Diabetes & Metabolism Journal

Volume 28(5); October 2004

Review

Recent Advances in the Treatment of Obesity.: Woo Je Lee, Eun Hee Koh, Min Seon Kim, Joong Yeol Park, Ki Up Lee; Korean Diabetes J. 2004;28(5):347-355. Published online October 1, 2004

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Original Articles

The Effects of Dexamethasone on the Expansion and Transdifferentiation of Transplanted Porcine Neonatal Pancreas Cell Clusters into beta-cells in Normal Nude Mice.: Ji Hun Yang, Sun Hee Suh, Sung Yoon Jeon, Oak Kee Hong, Kun Ho Yoon; Korean Diabetes J. 2004;28(5):356-366. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Several studies have suggested that glucocorticoid has an influence on the development and function of the -cells. Thus, we undertook this study to determine whether exposure to dexamethasone (Dx) has an influence on the expansion or transdifferentiation of transplanted porcine NPCCs. METHODS: After transplantation (Tx) of 4,000 islet equivalents (IEQs) of porcine NPCCs into normal nude mice, Dx (1mg/kg) or the control vehicle were injected daily for 10 weeks. To clarify the effects of timing and duration of the Dx, one group was treated by Dx at the first 2 weeks (n=10) and the other group was treated later 8 weeks (n=10) during the 10 weeks treatment period. Thr total graft and beta-cell masses were determined by morphometric analysis. We preformed semi-quantitative RT-PCR for evaluating the pancreas transcription factors. RESULTS: The relative volume and absolute mass of the beta-cells and the total graft were significantly decreased by 10 weeks Dx treatment. Moreover, Dx treatment at thr first 2 weeks (n=10) also significantly decreased the total graft mass and absolute mass of the beta-cells. The relative volume of the beta-cells was negatively correlated and the area of the duct cysts was positively correlated with the duration of the Dx treatment. Pancreas transcription factors including PDX1, Ngn 3, ISL1 and NKx6.1 were decreased in the graft by 2 days treatment of Dx. CONCLUSION: These results suggest that Dx treatment suppresses the expansion and transdifferentiation of transplanted pancreas precursor cells into beta-cell.

Effect of Peroxisome Proliferator Activated Receptor-gamma Agonist, Angiotensin II Receptor Blocker and alpha-lipoic Acid on Renal VEGF Expression in Diabetic Nephropathy.: Jang Hyun Koh, Yeon Lee, Mi Jin Kim, Young Goo Shin, Eun Young Lee, Choon Hee Chung; Korean Diabetes J. 2004;28(5):367-376. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Diabetic nephropathy is one of the most serious complications in diabetes mellitus, and it is the leading cause of end stage renal disease. It has been reported that angiotensin converting enzyme inhibitor (ACEi) reduces the vascular endothelial growth factor (VEGF) expression, and so it plays an important role in reducing the renal damage. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonist is known to reduce insulin resistance in type 2 diabetic patients. In the previous study, PPAR-gamma agonist was shown to lower VEGF expression in the retina, but it increased the plasma VEGF level. Alpha-lipoic acid (alpha-LA), which is an antioxidant, lowers the increased level of VEGF in retina as well. The precise role of PPAR-gamma agonist and alpha-LA on renal VEGF expression in diabetic nephropathy is still uncertain. We studied the effect of PPAR-gamma agonist, angiotensin II receptor blocker (ATIIRB) and alpha-LA on the renal VEGF expression in diabetic rats. METHODS: We used 60 Sprague-Dawley male rats, those were 8 weeks old and weighted about 300 g each as the study subjects. Among them, 48 rats were chosen and injected with streptozotocin (70 mg/kg) into peritoneal cavity to induce diabetes mellitus. The rast were than divided into 5 groups. Group I was a normal control group (n=12), group II was diabetic control group (n=12), group III was diabetic group that was given with PPAR-gamma agonist (n=12), group IV was the diabetic group that was given ATIIRB (n=12), and group V was the diabetic rats that were given alpha-LA (n=12). We measured their body weight, blood glucose levels, 24 hour urine protein and albumin levels at the baseline, the 8th and the 16th weeks of the experiment. On the 16th weeks of our experiment we extracted the kidneys to measure the glomerular volume, the optical density of the VEGF staining and VEGF mRNA expression. RESULTS: At the beginning of the study, the 5 groups all showed similar 24 hour urine albumin levels. At the 8th week, group II showed an increased urine albumin level of 143.4 +/- 117.2 mg/day; this was greater than that of group IV (60.7+/-30.6 mg/day) (p<0.05). The glomerular volume and optical densities of VEGF expression were significantly reduced in group III, IV and V compared to group II. For group IV and V, the renal VEGF mRNA expression was significantly lower than that of group II, but group III showed no significant difference. from group II. CONCLUSION: Angiotensin II receptor blocker delayed the progression of diabetic nephropathy. PPAR-gamma agonist and alpha-lipoic acid did not have any protective effect against the progression of diabetic nephropathy in spite of the decreased VEGF expression noted in this study.

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.

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

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

The Effect of High Glucose on the Proliferation and Migration of Vascular Smooth Muscle Cells.: Mi Kyoung Kim, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim; Korean Diabetes J. 2004;28(5):407-415. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Oxidative stress contributes to vascular diseases for patients with diabetes by promoting vascular smooth muscle cell (VSMC) proliferation, monocyte/macrophage infiltration, and vascular tone alteration. As the mechanism of development and progression of diabetic vascular complications is poorly understood, this study was aimed to assess the potential role of hyperglycemia-induced oxidative stress and to determine whether thise oxidative stress is a major factor in hyperglycemia-induced migration and proliferation of VSMCs. METHODS: Rat aortic VSMCs were incubated for 48 hours in either a normal glucose (NG, 5.5 mM) or a high glucose (HG, 30 mM) condition. We then measured the proliferation and migration of VSMCs and the superoxide production. RESULTS: The migration and proliferation of VSMCs incubated under a HG condition were markedly increased compared to the NG condition. Treatment with diphenyleneiodonium (DPI, 10 M) and superoxide dismutase (SOD, 500 U/mL) significantly suppressed the HG-induced migration and proliferation of VSMCs. Superoxide production was significantly increased in the HG condition, and it was markedly decreased after a treatment with DPI and SOD. CONCLUSION: These data suggest that HG-induced VSMC migration and proliferation are related to the production of superoxide anion that is derived from NAD(P)H oxidase.

Effect of Captopril on Insulin Sensitivity for Subjects with Insulin Resistance.: Hye Jung Lee, Hyuk Sang Kwon, Jin Hee Lee, Sung Koo Kang, Yoon Hee Choi, Sung Ha Hwang, Seung Hyun Ko, Jung Min Lee, Kun Ho Yoon, Bong Yun Cha, Won Chul Lee, Kwang Woo Lee, Ho Young Son; Korean Diabetes J. 2004;28(5):416-424. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors are becoming increasingly popular as the first-choice antihypertensive agents for diabetic patients. This could be partly related to their suggested beneficial effects on insulin sensitivity. This study was designed to compare the effect of captopril with that of control (nitrendipine) on insulin sensitivity for subjects with insulin resistance. METHODS: 24 subjects, aged less than 60 years, with their insulin resistance being defined as the area under the curve (AUCi) of insulin that was 2 standard deviations (SD) more than that of the control subjects during oral glucose tolerance test were recruited. A randomized, double-blind, crossover trial was conducted for an 8 weeks treatment period with captopril and the control (nitrendipine) that was given after an initial 6 weeks run-in period. Anthropometric measurement including weight, height, waist and hip circumference, blood pressure (systolic & diastolic), lipid profile blood chemistry, electrolytes levels & renal function testing, and frequently sampled intravenous glucose tolerance tests (FSIGT) for the insulin sensitivity index (SI) & acute insulin response to glucose (AIRg) were also done before and after treatment, respectively. RESULTS: 18 subjects (6 males, 12 females) completed the study. The mean age of the study subjects was 47.9+/-2.9 years (mean+/-SEM), and their BMI was 28.0+/-0.7 kg/m2 (mean+/-SEM).There was a significant decrease in weight (baseline; 71.5+/-9.2 kg vs. captopril; 70.7+/-9.0 kg and nitrendipine; 709+/-9.2 kg, p<0.05, respectively) and BMI (baseline; 28.0+/-3.0 kg/m2 vs. captopril; 27.7+/-2.8 kg/m2 and nitrendipine; 27.8+/-2.9 kg/m2, p<0.05, respectively) for both groups compared with the baseline, but there are no significant differences between the two groups. Triglyceride was significantly decreased after treatment with captopril compared to the baseline and nitrendipine (187.0+/-99.5 mg/dL vs. 224.5+/-134.2 mg/dL, respectively, p<0.05). The SI was significantly increased after captopril treatment compared with the baseline (1.4+/-1.0 vs. 2.5+/-0.8 min-1 per mU/ml, respectively, p<0.05), and the captopril group was significantly higher than that of nitrendipine (1.5+/-1.0 min-1 per mU/ml, p <0.05). Acute insulin response to glucose in both groups was also increased after treatment, but there was no statistically significance. CONCLUSION: Captopril therapy improved insulin sensitivity, and it decreased the concentration of fasting insulin in subjects with insulin resistance.

The Clinical Characteristics of Anemia in Type 2 Diabetic Patients Without Overt Nephropathy.: Eun Young Ko, Se In Kim, Yong Bum Jang, Kyoung Hun Min, Sung Hun Kim, Kyu Sun Lee, So Ri Kim, Eun Kyoung Choi, Ji Hyun Park, Tae Sun Park, Hong Sun Paek; Korean Diabetes J. 2004;28(5):425-431. Published online October 1, 2004

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Abstract PDF: BACKGROUND
It is well known that anemia occurs early in diabetic patients before they reach to end stage renal failure. This anemia is considered to be due to the reduced endogenous erythropoietin synthesis, tubulointerstitial damage, autonomic dysfunction, and to the use of angiotensin-converting- enzyme inhibitors. Because anemia has a significant impact on the quality of life for diabetic patients, we examined the clinical characteristics of anemia in those diabetic patients who did not have overt nephropathy. METHODS: We retrospectively reviewed the medical records of 200 type 2 diabetic patients with anemia who had been followed up from 1998 to 2002 by Chonbuk University Medical School Hospital. We measured the total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, and the presence of complications (retinopathy or neuropathy) for about 90 diabetic patients who were under the age of 65, they were without other underlying disease and they had a hemoglobin concentration 110g/L, GFR 1.0 mL/s. We excluded the causes of anemia as being from malignancy, liver disease, coexisting iron deficiency, chronic inflammatory disease and chronic infection. RESULTS: The clinical characteristics of the patients are as follows; the mean age was 59.6 +/- 8.4 years, the mean HbA1C was 9.4 +/- 2.3%, and the mean Hb concentration was 96 +/- 12 g/L. Our results showed that an inverse relation existeds between Hb concentration and total cholesterol (p<0.04), LDL cholesterol (p<0.05), age (p<0.02), and the duration of diabetes (p<0.01).Our results also showed that a linear relation existed between the Hb concentration, HDL cholesterol (p<0.02), and the GFR (p<0.01). CONCLUSION: Diabrtic patients with anemia are in need of intensive management for the lipid and GFR that causes thair anemia.

Correlation of C-reactive Protein with Components of Metabolic Syndrome in Elderly Korean Women with Normal or Impaired Glucose Tolerance.: Soon Beom Kwon, Kyung Mook Choi, Soo Yeon Park, Hye Jin Yoo, Ohk Hyun Ryu, Sang Soo Park, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(5):432-440. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Previous studies have reported that type 2 diabetes is associated with the increased blood concentrations of markers for the acute phase response, such as C-reactive protein (CRP), serum sialic acid and fibrinogen. The purpose of this study was to verify whether the pro-inflammatory cytokine- induced acute-phase response is a major pathogenic mechanism for type 2 diabetes in elderly Korean women. METHODS: We randomly selected a total of 232 non-smoking and non-diabetic female subjects among a total of 1,737 elderly subjects aged over 60 years who had participated in a population based study in Seoul, Korea (SWS Study 1999). We compared concentrations of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as the acute-phase reactant C-reactive protein (CRP), between the subjects with normal glucose tolerance (NGT) and the subjects with impaired glucose tolerance (IGT). RESULTS: The IGT group showed higher serum high-sensitivity CRP (hs-CRP) concentrations than did the NGT group (the median was 1.2 versus 0.9, respectively, p<0.05). Moreover, a close relationship between serum hs-CRP concentrations and many components of the metabolic syndrome was found. However, serum concentrations of pro-inflammatory cytokines, IL-6 and TNF-alpha were not increasedin the IGT group, and they were not closely correlated with the components of metabolic syndrome. Multiple regression analysis using a stepwise selection method showed that the white blood cell counts, body mass index (BMI), fasting insulin, post-load 2h glucose, hematocrit and LDL cholesterol were associated with hs-CRP. CONCLUSIONS: The present study confirms the relationship between C-reactive protein, impaired glucose tolerance and metabolic syndrome in elderly Korean women.

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.

Case Report

A Case of Necrobiosis Lipoidica at the Insulin Injection Site in a Patient with Type 2 Diabetes Mellitus.: Woo Tae Kim, Tae Hoon Kim, Se Min Lee, Kang Hyun Choi, Seung Hyun Ko, Yu Bai Ahn, Ki Ho Song, Ho Young Son, Kyung Moon Kim, Si Young Kim; Korean Diabetes J. 2004;28(5):452-457. Published online October 1, 2004

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Abstract PDF: Nearly one third of patients with diabetes mellitus have some kinds of dermatologic complication. Necrobiosis lipoidica (NL) is a rare degenerative disease of the collagen in the dermis occurring in 0.3~0.7% of the diabetic population. This is a dermatologic condition presenting plaques that have an erythematous, violaceous border and yellowish atrophic center with telangiectasis on its surface. One third of these lesions may progress to ulcer if exposed to any trauma. There is some controversy regarding the degree of association between NL and diabetes mellitus. Necrobiosis lipoidica is commonly seen in patients with type 1 diabetes, but 7~30% of diabetic patients with NL have type 2 diabetes. We report a case of 54 year-old woman with 25 years of diabetic history. Her skin lesion was oval or irregular indurated plaques with central atrophy occurring both arm, lower abdomen and both anterior thigh, especially at insulin injecton site. We focused glycemic control as a treatment and used antiplatelet agents such as aspirin and cilostazol on the basis of microangiopathic athophysiology, combined with antibiotics. We need to inspect more closely any of skin lesions in diabetic patients, thus misdiagnosis and improper treatment should be reduced.

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