Diabetes & Metabolism Journal

Volume 25(5); October 2001

Reviews

Genetics of Diabetic Nephropathy.: Moon Suk Nam; Korean Diabetes J. 2001;25(5):323-327. Published online October 1, 2001

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Abstract PDF: No abstract available.

New Diagnostic Methods and Therapeutic Evaluation of Diabetic Neuropathy.: Park Tae Sun, Hong Sun Baek; Korean Diabetes J. 2001;25(5):328-331. Published online October 1, 2001

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Abstract PDF: No abstract available.

Editorial

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.

Original Articles

Interleukin-6 polymorphism in Korean Obese and Type 2 Diabetic Subjects.: Jae Taek Kim, Seung Jin Choi, Mi Kyung Lee, Ae Ja Park, Yeon Sahng Oh, Soon Hyun Shin; Korean Diabetes J. 2001;25(5):337-342. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Interleukin (IL)-6 is produced by many different cell types, including adipose tissue, and the release is greater in obese subjects. Recently, it has been reported that polymorphism in the 5' flanking region of the IL-6 gene may contribute to the insulin resistance and lipid abnormality. However, there are limited number of studies reported on the relationship between IL-6 polymorphism and insulin resistance syndrome. Therefore, the aim of this study was to examine the relationships among this polymorphism, obesity and diabetes in Korean subjects. METHODS: We examined a total of 177 Korean individuals, including 113 type 2 diabetic subjects. Sixty-three subjects were non-obese diabetics (age; 56.4+/-9.8 yr, body mass index (BMI); 22.5+/-1.7 kg/m2), 50 of them were obese diabetic subjects (age; 54.8+/-10.7 yr, BMI; 27.6+/-2.2 kg/m2), and 64 were overweight or obese subjects (age; 49.1+/-11.4 yr, BMI; 25.4 1.5 kg/m2). We evaluated IL-6 gene polymorphism using PCR-restriction fragment length polymorphism. RESULTS: There were 176 GG (99.4%), 1 GC (0.56%) and 0 CC (0%) individuals, and the allele frequencies were 99.7% for G and 0.28% for C. Allele frequencies of C in obese diabetic subjects were 1.02%. The frequency of C allele was substantially lower than that reported in Caucasian. CONCLUSION: This results suggest that the IL-6 polymorphism is not associated with obesity nor diabetes in Korean subjects.

Effect of Heat Shock on the Vascular Reactivity in Diabetic Rat Aorta.: Seong Mo Koo, Soon Hee Lee, Jung Hun Han, Gi Young Jeong, In Kyum Kim, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 2001;25(5):343-353. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Heat shock has been known to change cellular response to noxious stimuli by inducing heat shock proteins (HSP). HSP are expressed in many tissues, and increased expression of some HSP enhances the survival of cells exposed to oxidative stress. Recently, Some HSP are known to associate with vascular reactivity. Under diabetic conditions, there is abnormal vascular reactivity to relaxing or contracting factors. Abnormal vascular response to some stimuli is an important role in the development of diabetic complications. However, the effects of heat shock on the vascular reactivity in diabetic condition is unclear. Therefore, we investigated effects of heat shock on the vascular reactivity in isolated aorta of streptozotocin-induced diabetic rats. METHODS: After mounced in organ bath, aortic ring preparations were exposed to 42 for 45 minutes followed by being subjected to contraction and relaxation in 4 hours. Tissues were frozen for measurement of HSP 70 and phosphorylation of myosin light chain after functional study. RESULTS: Heat shock not only increased expression of HSP70 in rat aorta but also augmented contraction to KCl and phenylephrine in the aorta of control and diabetic rats (p<0.05). Relaxation responses to acetylcholine (ACh) were not changed in the aorta of control rats with and without heat shock for 45 minutes. However, heat shock for 45 minutes decreased relaxative responses to ACh in the aorta of diabetic rats compared to those in the aorta of control rats. CONCLUSION: This result suggests that heat shock increases vascular contractility in the aorta of diabetic and control rats through the induction of HSP70 while heat shock seems to decrease relaxative response in the aorta of diabetic ratscompared to control rats (p<0.05). Whether heat shock impaired relaxative response in the aorta of diabetic rats deserves additional studies.

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.

Randomized Controlled Trial

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.

Original Articles

Effect of Red Ginseng Extract on Lipid Peroxidation in Streptozotocin-induced Diabetic Rats.: Hee Jong Jin, Sung Hee Ihm, Ja Hei Ihm; Korean Diabetes J. 2001;25(5):374-383. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus is postulated to be associated with increased oxidative stress and lipid peroxidation which may contribute to vascular complications. Recently ginseng (Panax) has been shown to have an antioxidant effect by enhancing nitric oxide synthesis in endothelial cells and by directly scavenging hydroxyl radicals. It is unknown whether ginseng might act as an antioxidant against lipid peroxidation in diabetes. METHODS: We studied the in vitro effect of red ginseng extract on lipid peroxidation employing phospholipid liposome and low-density lipoprotein (LDL) as a model system. To investigate the in vivo effect on lipid peroxidation in diabetes, we administered red ginseng extract (1 g/L in drinking water) to streptozotocin (STZ)- induced diabetic rats for 12 weeks and measured lipid peroxidation products in plasma, liver, kidneys and heart. RESULTS: The Fe(3+)- or Cu(2+)- mediated lipid peroxidation in phospholipid liposome and LDL, measured by the concentration of TBARS, was inhibited in the presence of red ginseng extract. MDA level in plasma measured by HPLC was higher in STZ-induced diabetic rats than in control rats. Plasma MDA level was lower by 41% in red ginseng-treated diabetic rats than in untreated diabetic rats. Tissue MDA levels measured by TBA method in liver, kidneys and heart were higher in STZ-induced diabetic rats than in control rats. In red ginseng-treated diabetic rats tissue MDA levels were lower by 14~30% than in untreated diabetic rats. CONCLUSION: We observed that red ginseng extract has an effect in inhibiting lipid peroxidation both in vitro and in STZ-induced diabetic rats. These results suggest that red ginseng might have a beneficial effect in diabetes as an antioxidant against lipid peroxidation and diabetic vascular complications.

Mortality in Adults with and without Diabetes in Yonchon, Korea.: Kang Woo Bae, Youn Jhin Ahnn, Yong Su Park, Kyoung Soo Park, Byung Goog Yang, Hong Kyu Lee; Korean Diabetes J. 2001;25(5):384-398. Published online October 1, 2001

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Abstract PDF: BACKGROUND
This study is designed to estimate the mortality rate and to assess the relation between other risk factors for mortality and death in adults with diabetes by analysis of death certificates in Yonchon cohort population. METHODS: A population-based cross-sectional study was conducted in 1993 in Yonchon county to estimate the prevalence and risk factors of diabetes. This study population consists of respondents (2,463 persons) from Yonchon study and followed for 6 years from 1993 to 1998. Status of death and causes of death were determined from death certificates from National Statistical Office. RESULTS: During the 6 year follow-up, 18 deaths (10%) occurred in the 184 persons with diabetes and 69 deaths (3.3%) occurred in the 2,113 persons without diabetes. After adjustment for multiple variable (age, sex, total cholesterol, systolic blood pressure, smoking and body mass index (BMI)), mortality rate was significantly higher for diabetic adults than non-diabetic adults (RR, 2.03). The proportional hazard analysis for all-cause mortality in the 190 persons with diabetes showed that smoking, high total cholesterol, and high LDL-cholesterol were significantly associated with increased risk for mortality (p value < 0.05), but BMI, HDL-cholesterol, and high systolic blood pressure were not significantly associated with increased risk for mortality. CONCLUSIONS: This study was a prospective cohort study that followed 2,463 persons of Yonchon cohort for 6 years and showed that diabetic adults had higher mortality than non-diabetic adults. The strength of the association between risk factors and mortality was less clear because follow-up period was short and study population size was small, therefore further follow-up study are needed.

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