Diabetes & Metabolism Journal

Bong Soo Cha (Cha BS)

55 Articles

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan.: Eun Seok Kang, Beom Seok Kim, Chul Hoon Kim, Gi Ho Seo, Seung Jin Han, Sung Wan Chun, Kyu Yeon Hur, Chul Woo Ahn, Hunjoo Ha, Mankil Jung, Bong Soo Cha, Hyun Chul Lee; Korean Diabetes J. 2008;32(1):10-20. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.10

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BACKGROUND
Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

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An Overview on Naturally Occurring Phytoconstituent: Lithospermic Acid
Bhupesh Chander Semwal, Amjad Hussain, Sonia Singh
The Natural Products Journal.2024;[Epub] CrossRef

In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications.: Ji Sun Nam, Young Jae Cho, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Min ho Cho, Hai Jin Kim, Ji Eun Yoon, Han Young Jung, Eun Seok Kang, Yu Mie Rhee, Hyung Keun Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2007;31(4):351-361. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.351

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Abstract PDF: BACKGROUND
In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels. METHODS: IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels. RESULTS: Patients with more severe neuropathy had less corneal endothelial cells (3105 +/- 218 vs. 2537 +/- 142 vs. 2350 +/- 73/mm3 vs. 1914 +/- 465/mm3, P = 0.02), higher serum NGF (36 +/- 15 vs. 60 +/- 57.66 vs. 80 +/- 57.63 vs. 109 +/- 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 +/- 11.94 vs. 304.29 +/- 242.44 vs. 538.50 +/- 251.92 vs. 719.50 +/- 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well. CONCLUSION: Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

Activation of NF-kappaB and AP-1 in Peripheral Blood Mononuclear Cells Isolated from Patients with Diabetic Nephropathy.: Jisun Nam, Min Ho Cho, Jong Suk Park, Geun Taek Lee, Hai Jin Kim, Eun Seok Kang, Yu Mie Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hun Joo Ha, Hyun Chul Lee; Korean Diabetes J. 2007;31(3):261-273. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.261

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Abstract PDF: BACKGROUND
We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC). METHODS: From 66 diabetic patients with or without diabetic nephropathy (Group III and II, respectively) and 49 normal control subjects (Group I), spontaneous and stimulated ROS levels, activities of nuclear factor-kappa B (NF-kappaB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-beta1 (transforming growth factor-beta1), and 24-hour urinary albumin excretion (UAE) were measured. RESULTS: Spontaneous ROS was significantly higher in group III and II than group I (60.7 +/- 3.3 vs. 60.0 +/- 3.0 vs. 41.1 +/- 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 +/- 2.2 vs. 11.1 +/- 2.0%, respectively; increment of PMA-induced ROS production 23.5 +/- 4.5 vs. 21.6 +/- 2.2%, respectively). The activities of NF-kappaB and AP-1, but not of Sp1, were significantly higher in Group III than in Group II (2.53 vs. 2.0 vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23 +/- 0.39 vs. 1.99 +/- 0.68 ng/mg in PBMCs, 16.88 +/- 6.84 vs. 5.61 +/- 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-kappaB and AP-1 and 24-hour UAE. CONCLUSIONS: Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy through activation of NF-kappaB and AP-1, but not Sp1, and increased expression of TGF-beta1.

Efficacy and Safety of Mitiglinide in Korean Type 2 Diabetic Patients: Prospective Randomised Multicenter Comparative Phase III Study.: Se Young Kim, Hyo Jeong Kim, Kyung Ah Han, Se Hyun Baek, Hyun Sik Son, Bong Soo Cha, Kyung Wan Min; Korean Diabetes J. 2007;31(2):163-174. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.163

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BACKGROUND
Mitiglinide, one of the meglitinides, is expected to prevent postprandial hyperglycemia of type 2 diabetes by enhancing early phase insulin secretion. The aim of this study was to verify the efficacy and safety of mitiglinide compared to nateglinide. METHODS: One hundred eleven of diabetic patients were randomised and administered of mitiglinide (n = 56) and nateglinide (n = 55) before a meal time for 12 weeks. The changes of HbA1c, fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) were analyzed. The safety of this drug was investigated as well. RESULTS: The change of HbA1c was not significantly different between two groups (-0.77 +/- 1.08% in mitiglinide vs. -0.66 +/- 0.79% in nateglinide, P = 0.57). The reduction of FPG (-12.2 +/- 25.0 mg/dL vs. -6.1 +/- 22.3 mg/dL, P = 0.218), PPG 1 hr (-48.0 +/- 47.1 mg/dL, vs. -29.4 +/- 43.2 mg/dL, P = 0.051), and PPG 2 hr (-59.2 +/- 58.0 mg/dL vs. -43.3 +/- 59.0 mg/dL, P = 0.194) were not significantly different between the mitiglinide and the nateglinide, respectively. Drug-related adverse effects were not different between two groups (16.1% in mitiglinide vs. 27.8% in nateglinide, P = 0.137). The frequency of hypoglycemic events were not different between two groups (8.9% in mitiglinide vs. 14.8% in nateglinide, P = 0.339). There were two patients who had complained shoulder pain in the mitiglinide or deterioration of visual acuity in the nateglinide, but those were found to be unrelated with medications. CONCLUSION: This study showed that mitiglinide had reduced HbA1c as similar to nateglinide and that significantly improved HbA1c, FPG and PPG during 12 weeks of treatment. The safety of mitiglinide was also comparable to nateglinide. Mitiglinide could be used as an effective glucose-lowering agent by enhancing early insulin secretion and reducing postprandial glucose excursion, and thereby might contribute long-term cardioprotective effect in Korean type 2 diabetic patients.

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Monotherapy in Type 2 Diabetes Mellitus Patients 2017: A Position Statement of the Korean Diabetes Association
Sang Youl Rhee
The Journal of Korean Diabetes.2018; 19(1): 15. CrossRef
Monotherapy in patients with type 2 diabetes mellitus
Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 959. CrossRef
Monotherapy in Patients with Type 2 Diabetes Mellitus
Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 349. CrossRef

Comparison of the Efficacy and Safety of Glimepiride/Metformin Fixed Combination Versus Free Combination in Patients with Type 2 Diabetes: Multicenter, Randomized, Controlled Trial.: Seung Hwan Lee, In Kyu Lee, Sei Hyun Baik, Dong Seop Choi, Kyong Soo Park, Ki Ho Song, Kwan Woo Lee, Bong Soo Cha, Chul Woo Ahn, Hyoung Woo Lee, Choon Hee Chung, Moon Suk Nam, Hong Sun Baek, Yong Ki Kim, Hyo Young Rhim, Ho Young Son; Korean Diabetes J. 2006;30(6):466-475. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.466

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BACKGROUND
Failure to manage diabetes mellitus receiving monotherapy increases as the duration of the disease is protracted, and in many cases it becomes inevitable to introduce combined therapies. However, compliance of the patients tends to decrease. We conducted a clinical study to compare the efficacy and safety of preconstituted and fixed combination therapy of glimepiride plus metformin to those of free combination therapy. METHODS: Two hundred and thirteen patients with type 2 diabetes who had been diagnosed at least six months ago were randomly assigned either to a fixed group or a free group. The initial dosage was chosen according to the previous treatment history and then adjusted every two weeks following a predefined titration algorithm to meet the target mean fasting glucose levels (140 mg/dL). The medications were given for 16 weeks. The primary endpoint was the change in HbA1c level from baseline to week 16. Various parameters were checked as secondary outcome measures and safety criteria. RESULTS: HbA1c level of the fixed group and the free group decreased by 1.09% and 1.08%, respectively. The 95% CI of the changes' difference between the two groups (-0.21%, +0.19%) was within the predefined equivalence interval (-0.5%, +0.5%). Secondary outcome measures (the changes of fasting and postprandial plasma glucose level, response rate and compliance) and safety criteria (frequency of hypoglycemia and adverse reactions) were similar between the two groups. CONCLUSION: Fixed combination of glimepiride/metformin is as effective and safe therapy as free combination in type 2 diabetes patients.

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Efficacy and safety of glimepiride/metformin sustained release once daily vs. glimepiride/metformin twice daily in patients with type 2 diabetes
Y.-C. Hwang, M. Kang, C. W. Ahn, J. S. Park, S. H. Baik, D. J. Chung, H. C. Jang, K.-A. Kim, I.-K. Lee, K. W. Min, M. Nam, T. S. Park, S. M. Son, Y.-A. Sung, J.-T. Woo, K. S. Park, M.-K. Lee
International Journal of Clinical Practice.2013; 67(3): 236. CrossRef
Pharmacokinetic comparison of a new glimepiride 1-mg + metformin 500-mg combination tablet formulation and a glimepiride 2-mg + metformin 500-mg combination tablet formulation: A single-dose, randomized, open-label, two-period, two-way crossover study in
Bo-Hyung Kim, Kwang-Hee Shin, JaeWoo Kim, Kyoung Soo Lim, Kyu-pyo Kim, Jung-Ryul Kim, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang, Kyung-Sang Yu
Clinical Therapeutics.2009; 31(11): 2755. CrossRef

Randomized, Open Label, Multicenter Clinical Trial about the Effect of Cilazapril on Vascular Endothelial Function in Patients with Type 2 Diabetes Combined with Hypertension.: Sang Youl Rhee, Jeong Taek Woo, Sei Hyun Baik, Hyoung Woo Lee, In Kyu Lee, Hye Soon Kim, Moon Kyu Lee, Min Ho Shong, Chung Gu Cho, Byoung Hyun Park, Bong Soo Cha, Young Seol Kim; Korean Diabetes J. 2006;30(6):450-458. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.450

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BACKGROUND
The angiotensin converting enzyme inhibitor (ACEi) improves the vascular endothelial cell function and has a better clinical outcome by decreasing the LDL cholesterol oxidation, hypercoagulability, oxidative stress and improving the level of endothelial nitric oxide synthesis in patients with type 2 diabetes and hypertension. However, the correlations between the ACEi and the serum markers for the vascular endothelial function in previous studies were not consistent. SUBJECTS AND METHODS: Between July 2003 and April 2005, 104 type 2 diabetes patients with hypertension, who had been admitted to 9 major university hospitals in Korea, were examined. The subjects were randomly allocated to the cilazapril (2.5~5 mg/day) and atenolol (50~100 mg/day) treatment group and given a combination of hydrochlorothiazide and amlodipine. The lipid profile and the markers for endothelial function, such as vWF, VCAM, E-selectin, tPA, fibrinogen, adiponectin, hsCRP, nitrotyrosine were evaluated and the differences in the variables were compared with those obtained 6 months later. RESULTS: A total 56 subjects completed the 6-months follow up period. Regarding the baseline characteristics, there were no significant differences in the variables observed in the two groups except for HbA1c (P = 0.037), vWF (P = 0.048), and hsCRP (P = 0.038). After 6 months, both groups showed a significant and identical decrease in the systolic and diastolic blood pressure compared with the baseline (P < 0.002). However, there were no significant differences in the endothelial markers between each group. On the other hand, there was some deterioration in the triglyceride (P = 0.009) and HbA1c (P = 0.017) levels in the atenolol treatment groups. CONCLUSIONS: There were no significant differences in the endothelial function markers observed between the cilazapril and atenolol groups. However, cilazapril had an identical effect on the blood pressure reduction compared with atenolol but had fewer adverse effects on the glucose and lipid metabolism.

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Potential Protective Role of Blood Pressure-Lowering Drugs on the Balance between Hemostasis and Fibrinolysis in Hypertensive Patients at Rest and During Exercise
Annabella Braschi
American Journal of Cardiovascular Drugs.2019; 19(2): 133. CrossRef

Relation between Cerebral Arterial Pulsatility and Insulin Resistance in Type 2 Diabetic Patients.: Jong Suk Park, Chul Sik Kim, Hai Jin Kim, Ji Sun Nam, Tae Woong Noh, Chul Woo Ahn, Kyung Yul Lee, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(5):347-354. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.347

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BACKGROUND
Diabetic patients have a 3-fold risk for cerebrovascular disease compared with nondiabetic controls. The aim of the present study was to investigate the association of insulin resistance with pulsatility index (PI) of cerebral arteries in type 2 diabetic patients. METHODS: We compared a group of 90 patients with stroke free, type 2 diabetes and an age- and sex-matched control group of 45 healthy subjects without diabetes. Diabetic patients were divided into 3 groups according to the ISI (insulin sensitivity index). We evaluated PI of the middle cerebral artery (MCA) by transcranial Doppler ultrasonography (TCD) and insulin resistance determined by short insulin tolerance test. RESULTS: The PI was significantly higher in diabetic patients than that in healthy controls (P < 0.05), and also higher in patients with insulin resistance than that in insulin sensitive diabetic patients (P < 0.05). The PI of the MCA was significantly correlated with age (r= 0.465, P < 0.01), duration of diabetes (r = 0.264, P = 0.025), hypertension (r = 0.285, P = 0.015) and inversely correlated with insulin resistance (r = -0.359, P = 0.030).Multiple regression analysis was performed with PI as a dependent variable and insulin resistance as an independent variable along with known clinical risk factors. Age (beta = 0.393, P < 0.01) and duration of diabetes (beta = 0.274, P = 0.043) exhibited a significant independent contribution to PI. CONCLUSIONS: PI might be useful markers of the detection of diabetic cerebrovascular changes and insulin resistance, measured with short insulin tolerance test, showed correlations with PI, but age and duration of diabetes contributed independently to the variability in the PI.

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Factors Affecting Basilar Artery Pulsatility Index on Transcranial Doppler
Ho Tae Jeong, Dae Sik Kim, Kun Woo Kang, Yun Teak Nam, Ji Eun Oh, Eun Kyung Cho
The Korean Journal of Clinical Laboratory Science.2018; 50(4): 477. CrossRef

Effects of PPAR-alpha and-gamma Agonists on Fatty Acid Metabolism of Muscle Cells in Hyperlipidemic and Hyperglycemic Conditions.: Yong jik Lee, Zheng Shan Zhao, Soo Kyung Kim, Hae Jin Kim, Wan Sub Shim, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(5):324-335. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.324

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BACKGROUND
Studies for the regulation of fatty acid metabolism are deficient relatively in skeletal muscle and heart. The investigations in pathological conditions for malonyl-CoA decarboxylase (MCD) and for the relation of MCD and PPAR-alpha.-gamma agonists are insufficient in particular. METHODS: In the current study, fully differentiated H9c2 muscle cells were exposed to pathological conditions such as hyperlipidemic (0.1 mM Palmitate) and hyperglycemic (16.5 mM Glucose) condition with 5 uM PPAR-gamma agonist (rosiglitazone) and 10 uM PPAR-alpha agonist (WY14,643) and then experiments such as MCD activity assay, MCD real-time RT-PCR, MCD reporter gene assay, MCD Western blotting, PPAR-alpha Western blotting, and palmitate oxidation test were carried out. RESULTS: Only PPAR-alpha agonist increased MCD activity. In the result of real-time RT-PCR, both PPAR-alpha and PPAR-gamma agonists elevated MCD mRNA expression in hyperlipidemic condition. MCD protein expression was decreased in hyperlipidemic condition, however, increased in rosiglitazone, or WY14,643 treated conditions. Rosiglitazone, and WY14,643 treated groups showed incresed MCD protein expression in hyperglycemic condition. Hyperlipidemic control group and PPAR-alpha.-gamma agonists treated groups presented about 3.8 times more increased palmitate oxidation level than normolipidemic control group in hyperlipidemic condition. PPAR-alpha agonist treated group showed 49% more increased palmitate oxidation rate than hyperlipidemic control group in primary cultured rat skeletal muscle cells. The amount of palmitate oxidation from differentiated H9c2 muscle cells that had overexpressed PPAR-alpha structural genes was more increased than control group. CONCLUSION: This study suggests that PPAR-alpha agonist ameliorates the defects induced by hyperlipidemic condition through the regulation of MCD. In summary, a closely reciprocal relation among PPAR-alpha agonist, MCD, and fatty acid oxidation existed distinctly in hyperlipidemic condition, but not in hyperglycemic condition.

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Beneficial effect of Combination with Korean Red Ginseng and Morus alba in metabolic syndrome
Yun Jung Lee, Hye Yoom Kim, Jung Joo Yoon, So Min Lee, You Mee Ahn, Joung Hyun Kho, Min Chul Kho, Ho Sub Lee, Kyung Min Choi, Dae Gill Kang
The Korea Journal of Herbology.2012; 27(6): 99. CrossRef
Effects of Mixed Extract from Lycium chinense, Cordyceps militaris, and Acanthopanax senticosus on Glucose-Regulating Enzymes of HepG2 in Hyperglycemic Conditions
Dae-Jung Kim, Jeong-Mi Kim, Tae-Hyuk Kim, Jong-Mi Baek, Hyun-Sook Kim, Myeon Choe
Journal of the Korean Society of Food Science and Nutrition.2010; 39(9): 1257. CrossRef

Insulin Resistance and PPARgamma.: Bong Soo Cha, Se Eun Park; Korean Diabetes J. 2006;30(5):317-323. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.317

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Caulerpa okamuraeethanol extract improves the glucose metabolism and insulin sensitivityin vitroandin vivo
Chul-Min Park, Laxmi Sen Thakuri, Dong-Young Rhyu
Journal of Applied Biological Chemistry.2021; 64(1): 89. CrossRef
Impacts of High Sodium Intake on Obesity-related Gene Expression
Minjee Lee, Miyoung Park, Juhee Kim, Soyoung Sung, Myoungsook Lee
Journal of the East Asian Society of Dietary Life.2018; 28(5): 364. CrossRef

Long-term Effect of Pioglitazone Treatment in Patients with Type 2 Diabetes.: Jae Hoon Moon, Hye Jin Kim, Soo Kyung Kim, Wan Sub Shim, Eun Seuk Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(4):264-276. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.264

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BACKGROUND
Type 2 diabetes is characterized by impaired insulin secretion and/or insulin resistance. Thiazolidinediones have been shown to ameliorate insulin resistance. The purpose of the present study was to evaluate the long term serial effect of pioglitazone on anthropometrics and metabolic parameters in Korean type 2 diabetes patients. METHODS: One hundred thirteen type 2 diabetes patients (male, 67; female, 46; mean age, 49.1+/-10.8 years) were evaluated before and after 3 months, 6 months and 12 months of treatment with pioglitazone (Actos(TM), 15 mg/day). Anthropometric parameters and metabolic variables were measured. RESULTS: Body weight and body mass index (BMI) were increased in 3 months after pioglitazone treatment (body weight, 68.8+/-12.2 vs 69.8+/-11.9 kg, P < 0.01) without further increase. In women, body weight and BMI tended to increase more (body weight change after 3 months, 0.6+/-1.7 kg vs 1.6+/-1.7 kg, P < 0.01) and longer (3 months vs 6 months) than in men. Fasting plasma glucose (FPG) and HbA1c were decreased in 3 months after pioglitazone treatment (FPG, 7.97+/-2.29 vs 6.94+/-2.01 mmol/L, P < 0.01; HbA1c, 7.7+/-1.5 vs 7.0+/-1.1%, P < 0.01). Hypoglycemic effect of pioglitazone was prominent in women than in men (FPG change after 12 months, -1.80+/-2.54 vs -0.09+/-1.72 mmol/L, P < 0.001; HbA1c change after 12 months, -0.9+/-1.3 vs -0.4+/-1.1%, P < 0.05). Serum high-density lipoprotein cholesterol was increased after 3 months of pioglitazone treatment (1.16+/-0.24 vs 1.31+/-0.28 mmol/L, P < 0.01) without return until the end of this study. Serum triglycerides level decreased at 3 months (basal vs 3 months, 2.29+/-1.86 vs 1.88+/-1.21 mmol/L, P < 0.01) and 6 months (basal vs 6 months, 2.29+/-1.86 vs 1.97+/-1.40 mmol/L, P < 0.05) of pioglitazone treatment, but returned to basal level at 12 months. Liver enzyme, especially serum alanine transferase level decreased after 3 months of pioglitazone treatment (30.8+/-23.7 vs 24.5+/-18.5 IU/L, P < 0.01) without return until the end of this study. Hypoglycemic effect of pioglitazone was associated with basal BMI, fat contents and serum leptin level. CONCLUSION: Korean type 2 diabetes patients with pioglitazone use showed favorable metabolic effect for glycemic control, lipid metabolism and liverfunction, but pioglitazone induced body weight increase may be limited.

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Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations
Won Sang Yoo, Do Hee Kim, Hee Jin Kim, Hyun Kyung Chung
The Journal of Korean Diabetes.2019; 20(2): 117. CrossRef

The Relationship between Visceral & Subcutaneous Fat and Small Dense Low Density Lipoprotein Cholesterol Concentration in Type 2 Diabetic Patients.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Eun Seok Kang, Chul Woo Ahn, Sung Kil Lim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(3):207-216. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.207

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Abstract PDF: BACKGROUND
Visceral obesity is closely associated with cardiovascular disease (CVD). Small dense (sd) LDL is closely associated with CVD. The aim of this study was to evaluate the relationship between visceral and subcutaneous fat accumulation and sd LDL-C concentration. METHODS: 264 type 2 diabetic patients underwent ultrasonography to estimate visceral & subcutaneous fat accumulation and sd LDL-C concentrations were measured. RESULTS: BMI, total cholesterol, sd LDL-C concentration and percentage of sd LDL-C were higher in highest tertile of visceral fat length in male than those in lowest tertile. BMI, total cholesterol, triglyceride, LDL-C, sd LDL-C concentration and percentage of sd LDL-C were higher in highest tertile of visceral fat length in female than those in lowest tertile. But sd LDL-C concentration and percentage of sd LDL-C were not different among three groups based on the tertile of subcutaneous fat length in male and female. Visceral fat length was correlated with sd LDL-C concentration and percentage of sd LDL-C, total cholesterol, triglyceride, LDL-C, but negatively with percentage of large buoyant LDL-C and HDL-C after adjustment of age, sex and BMI. Subcutaneous fat length was not correlated with sd LDL-C and percentage of sd LDL-C, total cholesterol, triglyceride, HDL-C and LDL-C. CONCLUSION: The association between visceral fat length and sd LDL-C could be a factor that explains the association between visceral obesity and CVD.

Effects of Pioglitazone on Cerebral Hemodynamics in Patients of Type 2 Diabetes.: Jong Suk Park, You Jung Lee, Chul Sik Kim, Hai Jin Kim, Jina Park, Chul Woo Ahn, Kyung Yul Lee, Hyeong Jin Kim, Young Jun Won, Hun Ju Ha, Hae Sun Kwak, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(2):96-103. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.96

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Abstract PDF: BACKGROUND
Atherosclerosis is one of the major causes of morbidity and mortality in patients with type 2 diabetes and pioglitazone has been reported to have antiatherogenic effect. The aim of this study was to investigate whether pioglitazone affects carotid intima-media thickness (IMT) and pulsatility index (PI) in type 2 diabetic patients. METHODS: A total of 40 type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (pioglitazone 15 mg/day with gliclazide 80~320 mg/day for 12 weeks) (n = 20) and control group (gliclazide 80~320 mg/day for 12 weeks) (n = 20). The changes in lipid profile, insulin resistance, IMT, and PI were monitored to determine that pioglitazone improves cerebrovascular blood flow. RESULTS: The pioglitazone treatment significantly increased HDL-C, reduced triglyceride, insulin resistance and PI. IMT tended to decrease but the change was not significant. This study revealed that treatment with pioglitazone was associated with the improvement of cerebrovascular blood flow. CONCLUSIONS: Pioglitazone appears to be effective for the improvement of cerebrovascular blood flow in type 2 diabetic patients

The long term effects of rosiglitazone on serum lipid concentration and body weight.: Wan Sub Shim, Mi Young Do, Soo Kyung Kim, Hae Jin Kim, Kyu Yeon Hur, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(1):17-24. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.17

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Abstract PDF: BACKGROUND
Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentration and low density lipoprotein (LDL) particle size, it has adverse effects on the increment of total cholesterol (TC) and LDL cholesterol (LDL-C), and body weight in some studies. Such adverse effects of rosiglitazone on the serum lipid profiles and body weight seem to be attributed to the fact that most studies with rosiglitazone are limited to a short period of follow up. The aim of this study was to evaluate the long term effects of rosiglitazone on the serum lipid levels and body weight. MATERIALS AND METHODS: We prospectively evaluated fasting serum glucose, HbA1c, TC, LDL-C, triglyceride, HDL-C and body weight at baseline and every three months after rosiglitazone usage (4mg/d) in 202 type 2 diabetic patients. RESULTS: TC levels had increased maximally at 3 months and thereafter decreased, but were significantly higher at 18 months than those at baseline. LDL-C levels from the first 3 months to 12 months were significantly higher than those at baseline, but after 15 months, LDL-C concentration was not significantly different from the basal LDL-C concentration. HDL-C levels had increased after first 3 months and the increment of HDL-C concentration were maintained. The increment of HDL-C was more prominent in patients with low basal HDL-C concentration than in patients with high basal HDL-C concentration. Body weight from 3 months to 18 months were higher than that at baseline, but after 3 months, body weight did not increase furthermore significantly. CONCLUSIONS: The adverse effects on lipid concentration and body weight of rosiglitazone may attenuate after long term usage of rosiglitazone.

Clinical Characteristics of Non-obese, Adult-onset Diabetes Requiring Insulin Treatment.: Se Eun Park, Wan Sub Shim, Mi Young Do, Eun Seok Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):557-565. Published online November 1, 2005

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Abstract PDF: BACKGROUND
The aim of this study is to clarify the clinical characteristics of non-obese, adult-onset diabetes requiring insulin treatment and to compare the different characteristics of the three groups categorized according to diabetes classification. METHODS: Total 128 diabetic patients who were non-obese (BMI < 25kg/m2) and had been diagnosed with diabetes after 20 years old, requiring insulin treatment were enrolled in the study. We divided the patients into three groups : 56 patients with type 1, 37 with unclassifiable, and 35 with type 2 diabetes. The type of diabetes was assigned by comparing serum C-peptide concentration and clinical phenotypes. RESULTS: Type 2 and unclassifiable diabetes had no differences in BMI, the interval to use insulin, daily insulin dose, the level of HDL cholesterol and the positive rate for GAD Ab, but type 1 diabetes didn't. However, type 1 diabetes and unclassifiable group was lower prevalence of microvascular complications than type 2 diabetes (retinopathy 38.2, 52.8, 84.8 % ; nephropathy 37.7, 36.7, 74.2 % ; neuropathy 36.7, 36.7, 72.7 %, P<0.05). The prevalence of macrovascular complications was higher in the order of type 1, unclassifiable, and type 2 diabetes (11.1, 29.4, 72.7 %, respectively, all P<0.05). CONCLUSION: The clinical characteristics were similar between unclassifiable and type 2 diabetes, but the prevalence of microvascular complication in unclassifiable group had no significant difference compared with type 1 diabetes. The prevalence of macrovascular complications was significantly higher in the order of type 1, unclassifiable, and type 2 diabetes.

The Relationship between Metabolic Syndrome and Small Dense Low Density Lipoprotein-Cholesterol.: Wan Sub Shim, Hae Jin Kim, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):548-556. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes mellitus and metabolic syndrome (MS) are associated with the increased risk of cardiovascular disease and with characteristic dyslipidemia which is composed of high level of triglyceride, low level of HDL-C and increased small dense LDL (sd-LDL). Recently a simple method was established for the quantification of sd-LDL-C using heparin-magnesium precipitation. The aim of this study was to evaluate the relationship between the sd-LDL-C and the number of components of MS in type 2 diabetic patients. METHODS: 287 type 2 diabetic patients, who did not use the medication which can affect the concentration of lipid such as statin, fibrate, thiazolidinediones and corticosteroid, were enrolled. The NCEP-ATP III criteria of MS were used except obesity. RESULTS: Although LDL-C concentrations were not changed according to the number of components of MS, absolute level and percentage of sd-LDL-C were increased. Although LDL-C concentrations were not different between presence and absence of MS, in the case of MS, absolute level and percentage of sd-LDL-C were higher than not in the case of MS. Sd-LDL-C concentration was positively correlated with fasting plasma glucose, HbA1c, total cholesterol, triglyceride, LDL-C and percentage of sd-LDL-C, and negatively with HDL-C. The percentage of sd-LDL-C was positively correlated with total cholesterol, triglyceride and sd-LDL-C, and negatively with HDL-C. CONCLUSION: The sd-LDL-C may a factor that explains the higher risk of CVD in diabetic patients with the MS.

The Association of Family History of Diabetes and Obesity in the Development of Type 2 Diabetes.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Seung Jin Han, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):540-547. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by defects in both insulin secretion and insulin action. Type 2 diabetes has a strong genetic basis, and obesity is also known as a important risk factor for development of diabetes. The relative effects of obesity and family history of diabetes (FHx) to develop diabetes have not been well characterized. The aim of this study was to analyze the relative role of insulin resistance and insulin secretion in the newly diagnosed type 2 diabetic patients according to the presence of FHx and obesity. METHOD: We evaluated the presence of FHx, fasting and postprandial glucose, C-peptide and insulin in 219 newly diagnosed type 2 diabetic patients without the history of drug therapy from Jan. 2003 to Oct. 2004. RESULT: The mean age of patients was 54.7+/-10.2(yr) and the mean BMI was 25.5+/-3.0 kg/m2. The patients with FHx develop diabetes earlier than them without FHx. BMI, fasting glucose, postprandial glucose, fasting C-peptide and HOMAIR value were not different between groups. But postprandial C-peptide, fasting insulin, postprandial insulin and HOMAbeta-cell value were significantly lower in patient with FHx than in them without FHx. Interestingly, obese (BMI > or = 25kg/m2) patients with FHx developed diabetes earlier than nonobese (BMI <25kg/m2) patients with FHx. CONCLUSION: Obesity plays an important role in the determination of the earlier onset of diabetes in patients with FHx. Intentional prevention of obesity may be an important means to prevent, at least delay, the onset of diabetes in the subjects with FHx.

The Association Between White Blood Cell Count and Metabolic Syndrome in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Shin Ae Kang, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(5):460-468. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Type 2 diabetes and metabolic syndrome are associated with an increased risk of cardiovascular disease, and inflammation is also closely associated with cardiovascular disease. The white blood cell count, which is a marker of systemic inflammation, has been found to correlated with the risk of cardiovascular disease. The aim of this study was to evaluate the association between metabolic syndrome and the WBC count in type 2 diabetic patients. METHODS: 606 patients (males 318, females 288, BMI 25.6+/-3.2 kg/m2 and duration of diabetes 4.8+/-5.9year) were enrolled. The WBC and differential counts, anthropometry, blood pressure, fasting glucose, insulin and lipid profiles were measured. RESULTS: According to the quartiles of the WBC count, the number of components of metabolic syndrome and percentage of patients with metabolic syndrome were increased in the highest WBC count quartile. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts increased with increasing number of components of metabolic syndrome, but not that of the basophil count. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were higher in patients with metabolic syndrome than in those without. The WBC count was found to be positively correlated with the waist circumference(gamma=0.090), systolic blood pressure(gamma=0.090), diastolic blood pressure(gamma=0.104), triglyceride(gamma=0.252), insulin(gamma=0.168) and HOMAIR(gamma=0.170), but negatively with high-density lipoprotein cholesterol(gamma= -0.167)(P<0.05, respectively). CONCLUSION: Chronic inflammation, as indicated by a higher than normal WBC count, may increased with the increasing number of components of metabolic syndrome.

Association of Haplotype Combinations of Calpain-10 Gene Polymorphisms and the Metabolic Syndrome in Type 2 Diabetes.: Eun Seok Kang, Hye Joo Kim, Sung Min Myoung, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Moonsuk Nam; Korean Diabetes J. 2005;29(5):451-459. Published online September 1, 2005

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Abstract PDF: OBJECTIVE: Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, SNP-19, and SNP-63 of the Calpain 10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes (T2DM) in many populations. The aim of this study was to examine the association of the CAPN10 polymorphisms with metabolic syndrome in Korean patients with T2DM. METHODS: Overall, 382 T2DM patients were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, SNP-19 and SNP-63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of the components of metabolic syndrome was determined. RESULTS: 265 (69.4 %) patients were found to have metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (OR=2.334, P=0.010) and also had a significantly higher risk of having metabolic syndrome (OR=1.927, P=0.042). CONCLUSION: The results of this study suggest a role of the novel 111/121 haplotype combination created by the CAPN10 SNPs -43, -19 and -63 in the susceptibility to metabolic syndrome of T2DM patients.

Clinical Meaning of Postprandial Insulin Secretory Function in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Se Eun Park, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(4):367-377. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Impaired pancreatic beta-cell responsiveness is associated with type 2 diabetes mellitus. Postprandial insulin deficiency is closely related with fasting plasma glucose, HbA1c and insulin responses to meals, but most studies examining postprandial beta-cell responsiveness have been limited by the small number of type 2 diabetic patients examined. The aim of this study was to evaluate fasting and postprandial insulin secretions in relation to the duration of diabetes, BMI and glycemic control in a large number of patients with variable disease durations. METHODS: We evaluated the fasting plasma glucose, insulin, C-peptide, HbA1c, BMI, postprandial 2 hour glucose, insulin and C-peptide in 1,170(male 662, female 508, age 54.6+/-1.6 years, duration of diabetes 5.2+/-6.3 years, BMI 25.4+/-3.3kg/m(2)) type 2 diabetic patients. The delta C-peptide, delta insulin, fasting(M0) and postprandial(M1) pancreatic beta-cell responsiveness were also calculated. The subjects were divided into three groups according to their duration of diabetes, BMI, and fasting and postprandial C-peptide levels. After adjusting for age, sex and BMI, the correlation of diabetes and HbA1c were correlated parameters. RESULTS: In the group of patients whose duration of diabetes was longer than 10 years, the BMI, fasting, postprandial and delta C-peptide, and M0 and M1 were significantly lower, but age, fasting and postprandial glucose, as well as HbA1c were significantly higher than those in the other groups. There were no significant differences in the fasting and postprandial glucose and HbA1c according to their fasting C-peptide tertiles. However, in the group of patients with the highest postprandial C-peptide tertile, the fasting and postprandial glucose and HbA1c were significantly lower than those in the other groups. The duration of diabetes, after adjustment of age, sex and BMI, was negatively correlated with the fasting, postprandial and delta C-peptide, M0 and M1, but was positively correlated with the fasting and postprandial 2 hour glucose and HbA1c. The HbA1c after adjustment of age, sex and BMI, was positively correlated with duration of diabetes, and fasting and postprandial glucose, but was negatively correlated with fasting postprandial and delta C-peptide, M0 and M1. CONCLUSION: Although the fasting and postprandial insulin secretions were decreased with duration of diabetes, the decrease in the postprandial insulin secretion was more prominent. The postprandial pancreatic responsiveness may be a more important factor in predicting glycemic control in Korean type 2 diabetic patients than the fasting pancreatic responsiveness.

Relationship of LDL Particle Size to IMT and Insulin Resistance in Non-Diabetic Adult.: Jina Park, Chul Sik Kim, Jong Suk Park, Dol Mi Kim, Min Ho Cho, Jee Hyun Kong, Hai Jin Kim, Jeong Ho Kim, Chul Woo Ahn, Kyung Rae Kim, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee; Korean Diabetes J. 2005;29(4):333-343. Published online July 1, 2005

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Abstract PDF: BACKGROUND
The aims of this study were to investigate the predictor of the low density lipoprotein(LDL) particle size and the relationship of the LDL particle size to the levels of insulin resistance and the carotid intima-media thickness (IMT) in healthy Koreans. METHODS: The subjects were 47 and 89 clinically healthy males and females, aged between 32 and 70years, without medications that could potentially alter glucose and lipid metabolisms. The mean LDL particle size was determined by polyacrylamide tube gel electrophoresis(Lipoprint(r) LDL, Quantimetrix), the insulin resistance using a short insulin tolerance test kit, and the subclinical atherosclerosis from the carotid intima-media thickness. RESULTS: The LDL particle size was found to be significantly correlated with insulin resistance using a simple Pearson's correlation(r=0.233, P<0.01), but the independent predictors of the LDL particle size, as determined by a multiple stepwise regression analysis, were serum triglyceride(TG), high density lipoprotein(HDL) cholesterol level and age(beta=-0.403, P=< 0.001; beta=0.309, P=0.003; beta=-0.219, P=0.016, respectively). Significant relationships were found between an increasing IMT and the traditional risk factors of atherosclerosis: age, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure(r=0.490, P<0.001; r=-0.251, P<0.01; r=0.211, P<0.05; r=0.298, P<0.01; r=0.263, P<0.01, respectively). However, no significant correlation was found between an increasing IMT and the LDL particle size (r=-0.172, P=0.075). CONCLUSION: The best predictors for the LDL particle size were the serum TG level, HDL cholesterol level and age. Insulin resistance was not found to be an independent predictor of the LDL particle size. Small dense LDL was not found to be a predictor of the IMT in healthy Koreans.

Protective Effects of Lithospermate B on Diabetic Nephropathy in OLETF Rat.: Hyun Joo Lee, Geun Taek Lee, Eun Seok Kang, Kyu Yeon Hur, Zheng Shan Zhao, Chul Woo Ahn, Hun Joo Ha, Man Kil Jung, Bong Soo Cha, Hyun Chul Lee; Korean Diabetes J. 2005;29(4):322-332. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Magnesium lithospermate B(LAB), an active component isolated from Salvia milltiorrhizae, has been reported to have renoprotective effects in type 1 diabetic animal model. The purpose of this study was to examine the effects of LAB on the prevention of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty(OLETF) rat which is regarded as an animal model of type 2 diabetes. METHODS: Ten microgram of LAB/kg or Vehicle(PBS) was given orally once daily to 10-week-old male OLETF rats and LETO rats for 40 weeks. Intra-peritoneal glucose tolerance test was performed at 50 weeks. 24 hr urinary protein excretion amounts were measured. Lipid peroxidation, TGF-beta1 and ED-1 of renal cortex were measured. RESULTS: The mean body weight of LAB+OLETF was not significantly different from that of OLETF rats. LAB treatment decreased proteinuria, lipid peroxidation, and free fatty acid in OLETF rats without decrease in the plasma glucose concentration. Also, LAB inhibited the progression of glomerular hypertrophy and mesangial expansion. LAB effectively decreased ED-1 positive cells, ECM expansion, and TGF-beta1 level in the renal cortex of OLETF rats. CONCLUSIONS: These results suggest that the beneficial effects of LAB on the diabetic renal damage in the OLETF rats may depend on a mechanism of decreasing oxidative stress. LAB might be a new therapeutic agent for the prevention of nephropathy in type 2 diabetes as well as type 1 diabetes.

Evaluation of the Indicator Test(NeurocheckTM) in the Diagnosis of Peripheral Neuropathy among Type 2 Diabetic Patients.: Tae Seo Sohn, Hyun Shik Son, Jae Myung Yu, Bong Soo Cha, Kyung Wan Min, Sei Hyun Baik; Korean Diabetes J. 2005;29(3):247-253. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Eighty-five percent of the lower-limb amputations that are done for patients with diabetes are preceded by foot ulceration, and this suggests that prevention and the appropriate management of foot lesions are of paramount importance. Ulceration is caused by several factors acting together, but they are particularly caused by neuropathy. Various aspects of the neurovascular function can be evaluated with specialized tests, but these tests have generally not been well standardized and they have limited clinical utility. A new indicator test(NeurocheckTM) that utilizes the water-induced color change of a cobaltII compound from blue to pink has been introduced. The aim of the present study was to evaluate this new indicator test in the diagnosis of peripheral neuropathy among type 2 diabetic patients. METHOD: This study included 124 diabetic patients(45 men and 79 women) who were recruited from 5 diabetic centers in Korea. The presence of diabetic neuropathy was diagnosed by nerve conduction study. The degree of the patient's symptom was checked as the total symptom score(TSS). Autonomic sudomotor neuropathy was assessed by means of the new indicator test(NeurocheckTM). The degree of color change in 10 minutes was assessed as a complete color change, an incomplete color change or no color change. RESULTS: Of the 124 diabetics patients we investigated, 109 patients were proven to have peripheral neuropathy by nerve conduction study. Autonomic sudomotor neuropathy by NeurocheckTM was diagnosed in 94 patients with peripheral neuropathy(86.2%) and in 6 patients(40%) without peripheral neuropathy. The overall measure of agreement between NeurocheckTM and the electrodiagnostic test was 0.3673(0.1547, 0.58). The sensitivity and specificity of NeurocheckTM was higher in women(91.2% and 63.6%, respectively) than in men(78.0% and 50.0%, respectively). The measure of agreement in women was 0.5093(0.2396, 0.9601) and in the men it was 0.1567(-0.1423, 0.4588). CONCLUSION: The new indicator test has a high sensitivity for the diagnosis of peripheral neuropathy among diabetic patients, especially in women. It is likely that the new indicator test is useful clinically as a screening and diagnostic tool for diabetic neuropathy. Since the specificity of the test is somewhat low, the patients with a high total symptom score and who are without sudomotor neuropathy may need further diagnostic evaluation on neuropathy

Resurvey of Alternative Medicine in Korean Type 2 Diabetes Mellitus after 10Years.: Kyung Wook Lee, Seong Bin Hong, Kee Young Min, Seung Yong Lee, Moonsuk Nam, Yong Seong Kim, Chul Woo Ahn, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Kwan Woo Lee, Tae Sun Park; Korean Diabetes J. 2005;29(3):231-238. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Despite tremendous advances in modern medicine, the interest in alternative medicine, including those medicines used for the treatment of diabetes has intensified throughout the industrialized world. We conducted a clinical resurvey of the dlternative medicines used for diabetic treatment, and we compared the results with those from the previous survey. METHODS: From July through October 2004, a total of 1,233 type 2 diabetics attending diabetes clinics in five university hospitals were interviewed and asked 14 questions that were identical to those questions asked 10 years ago during the earlied study. RESULTS: On the average, the respondents, having an average age of 58.9+/-11.4years, suffered diabetes for 8.7+/-7.3years with 7.7+/-1.4% HbA1c. The percentage of patients who experienced using alternative medicine for diabetic treatment plummeted from 73.9% to 33.2% over the last 10 years. Herbal medicine maintained its high popularity with increase an being seen in supplementary food use. The average per-capita spending on alternative medicine changed from 520,000 Korea Won on five types of medicine in 1994 to 730,000 on two types of medicine in 2004. Regarding the information sources, the family and relatives topped the list again(70.3%). Information sources such as mass media almost doubled to 20.2%, and the internet accounted for 1.2% in 2004. The majority of the users said again in 2004 that the medicine was `inefficacious'(63.5%) but those who answered positively inched up by 3.1% from 14.5% in 1994. To the question if they would try a new alternative medicine, the majority answered negatively in 2004(43% of the experienced group, 52.3% of the inexperienced group), and this was unlike the results in 1994 when the positive responses prevailed(78.6% and 72.7% respectively). CONCLUSION: Alternative medicine use among the type 2 diabetic patients has declined in the last 10 years. The patients overall attitude toward alternative medicine has turned negative, and this is primarily attributable the to continuous, proper education by mass media and social groups

Analysis of the Relative Importance of Insulin Resistance and Insulin Secretion Defect by Homeostasis Model Assessment in Korean Type 2 Diabetic Patients.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Jae Hoon Moon, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(3):206-214. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by defects in both insulin secretion and insulin sensitivity. However, the relative importance of insulin secretion and insulin resistance in Korean type 2 diabetic patients has not been well characterized in any study that has included a large number of subjects. Therefore, this study aimed to evaluate the relative importance of insulin sensitivity and the function of the beta cell in Korean type 2 diabetic patients. METHODS: We applied the HOMA model to 1,162 type 2 diabetic patients (654 males and, 508 females) who did not use insulin and we assessed HOMAIR and HOMAbetacell & its relation to the other parameters. RESULTS: The HOMAIR of Korean type 2 diabetic patients was 2.29(range: 0.31~37.17) and the HOMAbetacell of Korean type 2 diabetic patients was 32.17(range: 1.04~1310.79). The HOMAIR of Korean type 2 diabetic male patients was 2.15(range: 0.31~16.6) and that of Korean type 2 diabetic female patients was 2.47(range: 0.36~37.17). The HOMAbetacell of Korean type 2 diabetic male patients was 30.1(range: 1.04~462.34) and that of Korean type 2 diabetic female patients was 35.42(range: 2.60~1310.79). The HOMAIR and HOMAbetacell were significantly higher in females than males. There was no significant correlation between HOMAIR and age, and the duration of diabetes, but there was significant correlation between HOMAIR and BMI, fasting glucose, HbA1c and the fasting insulin. There was no significant correlation between age and HOMAbetacell. However, there was significant correlation between HOMAbetacell and BMI, the duration of diabetes, the fasting glucose, HbA1c and the fasting insulin. The longer the duration of diabetes, the more the HOMAbetacell was decreased but there was no change of HOMAIR with respect to the duration of diabetes. As expected, the subjects with a lower HOMAIR and a higher HOMAbetacell had the best glycemic control. Those with a higher HOMAIR and lower HOMAbetacell had the worst glycemic control although they had taken larger amount of oral hypoglycemic agents. Interestingly, the patients with a lower HOMAIR and higher HOMAbetacell had better glycemic control than those patients with a higher HOMAIR and lower HOMAbetacell. CONCLUSION: Both insulin secretion and insulin resistance are important in glycemic control but it seems that insulin secretion is a more important factor in glycemic control than insulin resistance in the Korean type 2 diabetic patients

Prevalence of Diabetes Mellitus(Fasting Plasma Glucose by the ADA Criteria) and Impaired Fasting Glucose according to Anthropometric Characteristics and Dietary Habits: 1998 National Health and Nutrition Survey.: Chul Sik Kim, Eun Kyong Jeong, Jina Park, Min Ho Cho, Ji Sun Nam, Hai Jin Kim, Jee Hyun Kong, Jong Suk Park, Joo Young Nam, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Chung Mo Nam; Korean Diabetes J. 2005;29(2):151-166. Published online March 1, 2005

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Abstract PDF: BACKGROUND
The study is based on the National Health and Nutrition Examination Survey in Korea(1998). With these data, we want to predict the prevalence of diabetes mellitus(DM) and impaired fasting glucose(IFG), By investigating anthropometric characteristics and dietary intake habits, we also wanted to analyze any significant correlation between those factors and the prevalences of DM and IFG. METHODS: The study group was comprised of 8,166 people, a representative group of Koreans, who had undergone a health check-up and food intake survey among the total 39,331 members of 12,189 families who were surveyed. RESULTS: The final results are as the follows. 1) The peak prevalence of DM was 15.92% among women in their sixties and 18.21% among men in their fifties, and that of IFG was found to be 16.27% of women in their seventies and 14.09% of men in their sixties. 2) When analyzing the eating habits and the prevalences of DM and IFG, we found that women with more glucose intake had a lesser risk of DM, but this was of no statistical significance. 3) In men, age, total cholesterol, triglyceride(TG), and hypertension(HTN) were revealed as meaningful factors and in women, age, TG, and HTN were revealed as meaningful factors. As to the IFG, in females, age and TG were meaningful factors, and in males, age, TG, the waist/hip ratio (WHR), and body mass index (BMI) were meaningful factors. CONCLUSION: Although this study could not demonstrate meaningful correlation between diet habits and DM, the prevalence of IFG and the recent increase in the prevalence of DM in Koreans, owing to alterations in their diet habits, demands further organized group study for a better understanding of their relationship

A Case of Severe Prolonged Hypoglycemia Caused by Combined Ramipril and Amiloride Treatment in a Nondiabetic Woman.: Min Ho Cho, Dol Mi Kim, Chul Sik Kim, Joug Suk Park, Joo Young Nam, Jin Hyuck Chang, Jina Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(6):554-557. Published online December 1, 2004

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Abstract PDF: The relationship between angiotensin converting enzyme inhibition and hypoglycemia remains controversial. An 82-year-old, nondiabetic woman who had taken ramipril 5 mg with amiloride 5 mg for two months was admitted to the hospital because of her altered mentality. Her plasma glucose was 1.5 mmol/L and she regained her consciousness after normalization of the plasma glucose. The recurrent attacks of hypoglycemia ended when she stopped taking ramipril. Her hypoglycemia was thought to result from the combined deficiency of catecholamines and cortisol that was induced by a deficiency of angiotensin II. The glucagoninsensitivity was thought to result from a chronic elevation of bradykinin due to the ACE inhibitor, and the relative hyperinsulinemia was though to be cased by the amiloride.

Apolipoprotein E Genetic Polymorphism and Diabetic Microangiopathy in Type 2 Diabetic Patients.: Jong Suk Park, Joo Young Nam, Chul Sik Kim, Dol Mi Kim, Min Ho Cho, Jina Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(6):511-520. Published online December 1, 2004

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Abstract PDF: BACKGROUND
The pathophysiological causes for the development and progression of diabetic microangiopathy are not well known, but the apo E genetic polymorphism has been proposed to be involved in the disease's development and progression. The aim of this study was to investigate the association between the apo E genetic polymorphism and diabetic microangiopathy in Korean type 2 diabetic patients. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (the E2, E3 and E4 groups). The plasma levels of lipids were measured. The frequency of diabetic nephropathy, retinopathy and neuropathy were compared among the three apo E genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater for the apo E2 patients with diabetes (46.7%) than for the apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that the odds ratio of the apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (P < 0.01) and 0.643 (P = 0.583), respectively. Plasma TG levels were significantly greater for the apo E2 patients. This study did not find any association between diabetic retinopathy, neuropathy and apo E polymorphism. CONCLUSION: Apo E2 is a positive risk factor for diabetic nephropathy in Korean type 2 diabetic patients. TG may have an important role in diabetic nephropathy.

The Effects of Lifestyle Modification on the Metabolic Parameters of Type 2 Diabetes.: So Hun Kim, Eun Seok Kang, So Young Park, Suk Jeong Lee, Mi Jin Kim, Ji Soo Yoo, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee; Korean Diabetes J. 2004;28(5):441-451. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Lifestyle modification is known to have positive effects on glycemic control and improving the cardiovascular risk factors. Although lifestyle modification is considered to be important in treating diabetic patients, there are few studies concerning the direct effect of lifestyle modification on the patients with type 2 diabetes (T2DM). The aim of this study is to evaluate the effects of lifestyle modification on glycemic control, lipid profiles, body indices, serum adiponectin and the hsCRP levels for patients with T2DM in Korea. METHODS: Twenty two patients with T2DM who had no medication changes for the recent 3 months and who also had a HbA1c> or =7.0% were enrolled in a lifestyle modification program. These patients visited Severance Hospital Diabetes Center once every week for 12 weeks, and they were educated about exercise and diet control. Their metabolic and anthropometric parameters were compared with 22 control T2DM patients who were not in the program. RESULTS:Lifestyle modification group patients showed significant decrements in HbA1c (-0.62 +/- 1.29 vs. 0.14 +/- 0.91%, p=0.044), total cholesterol (-0.57 +/- 0.54 vs. -0.06 +/- 0.61 mmol/l, p=0.007), LDL cholesterol (-0.57 +/- 0.62 vs. 0.02 +/- 0.59 mmol/l, p=0.003), body weight (-1.5 +/- 19 vs. 0.2 +/- 1.5 kg, p=0.005) and BMI (-0.6 +/- 0.7 vs 0.0 +/- 0.6 kg/m2, p=0.003) compared with the control subjects. HOMAIR, serum triglyceride, adiponectin, and hsCRP levels showed no significant difference compared to the control subjects. CONCLUSION: Lifestyle modification in Korean T2DM patients had positive effects on weight loss, glycemic control, and lipid profiles. These changes imply that lifestyle modification will be helpful for managing DM and its complications.

The Degree of Atherosclerosis and the Metabolic Characteristics according to the Abdominal Obesity in Type 2 Diabetic Patients.: Chul Sik Kim, Jong Suk Park, Joo Young Nam, Jina Park, Min Ho Cho, Ji Sun Nam, Dol Mi Kim, Soo Jee Yoon, Jae Hyun Nam, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(5):377-391. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Many of the maturity-onset type 2 diabetic patients with hypertension and dyslipidemia in Korea are not associated with obesity. However, these patients are at risk for developing macrovascular complications such as atherosclerosis due to hyperinsulinemia, insulin resistance and abdominal obesity. The aims of this study were to compare the clinical and biochemical differences between the type 2 diabetic patients that are with and without abdominal obesity, and we also wished to investigate the degree of insulin resistance and atherosclerosis in these patients. METHODS: Among 530 type 2 diabetes mellitus (DM) patients, the percentages of under-weight (UW), normal-weight (NW), over-weight (OW) and obese (OB) (BMI <20, 20-25, 25-29.9 and > or =30, respectively) subjects were 8.9%, 62.1%, 25.1% and 3.9%, respectively. To evaluate the severity of their atherosclerosis, the coronary artery calcification (CAC) score was measured by electron beam computed tomography, and the intima-media thickness (IMT) of the common carotid artery and the ankle-brachial pressure index (ABPI) were also measured. The Insulin sensitivity index (ISI) was measured by the plasma glucose disappearance rate (kitt: %/min). RESULTS: 1. There were no differences in age, duration of DM and the HbA1c levels according to BMI for both the men and women, but the waist-hip ratio (WHR) and systolic blood pressure (SBP) were significantly different among each group. Serum triglyceride (TG), HDL-cholesterol (HDL-C), free fatty acid (FFA), fibrinogen, and fasting c-peptide levels, {excluding total cholesterol (TC)}, were also significantly different. The ISI, which is a marker for insulin resistance, as well correlated with the patients' BMI. Subjects having an with ISI above 2.5%/min were considered as having insulin resistance, and 28%, 60%, 68% and 75% of patients in the UW, NW, OW and OB groups, respectively, demonstrated insulin resistance. The visceral fat area/subcutaneous fat area ratio and visceral fat area/thigh muscle area ratio also increased with BMI. 2. The median values of the WHR were 0.95 for the men and 0.91 for the women. There were no significant differences for age, BMI, duration of DM and HbA1c between patients with and without abdominal obesity, but the SBP, TG, HDL-C, FFA, fibrinogen and ISI were significantly different between those two groups. 3. For the OW group as well as the NW group, the carotid IMT, ABPI and CAC scores were significantly different between the patients with and without abdominal obesity. However, there were no differences between the NW group and the OW group. CONCLUSION: In conclusion, those patients with abdominal obesity, regardless of their BMIs, have a higher prevalence for atherosclerosis, dyslipidemia, and hypertension, compared to those patients without abdominal obesity. Therefore, it is important to screen for atherosclerosis and to manage it accordingly, for the patients with insulin resistance or abdominal obesity in order to decrease their risk of developing atherosclerotic events.

Role of Activation of NF- B and AP-1 by Oxidative Stress in Atherosclerosis in Diabetic Patients.: Chul Sik Kim, Geun Taek Lee, Jina Park, Min Ho Cho, Joo Young Nam, Jong Suk Park, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(4):255-264. Published online August 1, 2004

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Abstract PDF: BACKGROUND
The aim of this study was to evaluate the possible role of NF- B activation and AP-1 by oxidative stress in atherosclerosis in diabetic patients by measuring the carotid intima-media thickness, intracellular ROS generation and activation of transcription factors, including nuclear factor-kappa B (NF- B) and activator protein-1 (AP-1). METHODS: Sixty-six patients (28 males, 38 females; age 56.1 13.4 years; duration of diabetes 115.7 83.4 months) with type 2 diabetes mellitus (DM) were selected for this study. The DM patients included in this study were divided into those with a normal carotid intima-media thickness (Group II) and those with an increased intima-media thickness (Group III). 57 healthy controls matched for age and sex with the DM patients (Group I) were randomly selected. Dichlorodifluorescein (DCF)-sensitive intracellular ROS was measured by fluorescent spectrometry. The activities of NF- B and AP-1 in PBMCs were measured by an electrophoretic mobility shift assay. RESULTS: No differences were evident between the groups in terms of gender, age, BMI, blood pressure, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol. Spontaneous and H2O2 (or phorbol-12-myristate-13-acetate, PMA) stimulated ROS were significantly higher in the PBMCs from the DM patients with an increased intima-media thickness (Group III) than in those without (Group II), and were also higher in the control group (Group I). Moreover, the activities of NF- B and AP-1 were significantly higher in Group III than in Groups I or II. CONCLUSION: The present study demonstrates that intracellular ROS generation, and NF- B and AP-1 activation in PBMCs strongly correlates with the carotid artery IMT. These clinical results suggest that increased oxidative stress in PBMCs may play a role in the pathogenesis of atherosclerosis in DM patients .

Frequency of Anti-GAD Antibody in Non-obese, Adult-onset Type 2 Diabetes in Korea and Clinical and Biological Characteristics According to Anti-GAD Antibody.: Chul Sik Kim, Jina Park, Min Ho Cho, Jong Suk Park, Joo Young Nam, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(2):66-74. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Some of the characteristic features of diabetes mellitus in Korea are that 70-80% of patients are non-obese or adult-onset type, and type 1 diabetes is very rare. Occasionally, autoantibodies to glutamic acid decarboxylase(GAD) are found in typical, type 2 diabetes mellitus patients(T2DM). The role of the autoantibody to GAD in T2DM is unknown. The aim of this study was to determine the clinical and biochemical characteristics between GAD-positive and GAD-negative non-obese, adult-onset diabetics in Korea. METHODS: A cohort of 428 type 2 diabetes patients was included. The measured autoantibodies to GAD were measured, and the C-peptide and HbA1c levels, anthropometric data(weight, height, body mass index and waist circumference), blood pressure and lipid profiles compared between the two groups. RESULTS: Compared to the antibody-negative group(n=374; 87.4%), patients with the anti-GAD antibody(n=54; 12.6%) had significantly lower C-peptide levels and were significantly younger. The anti GAD-positive group had a lower BMI, more frequently needed insulin supplements, and a lower prevalence of hypertension. There were no significant differences in gender and family history of diabetes between the two groups. CONCLUSION: The presence of the autoantibody to GAD allowed the group with more deteriorated beta-cell function and more frequent need for insulin supplements, but a lower prevalence of obesity and hypertension to be determined.

A Case of Primary Insulin Autoimmune Syndrome in a Patient Suspected of Having an Insulinoma.: Sung Ju Lee, Jee Hyun Kong, Joo Young Nam, Jong Suk Park, Chul Sik Kim, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(1):45-50. Published online February 1, 2004

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Abstract PDF: Insulin autoimmune syndrome consists of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients never been exposed to exogenous insulin. Most affected patients present with other autoimmune disorders, most often Graves' disease. A significant increase in the insulin and C-peptide plasma concentrations and the presence of other anti organ antibodies are also observed. Awareness of insulin autoimmune syndrome hypoglycemia is important as this may produce severe neuroglycopenic symptoms, which may be confused with the presence of an insulinoma. The correct diagnosis is important to avoid unnecessary surgical intervention in patients who are best treated with conservative support, watchful waiting, or in some cases, immunosuppressive therapy. Herein, a case of autoimmune insulin syndrome, suspected as being an insulinoma is reported.

Efficacy of Serum Leptin Level as an Indicator to Predict the Clinical Response of Rosiglitazone in Patients with Type 2 Diabetes Mellitus.: Jae Hyuk Lee, Soo Kyung Kim, Kyu Yeon Hur, Han Seok Choi, Ji Young Jung, Wan Sub Shim, Hyun Joo Lee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2003;27(5):420-432. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Leptin is a protein secreted by adipocytes that regulates food intake by acting on the hypothalamus and is correlated with body fat mass. Insulin resistance is also correlated with body fat mass and obesity. Rosiglitazone (RSG) is known as a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma). It improves glycemic control by improving insulin sensitivity in peripheral tissue. This study was performed to evaluate the antidiabetic and insulin sensitizing effects of RSG combination therapy and the efficacy of serum leptin level as an indicator to predict the clinical response of RSG in type 2 diabetic patients with oral agents such as metformin and/or sulfonylurea. METHODS: The study subjects were 140 type 2 diabetic patients (90 male, 50 female) who received a 12-week course of daily 4 mg RSG, in addition to the previous medications. The glucose level, indices of insulin resistance and metabolic parameters were measured. Serum leptin level was measured by radioimmunoassay before and after RSG treatment. Visceral fat and subcutaneous fat were measured by sonography. RESULTS: After 12 weeks of RSG treatment, FPG (12.6+/-28.1 mg/dL), HOMAIR (0.3+/-0.9), serum fasting insulin (1.9+/-4.7 microU/mL), SBP and DBP had all decreased significantly, whereas body weight, BMI, waist circumference, WHR, body fat mass, and subcutaneous fat had all increased. Serum leptin level also tended to increase after RSG treatment, but without significance. deltaFPG (delta=value after treatment- value before treatent) was inversely correlated with basal serum leptin level (r=-0.202), basal HOMAIR (r=-0.226) and basal FPG (r=-0.565). There was no correlation between deltaFPG and basal BMI or serum insulin level. RSG treatment showed significant inverse correlation between serum leptin level and deltaHOMAIR (r=-0.416), delta insulin (r=-0.365) and deltaHbA1c (r=-0.189). Serum leptin level was positively correlated with the subcutaneous fat amount (r=0.548), basal BMI (r=0.521), and basal HOMAIR (r=0.343). CONCLUSION: These results showed that RSG treatment can improve not only hyperglycemia but also insulin resistance in type 2 diabetic patients. The serum leptin level at baseline can be used as an indicator to predict the clinical response of RSG treatment in type 2 diabetes patients.

Relationship Between Diabetic Nephropathy and Plasminogen Activator Inhibitor-1.: Bong Soo Cha, Hae Jin Kim; Korean Diabetes J. 2003;27(3):179-185. Published online June 1, 2003

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Abstract PDF: No abstract available.

A Case of Primary Antiphospholipid Syndrome in a Patient with Diabetes Presenting as Foot Ulcer.: Chul Sik Kim, Dae Hoon Song, Jina Park, Jong Suk Park, Joo Young Nam, Young Kim, Hee Jung Yoon, Dol Mi Kim, Soo Jee Yoon, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2003;27(2):165-171. Published online April 1, 2003

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Abstract PDF: Antiphospholipid syndrome is a disorder characterized by recurrent vascular thrombosis, pregnancy loss and thrombocytopenia, and the presence of the lupus anticoagulant or a positive anticardiolipin test. A link of antiphospholipid syndrome to diabetes mellitus has not been established. There have been no reports of large artery thrombosis associated with antiphospholipid syndrome or diabetes mellitus. We present a case of an adult with large artery thrombosis, elevated anticardiolipin antibodies and lupus anticoagulant associated with diabetes. The patient was managed by successful primary percutaneous transluminal angioplasty and stent implantation, with accompanying anticoagulation therapy. To our knowledge, this is the first case where the occluded large artery was treated with primary stent implantation in primary antiphospholipid syndrome with diabetes mellitus

The Effect of Growth Hormone on Insulin Resistance and Atherosclerotic Risk Factors in Obese Patients with Uncontrolled Type 2 Diabetes Mellitus.: Jae Hyun Nam, Soo Jee Yoon, Dol Mi Kim, Chul Sik Kim, Joo Young Nam, Jong Suk Park, Jina Park, Chul Woo Ahn, Suk Won Park, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2003;27(2):141-152. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Insulin resistance in visceral obesity constitutes a risk factor for the development of atherosclerosis. The insulin resistance in obese type 2 diabetic patients can be improved by a decrease in the visceral fat and an increase in the skeletal muscle, which may influence the insulin sensitivity. Growth hormone (GH) accelerates lipolysis and promotes protein conservation. The effects of GH therapy, with diet restriction, on lipolysis and protein anabolism, were evaluated, which may change body composition, insulin resistance and atherosclerotic risk factors in obese type 2 diabetes mellitus. METHODS: Sixteen obese type 2 diabetic patients (31~56yrs), who had high glucose levels (glucose 12.8+/-1.7 mmol/L, HbA1c 10.2+/-2.1%), were treated with recombinant human GH (GH; 1 unit/d, 5 times/week), diet restriction (25 kcal/kg ideal body weight/day) and exercise (250 kcal/day) for 12 weeks. They underwent anthropometric measurement, bioelectrical impedance for total body fat and lean body mass, as well as computed tomography, for visceral and subcutaneous fat, at the umbilicus and muscle area at the mid-thigh levels. All subjects underwent the test for GH response to hypoglycemia. The insulin sensitivity index (ISI) was measured using insulin tolerance tests (ITT). RESULTS: 1. The visceral fat area (VFA)/thigh muscle area (TMA) ratio was more decreased in the GH-treated group than in the control group, but there was no change of body weight. 2. The ISI was significantly increased in only the GH-treated group, which was negatively correlated with the VFA/TMA ratio. The serum free fatty acid, fibrinogen and plasminogen activator inhibitor-1 were significantly decreased after the GH treatment. The serum glucose level and HbA1c remained unchanged during the GH therapy, but were significantly decreased after 3 months. 3. The total cholesterol and triglyceride levels were decreased in the GH treated group. 4. The insulin-like growth factor-I, fasting c-peptide and insulin level were all significantly increased after the GH treatment. CONCLUSION: This study suggested that in type 2 diabetic patients, with insulin resistance and uncontrolled blood sugar, GH treatment caused a decrease in the visceral fat and an increase in the muscle mass, which could result in the improvement of the ISI, atherosclerotic risk factors and dyslipidemia.

High Sensitive C-reactive Protein and Carotid Intima Media Thickness in Korean Population.: Dae Jung Kim, Seung Hee Choi, Se Hwa Kim, Sang Su Chung, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2003;27(1):49-62. Published online February 1, 2003

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Abstract PDF: BACKGROUND
A chronic inflammatory response is an important component in the development and progression of atherosclerosis. Since the development of the high-sensitive C-reactive protein (hs-CRP) assay, the association between subtle increases in the hs-CRP concentration and the development of atherosclerosis, has recently been reported. In this study, the relationship between hs-CRP, conventional cardiovascular risk factors and carotid intima media thickness (IMT), were investigated, and whether hs-CRP concentrations analyzed to see if it could be used as an independent risk factor, of early subclinical atherosclerosis in apparently healthy subjects. METHODS: This report was conducted as part of the Korean Metabolic Syndrome Study. Of 1,230 individuals having undergone a routine check-up, 849 were selected, based on their medical history of cardiovascular diseases. The hs-CRP was measured by an ELISA method, using human anti-CRP (CRP II Latex X2, Denka Seiken, Japan). RESULTS: The distribution of the hs-CRP concentration was positively skewed, and the hs-CRP levels ranged from 0.10 to 43.7 mg/L (mean 2.06, median 0.77 mg/L). There were significant positive correlations between the hs-CRP and age, BMI, waist, BP, insulin resistance (HOMA-IR) and the TC/HDL-C ratio. From a multiple regression analysis, independent relationships between the hs-CRP and obesity, hypertension, age ( 60 years), current smoking, male and insulin resistance were found. There were positive correlations between the carotid IMT and age, BMI, waist circumference, SBP, DBP, TC, TG, LDL-C, fasting blood glucose, HOMA-IR and hs-CRP, and a negative correlation between the carotid IMT and the HDL-C. From the multiple regression analysis, independent relationships between the carotid IMT and age, SBP, TC/HDLc, HOMA-IR, waist circumference, and DBP also persisted. After adjusting for the conventional risk factors in the multiple regression, there was no longer a significant relationship between the hs-CRP and the carotid IMT. CONCLUSION: There were strong correlations between the hs-CRP and the conventional cardiovascular risk factors, especially with that of obesity. Also, a highly significant association was also found between the hs-CRP and the carotid IMT. However, the hs-CRP, per se, is not a major independent risk factor of early subclinical atherosclerosis in Koreans.

Prevalence of Metabolic Syndrome according to the New Criteria for Obesity.: Hae Won Chung, Dae Jung Kim, He Dong Jin, Seung Hee Choi, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2002;26(5):431-442. Published online October 1, 2002

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Abstract PDF: BACKGROUND
The prevalence of obesity is known to be lower in Asian population than that in Europe. But, the health risks associated with obesity occur at a lower body mass index (BMI) in Asian. The aim of this study was to assess the prevalence of the metabolic syndrome and its components in Korean adult population according to the new criteria for obesity proposed in Asia-Pacific Perspective. METHODS: From individuls, who participated in medical check-up of Korean Association of Health (KAH), 1,230 individuals were included in the analysis. In patients with type 2 diabetes (n=131), subjects with impaired fasting glucose (IFG) (n=84), or individuals who have insulin-resistance but show normal fasting glucose (NFG) (n=1015), the metabolic syndrome was defined as presence of at least two of the following components; hypertension, dyslipidemia, and obesity. RESULTS: Metabolic syndrome was present in 19% of men and 16% of women. In detail, about 10% in NFG, 50% in IFG, and 70% of patients with type 2 diabetes fulfilled the criteria of metabolic syndrome. In comparison with the lowest tertile of waist circumference and BMI, the prevalence of the metabolic syndrome increased about 13 fold in subjects with the highest tertile. Using a multiple regression analysis, HOMA-IR was associated with an increased risk for the metabolic syndrome (RR=2.23, p=0.001). CONCLUSION: The metabolic syndrome, according to the new criteria for obesity in Asian-Pacific Perspective in Korean adult population, is seen as much as Western countries. Insulin resistance and hyperinsulinemia can be suggested as the main causes of the metabolic syndrome.

Polymorphism of the Hepatocyte Nuclear Factor-1alpha Gene in the Early-onset of Type 2 Diabetes Mellitus with a Strong Family History in Korea.: Eun Seok Kang, Si Hoon Lee, Zheng Shan Zhao, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kab Bum Huh, Young Soo Ahn; Korean Diabetes J. 2002;26(5):328-335. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Maturity-onset diabetes of the young (MODY) is a genetically heterogenous subtype of type 2 diabetes characterized by an early onset, usually before 25 years of age, autosomal dominant inheritance and a primary defect in insulin secretion. Mutation of the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene is known to be a cause of MODY3. This study was carried out to reveal whether HNF-1alpha gene polymorphism is a common cause of early-onset type 2 diabetes and MODY in the Korean population. METHODS: Members of 12 pedigrees families with MODY and early-onset of type 2 diabetes were selected for the mutation detection. All of the families involved had at least two members with type 2 diabetes diagnosed before the age of 40 years, where the diabetes was inherited as an autosomal dominant trait, with at least 3 generations of diabetic subjects. Genomic DNA was extracted from whole- blood samples. The 10 exons and the promotor of the HNF-1alpha gene were sequenced. RESULTS: In codon 17 of exon 1, 2 of the 10 control subjects and 5 of the 12 patients had nucleotide replacement where the CTC nucleotide was replaced by the CTG (p=0.381). This is a silent mutation where both the CTC and CTG code have the same amino acid leucine. In codon 27 of exon 1, 5 patients had a silent mutation, where the codon ATC is replaced by CTC and the amino acid changes from isoleucine to leucine, but no mutation was found in the control group (p=0.040). In codon 459 of exon 7, 2 of the controls and 3 of the patient group had a silent mutation (CTG -> TTG) that were both codon code leucine (p=1.000). Another missense mutation was observed in codon 487 of exon 7. Nucleotide AGC (serine) was replaced by AAC (asparagines). This mutation was observed in 5 control subjects and 10 patients (p=0.172). CONCLUSION: This study did not reveal a new HNF-1alpha gene polymorphism. We conclude that the HNF-1alpha gene polymorphism does not play a major role in the early-onset of type 2 diabetes with a strong family history in Korea.

Insulin Resistance and severity of coronary artery diseases in Patients with Coronary Artery Diseases.: Dae Jung Kim, Jae Hyun Nam, Dong Hoon Choi, Hyeung Jin Kim, Soo Kyung Kim, Se Hwa Kim, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2002;26(3):189-198. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Insulin resistance (IR) has been identified as a risk factor of atherosclerosis, which may be induced through a mechanism brought about by hypertension, obesity, glucose intolerance and dyslipidemia. The purpose of this study was to investigate the relationship between coronary artery disease (CAD) and insulin resistance. METHODS: Of 92 subjects having undergone coronary angiography 70 with significantly stenotic coronary artery were designated as the CAD group, with the other 22, without stenosis, as the control group. The CAD group was subdivided into 3 smaller groups according to the severity of their CAD; these being 1-vessel disease (group 1, n=31), 2-vessel disease (group 2, n=25), and 3-vessel disease (group 3, n=14). RESULTS: Kitt for patients with CAD was significantly lower than in the control group, and also for those in group 1 compared to groups 2 and 3, 2.72+/-1.29, 2.25+/-0.68 and 2.21+/-0.78%/min, with that of the controls being 3.01+/-1.22%/min p<0.05). There were significant differences between the IR group and the non-IR group in the common carotid artery intima-media thickness (1.09mm vs. 0.87mm, p<0.05), the waist-hip ratio (1.09 vs. 0.93, p<0.05) and the body fat contents (32% vs. 27%, p<0.05).Insulin resistance was assessed by the short insulin tolerance test, and the insulin resistance (IR) group was defined as having a Kitt less than 2.5%/min. CONCLUSION: These results suggest that insulin resistance is an important risk factor for CAD, and is related to the severity of coronary atherosclerosis.

Protein Deficiency and Type 2 Diabetes Mellitus.: Bong Soo Cha, Soo Kyung Kim; Korean Diabetes J. 2002;26(1):16-20. Published online February 1, 2002

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Therapeutic Effect of Recombinant Human Erythropoietin on Anemia with Erythropoietin Deficiency in Early Diabetic Nephropathy.: Dae Jung Kim, Soo Kyung Kim, Hyeung Jin Kim, Yoo Mee Kim, Yong Seok Yun, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2001;25(5):364-373. Published online October 1, 2001

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Abstract PDF: BACKGROUND
We have previously reported that reduced erythropoietin (Epo) responsiveness to anemia could explain the anemia in diabetic patients before advanced diabetic nephropathy. Thus, the aim of this randomized prospective study is to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anemia with Epo deficiency in early diabetic nephropathy. METHODS: Twenty-nine diabetic patients with the normocytic normochromic anemia of Epo deficiency were randomized into Epo-treatment group (n=20, M:F= 8:12, mean age=52.9+/-9.2) and control group (n=9, M:F=4:5, mean age=53.6+/-12.4). Twenty patients of Epo-treatment group were treated with rHuEpo (Epokine (CheilJedang Co.) 4,000unit/day SC., 3 times/week) for 8 weeks. The Epo- treatment group were divided into the responder or non-responder. Patients with increments in Hemoglobin (Hb) during the follow-up duration was above 2 g/dL, or with the final Hb was above 14 g/dL in men or 13g/dL in women were decided the responder. In order to analyze factors affecting the therapeutic effects of rHuEpo, the clinical and biochemical characteristics were compared between the responder and non-responder group. RESULTS: There was no difference in the clinical and biochemical characteristics between the Epo-treatment and the control group at randomization. The responder group (n=14) had significant increments in Hb, compared to the non-responder group (n=6) or the control group (13.6+/-1.0 vs. 10.1+/-1.5 vs 11.2+/-1.2 g/dL, p < 0.001, respectively). The treatment duration of rHuEpo in the responder group was 4.9+/-2.3 weeks. Among the Epo-treatment group, there was no differences between the responder and the non-responder group in sex, age, duration of diabetes, serum creatinine level, 24 hour urinary albumin excretion rates, HbA1C, frequency or severity of microangiopathy, and serum Epo level. However, the responder group had higher serum ferritin (240.3+/-108.4 vs 25.8+/-3.0 g/L, p<0.05) and transferin saturation level (32.7+/-7.9 vs 21.2+/-5.3 %, p<0.05). CONCLUSION: These results concluded that the administration of rHuEpo could be useful in treating anemia with Epo deficiency in early diabetic nephropathy and that the degree of iron storage and functional iron deficiency might affect the therapeutic effects of rHuEpo on this type of anemia.

Significance of Plasma Thrombin-Antithrombin III and Pasmin- 2-Plasmin Inhibitor Complexes in Diabetic Patients.: Kyung Wook Kim, Un Suk Kim, Sang Su Chung, Soo Jee Yoon, Wook Il Park, Jun Hee Lee, Su Youn Nam, Chul Woo Ahn, Byung Soo Moon, Kyung Rae Kim, Bong Soo Cha, Young Duk Soung, Sung Kil Lim, Hyun Chul Lee, Gap Bum Huh; Korean Diabetes J. 2001;25(5):354-363. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Abnormality of coagulation and fibrinolytic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. METHODS: In our study, we measured plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. RESULTS: 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA1c, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8 1.2 ng/mL, 240.4+/-69.7 ng/mL in controls and 9.5+/-22.6 ng/mL, 472.2+/-258.7 ng/mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1+/-2.4 ng/mL, 362.2+/-272.0 ng/mL, 322.7+/-102.4 mg/dL in group without vascular complication and 5.3+/-4.1 ng/mL, 529.5+/-258.7 ng/mL, 374.9+/-106.2 mg/dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 6.0+/-4.9 ng/mL, 507.4+/-321.6 ng/mL, 427.1+/-194.7 mg/dL in macrovascular complication, and 10.4+/-6.7 ng/mL, 484.8+/-269.7 ng/mL, 388.4+/-132.4 mg/dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA1c (r=0.67). CONCLUSION: In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro- macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA1c. TAT was correlated with HbA1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients.

Role of Interleukin-6 in Human Obesity and Insulin Resistance.: Bong Soo Cha, Soo Kyung Kim; Korean Diabetes J. 2001;25(5):332-336. Published online October 1, 2001

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Abstract PDF: No abstract available.

Limitation of Validity of Homeostasis Model Assessment as a Index of Insulin Resistance.: Yong Seok Yun, Seok Won Park, Young Duk Song, Hyo Kyung Park, Oh Yoen Kim, Chul Woo Ahn, Jae Hyun Nam, Su Youn Nam, Bong Soo Cha, Chong Ho Lee, Sumg Gil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2000;24(5):541-551. Published online January 1, 2001

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Abstract: BACKGROUND
Homeostasis model assessment of insulin resistance (HOMAIR) had been proposed as a simple and inexpensive alternative to other complex procedures measuring insulin resistance. We evaluated the validity of HOMAIR, comparing to total glucose disposal rate measured by euglycemic clamp test in 63 subjects with normal glucose tolerance, 21 with impaired glucose tolerance and 47 with type 2 DM. METHODS: HOMAIR and HOMA cell function (Homeostasis model assessment of cell function) were calculated with formula described by Matthews [HOMAIR: fasting insulin ( U/mL) X fasting glucose (mmol/L) / 22.5, HOMA cell function: 20 X fasting insulin ( U/mL) / (fasting glucose (mmol/L) - 3.5)]. 2-hour euglycemic (5 mmol/L) hyper insulinemic (717 pmol/L) clamp test were carried out. RESULTS: The strong inverse correlation (r=-0.658, <0.001) was shown between log transformed HOMAIR and total glucose disposal rates. The agreement of two methodes in the categorization according to insulin resistance was moderate (weighed kappa=0.45). The magnitude of correlation coefficients were smaller in subjects with lower BMI (BMI < 23.7 kg/m2, r = -0.441 vs BMI > or = 23.7 kg/m2, r = -0.693, p = 0.0183), lower HOMA cell function (HOMA cell function < 57.2, r = -0.514 vs HOMA cell function > or = 57.2, r = -0.773, p = 0.0091) and higher fasting glucose levels (fasting glucose < 102 mg/dL, r = -0.697 vs fasting glucose > or = 102 mg/dL, r = -0.59, p = 0.0735). The results of correlation analysis was not significant in diabetics with lower BMI. CONCLUSION: Limitation of validity of HOMAIR should be carefully considered in subjects with lower BMI and lower fasting insulin to glucose levels, such as lean type 2 diabetes with insulin secretory defects.

The Combined Effects of Protein Malnutrition and Chronic Alcohol lntake on lnsulin Secretion and Sensitivity in Growing Rats.: Bong Soo Cha, Chul Woo Ahn, Hae II Lee, Yong Seok Yoon, Jae Kyeung Sung, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2000;24(1):19-36. Published online January 1, 2001

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Abstract PDF: BACKGROUND
This investigation was performed to examine the combined effects of protein malnutrition and chronic moderate amount of alcohol intake on insulin secretory capacity and sensitivity in growing rats. METHODS: Weanling 4-week-old male Sprague-Dawley rats were fed low protein [5%, (wt/wt)] or control (C, 20%) diet from 4 to 12 weeks and alcohol (5g/kg/d) or saline gavage from 8 to 12 weeks. All rats were divided into the 4 groups according to different diet protocols: group 1 (protein-deficient alcohol rats), group II (protein-deficient saline rats), group III (protein-sufficient alcohol rats), and group IV (protein-sufficient saline or control rats), At the age of 12 weeks, we determined the insulin secretory capacity and sensitivity in the 4 different diet groups. RESULTS: The results are summarized as following: 1. Normal weight gain was nearly completely arrested in protein-deficient rats compared to control rats. In protein-sufficient rats, chronic alcohol intake decreased body weight gain. Pancreatic weight adjusted with body weight was not different among the 4 groups, but epididymal fat weight adjusted with body weight was decreased in group II compared to group IV. 2. Intraperitoneal glucose tolerance was improved in group I compared to the other groups. Insulin responses to glucose challenge were markedly decreased in group II compared to group IV, but not in group l. 3. Glucose disposal rate during euglycemic clamp test was diminished in group II compared to qroup IV, but there were no differences between group I and group I 3. Glycogen synthase activities of skeletal muscle after 2 hour hyperinsulinemic state were not different among the 4 groups. 4. There were no differences of reserved insulin content of whole pancreas adjusted with pancreas weight among the 4 groups. 5. In light microscopic findings of pancreatic islets, sizes of islets, islet cells and nuclei were decreased in protein-deficlent rats compared to control rats. However, the sizes of islet cells and nuclei were further decreased in group II compared to group l. CONCLUSION: These results suggest that impaired insulin secretion and decreased insulin sensitivity due to protein malnutrition can be restored by chronic, moderate amount of alcohol intake, but these beneficial effects may not be appeared in protein-sufficient state. Therefore, the chronic alcohol intake differently influences glucose metabolism according to individual nutritional status, and further studies for the effects of alcohol intake in lean diabetic patients are required to extrapolate these resuits in human.

Insulin Resistance and Related Factors in the Healthy Young Men.: Seok Won Park, Yoon Sok Chung, Yong Seok Yun, Bong Soo Cha, Young Duk Song, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1998;22(4):504-512. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Resistance to insulin-stimulated glucose uptake is present in the majority of patients with obesity, glucose intolerance, hypertension, dyslipidemia, and coronary artery disease. It is known that values for insulin-stimulated glucose uptake(insulin sensitivity) vary widely within individuals with normal glucose tolerance. We investigated the variations in insulin sensitivity and related factors in the nonobese healthy young men. METHODS: Insulin sensitivity was considered as whole body insulin-stimulated glucose uptake rate(M), determined by euglycemic hyperinsulinemic clamp technique in 44 non-obese healthy young men with normal glucose tolerance. Plasma glucose, insulin, and C-peptide concentrations after a standard oral glucose tolerance test and total cholesterol, triglyceride, and HDL-cholesterol levels were measured after 12-hours fasting. The subjects were divided into four quartiles based on the insulin sensitivity (M) and their clinical and biochemical characteristics were compared. RESULTS: Glucose disposal rates (M-values) were ranged from 4.14 to 11.06 mg/kg/min and distributed normally. The plasma glucose levels were not different between quartiles but plasma insulin levels of quartile 1 were significantly higher than the other three quartiles during oral glucose tolerance test. There was a curvilinear relationship between insulin sensitivity and acute insulin response (Ins[o-30]) to oral glucose challenge. There were negative cnrrelations between insulin sensitivity and BMI, percent ideal body weight, WHR, body fat content, fasting insulin level, insulin response area during OGTT, and fasting serum triglyceride level. HDL-cholesterol concentration was positively correlated with insulin sensitivity. In multiple linear regression analysis, body fat content, fasting insulin, and HDL-cholesterol were independent variables, which were related to the insulin sensitivity. CONCLUSION: There were considerable variations in insulin sensitivity in the nonobese healthy young men with normal glucose tolerance and the related independent factors were body fat content, fasting insulin, and HDL-cholesterol cancentrations.

Insulin Gene Polymorphisms in non-insulin-dependent Diabetes Mellitus ( NIDDM ) in Korean.: Jin Suk Kwon, Seok Won Park, Bong Soo Cha, Young Duk Song, Churl Woo Ahn, Keun Soo Jang, Soo Jin Kim, Seung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1998;22(4):442-449. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Many epidemiologic and family studies indicated stronger influence of genetic factors in NiDDM compared to IDDM, and there has been investigations to identify the susceptibility genes but without definite results. Insulin gene with its regulator region has been considered as a possible candidate gene of NIDDM because of relative deficiency in insulin secretion. So, we investigated the possible relationship between insulin gene polymorphisms and NIDDM in Korean. METHODS: we investigated -23 Hph I and +1,127 Pst I restriction site on insulin gene region in 67 NIDDM patients and 33 healthy controls by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method, and compared the allelic frequencies. We also compared the insulin secretory capacity, degree of blood glucose control, and family history of diabetes mellitus according to insulin gene polymorphism. RESULTS: l. Insulin gene polymorphism on -23 Hph I restriction site or +1,127 Pst I restrietion site does not confer susceptibility to NIDDM in Korea, 2. No differences were observed in onset age, family history of diabetes mellitus, insulin secretory capacity, and degree of blood glucose control, according to insulin gene polymorphism. CONCLUSION: Insulin gene polymorphism on Hph I site and Pst I site probably does not play an important role in the pathogenesis of NIDDM in Korean population.

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.

Comparison of the New Diagnostic Criteria for Diabetes Mellitus Recommended by the Expert Committee of the American Diabetes Association with the Criteria by the NDDG or WHO in Koreans with Fasting Plasma Glucose between 110 and 139 mg / dL.: Yeo Joo Kim, Moon Suk Nam, Mi Rim Kim, Yong Seong Kim, Kwan Woo Lee, Hyeon Man Kim, Choon Hee Chung, Su Youn Nam, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Sam Kweon, Yong Wook Cho, Kap Bum Huh; Korean Diabetes J. 1998;22(2):209-217. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The current diagnostic criteria for diabetes mellitus announced by National Diabetes Data Group(NDDG) in 1979 were revised by Expert Committee of World Health Organization(WHO) in both 1980 and 1985. However, according to advancement in the knowledge of the etiology and pathogenesis of diabetes mellitus, the International Expert Committee working under the sponsorship of the American Diabetes Association(ADA) decided to adopt the resolution proposing that the criteria of fasting glucose level applied to diagnosis of diabetes mellitus should be lowered at the 57 ADA conference held in Boston, USA in June 1997(97 ADA). Hereupon, by comparing the diagnostic criteria of the former (NDDG/WHO) with the later, the authors have examined the usefulness of new diaignostic criteria, 97 ADA. METHOD: We collected the data from 13 university hospitals in Korea which contain the results of 75 gram oral glucose tolerance test(OGTT) for 532 Kareans between 110 and 139 mg/dL in fasting plasma glucose. We have then evaluated the results by classifying and comparing them in accordance with the criteria of NDDG/WHO and 97 ADA, respectively. RESULTS: 1. The number which tested for oral glucose tolerance was 532 and the majority of tests have been carried out between 110 and 119 mg/dL in fasting plasma glucose. 2. When we have classified the same results of OGTT by respective diagnostic criteria of NDDG/ WHO and 97 ADA, the NDDG/WHO have diagnosed 50.4%(268/532) of the total number of people as diabetes mellitus, while the '97 ADA has shown that only 33.1%(176/532) of it corresponded to the same diagnosis. On the other hand, the diagnosis rate of impaired fasting glucose(IFG) or impaired glucose tolerance(IGT) has shown 28.8~ 31.8%(NDDG/ WHO) and 66.9%(97 ADA), respectively. 3. Following the diagnostic criteria of the 97 ADA, we have separated the results into two groups which were above and below 126 mg/dL in fasting glucose. In addition, when we have again classified two groups by the criteria of the NDDG/WHO, the group above 126mg/dL in fasting glucose, which was all diagnosed as diabetes mellitus in 97 ADA has represented a ratio of 72.2%(127/176) in same diagnosis. However, within the group below 126mg/ dL, in fasting glucose being classitied as IFG in the 97 ADA, its diagnosis rate of diabetes mellitus has also shown 39.7%(141/356) applying to the criteria of the NDDG/WHO. CONCLUSION: The criteria of the 97 ADA can simply make a diagnosis of diabetes mellitus with fasting plasma glucose and additionally fmd out the IFG whose rate is 17.9 20% regarded as a normal condition by NDDG/WHO, whereas the existing criteria of the NDDG/WHO have to carry out the OGTT which is difficult in clinics. However, since among the patients ot 50.4% diagnosed as diabetes mellitus by NDDG/WHO, the 97 ADA classifies 17.3% of them as IFG, it is regarded that the need of OGTT for the diagnosis of diabetes mellitus can not be passed over in the future.

Short Insulin Tolerance Test(SITT) for the Determination of in vivo Insulin Sensitivity-A Comparison with Euglycemic Clamp Test.: Seok Won Park, Yong Seok Yun, Churl Woo Ahn, Jae Hyun Nam, Suk Ho Kwon, Min Kyung Song, Seol Hye Han, Bong Soo Cha, Young Duk Son, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1998;22(2):199-208. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The euglycemic hyperinsulinemic clamp technique is currently regarded as gold standard for measuring insulin sensitivity, but it requires sophisticated equipment and highly trained personnel. We investigated the reliability of short insulin tolerance test as a simple tesl to measure in vivo insulin sensitivity. METHODS: Short insulin tolerance test(SITT) and euglyeemic hyperinsulinemic clamp test were performed at random order in 14 healthy subjects and 10 abnormal glucose tolerant subjects. The plasma glucose disappearance rate(kitt: %/min) after iv injection of regular insulin(0.1U/kg) was determinecl and compared to insulin sensitivitv indices(M, M/I) of euglycemic hyperinsulinemic clamp test. RESULTS: The mean Kitt value of healthy subjects was 3.50+0.75%/min and that of subjects with abnormal glucose tolerance was 2.56+0.56%/min. Changing sampling time from 15 min to 18~21 min and sampling interval from 3 min to 1.5 min had no influence on Kitt value. Kitt values were reproducible in six subjects, with a CV of 8.8+2.0%. There was a highly significant correlations between the Kitt value derived from SITT and M or M/I derived from euglycemic hyperinsulinemic clamp test. There were no significant adverse effects including hypoglycemic symptom while performing SITT. CONCLUSION: SITT is simple, safe, rapid to perform, and provides reliable index of in vivo insulin sensitivity. It seems particularly suitable for studies involving large series of subjects or including repeated evaluation of insulin sensitivity.

Measurement of Insulin Sensitivity Index Estimated from LDIGIT ( Continuous Low Dose Insulin and Glucose Infusion Test.: Young Duk Song, Bong Soo Cha, Suk Won Park, Young Joon Won, Soo Yeon Nam, Sung Kil Lim, Kyung Rae Kim, H C Lee, K B Huh; Korean Diabetes J. 1997;21(4):425-431. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Measurement of insulin sensitivity index by continuous low dose insulin and glucose infusion test(LDIGIT) has been reported to be simple and reliable. METHODS: The method is a refinement of the modified Harano test and consisted of continuous low dose insulin(25mU/kghr) and glucose(4mg/kghr) infusion lasting 150 min. Insulin sensitivity was evaluated as the amount of glucose infusion divided by the steady state serum insulin and glucose levels achieved at the end of the test. Insulin secretion was expressed as the incremental area for C-peptide concentration during the first 15 min of the test. The indices of insulin sensitivity and insulin secretion yielded by LDIGIT were compared with those derived from the euglycemic clamp and oral glucose tolerance test (OGTT), respectively. Thirteen subjects underwent LDIGIT and euglycemic clamp. RESULTS: LDIGIT resulted in stable final glucose levels but 3 subjects showed hypoglycemia during the test. The index of insulin secretion provided by LBIGIT did not correlate well with that of OGTT. There was a significant correlation between the ISI (insulin sensitivity index) determined by LDIGIT and the ISI determined by clamp(r=0.60, p<0.05). CONCLUSION: LDIGIT is a simple and accurate methcd to assess insulin sensitivity. It can be used in population studies and in situations when more complex technique is not feasible. However, it is desirable to reduce the insulin infusion rate to avoid the occurrence of hypoglycemia in Koreans.

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.

A Case of Diabetic Muscle Infarction in a Patient with Insulin Dependent Diabetes Mellitus.: Joon Ho Jang, Jae Hyun Nam, Woong Chul Kang, Jung Il Jung, Suk Ho Kwon, Yong Suck Yoon, Bong Soo Cha, Young Joon Won, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1997;21(3):314-320. Published online January 1, 2001

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Abstract PDF: Diabetic muscle infarction(DMI) is an uncommonly reported complicatian of diabetes mellitus, DMI tends to occur in younger, poorly controlled diabetic patients with other end organ complications(retinopathy, nephropathy, neuropathy). The typical feature of DMI is abrupt onset of thigh pain, tenderness, and swelling, over a period of days, and a firm mass develops. There are no associated systemic symptoms or signs indicative of infection and no skin discoloration suggestive of cellulitis or thrombophlebitis. The patient was diagnosed as DMI with the findings of ultrasonographic, bone scan and magnetic resonance imaging as well as typical clinical and laboratory findings. The painful mass persists for weeks, occasionally with exacerbation of symptoms, and then spontaneously resolves over several montks. Immobilization of the extremity with prolonged bed rest and strict sugar control has had beneficial results. We report a case of diabetic muscle infarction in a 30-year-old woman with insulin dependent diabetes mellitus

Thebeta3-adrenergic Receptor Gene Polymorphism in Non-Insulin Dependent Diabetes Mellitus.: Ji Hyun Lee, Hai Ri Li, Sang Won Lee, Su Youn Nam, Young Jun Won, Bong Soo Cha, Moon Suk Nam, Young Duk Song, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1997;21(2):130-137. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The B3-adrenergic receptor, located mainly in adipose tissue, is known to be involved in the regulation of lipolysis and thermogenesis. Recently studies have shown that the B3-adrenergic receptor gene polymorphism is associated with Non-Insulin Dependent Diabetes Mellitus(NIDDM) and insulin resistance. We investigated the relationship between the B3-adrenergic receptor gene polymorphism and the cli!ical and biochemical features of NIDDM patients. METHODS: Anthropometeric and biochemi al characteristics were determined for 134 NIDDM subjects and 30 nondiabetic controls. All subjects were genotyped for the 0-adrenergic receptor gene mutation using restriction fragment length polymorphism assay. RESULTS: The allelic frequency of the mutated allele was similar in NIDDM subjects and nondiabetic controls(11%, 12% respectively). There was no difference in the Arg64 allelic frequency of the B3-adrenergic receptor gene according to the onset age of diabetes. In diabetic group, the clinical and biochemical characteristics were not statistically different between the B3-adrenergic receptor gene mutation and nonmutation group. In control group, also no clinical differences were found between mutation and non-mutation group. When comparing frequency of obesity according to the B3-adrenergic receptor gene mutation in diabetic patients, we did not find the difference between the two groups. CONCLUSION: These results suggest that the b3-adrenergic receptor gene is not a major determinant for the development of obesity and NIDDM in Korea.

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