Diabetes & Metabolism Journal

Volume 25(1); February 2001

Review

Diabetes Epidemiology in Korean.: Nam Han Cho; Korean Diabetes J. 2001;25(1):1-10. Published online February 1, 2001

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Abstract PDF: No abstract available.

Editorial

Clinical Assessment of Macrovascular Complications in Diabetic Patients .: Chung Gu Cho, Park Byoung Hyun; Korean Diabetes J. 2001;25(1):11-19. Published online February 1, 2001

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Abstract PDF: No abstract available.

Original Articles

Atherosclerotic Severity and Risk Factors in Type 2 Diabetic Patients with Visceral (Metabolic) Obesity in Korea.: Jae Hyun Nam, Suk Won Park, Chul Woo Ahn, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2001;25(1):20-34. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes with hypertension and dyslipidemia are frequently associated with metabolic obesity. It is proposed that such individuals might be characterized by increased insulin resistance and visceral fat, and that macrovascular complications might be more common in these individuals. Thereofer, the aim of this study was to investigate the atherosclerotic severity and risk factors in type 2 diabetic patients with metabolic obesity (MO) in Korea. METHODS: Coronary artery calcification (CAC) score, intima-media thickness (IMT) of common carotid artery, and ankle-brachial pressure index (ABPI) were measured. Insulin sensitivity index (ISI) was also measured by the plasma glucose disappearance rate (kitt: %/min). RESULTS: 1. Among 530 type 2 diabetes mellitus (DM) patients, the percent of under-weight (UW), normal-weight (NW), over-weight (OW) and obese (OB) (BMI< 20, 20-25, 25-29.9 and >30, respectively) were 8.9%, 62.1%, 25.1% and 3.9%, respectively. Waist-hip ratio and systolic blood pressure (sBP) were significantly different among the groups according to BMI. Serum triglyceride (TG), HDL-C, free fatty acid (fFA), fibrinogen and fasting c-peptide were significantly different among the groups. The percents of patients with insulin resistance in UW, NW, OW and OB groups were 28%, 60%, 68% and 75%, respectively. The visceral fat area/subcutaneous fat area ratio and visceral fat area/thigh muscle area ratio were significantly increased according to ISI. 2. The patients with MO have above the median values of WHR (0.95 in men and 0.91 in women). sBP, TG, HDL-C, fFA,fibrinogen and ISI were significantly different between the patients with MO and the patients without MO. 3. In OW group as well as NW group, carotid IMT, ABPI and CAC score were significantly different between the patients with MO and the patients without MO. However, these were not different between NW group and OW group. CONCLUSION: In conclusion, this study suggest that patients with MO have more advanced atherosclerosis and aggravated risk profiles for atherosclerosis than those without MO, regardless of BMI.

Study on the Mechanism of Neutrophil Adhesion to Retinal Capillary Endothelial Cells under High Glucose Condition.: Seok Man Son, Young Sil Lee, Chang Won Lee, Seok Dong Yoo, In Ju Kim, Yong Ki Kim; Korean Diabetes J. 2001;25(1):35-49. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leukocytes each may play a major role. Thus, we investigated the pathogenesis of leukocyte stasis by exposing bovine retinal capillary endothelial cells (BRCECs) for high glucose concentration. METHODS: We examined the adhesion of neutrophils to BRCECs incubated in media containing 5.5-30 mmol/L D-glucose for 24 hours. We also measured the expression of E-selectin on endothelial cells and the activation of NF(nuclear transcription factor)-kappaB in nuclear fractions of endothelial cells by using electrophoretic mobility shift assay. RESULTS: We observed that 30 mmol/L D-glucose significantly increased the adhesion of neutrophils to BRCECs (12.5% vs. 3.0%, p<0.01) and migration of neutrophil across cultured BRCEC monolayers (41.0% vs. 21.0%, p<0.05) in respect to 5.5 mmol/L D-glucose. The expression of E-selectin was increased incubated with 30 mmol/L D-glucose compared with 5.5 mmol/L D-glucose (1.45 OD vs. 0.54 OD, p<0.01). Electrophoretic mobility shift assay of nuclear extracts of BRCECs exposed for 24 h to 30 mmol/L D-glucose revealed an intense NF-kappaB activation compared with cells cultured in 5.5 mmol/L D-glucose (8.72x104 countsxmm2 vs.1.88x104 countsxmm2, p<0.01). CONCLUSION: These results suggest that high glucose concentration promote neutrophil adhesion to the BRCECs through upregulation of cell surface expression of E-selectin, possibly depending on NF-kappaB activation and may have implications for the induction of microvasculopathy of diabetic retinopathy.

The Changes of Beta Cell Mass and Islet Morphology in OLETF (Otsuka Long Evans Tokushima Fatty) Rats After Partial Pancreatectomy .: Seung Hyun Ko, Kun Ho Yoon, Sun Hee Suh, Yu Bae Ahn, Soon Jib Yoo, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(1):50-62. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Insulin resistance and incomplete beta cell compensation play a major role for development of type 2 diabetes. When insulin resistance were induced by any cause, appropriate beta-cell proliferation is a key factor for maintaining the normal glucose metabolism. Compensatory beta-cell proliferation for adapting to increased insulin resistance might be achieved by neogenesis of beta-cell from duct cells, replication of preexisting beta-cells and also inhibition of beta-cell apoptosis. Previously incomplete beta-cell compensation was observed in OLETF rat, animal model of type 2 diabetes, after partial pancreatectomy, but there were no reports about the underlying pathogenesis. Therefore, this study was designed to study on the mechanism of incomplete beta-cell compensation in OLETF rat after partial pancreatectomy especially focus on beta-cell proliferation. METHODS: 12 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 280-320 g were used. 80% partial pancreatectomy was done. Experimental animals were divided into the 4 subgroups by date of killing after surgery: 0, 3, 90 days. After glucose tolerance test, pancreas remnant was excised and immunohistochemical staining was done for insulin to quantify the beta cell mass by point-counting method and also observed the amount of fibrosis of the islets after Masson's trichrome staining of the pancreas. RESULTS: We observed that impaired glucose tolerance or diabetes were developed after 80% pancreatectomy. We observed rapidly proliferating duct cells in the adjacent area of common pancreatic duct and main duct even up to 90 days after partial pancreatectomy. In OLETF rats, beta cell mass was not increased enough compared to LETO rats and some destructive features of islet architectures were noted at 90 days after pancreatectomy. CONCLUSION: The changes of beta cell mass seems to be a dynamic process adjusting to metabolic demand. Severe hyperglycemia and islet disorganization were apparent in OLETF rats despite of existence of beta cell regeneration and renewal process. So it seemed that hyperglycemia accelerated aging process or senescence of beta cells in OLETF rats.

Effects of Cilostazol on Insulin Resistance in OLETF Rats.: Sung Rae Kim, Ki Hyun Baek, Seung Hyun Ko, Jung Min Lee, Sang Ah Chang, Yoo Bae Ahn, Soon Jib Yoo, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(1):63-70. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Insulin resistance is one of the major pathophysiology of type 2 diabetes mellitus. It is reported that cilostazol and cyclic AMP phosphodiesterase inhibitor has the anti-platelet effect as well as an improvement of hypertriglyceridemia in addition to vasodilatation. Furthermore, the previous reports indicated that there is a positive relationship between insulin resistance and dyslipidemia. Thus, we investigated the effects of cilostazol on insulin resistance in OLETF rats using the euglycemic hyperinsulinemic glucose clamp technique, and lipid levels. METHODS: Fifteen five months old OLETF rats were fed for 4 weeks(8 treated with cilostazol and 7 were control), and compare to 20 same aged LETO rats (8 treated with cilostazol and 12 were control) through the glucose infusion rate on euglycemic hyperinsulinemic glucose clamp and lipid profiles. RESULTS: The glucose infusion rate was higher in the cilostazol treated OLETF rats than in the non-cilostazol treated OLETF rats (0.021+/-0.0031 vs 0.027+/-0.0036 mL/min). The levels of free fatty acids (2424.8+/-652.7 vs 1061.8+/-223.2 Eq/L), total cholesterol (145.7+/-17.9 vs 115.4+/-7.6 mg/dL) and triglyceride (146.5+/-46.6 vs 76.1+/-12.5 mg/dL) of cilostazol treated OLETF rats were significantly lower than those of non-cilostazol treated OLETF rats. CONCLUSION: This study result suggest that cilostazol may improve the insulin resistance through the improvement of dyslipidemia in OLETF rats.

Effect of Oxidized LDL on the Amount of Insulin Receptor and Gi-proteins in the Caveolae of Bovine Aortic Endothelial Cells (BAEC).: Sung Yoon Jeon, Hyun Shik Son, Jung Min Lee, Sung Dae Moon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(1):71-82. Published online February 1, 2001

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Abstract PDF: BACKGROUND
AND AIMS: Oxidized LDL (ox-LDL) may induce endothelial cell dysfunction and suggested to have an association with atherosclerosis or insulin resistance. Several studies have shown that ox-LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi-proteins). G-protein coupled receptors (GPCRs) can be internalized via caveolae. Caveolae are small flask-shaped invaginations of the plasma membrane, characterized by high levels of cholesterol and glycosphingolipids and also by the presence of caveolin, a 20-24 kDa integral membrane protein. G-proteins are enriched within caveolae membranes, where caveolin-1 directly interacts with the -subunits of G-proteins. It is reported that functional changes of G-proteins such as mutational or pharmacological activation of G-proteins affect direct interaction between G-proteins and caveolin-1. Thus, we investigated the effect of ox-LDL on the change of the amount of insulin receptor and Gi proteins in the caveolae. MATERIALS AND METHODS: ox-LDL was prepared by exposing samples of native LDL (n-LDL) to CuSO4 for 24 hours. Caveolae were extracted after treating BAECs at several concentrations of ox-LDL (10, 50, 100 g/mL) for various durations (0-48 hr), and we investigated the changes of the amount of caveolin-1, Gi -proteins and insulin receptor using immunoblot. RESULTS: While the amount of caveolin-1 was decreased, the amount of insulin receptor, Gi 2 and Gi 3 proteins in caveolae were also decreased after treatment of ox-LDL on the BAECs (insulin receptor: 66%; Gi 2 protein: 33%; Gi 3 protein: 66%, p<0.05). The amount of caveolin-1 was increased for the first 6 hours and then decreased, however, the amount of Gi -proteins and insulin receptor were vice versa during 48 hours incubation. CONCLUSION: These results indicate that ox-LDL can affect the change of the amount of insulin receptor and Gi-proteins in caveolae and it may induce endothelial cell dysfunction.

Gastric Dysfunction Assessed by Electrogastrography and the Acetaminophen Absorption Technique in Patients with Diabetic Neuropathy.: Hyun Ha Chang, Young Seol Kim, Sang Hwa Kim, Cheol Young Park, Seung Joon Oh, Jeong Taek Woo, In Myung Yang, Sung Woon Kim, Jin Woo Kim, Young Kil Choi; Korean Diabetes J. 2001;25(1):83-92. Published online February 1, 2001

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Abstract PDF: BACKGROUND
In patients with diabetes mellitus, dysrhythmias of gastric myoelectrical activity are frequently associated with gastroparesis. Thus, we investigated the relationships between abnormal gastric myoelectrical activity and gastric emptying rate in patients with diabetes mellitus. METHODS: Using surface electrogastrography (Nippro, Tokyo, Japan) and acetaminophen absorption technique, we studied EGG and gastric emptying rate in 39 patients with diabetic neuropathy and 15 healthy volunteers as the control group. RESULTS: In two thirds of the patients with diabetes mellitus, fasting electrogastrography revealed instability of electrical control activity (ECA), as compared to 13% of the control. Postprandial amplitude and frequency increases in electrogastrography were observed in the control group. However, these postprandial responses were obtunded in patients with diabetes mellitus. In the assessment of gastric emptying rate, increases of plasma acetaminophen levels were delayed in obtunded postprandial responses of gastric myoelectrical activity. CONCLUSION: These results showed that the abnormal electrogastrography patterns were related to abnormal finding assessed acetaminophen absorption technique. Electrogastrography was thought to be a useful and non-invasive technique in assessing diabetic gastroparesis.

Effect of Self-monitoring of Blood Glucose on Pregnancy Outcome in Women with Mild Gestational Diabetes.: Hak Chul Jang, Jeong Eun Park, Chang Hoon Yim, Ho Yeun Chung, Ki Ok Han, Hyun Koo Yoon, In Kwon Han, Moon Young Kim, Jae Hyug Yang, Mi Jung Kim, Sun Young Ko, Yeon Kyung Lee; Korean Diabetes J. 2001;25(1):93-102. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Self-monitoring of blood glucose (SMBG) and intensive therapy with insulin demonstrated to have a positive effects in the reduction of the neonatal complications in women with gestational diabetes (GDM). However the utility of SMBG in the mild GDM who does not requiring insulin has not been formally reported. Therefore, to evaluate the effectiveness of SMBG in the management of mild GDM, we compared the pregnancy outcome and the postpartum glucose tolerance of women who monitored their glycemic control by SMBG to those of women who monitored by laboratory glucose test at each office visit during pregnancy. METHODS: We studied 185 women diagnosed as a GDM by NDDG criteria and their fasting glucose concentration < 5.8 mM. All subjects had singleton pregnancy,and no medical diseases that may affect fetal growth, and were certain of gestational age by early ultrasonography. They were treated with an identical GDM management protocol except glucose monitoring. One hundred five women were monitored by laboratory glucose test at each office visit (office group) and 80 women were monitored by SMBG (SMBG group). Pregnancy outcome including rates of cesarian section, obstetric complication, LGA infant and glucose tolerance status at postpartum were compared between two groups. RESULTS: The age, height, prepregnancy weight, weight at delivery and parity were not significantly different between the two groups. Fasting, 1-h, 2-h glucose concentration during the diagnostic test of GDM in SMBG group were similar to those of office group. However, 3-h glucose concentration of office group was 0.3 mM higher than that of SMBG group. The rate of primary cesarian section, preterm labor and pregnancy-induced hypertension of SMBG group were similar to those of office group. The mean postprandial 2-h glucose concentration of office group measured at each office was 0.5 mM higher than that of SMBG group. Although 5% of office group were treated with insulin, 24% of SMBG group were requiring insulin therapy. The birth weight and LGA infant rate of office group were 3403 432 g and 28%, those were heavier and higher than those of SMBG group (3169 447 g, 13.8%). The 90% of office group and 84% of SMBG group were performed 75 g oral glucose tolerance test at postpartum 6-8 weeks. There was no significant difference in rates of diabetes and IGT between office and SMBG group (9.5%, 11.6%; 7.5%, 9.0% respectively). CONCLUSIONS: This study demonstrated that SMBG is very seful in early detection of maternal hyperglycemia and lowing the postprandial glucose, as well as reducing the rate of LGA infants in women with mild GDM.

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