus was mainly related to PAO of the common femoral artery and dorsalis pedis artery. DITI is a useful method used in detecting the early state of artherosclerosis. As a result, it can be employed in early prevention and treatment of diabetic angiopathy. If DITI is combined with doppler ultrasonography, we can practice more precise diagnosis and follow-up in diabetic peripheral angiopathy.

The Relation of Carotid Arterial Plaque to Apolipoprotein E Polymorphism in Subjects with Type 2 Diabetes Mellitus.: Seung Hyun Lee, Chi Young Moon, Jeong Ki Choi, Kyoung Deok Shin, Hyun Kag Kim, Wan Hee Yoo, Tae Sun Park, Hong Sun Baek, Dal Sik Kim; Korean Diabetes J. 1999;23(5):678-685. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Apolipoproiein (Apo E) is one of the major proteins involved in catabolism of triglyceride (TG)-rich lipoproteins. Apo E poly-morphism contributes to the variation in plasma cholesterol levels and may influence the risk of atherosclerosis. This study was undertaken to know whether apo E polymorphism is associated with carotid artery intima, media thickness and plaque formation in type 2 diabetic patients. METHODS: We determined the apo E genotypes of 130 type 2 diabetic patients by modified Amplification Refractory Mutation System (ARMS) and classified all patients into E2, E3, E4 subgroups. The carotid artery IMT and plaque formation were determined with B-mode ultrasonography. RESULT: The apo E allele frequency of patients were E2 11.5%, E3 76.2%, FA 12.3% (p=0.0001). LDL-cholesterol levels were higher in patients with E4 allele, and HDL-cholesterol levels were lower in patients with FA allele than in patients with E2, E3 subgroups. The patients with carotid artery plaque have more E4 alleles in comparison to the patients without it(p=0.0001). FA allele group has higher carotid IMT than E2 and E3 allele groups (p=0.013). CONCLUSIONS: Apo E polymorphism is associated with carotid artery IMT and plaque formation in type 2 diabetic patients. Patients with E4 isoform is more likely to develop the atherosclerosis, carotid and coronary artery diseases than other apo E isoforms.

Clinical Study on Cerebral Infarction Complicated with CIDDM pateints.: Sang Jong Lee, Yoon Sang Choi, Seong Chun Shim, Hi Moo Lee, Kwon Choi, Hwa Young Lee; Korean Diabetes J. 1999;23(4):585-591. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus increases the risk of cardiovascular disease by two-fold and ischemic cerebrovascular disease by two to four-fold compared with the risk for non-diabetic patients. In patients with NIDDM, the risk of athero- thromboembolic cerebral infarction is known to be increased. We evaluated the significance of clinical variables with respect to the risk of cerebral infarction in NIDDM patients. METHODS: We assessed clinical variables retrospectively in 170 patients (90 men, 80 women) from April 1, 1991 through March 31, 1996, divided into 3 groups;100 NIDDM patients with cerebral infarction (58 men, 42 women), 40 NIDDM patients (17 men, 23 women) and 30 non-diabetic patients with cerebral infarction(15 men, 15 women). We evaluated 130 patients with cerebral infarction employing brain CT or MRI. RESULTS: 1) The mean values of age, serum total cholesterol, LDL, TG, HbA1C, systolic and diastolic BP were significantly higher in patients with NIDDM complicated by cerebral infarction than in those without cerebral infarction. 2) There were no statistically significant differences in body mass index (BMI), duration of DM and HDL between the two groups, respectively. 3) Diabetic retinopathy (especially, proliferative retinopathy) andmacroproteinuria(550 mg/day) were found significantly higher in diabetic patients with cerebral infarction than in those without cerebral infarction. 4) Multiple lacunar infarctions were more frequently observed in patients with NIDDM than non-diabetic patients with cerebral infarction. However, there were no statistically significant differences between the two groups. Conclusion: We suggest that increased age and HbAlC, hypertension, dyslipidemia, macroproteinuria and proliferative diabetic retinopathy could be associated with the risk of cerebral infarction in patients with NIDDM. The results showed that multiple lacunar infarctions were more frequent in patients with NIDDM than in non-diabetic patients. However, there were no statistical significances between the two groups.

Solyble ICAM-1 and BCAM-1 in Patients with NIDDM.: Young Min Kim, Yong Gi Kim, Seok Man Son, In Ju Kim, Seok Dong Yoo, Young Keun Choi, Chang Won Lee, Jun Hyup Ahn; Korean Diabetes J. 1999;23(3):315-325. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The development of vascular complications in diabetic patients changess their quality of life, as well as shortens their life expectancy. It has been recently discovered that the expressions of the cell adhesion molecules initiate vascular complications and have major effects on the progress of atherosclerosis. We measured soluble forms of intercelluar adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1), the immunoglobulin superfamily members of the cell adhesion molecules concerning firm adhesion and transendothelial migration during leukocyte- endothelial cell interactions to clarify their concentrations and their relation with glycemic control and plasma lipoproteins as well as differences in concentration according to the presence of diabetic microvascular complcations in non-insulin dependent diabetes mellitus (NIDDM) patients. METHODS: Serum sICAM-1and sVCAM-1 levels were measured by commercial ELISA kits in 35 NIDDM patients without overt macrovascular complications of diabetes or acute inflammation and 10 normal controls matched with body mass index and plasma lipoprotein levels. The mean age of the patient group and control group was 55.82+3.43 years and 46.30+15.15 years, respectively. Clinical characteristics and laboratory parameters such as fasting plasma glucose, HbAplasma lipoproteins and status of diabetic microvascular complications were evaluated and their relations with the levels of sICAM-1 and sVCAM-1 were analyzed. RESULTS: 1) The level of sICAM-1 in NIDDM patients was significantly higher than that of normal controls (15.79+6.21 ng/mL vs. 11.98+2.35, p<0.05). sVCAM-1 showed the trend in elevation in NIDDM patients, but had no statistical significance (p=0.053). 2) The level of soluble ICAM-1 was positively correlated with HbAlc>, and plasma triglyceride levels (r=0.38, p<0.05, r=0.36, p<0.05, respectively) and negatively correlated with HDL (r=-0.44, p<0.01) in the patient group. There were no differences in their age, sex, and the presence of hypertension with the levels of sICAM-1 and no relation between sICAM-1 level and body mass index, plasma total cholesterol, Lp (a), fasting plasma glucose, fasting plasma C-peptide levels. Plasma LDL was partially correlated with the level of sICAM-1, but failed to reveal statistical significance. sVCAM-1 level was not correlated with any parameters discussed above, but had a tendency of correlation with HbAlc level (r=0.31, p=0.06). 3) No significant correlation was noted between the levels of sICAM-1 or sVCAM-1 and the duration of diabetes. 4) Both sICAM-1 and sVCAM-1 levels were significantly higher in patients with diabetic nephropathy when compared to patients without nephropathy (21.58+7.11 ng/mL vs. 14.06+4.84 ng/mL, p<0.05, 37.51+16.91 ng/mL vs. 22.26+8.89 ng/mL, p<0.05, respectively, but such differences were not noted when patients were classifed according to the presence of retinopathy or neuropathy. 5) Both sICAM-1and sVCAM-1 levels did not correlate in the patient group or in the normal control group. CONCLUSION: These findings suggest that enhanced expression of the the endothelial cell adhesion molecules in diabetic patients can be explained by endothelial dysfunction caused by persistent hyperglycemia and dyslipidemia. Furthermore, it can be suggested that endothelial dysfunction may be initiated by diabetes itself and can be deteriorated by combined dyslipidemia. From the result of the elevated concentrations of sICAM-1 and sVCAM-1 in patients with diabetic nephropathy, we can suggest that the elevation of these cell adhesion molecules may be useful as markers in diabetic nephropathy. More selective and prospective studies are necessary in order to reveal thesignificance of these cell adhesion molecules in the pathogenesis of diabetic vascular complications.

Serum Levels of Sialic acid, CRP, and TNF-a in Type 2 Diabetin Patients with Syndrome X.: Dong Seop Choi, Sang Jin Kim, Se Hyeon Paek, Kyung Mook Choi, Nan Hee Kim, Jung Heon Oh, Young Hyun Kim; Korean Diabetes J. 1999;23(3):307-314. Published online January 1, 2001

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Abstract PDF: diabetic nephropathy and macro- vascular complications. Thus it is possible to conBACKGROUND: Type 2 diabetes is associated with increased blood concentrations of acute phase reactants including; sialic acid, ai-acid glycoprotein, serum amyloid A, and the main cytokine mediator of acute phase response, interleukin-6. Through the action of cytokines on many tissues, acute phase response could be a major contributor of biochemical and clinical features of metabolic syndrome X and type 2 DM. We investigated whether sialic acid, CRP, and TNF-a levels were elevated in type 2 diabetic patients who had features of syndrome X and whether they were correlated with diabetic vascular complications. METHODS: Group 1 was type 2 diabetic patients with any of 4 or 5 features of syndrome X (n=24). Group 2 was type 2 diabetic patients with 0 or 1 features of syndrome X (n=29), and group 3 was healthy nondiabetic control subjects (n=19). We compared the levels of sialic acid, CRP, and TNF-a in group 1, 2 and 3. We also observed the relationship between sialic acid, CRP, TNF-a levels and diabetic micro, macrovascular complications and studied the correlation between these markers and components of syndrome X. RESULTS: Group 1 had significantly higher sialic acid levels than group 2 (68.3+19 vs. 59.9+9.7 mg/dL, p=0.047). But the CRP, and TNF-a levels were similar in three groups. Serum sialic acid levels were signifieantly higher in proteinuria group than in normo- and microalbuminuria groups (81+27.6 vs. 59.9+7.1, 61.2+7.9 mg/dL, p=0.001, 0.005). Serum CRP levels were also higher in proteinuria groups (32.9+59.8 vs. 6.4+1.9, 6.0+3.1mg/L, p=0.017, p=0.037). Serum sialic acid levels were significantly higher in the macrovascular complication group (70.5 +21.3 vs. 60.5+ 6.8 mg/dL, p=0.015). Levels of sialic acid were correlated with urinary albumin excretion rate, log triglyceride, CRP, and fasting C-peptide. Levels of CRP were correlated with sialic acid and fasting C-peptide. CONCLUSION: Serum sialic acid levels were significantly elevated in type 2 diabetic patients who had features of syndrome X, and were also elevated in patients with sider that the mechanisms involved in the acute phase response can contribute to the pathophysiology of type 2 diabetes and syndrome X. Vascular complications do further increase stress reactions in type 2 diabetes.

Risk Factors for Peripheral Arterial Disease as Screened by Plethysmography in Patients with NIDDM.: Hyuk Jae Chang, Dae Jung Kim, Byoung Joo Choi, Young Guk Ko, Churl Woo Ahn, Dong Ryeol Ryu, Yong Seok Yun, Seol Hye Han, Jae Hyun Nam, Seok Won Park, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Won Heum Shim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1999;23(2):172-181. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Peripheral arterial disease (PAD) is one of the clinical manifestations of the atherosclerotic disease process. Early onset and rapid progression of PAD in diabetic patients has been well documented. PAD in diabetic patients has also been associated with an increased risk for total and cardiovascular mortality. Plethysmography is a noninvasive test to screen for the presence of PAD. Thus the aim of this study is to assess the risk factors for PAD screened by plethysmography in NII)DM patients. METHODS: A total of 289 NIDDM patients who undlerwent plethysmography were entered into our annlysis. Clinical characteristics of 38 patients with an ankle-brachial index of <0.9 (group B) were conapared with those of 231 patients with an ankle-brachial index of >1.0 (group A). RESULTS: Abnormalities in plethysmographic findings were found in 45.7% of diabetic patients. Age, duration of diabetes, hypertension, smoking, previous history of vascular diseases, HDL cholesterol, TC/HDL, and LDL/HDL appeared to be factors significantly related to PAD. Fasting sugar, HbAlc, total cholesterol, LDL cholestero1, trigly ceride, fibrinogen, lipoprotein(a), and waist-hip ratio were not significantly different between the two groups. The multiple logistic regression analysis showed the signficant contribution of the previous history of vascular disease (p=0.0028) and age (p-0.0115) to PAD in diabetic patients. CONCLUSION: The prevalence of PAD defined by plethysmography in our subjects was 45.7% higher than expected, suggests that efforts for early detection and prevention of PAD should be emphasized in diabetic patients.

The Risk Factors of Diabetic Retinopathy in NIDDM Patients.: Won Tae Seo, Seung O Song, Sy Young Kim, Yoon Sang Choi, Hye Ran Jang, Sang Jong Lee; Korean Diabetes J. 1999;23(2):162-171. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic retinopathy, which is one of the microvascular complications, has been shown to be related to visual disturbance and blindness. In this report we examined the risk factors for diabetic retinopathy in NIDDM patients and investigate the relationship between the prevalence of diabetic retinopathy and other risk factors. METHODS: Clinical characteristics and laboratory findings such as HbAlc, fasting plasma glucose, hemoglobin, BUN, creatinine and lipid profile and treatment modality were evaluated and their relation with diabetic retinopathv were analyzed. Fundoscopic examinations of the retina were performed using direct/indirect opthalmoscopy and fundus photograph. The grade of retinopathy was judged from the results of opthalmological examinations and were elassified into non-proliferative retinopathy and proliferative retinopathy. RESULTS: A total of 163 patients with NIDDM (M/F=59:104) were evaluated. Of these patients, 80 of them developed diabetic retinopathy. 71 patients were detected to have non-proliferatie and 9 patients to have proliferative retinopathy. The presence of proteinuria, the long diabetic duration, hypertension, anemia, the high plasma glucose levels, the high level of HbA1c, old age were all associated with the development of diabetic retinopathy. I-lowever, sex, body mass index, type of therapy, lipid profile, C-peptide levels, insulin levels had little impact on the development of retinopathy. CONCLUSIONS: The presence of proteinuria, the long diabetic duration, hypertension, anemia, high plasma glucose levels, high HbA., and old age are important risk factors for the development of rc;tinopathy in patients with NIDDM.

Plasma Concentrations of Plasminogen Activator Inhibitor-1(PAI-1) and Lipoprotein(a) in Non-Insulin-Dependent Diabetes Mellitus with Peripheral Vascular Disease.: Sung Jin Nam, Sung Rae Cho, Choo Sung Kim, Sang Gyun Woo, Hee Jin Choi, Sang Ki Kim, Jae Hong Park, In Kyu Lee, Seong Bum Han, Seung Yup Han, Chung Chul Kim; Korean Diabetes J. 1999;23(1):55-61. Published online January 1, 2001

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Abstract PDF: OBJECTIVES
The plasminogen activator inhibitor-1 (PAI-I) and lipoprotein(a) are considered as important fibrinolysis inhibitors. We evaluated PAI-1 and Lp(a) concentrations in Korean non-insulin- dependent diabetes mellitus (NIDDM) patients with or without peripheral vascular disorder. METHODS: By using National Diabetes Data Group (NDDG) criteria as a diabetes mellitus diagnostic criteria, a total of 127 Korean NIDDM patients were seleeted. The ankle brachial index was measured by segrnental volume plethysmography to diagnose peripheral vascular disease. We also examined clinical and biochemical parameters in NIDDM patients. RESULTS: The duration of diabetes, systolic and diastolic pressures was significantly higher in diabetic patients with peripheral vascular disease (Group 2) than in diabetic patients without peripheal vascular disease (Group 1). The 24 hour urine microalbumin and PAI-1 levels in Group 2 were also significantly higher and the HDL-cholesterol level was lower than in Group 1. There were significant correlations between the plasma level of PAI-1 and BMI (r=0.466, p=0,007) or C-peptide level(r=0.517, p=0.012). Multivariate logistic regression analysis showed that Lp(a) and PAI-1 are independent risk factors for peripheral vascular disease. CONCLUSION: In the light of these results, it seems reasonable to suggest that high levels of PAI-1 and Lp(a) in NlDDM patients may play a role in the pathogenesis of peripheral vascular disease.

Relationship between Circadian Mean Blood Pressure ( MBP ) Rhythm and Microvascular Complications in Normotensive NIDDM Patients.: Hyang Kim, Seong Chun Shim, Dae Jung Shim, Hi Moo Lee, Yoon Sang Choi, Jin Ho Kang, Byung Ik Kim, Sang Jong Lee, Yoo Lee Kim, Yoon Kyung Cho; Korean Diabetes J. 1998;22(4):552-560. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Thanks to ambulatory 24-h blood pressure monitoring device, it became possible to investigate circadian pressure rhythm under variable physiologic and pathologic conditions. Moreover, ambulatory 24-h blood pressure has allowed us to detect in diabetic patients unsuspected abnormalities of the blood pressure circadian rhythm and to relate them to autonomic or renal dysfunction. This study was designed to evaluate the relationship between circadian rhythm of mean blood pressure (MBP) and microvascular complications in patients with noninsulin-dependent diabetes mellitus (NIDDM). METHODS: 24hr blood pressure monitoring was applied to 63 normotensive NIDDM patients(mean age 55.3+7.2 year, male: 35, female: 28) who have been hospitalized at our hospital from March 1993 to December 1994 to measure systolic, diastolic and hourly mean pressure of daytime, night time and 24hr. In addition, NIDDM patients were divided into 2 groups according to 24 hour circadian blood pressure rhythm by measuring hourly mean pressure. These 2 groups, group 1 who had a circadian MBP rhythm, with a peak value in the afternoon and group 2 who had an absent or reversed circadian rhythm with a peak value during the night time, were observed to evaluate the frequency of diabetic microvascular complication. RESULTS: The mean systolic and diastolic ambulatory BP values were significantly higher in the group 2 NIDDM during night-time compared with control group and group 1(systolic pressure: F=12.53 p<0.05 diastolic pressure: F:=15.159 p<0.05). Although there was no significant differences in day-time heart rate between three groups, 1 and 2 group showed significant higher level of night-time heart rate comparing with that of control group (F=3.444 p<0.05). Group 2 diabetes patients showed, both systolic and diastolic, higher night-time and day-time blood pressure ratio(systolic pressure: F=35.958 p<0.05> diastolic pressure F=40.126 p<0.05). Observing the night-time and day-time heart rate ratio, group 1 and 2 patients showed significantly higher level compared with that of cantrol group(F=12.144 p<0.05). Regarding the retmopathy, group 1 patient.; showed mild degree retinopathy or normal finding(X =3.65 p<0.05). However, many group 2 patients showed moderate 2 degree nonproliferative retinopathy(X =3.23 p<0.05). The prevalence of overt nepkuopathy (24-hour urine protein>500mg) and autonomic neuropathy (postural and abnormal E:I ratio during deep breathing test) was significantly higher in group 2 (overt nephropathy: X'=3.23 p

Serum Levels of Transforming Growth Factor ( TGF ) -beta1 in Type 2 Diabetic Patients.: Nan Hee Kim, Jung Heon Oh, Young Hyun Kim, Ie Byung Park, Sang Jin Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 1998;22(4):522-530. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Transforming growth factor(TGF)-Bl is a potent inducer of extracellular matrix production and of fibrogenesis and has been associated wnh the occurrence of diabetic complications. Our aim was to determine whether circulating levels of TGF-gl are altered in type 2 DM and, if so, whether they are correlated with blorxi glucose levels and show an association with diabetic complications. METHOD: Serum levels of TGF-gl were measured by quantitative sandwitch enzyme immunoassay in 76 type 2 DM patients and were correlated with clinical and biochemical parameters and the presence of diabetic complications. Result: 1) Serum TGF-B1 levels were correlated with fasting blood glucose levels (r=0.30, p=0.007) and inversely correlated with duration of diabetes (r=-0.31, p=0.007), BUN (r=-0.31, p=0.034), and creatinine (r=-0.40, p=0.004). In linear logistic regression analysis, duration of diabetes and HbA 1C <- were independently related to serum TGF-B1 levels. 2) Serum levels of TGF-B1 were significantly decreased in proteinuria group (n=23) than in normoalbuminuria group (n=26) (69.5+27.5 vs 85.7 +23 ng/mL, p=0.022). TGF-B1 concentrations were inversely correlated with serum creatinine and age in normoalbuminuria group (r=-0.40, p

The Role of Insulin Secretion and Insulin Resistance in the Development of Korean Type 2 Diabetes Mellitus.: Bong Nam Chae, Seong Kyu Lee, Eun Gyoung Hong, Yoon Sok Chung, Kwan Woo Lee, Hyeon Man Kim; Korean Diabetes J. 1998;22(4):491-503. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Impaired insulin secretinn, peripheral insulin resistance, a disproportionately elevated rate of hepatic glucose production and influence of inherited or enviromental factors contribute to the pathogenesis of type 2 diabetes mellitus(DM). But, which defect is primary is still controversial To determine whether insulin resistance or insulin deficiency is primary in the pathogenesis of type 2 DM, we studied normal glucose tolerant offsprings of type 2 diabetic patients. METHODS: 22 offsprings of type 2 diabetic patients with normal glucose tolerance, ranging in age from 20 to 40 years, and 17 control subjects in same age range who had no family history of diabetes, and 21 diabetic subjects were included. We performed 75 g oral glucose tolerance test, euglycemic hyper-insulinemic clamp test and hyperglycemic clamp test. RESULTS: With euglycemic clamp test, the values of peripheral insulin sensitivity, M, were 8.59+0.94 mg/kg/min in control group, 6.98+0.65 mg/kg/min in offspring group, and 5.19+0.89 mg/kg/min in diabetes group (P<0.05). Considering that lower limit of the normal range were 3.78 mg/kg/min in M and 3.10 mg/kg/min in M/I, the frequency of insulin resistance was 14.3% in the offspring group and 33.3 % in diabetes group. First and second phase insulin secretion during hyperglycemic clamp test were blunted in diabetes group. In the offspring group, first and second phase insulin secretion during hyperglycemic clamp test were increased greater than control group, though statistically insignificant. The mean first phase insulin secretion were 38.55+6.81 pU/mL in control group, 55.09+9.40 pU/mL in the offspring group and 6.02+0.98 pU/mL in diabetes group (P<0.05). The mean second phase insulin secretion were 65.11+15.5 pU/mL in control group, 90.25 + 11.9 pU/mL in the offspring group and 17.6 +2.71 pUmL in diabetes group(P<0,05). Considering that lower limit of the normal range were 19.5 pU/mL in the first phase insulin secretion and 26.1 pU/mL in the second phase insulin secretion, the frequency of impaired insulin secretion was 14.3 % in the offspring group and 100 % in diabetes group. There was an inverse relation between insulin resistance and insulin secretion in control subjects. But in the offspring group, this relation was absent. CONCLUSION: Our results show that both insulin resistance and impaired insulin secretion contribute to the development of type 2. DM in Koreans. In addifion, diabetic subjects had more severe impairment in insulin secretory capacity than insulin resistance.

Combined Measurements of Anti-ICA512 and Anti-GAD Antibodies in Insulin-dependent Diabetes Mellitus and Slowly Progressive Insulin-dependent Diabetes Mellitus in Korea.: Kyoung Ah Kim, Kyu Jung Ahn, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Phil Soo Oh, Dong Kyu Jin, Byung Tae Kim, Hae Joon Park, Kwang Won Kim, Myung Shik Lee; Korean Diabetes J. 1998;22(4):482-490. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is a chronic autoimmune disease in which circulating antibodies to various islet-specific antigens including autoantibodies to glutamic acid decarboxylase (GADAb), antibodies reacting with an islet tyrosine phosphatase-related molecule termed as ICA512 (ICA512Ab), and insulin autoantibodies are frequently detected. These autoantibodies could be useful for presymptomatic diagnosis of type 1 diabetes mellitus, and tbeir presence suggest some patients with atypical diabetes mellitus that appears to be more prevalent in Asian than in western countries have autoimmune characteristics. ICA512Ab was discovered in 1992 and, when combined with GADAb, may increase the diagnostic sensitivity in autoimmune diabetes. In an attempt to study the autoimmune feature of atypical diabetes mellitus, we studied the prevalence of ICA512Ab using an in vitro transcription and translation method in the patients with insulin-dependent diabetes mellitus (IDDM), slowly progressive insulin-dependent diabetes mellitus (SPIDDM) and non-msulin-dependent diabetes mellitus (NIDDM), and compared it with that of GADAb. METHODS: ICA512Ab were measured by a radioimmunoprecipitation method using in vitro transcribed and translated S-methionine-labeled ICA512. GADAb were measured using a commercial radioimmunoassay kit (RSR, United Kingdom). The subjects in this study consisted of 43 patients with IDDM, 32 with SPIDDM, and 40 witb NIDDM. Their mean age was 21.2+14.5 years, 50.1+17.1 years, 52.5+13.4 years, respectively. RESULTS: The prevalence of ICA512Ab and GADAb in IDDM was 29 % and 51 %, respectively. That in SPIDDM was 9 % and 29 %; in NIDDM, 0 % and 2.5 %, respectively. When two antibodies were combined, 60 % of IDDM and 50 % of SPIDDM had the autoantibodies. When we analyzed the prevalence of autoantibodies according to the duration of diabetes, the prevalence of ICA 512Ab in patients tested within 4 years after the rliagnosis and more than 4 years after the diagnosis was 35 % and 19 %, respectively in IDDM. And also that of GADAb was 59 % and 38 %, respectively. In SPlDDM, the prevalence of ICA512Ab was 13 % and 7 %, respectively, while that of GADAb was 67 % and 14 % (p<0.05), respectively. In IDDM, ICA512Ab were more frequently detected in patients younger than 15 years ot age (45 %) than in older ones (14%) (p<0.05) while the prevalence of GADAb was not different according to the age (55 % vs 44 %). CONCLUSION: ICA512Ab are detected in some patients with autoimmune diabetes, while their prevalence is lower than that of GADAb. However, ICA512Ab, in combination with GADAb, increases the sensitivity ot autoantibody tests in autoimmune diabetes. Some of SPIDDM have an autoimmune etiology.

Lowering Effect of Voglibose, Monotherapy on Uncontrolled Postprandial Glucose in Patients with Non-Insulin Dependent Diabetes Mellitus (NIDDM) Being Treated with Strict Diet Control: Multicenter Open-Study.: Jeong Taek Woo, Young Seol Kim, Young Kil Choi, Jin Woo Kim, In Myung Yang, Sung Woon Kim, Deog Yoon Kim, Kwang Won Kim, Moon Kyu Lee, Myung Shik Lee, Jae Hoon Jung, Kyu Jeong Ahn, Hyun Chul Lee, Young Deuk Song, Bong Soo Cha, Jee Hyun Lee, Hyung Joon Won; Korean Diabetes J. 1998;22(3):419-428. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is sometimes very difficult to control the elevation of postprandial glucose with diet therapy only in patients with NIDDM partly because of their defective insulin response to glucose. Recently the alpha-glucosidase inhibitors which inhibit carbohydrate digestion and suppress or delay absorption of the final breakdown products, glucose and fructose when it is taken orally with meal have been widely used in the treatment of diabetes. The drugs, however, provoke the adverse effects e.g. flatulence, diarrhea etc. in some patients. Therefore we studied the efficacy of the more recently developed alpha glucosidase inhibitor, Voglibose (Basen, Cheiljedang) METHODS: Fifty five patients whose postprandial two hour serum glucose levels were more than 11.1 mmol/L despite the strict diet therapy during the 4 week observation period were assigned to receive Voglibose 0.2 mg before each meal t.i.d. for 8 weeks. Of 55 subjects, 41 were given Voglibose 0.3 mg t..i.d. for the last 4 weeks because of their poor glucose control, RESULTS: The postprandial one and two hour serum glucose levels significantly decreased after therapy; 1 hour: 17.5+4.4 mmol/L(prior to therapy), 15.4+3.8 mmol/L(4 week after), 14.8+5.1 mmol/L(8 week), p <0.00l, 2 hour: 16.7+4.5 mmol/L, 14.8+3.9 mmol/ L, 14.8+4.5 mmol/L, p<0.00 l, t-tests for paired samples. Total serum cholesterol and HDL cholesterol levels also significantly decreased(5.24+1.06 - 4.90+1.27 mmol/L, p=0.036, 1.34+0.66 1.16 +0.3l mmol/L, p=0.035 respectively) However, HbAlc, serum fructosamine, insulin and triglyceride levels were not significantly changed. The prevalence of the adverse effects due to Voglibose was 14%(10/71). All of them were less than grade II of WHO criteria and disappeared despite continuing therapy. CONCLUSION: Voglibose monotherapy is considered as having an glucose lowering effect in patients with NIDDM whose adequate postprandial blood glucose cannot be achieved with diet therapy only.

Effects of Glycemic Control on Growth and IGF-I, IGF-II, IGFBPs in Insulin dependent Diabetic Children.: D H Kim, K S Rho, S C Chung; Korean Diabetes J. 1998;22(3):392-402. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is well known that linear growth velocity in diabetic children is closely related to metabolic control and age of onset. Many studies demonstrated growth impairment in diabetic children regardless of the degree of metabolic control, whereas other studies have found no growth retardation. We therefore compared growth status and growth factors in type I diabetic children with health children. METHODS: 50 patients with IDDM(27 F/23 M; mean age 12.4+4.6years)were studied. The mean duration of diabetes was 3.5+2.5years. The growth status and IGF-I, IGF-II, IGFBP-3 levels in type 1 diabetic children were comyared to those of age, sex-matched normal children(21 F/15 M; mean age 10.3+3.4 years). RESULTS: 1. HTSDS(height standard deviation score) in diabetic children was 0.2+1.1 and HTSDS in control 0.l+1.1. There is no significant difference in HTSDS between two groups. 2. Growth hormone in diabetic children was higher than control(3.1+1.7ng/mL in diabetes, vs 1.8 +2.3ng/mL in control, p<0.05). IGF-I and IGF-II levels in diabetes were lower than controls(IGF-I: 138.5+116.6ng/mL vs 232.7+190.4ng/mL, IGF-II: 552.0+178.5ng/mL vs 633.5+146.2ng/mL, p0.05). No significant difference in free IGF-I, IGFBP-1, IGFBP-3 between two groups. 3. HTSDS at onset of diabetes was 1.1+1.4 but HTSDS at study was much decreased to 0.2+1.3(p <0.05). Mean duration of diabetes was 3.5+ 2.5years. 4. HTSDS in diabetic children with less than 3 years duration was 0.6+1.0 and delta HTSDS was -0.4+0.8. HTSDS with more than 3 years duration was -0.2+1.5 and delta HTSDS was -1.2+1.3. HTSDS and delta HTSDS were much more decreased according to duration(p<0.01). 5. Delta HTSDS in diabetic children with poor control was significantly decreased(p<0.05). Delta HTSDS below 12% of HbAlc was -0.5+0.8 and delta HTSDS above 12% of HbAlc was -1.2+1.3. 6. Delta HTSDS was correlated with diabetic duration (r=0.50, p<0.01), There was no significant correlation between onset of age and HbAlc. Conclusions: The IGF-I dk. IGF-II levels were decreased in diabetic children compared with controls. HTSDS in diabetic children was not decreased compared to control, but delta HTSDS decreased with long duration of diabetes and poor metabolic control. There was no specific difference between diabetic control and serum concentration of free IGF-I, IGFBP-1 and IGFBP-3. These data suggest that the height of diabetic children could be impaired in case of long duration and poor metabolic control of diabetes.

The Frequency of ICA and anti-GAD Antibody in Korean IDDM and NIDDM Patients.: Kyung Soo Ko, Sung Kwan Hong, Ki Up Lee, Nan Hee Kim, Dong Seop Choi, Sung Hee Ihm, Sung Woo Park, Chul Hee Kim, Dong Won Byun, Kyo Il Suh, Hak Chul Chang, Byoung Doo Rhee; Korean Diabetes J. 1998;22(3):312-319. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been suggested that the clinical and immunological characteristics of diabetes mellitus in Koreans are different from those of Caucasians. This study was undertaken to investigate the prevalence of autoimmune markers in Korean adults with IDDM and recent-onset NIDDM. METHODS: Seventy-seven Korean adults with IDDM and 245 recently(within 2 years) diagnosed NIDDM were included in the study. Islet cell cytoplasmic antibody was measured by immunohistochemical method, and anti-glutamic acid decarboxylase (anti-GAD) antibody was measured by radioimmunoassay. RESULTS: 1) The prevalence of ICA, anti-GAD antibody positivity was 27% and 40% in IDDM patients, and 5% and 4% in recent-onset NIDDM patients, respectively. 2) The prevalence of ICA positivity in IDDM patients decreased from 42% within one year to 21% over one year after clinical onset of disease. On the other hand, the positivity of anti-GAD antibody did not change according to the duration of diabetes. 3) The prevalence of ICA tends to be lower in IDDW patients with low serum C-peptide concentrations. In contrast, the prevalence of anti-GAD antibody was not different according to sernm C-peptide levels. CONCLUSION: These results suggested that the prevalence of ICA and antii-GAD antibody was lower in Korean adult IDDM and recent-onset NIDDM patients than that in Caucasians.

Effect of Troglitazone on Glucose Transport in Human Skeletal Muscle Cell Cultures from Obese Non-diabetic and Obese Non-insulin Dependent Diabetes Mellitus.: Theodore Ciaraldi, Robert R Henry, Kyong Soo Park, Hong Kyu Lee; Korean Diabetes J. 1998;22(2):164-172. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Skeletal muscle is the principal tissue of insulin resistance in obese non-diabetic and non-insulin dependent diabetic(NIDDM) subjects. Troglitazone(Tgz), a member of thiazolidinedione class of compounds, has been shown to improve glucose tolerance in insulin resistant state. At the celluar level, troglitazone has been shown to improve insulin action in skeletal muscle, liver and adipose tissue. However, there has been little knowledge about the mechanism of this drug in human skeletal muscle from insulin resistant subjects. METHODS: To determine the effect of troglitzone on glucose transport(GT) in skeletal muscle of obese non-diabetic and obese NIDDM patients, muscle cultures from 7 obese nondiabetic and 8 obese NlDDM subjects were grown for 4 weeks and then fused for 4 days either with or without Tgz (05ug/mL). At the end of fusion, GT activity was measured and cells were harvested for the measurement of glucose transporter protein expression. RESULTS: Tgz treatment(4 days) increased GT activity dose-dependently in skeletal muscle cell culture of both obese non-diabetic and obese NIDDM subjects. 5ug/mL troglitazone increased basal GT by 2.3 +0.3 fold in obese non-diabetic and 5.7+1.3 fold in obese NIDDM subjects (p <0.05, respectively) Absolute rate of insulin-stimulated GT was significantly increased following Tgz treatment with no enhancement of the incremental response above basal value in either group. Total memhrane GLUTl protein increased 1.7+0.3 fold(p<0.05) following troglitazone treatment(5ug/mL) in NIDDM but were unchhanged in obese non-diabetic cells. GLUT4 protein levels were not affected by Tgz treatment in either group. CONCLUSION: Troglitazone increased both basal and insulin-stimulated GT activity without enhancing the incremental insulin response above basal value in muscle cultures from insulin resistant subjects. These results indicate that troglitazone is not an insulin sensitizer in muscle cultures but acts primarily by mimicking insulin's ability to stimulate basal glucose metabolism in the insulin resistant state of obesity and NlDDM

NcoI Restriction Fragment Length Polymorphism(RFLP) on the TNF-beta gene in Korean Patients with Type 1(insulin-dependent) Diabetes Mellitus.: Suk Kyeong Kim, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Hun Ki Min, Tae Gun O; Korean Diabetes J. 1998;22(2):155-163. Published online January 1, 2001

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Abstract PDF: BACKGROUND
To investigate whether a TNF-g gene polymorphism is associated with the development of insulin-dependent diabetes mellitus, we analyzed the TNF-g gene polymorphism with restriction enzyme Ncol in 38 Korean patients with insulin -dependent diabetes mellitus(IDDM) and in 150 healthy controls. METHODS: Genomic DNA was extracted from white blood cells, and amplified by polymerase chain reaction(PCR) on 735 base pairs fragment of TNF-g gene with NcoI polymorpnic site. 735 bp PCR product was digested with NcoI restriction endonuclease, then analyzed by agarose gel electrophoresis to detect the NcoI restriction fragment length polymorphism(RFLP). The TNF-g alleles were divided into two types according to the electrophoresis patterns. TNF-b*1 allele, which contains the Ncol restriction site(CCATGG), should be digested 539 bp and 196 bp fragments. On the other hand, TNF-g*2 allele, which lacks the restriction site, only showed 735 bp fragment. RESULTS: Six out of 38(15.8%) IDDM patients were homozygous for the TNF-b*1 allele, 11(28.9%) were homozygous for the TNF-b*2 alleie, and 21 (55.3%) were TNF-b*1/*2 heterozygous compared to 21.7%, 30.7% and 49.3%(p=0.83), respectively, in control subjects. CONCLUSION: The TNF-b gene polymorphism was not associated with insulin-dependent diabetes mellitus in Korean subjects.

Measurement of Anti-38kD Antibody in Korean patients with Insulin-Dependent Diabetes Mellitus by Western Blot Analysis.: Sun Ja Kwon, Hong Kyu Lee, Hyeon Kyu Kim; Korean Diabetes J. 1998;22(2):135-144. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Insulin-dependent diabetes mellitus (IDDM) is characterized by the destruction of pancreatic b-cells, which is associated with the genetic susceptibility and the production of antibodies to a numter of islet cell antigens(ICA). A possible target antigen, 38kD antigen, was suggested by the proliferation of CD4 T cells frorn a newly diagnosed patient in response to a 38kD polypeptide of the insulin-secretory-granule membrane. Autoantibody to a rat islet cell -protein of 38kD was detectable in the sera of diabetes-prone biobreeding rats by both immunoprecipitation and differential Westem blot analysis. Anti-38kD antibodies were also found to have a 76% sensitivity at the time of diagnosis in diabetic children by immunoprecipitation. In the Asian populations, it has been reported that clinical and immunologic characteristics of IDDM are quite different from those of Caucasians, say low prevalence of ICA. In Korean, there has never been reported the presence of the anti-38kD antibody. Moreover, the time-consuming and laborious nature of assay, such as T-cell proliferation and immuno-precipitation, makes it difficult to use for large population screenings. In the present study, we aimed to evaluate the prevalence of anti-38kD antibody as a immunologic marker in Korean IDDM patients by Western blot analysis. METHODS: Anti-38kD antibody was detected by Western blot analysis using the lysate of rat insulinoma cell line(RINmSF) as an antigenic source. ICA was determined by enzymatic immunohistochemical analysis. The prevalence of anti-38kD antibody and ICA was measured in 38 cases of IDDM, whose mean age at diagnosis and mean duration of IDDM were 25.2+14.2 years and 0.66+0.97 years, respectively. RESULTS: Using Western blot analysis with the lysate fraction of RIN cell, the prevalence of anti-38kD autoantibody(21.1%) in the IDDM paients was significantly higher than that in the control subjects(0.0%, P<0.05). Clinical characteristics between anti-38kD antibody-positive and -negative IDDM patients were not different. In immunohisto-chemical staining, ICA was detected in 18.2% of the IDDM patients, but not in the control subjects. The prevalence of anti-38kD antibody was 21.7%, 28.6% and 12.5% in the patients of less 1 year, 1 year and 2~4 years, respectively, showing no statistically significant difference in the prevalence according to the duration of IDDM. As previously reported, however, the prevalence of ICA decreased with increasing duration of IDDM. CONCLUSION: These results suggested that the anti-38kD autoantibody is a candidate of autoantibodies for the immunologic markers of Korean IDDM We expect the development of the more methods for the detection of anti-38kD in the future.

Lipoprotein (a) Level and Vascular Complications in NIDDM.: Ji Youn Kim, Mung Su Kim, Joung Min Kim, Jai Hong Park, Joung Hun Lee, Seung Won Yang, Dong Jin Chung, Min Young Chung, Tai Hee Lee; Korean Diabetes J. 1998;22(1):65-73. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The risk of atherosclerosis is increased in subjects with diabetes mellitus. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic vascular disease in subjects without diabetes. The contribution of Lp(a) to the increased risk for atherosclerosis and diabetic complications in subjects with diabetes is not well known. In this report we examined the relationship between Lp(a) levels and development of vascular (macro- and microvascular) complications, and the relationship between Lp(a) and other risk factors for vascular complications in subjects with non-insulin-dependent diabetes mellitus(NIDDM), METHODS: For this study we evaluated 152 patients with NIDDM(72 women and 80 men). Lp(a) level was measured with N-Latex Lp(a) Reagent. Electrocardiography, coronary angiography, brain CT/MRI, doppler velocimetry and peripheral angiography were done for diagnosis of macravascular complieations, and fundus camera, nerve conduction velocity, BBV (beat to beat variation), VPT(vibration perception threshold) and 24-hour urine protein amount were examined for diagnosis of microvascular complications. RESULTS: Lp(a) levels in subjects with ischemic heart disease, cerebrovascular disease and diabetic retinopathy were significantly higher than those in subjects without above mentioned diseases. ApoB/ApoA1 ratio and LDL-cholesterol levels in subjects with Lp(a) level>30mg/dL were significantly higher than those in subjects with Lp(a) level 30mg/dL, and Lp(a) has a positive correlation with ApoB/ApoA1 ratio and LDL-cholesterol in NIDDM patients with vasculopathy. CONCLUSION: These results suggest that high Lp(a) levels seem to be associated with macrovascular and microvascular(especially with retinopathy) complications in subjects with NIDDM and Lp(a) level should be measured in the NIDDM with high level of ApoB/ApoA1 ratio and/or LDL-eholesterol.

Decreased Mitochondrial DNA Content in Peripheral Blood Leukocyte procedes the Development of Type 2 Diabetes Mellitus.: Jae Joon Koh, Jong Ho Ahn, Soon Ja Kwon, Ji Hyun Song, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 1998;22(1):56-64. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Mitochondrial mutations and deletions, have been implicated in the pathogenesis of diabetes mellitus. This can explain only a very small proportion of the patients with diabetes mellitus. Mitochondrial DNA(mtDNA) is vulnerable to oxidative stress, resulting in both qualitative and quantitative changes. We reported that the amount of mtBNA decreased in the peripheral blood leukocyte of patients with NIDDM. In this study, we examined that decreased mtDNA content preceded the development of NIDDM{Non-insulin dependent diabetes mellitus) and correlated with various insulin resistance parameters.In this study, we demonstrated that the amount of mtDNA decreased in peripheral blood leukocyte of patients with NIDDM. Furthermore, we found that lower mtDNA levels preceded the development of diabetes mellitus. METHODS: We utilized the stored blood samples from two community-based survey conducted in Yonchon County, Korea in 1993 and 1995. We selected 23 newly diagnosed diabetic patients and 22 age- and sex-matched control subjects. The buffy coats of peripheral blood samples were used for the competitive PCR and the products pairs were separated by gel EP. The content of mtDNA was calculated with the densitometry. RESULTS: There were no difference in the initial anthropometric parameters, blood pressure and lipid profiles between subjects who became diabetic converters and non converters. The mean quantity of mtDNA was lower in the converters, with 102.8+ 41.5 copies/pg template DNA compared to 137.8+ 67.7 copies/pg template DNA of the controls(p 0.05). The significant inverse correlations were noted between mtDNA content and WHR(r=0.31, p<0.05) in the first, and fasting glucose level(r=-0.35, p<0.05), diastolic blood pressures(r=-0.36, p<0.05), and WHR(r=-0.40, p<0.01) in the second survey. The correlations with the serum levels of total and high density cholesterol, triglyceride, insulin and proinsulin were not statistically significant. CONCLUSION: Although a relationship between diabetes and mitochondrial dysfunction has been suspected. This study showed that decreased mtDNA content in peripheral blood proceded the development of NIDDM. This is the first study to demonstrate that quantitative changes in mtDNA precede the development of NIDDM.

Elevated Levels of Soluble E-selectin and P-selectin in Patients with NIDDM.: Seok Dong Yoo, In Joo Kim, Yong Ki Kim; Korean Diabetes J. 1998;22(1):23-34. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although there is wide spread agreement that patients with NIDDM are at increased risk of the premature development of atherosclerosis, it is not totally clear why this is so. This may be related to the interaction of blood leukocytes with vascular endothelium resulting from a loss of normal metabolic control. The adherence of leukocytes to the endothelium is at least partly mcdiated by cell adhesion molecules. In this study, we evaluated the level of soluble E-selectin and P-selectin in blood of normal controls and patients with NIDDM, and studied its relation to glycemic control and identifiable factors influencing the level of soluble E-selectin and P-selectin. METHODS: Serum soluble E-selectin and plasma soluble P-selectin levels were measured by ELISA method in 24 NIDDM patients without macrovascullar disease and 14 normal controls matched with age, sex and body mass index. Clinical characteristics and laboratory findings such as fasting plasma glucose, HbA1c and lipid profile were evaluated, and their relation with the levels of E-selectin and P-selectin was analized. RESULTS: 1) The levels of E-selectin and P-selectin in NIDDM patients were significantly higher than those of normal controls(55.69+21.97 vs. 42.11+13.57ng/ mL, P<0.05 for E-selectin, 41.60+20.90 vs. 27.16 +7.12ng/mL, P 0.01 for P-selectin). 2) The levels of E-selectin and P-selectin were positively correlated with the fasting plasma glucose level(r=0.400 P<0,05 for E-selectin, r=0.456 P<0.01 for P-selectin). They were also positively correlated with the levels of serum triglyceride(r=0.531 P<0.01 for E-selectin, r=0.415 P =0.05 for P-selectin) but not with the levels of serum total cholesterol, LDL and HDL cholestrol in NIDDM patients. 3) No significant correlation was noted between the levels of E-selectin or P-selectin and the duration of NIDDM. And the levels were not different according to the type of treatment. 4) E-selectin level, not P-selectin level, was significantly higher in the patients with nephropathy when compared to the patients without nephropathy. But such difference was not noted when the patients were classified according to the presence of retinopathy or neuropathy. 5) E-selectin level was positively correlated with P-selectin level in both NIDDM patients and normal controls(r=0.52, P<0.01). CONCLUSION: These findings suggest that endothelial dysfunction, revealed by increased cellular adhesion molecules, could play a role in the pathogenesis of diabetic atherosclerotic vascular disorders in NIDDM patients with increased fasting plasma glucose control and hypertriglyceridemia. In addition, elevated soluble E-selectin and P-selectin level in blood might be used as a marker of diabetic nephropathy.

Randomized Controlled Trial

The Effect of Acarbose as an Adjuvant Therapy in Sulfonylurea-Treated NIDDM Patients.: Yun Yong Lee, Geon Sang Park, Jin Seong Kim, Byeong Sool Mun, Do Joon Park, Chan Soo Shin, Kyeong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 1997;21(4):484-492. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Acarbose-an aglucosidase inhibitor-is known to have a glucose lowering effect by delaying the digestion of complex carbohydrates in the small intestine. Acarbose especially prevents the abnormally high increment of postprandial blood glucose, reduces postprandial hyperinsulinemia and probably, alleviates insulin resistance. The aim of this study is to evaluate the glucose lowering effect of acarbose as an adjunt with a sulfonylurea in the treatment of NIDDM patients who have been poorly controlled with the use of sulfonylurea alone. METHODS: Forty NIDDM patients, who were poorly controlled with sulfonylurea alone, were randomly selected frorn outpatient diabetic clinic for study. For 16 weeks, they recieved either acarbose or placebo in additian to sulfonylurea under double blind method. RESULTS: 1) The metabohc parameters measured before initiation of either treatment regimen were similiar. 2) The HbAlc in placebo group increased from 8.9% to 9.0%. In contrast, in the acarbose group, HbAlc value decreased from 9.3% to 8.1%(p<0.05). 3) Mean fasting plasma glucose and 1-h postprandial glucose levels were reduced significantly in the acarbose group(p<0.001), especially in I-h postpandial glucose level in comparison with placebo group(p <0.0001). 4) Mean fasting, 1-h postprandial insulin levels decreased with time in the acarbose group in comparison with placebo group, but the decrease was not statistically significant. 5) Lipid profiles did not change during 16weeks of treatment period. 6) Adverse effects were observed in 3 patients on acarbose and 2 patients on placebo. CONCLUSION: Acarbose can be used as an effective adjuvant therapy to sulfonylurea in NIDDM patients who are poorly controlled with sulfonylurea alone.

Original Articles

Relationship between Carotid Artery Plaque Measured by Ultrasound and Cerebral infarction in Patients with Non-insulin Dependent Diabetes.: Kil Hong Rhee, Sang In Choi, Seung Ok Lee, Cheol Su Lim, Tae Sun Park, Hong Sun Baek; Korean Diabetes J. 1997;21(4):469-475. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The frequency of cerebral infarction is significantly increased in diabetic patients. Early detection of artherosclerotic lesions will be a useful to predict and delay the occurence of cerebral infarction in diabetic patients. The purpose of this study was to investigate the relationship between extracranial carotid artery plaque and cerebral infarction in NIDDM patients, who have cerebral infarction or not, using non-invasive B-mode ultrasonography. METHODS: Ultrasound high resolution B-mode imaging of carotid arteries was conducted on cerebral infaretion patients with NIDDM and non cerebral infaretion patients with NIDDM to determine the presence of the carotid artery plaque. RESULTS: The incidence rate of cerebral infarction was increased in relation to extracranial carotid artery plaquie existence. The exeistence of carotid artery plaque was higher in NIDDM patients with cerebral infarction than without cerebral infarction(p<01050). Multiple logistic regression analysis showed that development of cerebral infarction in NIDDM patients, who had carotid plaque, was 2.8 fold higher than NIDDM patients who had not carotid plaque(p<0.05), Conclusions: Existence of carotid plaque was closely related to cerebral infarction. Therefore, early detection of extraeranial carotid plaque by B-mode ultrasonography is very useful in predicting cerebral mfarction in NIDDM patients.

Visceral Fat Accumulation and the Fatty Acid Composition of Serum Phospholipids in Middle-Aged Women with Different Degrees of Glucose Tolerance.: Jee Young Yoon, Jong Ho Lee, Yang Cha Lee, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1997;21(4):444-456. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The aim of this study was to determine visceral fat accumulation and the fatty acid composition of serum phospholipids(PL) in middleaged female volunteers with different degrees of glucose tolerance and to analyze the factors that could be responsible for the observed differences between different degrees of glucose tolerance. METHODS: Anthropometric measurements and computed tomography measurements at umbilicus and thigh midway between the patella and pubis were performed in 125 subjects with normal glucose tolerance(NGT), 62 subjects with impaired glucose tolerance(IGT) and 50 subjects with non-insulin-dependent diabetes mellitus(NIDDM), Normal weight subjects were divided into 3 groups; NGT, IGT and long term NIDDM and overweight subjects into 4 groups; NGT, IGT, newly-onset NIDDM and long-term NIDDM. An oral glucose tolerance test(OGTT), the fatty acid composition of serum PL, fasting serum levels of IGF-1 were determined. RESULTS: Visceral fat area and visceral to subcutaneous fat ratio were higher in overweight control than normal weight control and higher in long-term NIDDM groups than controls. Thigh fat and muscle areas and serum levels of growth hormone and IGF-1 were lower in long-term NIDDM groups than controls. Insulin response area during OGTT was the highest in IGT groups and the lowest in NIDDM groups. The progression from the NGT group to the NGT and NlDDM groups was associated with an increase in glucose and free fatty acid areas during OGTT. Overweight long-term NIDDM group showed the lowest serum level of IGF-1 and the highest areas of glucose and FFA. The low ratio(about 0.64.~0.71) of polyunsaturated to saturated fatty acids in serum PL was found in diabetic groups. Long-term NIDDM groups showed an increase in proportions of palrnitic (C16:0), stearic(C18:0), dihomo-r-linolenic(C20:3w6) and docosapentaenoic(C22:3w6) and and a decrease in linoleic(C18:2w6), a-linolenic(C18;3w3), C20:4/20:3 (5-desaturase activity) and C18:1/18:0(9-desa-turase activity) in their serum PL compared with NGT groups. CONCLUSION: This study suggests that an increase in visceral fat and a decrease in thigh fat and muscle may be related to reduced secretion of growth hormone and insulin in long-term NIDDM subjects, These endocrine perturbations can be exacerbated by the prolonged exposure of hyperglycemia and high serum level of free fatty acid. In addition, lang term NIDDM may decrease 5-desaturase activity and 9-desaturase activity. Thus, the factors regulating fatty acid composition of serum PL in long-term NIDDM are affected by not only dietary fat but stored fat and serum concentrations of glucose and hormones, including insulin.

Changes of Glomerular Filtration Rate and Urinary Albumin Excretion Rate in NIDDM patients with Microalbuminuria.: Hyo Jung Kim, Jung Min Koh, Eun Sug Shin, Yun Ey Chung, Young Il Kim, Chul Hee Kim, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee; Korean Diabetes J. 1997;21(4):414-424. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We previously suggested that micro-albuminuria in the presence of retinopathy may represent a state of real incipient diabetic nephropathy with declining glomerular filtration rate(GFR), while the meaning of microalbuminuria in the absence of retinopathy may be more heterogeneous. This study was performed to further test this hypothesis. METHODS: We prospectively followed up the changes in GFR and urinary albumin excretinn rate (UAE) in microalbuminuric NIDDM patients with or without diabetic retinopathy for 3.1 years. RESULTS: 1) Among 45 patients who completed the followup, 27 had retinopathy from the baseline(group A), while 18 patients did not have retinopathy throughout the study(group B). 2) UAE at baseline was not statistically different between the group A and group B. During follow-up, VAE remained stable in the group B patients(40.0 [20.5 ~ 158.0) to 60.0[20.2 ~ 231.0] ug/min, NS). On the other hand, UAE significantly increased in the group A patients(47.9[20.0~186.0] to 140.0[24.5~2862.0] ug/min, P <0.001). 3) Thirty percent of the group A patients(8/27) progressed to overt proteinuria, while 11%(2/18) of the group B patients developed overt proteinuria(NS). 4) GFR significantly decreased both in the group A (113.0+21.2 to 89.1+24.0 mL/min/1.73 m, P < 0,001) and in the group B patients(134.1+27.2 to 121.5+27.3 mL/min/1.73 m, P<0.01). However, the magnitude of change in GFR was significantly higher in the group A than in the group B patients(7.7+7.6 vs 3.9+4.2 mL/min/1.73 m /year, P <0.05), 5) Multiple logistic regression analysis revealed that the presence of retinopathy was a independent risk factor for faster decline in GFR. CONCLUSION: It appears that clinical course is different in NIDDM patients with microalbuminuria, according to the presence or absence of diabetic retinopathy. Microalbuminuria in the presence of retinopathy predicts aggravation of albuminuria and decline in GFR. In contrast, the renal function in microalbuminuric NIDDM patients in the absence of retinopathy may remain stable for years.

Hyperfibrinogenemia as an Important Risk Factor for Microvascular Complications in NIDDM Patients.: Suk Kyeong Kim, Hyeong Kyu Park, Sun Wook Kim, Do Joon Park, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; Korean Diabetes J. 1997;21(4):406-413. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Abundant evidences have accumulated to suggest that atherosclerosis is accelerated in both type I and type Il diabetes but, traditional risk factors(hyperlipidemia, hypertension, smoking, age, obesity) do not account fully for the increased prevalence and severity of vascular diseases in diabetes. In this study, we examined the relationship of plasma fibrinogen to microvascular complications in NIDDM patients METHODS: In this cross-sectional study, 104 NIDDM patients were chosen from subjects who were attending the metabolic ward of Seoul National University Hospital. None of them were smokers, nor had any clinical evidences of acute infections, cancers or liver diseases. Arnong 104 patients, 55 patients (male 26, fernale 29) had no evidence of microvascular complications and 49(male 30, female 19) had one or moe microvascular complications. Their mean age(55.7+11.6 and 57.2+8.9 years old) and BMI (23.34+2.98 kg/m and 23.74+3.41 kg/m) were similar between two groups. This study defined microvascular complications as follows: 1) retinopathy classified based on fundoscopic and fluorescein angiographic assessmeot to background and proliferative, 2) nephropathy defined by 24 hour urine protein over 500mg, and 3) pheripheral neuropathy assessed by symptoms or NCV. RESULTS: 1) Clinically, there was no differences between two groups with respect to diastolic BP, C-peptide, HbA1c, and triglyceride level. However statistically significant differences were noted in systolic blood pressure, and total and LDL-cholesterol. Also mean fibrinogen level was more elevated significantly in diabetic patients with microvascular complications than those without microvascular complications. 2) Univariate analysis shows significant correlations between fibrinogen and the other variables such as duration of diabetes, total cholesterol level and systolic blood pressure. 3) However, fibrinogen concentration was higher in NIDDM patients with microvascuiar complications regardless of duration of diabetes, hypertension and HbA1c in multivariate logisric regression analysis (P=0.010). Conclusions: These results indicated that hyperfibrinogenemia were observed in NIDDM patient with microvascular complications regardless of duration of diabetes, systolic BP, and total cholesterol. Therefore our study suggests that hyperfibrogenemia may be one of the important missing links in the pathogenesis of diabetic microvascular diseases.

Angiotensin 1 Converting Enzyme ( ACE ) Gene Polymorphism According to Micro- and Mocro - angiopathy in non-insulin Dependent Diabetes Mellitus.: Moon Suk Nam, Hyun Chul Lee, Ji Hyun Lee, Bong Soo Cha, Su Youn Nam, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1997;21(4):397-405. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Chronic micro- and macro-angiopathy in diabetes are clinically significant complications that affect both quality and length of life in diabetic patients. Angiotensin 1 converting enzyme (ACE) is of key importance in regulating systemic and renal circulation by converting angiotensin-1 into -2 and inactivating bradykinin, Recent reports suggest that the ACE gene polymorphism is associated with susceptibility to micro- and macro-angiopathy in diabetes. But the results are diffetent according to the type of diabetes and complication. METHODS: We investigated the alleles of the ACE gene and measured the ACE activity in the 169 cases of non-insulin dependent diabetic patients and in the 95 cases of controls matched with age and BMI. RESULTS: The measured ACE activity was well correlated with the count of D allele. We found no differences of ACE alleles between in diabetes and control. No association was found between ACE gene polymorphism and diabetic microangiopathy(retinopathy or nephropathy). But DD genotypes (homozy-gotes for the deletion polymorphism) and D allele were found more frequently in diabetic patients with coronary artery obstructive diseases than in patients without coronary artery obstructive diseases in coronary angiography. CONCLUSION: These data indicate that ACE gene polymorphism in non-insulin dependent diabetes is associated with coronary artery obstructive diseases, but not with chronic microangiopathy.

Serum Fasting Proinsulin Level as a Predictor for Development of NIDDM in Korean Subjects.: Geon Sang Park, Chan Soo Shin, Kyong Soo park, Seong Yeon Kim, Hong Kyu Lee, Sun Ja Kwon, Yong Soo Park; Korean Diabetes J. 1997;21(4):365-371. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Proinsulin is raised in people with NIDDM. Hyperproinsulinemia is thought to be a predictor for the subsequent development of NIDDM. We studied to investigate whether hyperproinsulinemia can predict the development of NIDDM in Korean subjects. METHOD: This study was performed as a nested case-control study. The case group was 67 newly developed diabetic patients out of 1193 initially non-diabetic cohott in Yonchon county. We have also selected 66 age-sex-B541-WHR matched control group who remain non-diabetic for 2 years. We compared baseline insulin, proinsulin and proinsulin/insulin ratio between two groups, RESULTS: There was no significant difference in baseline fasting insulin levels[46,77+/-17.3 vs 42.87+/- 11.6(pmol/L)] between converters to diabetes and non-converters. However, the baseline proinsulin levels in converters to diabetes were higher than those in non-converters.[16.07+/-14.3 vs 8.72+/-5.2(pmol/L)) The baseline proinsulin/imulin ratio in converters was also higher than those in non-converters. [0.30+/-0.17 vs 0.20+/-0.10] CONCLUSION: The results suggest that fasting hyper-proinsulinemia may be a predictor for subsequent development of NIDDM in Korean subjects.

Serum Proinsulin Responses during Oral Glucose Tolerance Test in patients with Non-insulin Dependent Diabetes Mellitus.: Moon Suk Nam, Seong Bin Hong, Yeo Joo Kim, Mi Rim Kim, Yong Seong Kim, In Young Hyun, In Ho Kwak; Korean Diabetes J. 1997;21(4):356-364. Published online January 1, 2001

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Abstract PDF: BACKGROUND
When insulin is secreted from the pancreas, a small amount of proinsulin is also secreted at the same time. Pancreatic beta cell may release immature granules richer in proinsulin contents as well as mature granules in the over-stirnulated state. The significance of hyperproinsulinemia was recently reevaluated in the pathogenesis of non-insulin dependent diabetes mellitus(NIDDM). We studied proinsulin response at fasting and oral glucose tolerance test(OGTT) in NIDDM with a simple and sensitive human proinsulin radioimmunoassay system. METHODS: 22 new onset non-obese NIDDM patients and 11 matched healthy controls were selected for the study. The NIDDM group was divided into 3 groups(group 1; 7.8, group 2; 7.8~11, group 3; 11.0 mmol/L) according to the fasting plasma glucose level. After an overnight fast, a 75 g OGTT was performed and samples were analyzed with proinsulin and specific human insulin radioimmunoassay kits. RESULTS: The basal serum proinsulin level was reported as 9.29+/-4.19 pmol/L in normal control and as 18.09+/-9.32 pmol/L(p=0.04, compared with control) in diabetic group. The values in NIDDM group 1 and 2(18.07+/-9.D2; p=0.04, 21.60+/-6.98; p=0.03) were higher than in control. The molar ratia of the basal proinsulin to total insulin were also increased in NIDDM group 1 and 2(0.24, 0.28) than in control subjmts(0.13, p=0.03). The basal proinsulin and proineulin/total insulin ratio were highest in the group 2(p 0,05, than group 3). During oral glucose loading, the proinsulin response increased more slowly than total insulin response. The proinsulin and proinsulin/ total insulin ratio during oral glucose loading were higher in NIDDM group 1 and group 2 than cantrols. CONCLUSION: The basal proinsulin level in diabetic group was higher than in normal control. The proinsulin responses during oral glucose loading were higher in diabetic group 1 and 2 than controls. The proinlulin response increased more slowly than total insulin response during oral glucose loading. So we conclude that the proinsulin secretion frorn pancreatic beta cell is impaired in diabetic group. The mechanism about the metabolic pathway of the proinsulin secretion should be studied more.

Clinical and Coronary Angiographic Findings of Coronary Artery Disease in Patients with Noninsulin Dependent Diabetes Mellitus.: Bon Jeong Ku, Bong Soo An, Jin Ok Jeong, In Whan Seong, Eun Seok Jeon, Min Ho Shong, Heung Kyu Ro, Young Kun Kim; Korean Diabetes J. 1997;21(3):308-313. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus has a major impact on cardiac morbidity and mortality. We analyzed the clinical characteristics and coronary angiographic findings in patients with a coronary artery disease and with noninsulin dependent diabetes mellitus. METHODS: We retrospectively reviewed the clinical and coronary angiographic findings in 74 patients with noninsulin dependent cliabetes mellitus and in 328 non-diabetic patients who had a coronary insufficiency. RESULTS: Significant coronary occlusions and multiple coronary artery diseases were more common in diabetics than in non-diabetics. The patients with noninsulin dependent diabetes mellitus has several limiting factors to perform the successful percutaneous coronary angioplasty, it could be a possible factor for rapid deterioration of coronary insufficiency in patients with diabetes mellitus. Smoking and hypertension significantly increased the incidence of signiftcant coronary occlusions whereas obesity and hypercholesterolemia did not any significant influence on incidence of the significant coronary occlusions. The longer duration of diabetes rnellitus associated with higher incidence of significant coronary occlusions and multiple coronary diseases. CONCLUSION: Significant coronary occlusions and multiple coronary artery diseases were occurred more common in diabetics than in non-diabetics. Coronary angiography should be performed routinely in noninsulin dependent diabetes.

Prevalence of ICA and anti-GAD, HLA DRB1 / DQA1 / DQB1 Polymorphism in Korean IDDM Patients.: Yong Soo Park, Jin Ho Shin, Jin Bae Kim, Woong Hwan Choi, You Hern Ahn, Tae Wha Kim, Mok Hyun Kim, Sei Won Yang, Seung Duck Hwang, Hee Bal Rhee; Korean Diabetes J. 1997;21(3):289-299. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although the HLA class II genes are cleaily associated with insulin-dependent diabetes mellitus(IDDM) in all ethnic. Groups, considerable variation in the associated genotypes is observed among the different ethnic groups. Mathods: In order to estimate what degree genetic and environmental determinants influence the true incidence of IDDM, ICA by imrnunohistochemistry, anti-GAD prevalence by radioimmunoprecipitation and HLA-DRB1, DQAl, and DQB1 polymorphisms after PCR amplification of genomic DNA were analyzed in 131 cases of IDDM, whose age at diagnosis were less than 15. RESULTS: 56% of them(73/131) were anti-GAD positive. 43% IDDM(56/131) were ICA positive. HLA DR3 and DR9 were susceptibility markers, whereas DR2 and DR5 were protective markers. DR3/4,, DR3/9, and DR3/X(X: other than 3, 4) were susceptible genotypes. HLA DQA1*0301 allele was increased, and DQB1*0301 and DQB1*0602 were decreased in IDDM. Not only HLA DQA1 Arg, but also DQBl non-Asp were found to be independent marker for IDDM, but their strength of association was weak. The highest prevalence of anti-GAD was observed in thosc homozygous for DR4(87.5%), exceeding that(47.8%) in those without this allele, and those with one DR4(63.5), whereas the highest prevealence of ICA was found in those homozygous for DR3(10G%), exceeding that in those with one DR3(64.3%) or in those without this allele(36.7%). There was a significant difference in numbers of HLA DQ susceptibility heterodimers in anti-GAD positive or negative patients. Conelusion: The prevalence of islet-specific auto-antibodies were present at comparable sensitivity and specificity in Korean IDDM patients. We could also assess that the immunoenetic markers for IDDM among Caucasians likewise confer disease susceptibility among Koreans. However, different HLA susceptibility alleles and a lower strength of association with known susceptibility markers, presumably because of differences in the genetic make-up of the population or in linkage disequilibrium patterns compared with other racial groups.

Distinct Pattern of GAD65 and GAD67 Gene Expression in the Pancreas of NOD Mouse.: In Young Ko, Yup Kang; Korean Diabetes J. 1997;21(3):243-253. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Glutamic acid decarboxylase(GAD; EC 4.1.1.15), one of the major B-cell autoantigens in IDDM, is an enzyme which catalyzes the synthesis of major inhibitory neurotransmitter, r-aminobutyric acid (GARA), in the mammalian brain, pancreas and other organs. Two isoforms of GAD, GAD65 and GAD67, have been identified which differ in their intracellular localization. Autoantibodies to GAD have been detected several years before the clinical onset of IDDM, implicating GAD as a leading autoantigen which somehow correlated with the pathogenesis of IDDM. We have determined the characteristics of GAD isoform expression in the pancreas of NOD mouse, an animal model extensively employed in IDDM study, using RT-PCR and Southern blot methods. METHODS: Pancreas was obtained from female NOD mouse(neonate, 4, 8, 12, 16, 20 week-old) and age-matched female ICR mouse. Total cellular RNA was I.solated by acid guanidinium thiocyanate method and employed in the RT-PCR amplification using GAD65- and GAD67-specific primer designed in our laboratory. The PCR product was blotted onto the nylon membrane and subjected to Southern analysis using 32P-ATP labelled hybridization probe. RESULTS: In NOD pancreas, GAD67 was expressed six times higher than GAD65 at neonatal stage. Then, the expression was dramatically decreased from 4 weeks when the pancreatic insulitis begins to occur. After 12 weeks of age, both GAD67 and GAD65 expression was almost undetectable. However, in control ICR mouse, there were no significant differenees between GAD65 and GAD67 expression throughout the ages. And, the expression of both GAD65 and OAD67 was not decreased with ages in contrast to NOD mouse. CONCLUSION: In this experiment, we found that the expression of GAD isoforms in NOD mouse shows distinct pattern in comparison to that of control ICR mouse. The expression of GAD67 was significantly higher than GAD65 in neonatal NOD mouse while, in control ICR mouse, same level of GAD isoforrns expression was observed. This finding clearly suggested the possibility that the expression of GAD isoforms in diabetic NOD mouse is quite distinct and may somehow play a role in the pathogenesis of diabetes although the precise mechanism remains to be unveiled. In addition, our data also supported the hypothesis that expressional pattern, and, if possible, ' the etiophysiological function of GAD isoforms in NOD mouse pancreas may be quite different from that in human pancreas.

Measurement of Anti-GAD antibody by EIA and RIA Methods in Korean Diabetic patients: Study for pathogenesis of slowly progressive IDDM.: Han Hyo Lee, Young Goo Shin, Hee Sun Kim, Chang Young Kim, Yon Soo Jeong, Hong Seung Kim, Deok Woo Park, Kap Jun Yoon, Choon Hee Chung; Korean Diabetes J. 1997;21(3):231-242. Published online January 1, 2001

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Abstract PDF: background
Sometimes it is difficult to discriminate between IDDM and NIDDM among adults with DM. Some NIDDM patients have autaantibodies and follow the course of IDDM, We call them as slowly progressive IDDM(SPII)DM). Since anti-GAD (Glutamic acid decarboxylase') Ab can be detected both before and for a long pe.riod after the diagnosis of DM it is helpful for the diagnosis of autoimmune diabetes. METHODS: The subjects were 68 diabetic patients who were admitted at Wonju Christian Hospital from May 1994 to Feb 1996. We classified them as IDDM, NIDDM and SPIDDM. We analyzed the following: a studied basic clinical study, oral glucose tolerance test, HLA DR typing, IgM anti-viral Abs, ICA, IAA and nti-GAD Ab. RESULTS: In measurement of anti-GAD Ab, IRMA was more sensitive than EIA. Anti-GAD Ab prevalence was significantly higher in IDDM patients than in NIDDM patients. By IRMA method, Anti-GAD titers showed significant correlation among VELISA, HEXT, IRMA and RSR methods(p<0.001). CONCLUSION: As seen by the results above, the positivity of antiGAD Ab by EIA and RIA method was lower for Korean diabetic patients than for Caucasians. We suggest that the other mechanisms as well as autoimmunity may be involved in the pathogenesis of SPIDDM in Koreans. We need follow-up studies about the clinical and immunogenetic characteristics of these patients.

The Effect of Metformin Monotherapy in Patients with NIDDM.: Yu Bae Ahn, Sung Dae Moon, Sang Ah Jang, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 1997;21(2):185-193. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We performed this study to investigate the effect of metformin on glycemia, insulin secretion and body weight in patients with non-insulin-dependent diabetes melltus(NIDDM) who could not aehieve satisfactory glycemic control by sulfonylurea or diet therapy. METHODS: A total of 167 patients with NIDDM were included in this study. At baseline the patients underwent anthropometry and a 75g oral glucose tolerance test. Jn addition, levels of hemoglobin Alc (HbAlc), setum lipids, fasting and postprandial 2hr glucose were measured. Metformin was given in an initial dose of 500mg twice daily and increased by 500mg every month as long as the fasting blood sugar(FBS) concentration exceeded 7.8mmol/L and the side effects were tolerable. After 3 rnonths of metformin therapy we defined a responder as a patient who experienced a FBS of under 7.8 mmol/L or a HbAlc of under 7%. Patients who failed to respond to metformin monotherapy were excluded in the study. Anthrapometric changes and results of a 75 g oral glucose tolerance test were reevaluated in the responder group after 6 months of metformin treatment. RESULTS: I) The overall response rate to metformin mono-therapy was 55.6%(79/142) in the study population. 2) There were significant changes in body weight (64.4+/-8.2 vs 62.9+/-8.4 kg, p(0.01) and body mass index(25.3+/-2.3 vs 24.6+/-2.3kg/m, p<0.01) during metformin treatment. 3) There were significant decreases in the fasting, postprandial 2hr serum glucose(10.1+/-2.8 vs 7.9+1.6, 15,2+/-5.0 vs 12.2+/-3.9 mmol/L, p 0.01) and HbAlc levels(8.4+/-1.7 vs 6.5+/-0.9%, p<0.05) after 6 months of metformin treatment. 4) There were significant decreases in the levels of AUC[g](59.2+/-15.5 vs 49.4+/-9.4mmol L-1. Min-1, p =C0.01) without changes of AUC[I] and AUC[I]/ AUC[g] ratio (558.0+486.0 vs 536.4+374.4 pmol.L-1. Min-1, p=0.71, 11.7+/-13.0 vs 11.8+/-10.0, p=0.89). 5) The incidence of side effects was 25% in the study population, but most of them were mild and fade away with continuous use of metformin, CONCLUSION: Metforrnin monotherapy improved glycemic control in NlDDM patients who failed to respond to diet or sulfonylurea therapy and may be a useful hypoglycemic agent for the treatment of NIBDM.

Urinary albumin excretion, von Willebrand factor and macrovascular disease in patients with NIDDM.: Sin Gon Kim, Soo Mi Kim, Dong Hyun Shin, Nan Hee Kim, Yoon Sang Choi, Ie Byung Park, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 1997;21(2):176-184. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Increased urinary albumin excretion (UAE) is not only an independent predictor of progressive renal disease but also an important marker of atherosclerotic disease in patients with NIDDM. However, the pathaphysiologic basis of this observation is poorly understood. Recently, one interesting hypothesis suggested: UAE rnerely reflects a glomerular manifestation of an otherwise generalized vascular dysfunction(hyperpermeable state), and Stehouwer et al. Reported a strong relationship between plasma von Willebrand factor level(a measure of endothelial dysfunction), UAE and cardiovascular diseases. Therefore, we studied the relationship between UAE, plasma vWF and macrovascular disease in patients with NIDDM. METHODS: We measured UAE and plasma vWF levels in 102 patients with NIDDM, and investigated the telationship between these values and macrovascular diseses. Also, we assesed the risk factars for macrovascular disease. RESULTS: 1) Among total of 102 patients, nonnoalbuminuria, microalbuminuria and macroalbuminuria group were 58 patients(56.9%), 28 patients(27.5%) and 16 patients(15.6%), respectively. 2) The prevalencies of hypertension, diabetic retinopathy and macrovascular diseases were the highest in macroalbuminuria group, followed by microalbuminuria and norrnoalbuminuria group in order of frequency. 3) Plasma vWF and UAE levels were significantly correlated(r=0.44). 4) Plasma vWF concentrations were higher in patients with macrovascular diseases than in those without macrovascular diseases, and also higher in patients with retinopathy compared with those without retinopathy. 5) Multivariate logistic regression analysis showed that age, smoking and vWF were independent risk factors for macrovascular diseases. CONCLUSION: 1) As plasma vWF and UAE values were increased, more macrovascular diseases were observed in patients with NIDDM. 2) Plasma vWF may be used as an indicator of macrovascular disease in patients with NIDDM.

Relationship between Angiotensin I Converting Enzyme Gene Polymorphism and Vascular complications in Non-Insulin Dependent Diabetic Patients.: Byoung Gue Na, Tae Geun Oh, Sang Moo Jung, Sang Woo Oh, Jae Hong Choi, Ji Hyun Lee, Seong Su Koong, Seung Taik Kim; Korean Diabetes J. 1997;21(2):138-146. Published online January 1, 2001

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Abstract PDF: No abstract available.

Disturbance of Cutaneous Microcirculation assessed by Laser Doppler Flowmetry in Non-Insulin Dependent Diabetic patients.: Jeong Hyun Park, Sang Hee Nam; Korean Diabetes J. 1997;21(1):56-64. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic microangiopathies are well-known long-term complication of diabetes mellitus, These are wide-spread phenomena, but little is known about the nature of cutaneous microcirculatory disturbance in diabetic patients which could be considered as cutaneous diabetic microangiopathy. To assess the cutaneous microcirculatory disturbance of diabetic patients, we performed this study. METHODS: We performed the laser Doppler flowmetry which has been known to be an accurate device for measuring cutaneous microcirculatory blood flow to 14 control subjects and 16 non-insulin dependent diabetic patients. We used thermal reactive hyperemic technique to the dorsum of right index finger and right great toe for measuring both baseline and maximum cutaneous microcirculatory blood flow. RESULTS: The baseline microcirculatory blood flow measured at 35C did not show any statistically significant differences between control subjects and diabetic patients, on both finger dorsum and toe dorsum. The maximurn microcirculatory blood flow measured at 44C showed statistically significant difference between control subjects and diabetic patients only at toe dorsum, but not at finger dorsum (p<0.05). CONCLUSION: From the above results, we conclude that cutaneous microcirculation is disturbed in noninsulin dependent diabetic patients, which was manifested at the toe dorsum in the condition of maximum blood flow induced by thermal stimulation. Further studies an exact pathophysiology and possible correlations with diabetic microangiopathies, diabetic duration and the level of glycemic control are needed along with more refinement of measurement techniques.

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