Diabetes & Metabolism Journal

Volume 28(4); August 2004

Reviews

Adiponectin and Diabetes Mellitus.: Hye Seung Jung, Kyong Soo Park; Korean Diabetes J. 2004;28(4):239-249. Published online August 1, 2004

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Abstract PDF: No abstract available.

Oxidative Stress in Pancreatic Islet beta-cells Exposed to High Glucose Concentration.: Kyu Chang Won; Korean Diabetes J. 2004;28(4):250-254. Published online August 1, 2004

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Abstract PDF: No abstract available.

Original Articles

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 .

Insulin Enhances Suppressive Effect of Lipopolysaccharide on Glucose-induced Proliferation of Vascular Smooth Muscle Cells.: Hyoung Chul Choi, Hyuk Jin Kwon, Kwang Youn Lee; Korean Diabetes J. 2004;28(4):265-272. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Vascular smooth muscle cell (VSMC) proliferation is a major pathologic finding of atherosclerotic vessels in diabetes mellitus. Lipopolysaccharide (LPS) inhibits the VSMC proliferation by NO production via iNOS expression. This study attempted to investigate the effect of LPS on the glucose-induced proliferation of VSMC and its mechanism of action. The effects of insulin on glucose induced VSMC proliferation and on the expression of iNOS were also investigated. METHODS: VSMCs were primarily cultured from rat aorta. A proliferation assay for VSMC was performed by a cell count. The concentrations of nitrite in culture media were measured using the Griess reaction. Western blots were performed to analyze for iNOS protein. RESULTS: D-glucose induced VSMC proliferation in a concentration-dependent manner. LPS inhibited the D-glucose induced VSMC proliferation by increasing ing nitrite production. Insulin suppressed the D-glucose induced VSMC proliferation and potentiated the LPS-induced inhibition of VSMC proliferation by increasing the nitrite production. Insulin potentiated the LPS-induced expression of iNOS. CONCLUSION: These results suggest that in diabetes mellitus, glucose induces VSMC proliferation, and LPS and insulin inhibit the stimulatory action of glucose on VSMC proliferation, and insulin potentiates the inhibitory action of LPS on VSMC proliferation via a increase in the expression of iNOS.

Increased ROS Production by High Glucose in Cultured Mouse Insulinoma Cell Line.: Jin Hwa Kim, Jung In Kim, Dong Hyun Choi, Young Uk Seo, Young Dae Kim, Jong Chan Oh, Beom Ju Lee, Keo Woon Park, Sang Yong Kim, Hak Yoen Bae, Byoung Rai Lee; Korean Diabetes J. 2004;28(4):273-283. Published online August 1, 2004

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Abstract PDF: BACKGROUND
To investigate the effects of high glucose on oxidative stress of islet beta cells, the effects of high glucose on antioxidant enzymes, the production of free reactive substances and paraquat-induced cytotoxicity were examined in cultured mouse insulinoma cells (MIN6N8a). METHODS: The MIN6N8a cell line (Obtained from Diabetic research center, Univer sity of Calgary, Canada) was maintained in RPMI1640 medium supplemented with 10% fetal bovine serum, at 37degrees C under an atmosphere of 5% CO2 and 100 % humidity. The MIN6N8a cells were cultured in high glucose (22.4 mM) and normogl-ucose (5.6 mM) containing RPMI1640 media, for 1-6 days, and the superoxide dismutase (SOD), catalase and glutathione peroxidase (GSHPx) activities in the MIN6N8a cells assayed. The levels of reactive oxygen species in the MIN6N8a cells was determined using dihydroethidium (DHE). Paraquatinduced cytotoxicity was determined using the 3-[4,5-dimethylthiazol-2-yl]-2, 5diphenyl tetraz olium bromide (MTT) method. RESULTS: No difference was observed catalase in the catalase and GSHPx activities in MIN6N8a cells between the high glucose (22.4 mM) and normoglucose (5.6 mM) groups. The CuZn-SOD activity of MIN6N8a cells was decreased by 32% in the high glucose (25.4 mM) medium compared to normoglucose (5.6 mM) medium, while the Mn-SOD activity was increased by 24% in high glucose group. The paraquat induced cytotoxicity of MIN6N8a cells was potentiated by high glucose. and the amount of DHE oxidation increased. CONCLUSION: The Oxidative stress in MIN6N8a cells was increased by high glucose as a resulted of the decreased CuZn-SOD activity and increased production of reactive oxygen species. Increased oxidative stress in MIN6N8a cells by high glucose may play some roles in the pathogenesis of diabetes.

The Relation Between Serum and Intracellular Magnesium Level And Diabetic Microvascular Complications.: Kyung Hoon Min, Ji Hye Kim, Eun Kyung Choi, Ji Hyun Park, Hong Sun Baek, Tian Ze Ma, Bing Zhe Hong, Yong Geun Kwak, Hyung Sub Kang, Tae Sun Park; Korean Diabetes J. 2004;28(4):284-292. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Low serum magnesium levels are related to diabetes mellitus (DM), high blood pressure (HBP) and metabolic syndrome (MS). However, as far as is known, there have been no previous studies analyzing the relevance of the serum and intracellular magnesium concentrations in diabetic microvascular complication individuals compared with healthy individuals. SUBJECTS AND METHODS: A pilot study was performed to compare 35 individuals with DM with 22 disease-free control subjects. The serum and intracellular magnesium levels of each group were measured, and found to be elevated in the diabetic group with diabetic microvascular complications. RESULTS: The mean serum magnesium levels among the subjects with DM and the control subjects were 0.0503 +/- 0.0750 and 0.9166 0.1149 mmol/L (p<0.001), respectively. The mean intracellular magnesium levels among the subjects with DM and the control subjects were 3.3548+/-0.1863 and 3.6732 0.2428 mM/mg protein (p<0.001), respectively. In those diabetic subjects whose serum magnesium concentration was measured, 28 had diabetic retinopathy, 30 diabetic nephropathy and 20 diabetic neuropathy. The mean serum magnesium concentrations of each diabetic microvascular complication were 0.9320 0.2813, 0.9259 0.1188 and 0.9305 0.1293 mmol/L, respectively, which that were significantly lower than those of the healthy subjects (p<0.001, p<0.001 and p<0.01). Also, the diabetic subjects whose intracellular magnesium concentrations were measured, 13 had diabetic retinopathy, 15 diabetic nephropathy and 9 diabetic neuropathy. The mean intracellular magnesium concentrations of each diabetic microvascular complication were 3.3484 0.1607, 3.3289 0.1832 and 3.3768 0.2096 mM/mg protein, respectively, and were also significantly lower than those of the healthy subjects (p<0.001and p<0.01). Each diabetic microvascular complication was also negatively correlated with the serum magnesium and intracellular magnesium levels. CONCLUSION: This study reveals that a significant relation ship exists between low serum and intracellular magnesium levels and diabetic microvascular complications, particularly retinopathy and nephropathy. A large scale study on these subjects will be required to generalize our results.

Plasma Fibrinogen Level is Associated with Carotid Plaque Progression in Type 2 Diabetic Patients.: Seong Hun Kim, Ji Hye Kim, Chong Hwa Kim, Ji Hyun Park, Tae Sun Park, Hong Sun Back; Korean Diabetes J. 2004;28(4):293-303. Published online August 1, 2004

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Abstract PDF: BACKGROUND
The level of plasma fibrinogen has emerged as an important risk factor for cardiovascular diseases. Raised fibrinogen levels result in enhanced fibrin deposition in areas of vessel wall injury, which in turn may accelerate the development of atherosclerotic disease. The aim of present study was to investigate whether the plasma fibrinogen levels was related to carotid atherosclerosis in type 2 diabetic patients. METHODS: The sbjects of this study were 210 type 2 diabetic patients. The intima-media thickness (IMT) and plaques in the each segment of the both carotid arteries were evaluated by a duplex scan. The mean of the total IMT values (7 points on each side), the each mean value of the CCA, bulb and ICA, and the maximal IMT, plaque count and score were measured. The plaque score was defined by the sum of longitudinal diameters of each plaque. RESULTS: The correlation between the plasma fibrinogen level and measured IMT values was statistically insignificant (r<0.15, P>0.05). However, there were significant positive correlations between the level of fibrinogen and the plaque count (r=0.20, P=0.019) or plaque score (r=0.24, P=0.006). Stepwise multiple regression analysis revealed the level of plasma fibrinogen as a predictor of the plaque score. CONCLUSION: These results suggest that an elevated plasma fibrinogen level may be related with carotid atherosclerosis in type 2 diabetic patients. Also, there a need to address the discriminating risk factors for the formation or progression of plaques, or IMT thickening.

Poor Prognosis Factors and Risk Factors of Amputation in Foot ulcers in Diabetes.: Mi Jung Eun, Jung Hoon Lee, Jin Ho Kim, Ji Eun Lee, Jae Hong Kim, Kyu Chang Won, In Ho Jo, Hyoung Woo Lee; Korean Diabetes J. 2004;28(4):304-314. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Foot ulcers are a common complication of diabetes mellitus, and their prevalence is increased relative to those without diabetes. Foot ulcers and related complications represent an important cause of morbidity among patients with diabetes mellitus. Most of the poor prognosis factors and amputation risk factors of diabetic foot ulcers have been found to be largely affected by male sex, inadequate blood glucose control, vascular disease, neuropathy, end organ defects, and the depth and size of ulcers, prior ulcer history, infection and ischemia. Currently, the poor prognosis factors and amputation risk factors of diabetic foot ulcers in the Korean diabetic population are unknown. The purpose of this study was to identify and quantify the poor prognosis factors of diabetic foot ulcers and the risk factors of lower extremity amputation. METHODS: This study comprised of involved 37 male and 14 female diabetics with foot ulcers aged 23 to 83 years. According to the results of treatment, the patients were divided into 4 groups; complete healing (CH), partial healing (PH), unhealing (UH), and amputation (AM) groups. The baseline characteristics of the study subjects (gender, age, duration of diabetes, BMI, drinking, smoking, insulin therapy, blood pressure, whole blood count, renal function test and the size and depth of ulcer, prior ulcer history, osteomyelitis, infection, ischemia, neuropathy and retinopathy) were examined. RESULTS: The following characteristics were not significantly related to the poor prognosis factors and amputation risk factors of diabetic foot ulcers: age, duration of diabetes, BMI; drinking, smoking, insulin therapy, blood pressure, whole blood count and renal function test. The following characteristics were significantly related to the poor prognosis factors and amputation risk factors of diabetic foot ulcers: male (p=0.021), ischemia (p<0.05), infection (p<0.01), osteomyelitis (p<0.01), prior ulcer history (p<0.05), retinopathy (p<0.05), size of ulcer (p<0.001) and depth of ulcer (p<0.001). The size and depth of an ulcer, prior ulcer history, ischemia and infection were found to be associated with poor prognosis factors of treatment and risk factors of amputation in diabetic foot ulcer patients by a multiple regression test (P<0.05). CONCLUSION: This study shows that the size and depth of an ulcer, prior ulcer history, ischemia and infection are poor prognosis factors of diabetic foot ulcer and amputation risk factors However, further studies will be required due to the smaill size of our study population.

Insulin Resistance in Normal Weight Women with Polycystic Ovary Syndrome.: Eun Kyung Byun, Hye Jin Lee, Jee Young Oh, Young Sun Hong, Hye Won Chung, Yeon Ah Sung; Korean Diabetes J. 2004;28(4):315-323. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Insulin resistance is considered a regular component of polycystic ovary syndrome (PCOS). However, several studies have failed to confirm insulin resistance in non-obese women with PCOS. The aim of the study was to identify whether insulin resistance is present in normal weight women with PCOS and the factors associated with insulin sensitivity. METHODS: Twenty-two normal weight (body mass index, BMI < 25 kg/m2) women with PCOS, and 16 age and BMI comparable control women with regular menstrual cycles were examined during their early follicular phase. The levels of serum hormones and lipids were measured. The visceral fat area was assessed by computed tomography at umbilical level. The standard 75g oral glucose tolerance test was performed to determine the glucose tolerance status. The insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique (target glucose 90 mg/dL, insulin~1 mu/kg/min). RESULTS: The levels of free testosterone (1.9+/-0.6 pg/mL vs. 0.8+/-0.3 pg/mL, p<0.001), androstenedione (14.5+/-3.7 nmol/L vs. 8.8+/-1.3 nmol/L, p<0.001), LH (10.7+/-4.5 IU/L vs 4.6+/-4.8 IU/L, p<0.001) and FSH (5.8+/-1.7 IU/L vs. 4.2+/-2.4 IU/L, p<0.05) of the women with PCOS were significantly higher than those of the control subjects. The fasting plasma glucose (4.92+/-0.31 mmol/L vs. 4.42+/-0.61 mmol/L, p<0.01) and post glucose load plasma insulin (233.2+/-119.5pmol/L vs. 109.0+/-46.4 pmol/L, p<001) levels of women with PCOS were significantly higher than those of the control subjects. The glucose disposal rate (M value) was significantly lower in women with PCOS compared to the controls (5.3+/-1.2 mg/kg min vs. 6.7+/-1.6 mg/kg min, p<0.05), even after adjusting for age and BMI. There was no significant correlation of the M value with the anthropometric and a metabolic indices, and a multiple regression analysis of the M value showed no significant variables. CONCLUSION: Our non-obese women with PCOS showed significant insulin resistance compared to their age and BMI comparable control subjects, and-their insulin resistance may be an intrinsic defect not associated with other features, such as hyperandrogenemia or body fat distribution patterns.

Serum CRP levels are associated with Estradiol levels and Insulin Resistance Syndrome in Korean Women.: Kwon Beom Kim, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Chol Shin, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(4):324-337. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Several reports have recently suggested a positive correlation between components of metabolic syndrome (MS) or insulin resistance syndrome (IRS) and markers of the acute-phase response, including C-reactive protein (CRP). These results imply that MS and type 2 diabetes are the results of ongoing inflammatory process. Whether estrogen plays a beneficial role in preventing atherosclerosis has been a matter of controversy. The objective of this study was to evaluate the relationship between the serum levels of estradiol (E2) and the components of the MS and CRP in nondiabetic subjects of Ansan Health Study (AHS). METHODS: Eight-hundred and ninety-one healthy non-diabetic women aged over 18 years were enrolled. After measurements of the anthropometric and metabolic parameters, correlation and multiple linear regression analyses were performed with regard to the CRP level, as a dependent variable, and with regards to age, blood pressure (BP), body mass index (BMI), lipid profiles, fasting plasma glucose levels, HOMA-IR and fat content as independent variables. RESULTS: In the multiple linear regression analysis, the CRP concentration was found to be independently associated with the E2 level, total fat content, leukocyte counts, and total cholesterol level in all subjects and the serum E2 levels was correlated with age, HOMA-IR, total cholesterol and the CRP level. When subjects were grouped according to their number of MS or IRS components, the CRP levels were found to show statistically significant differences between the MS and IRS groups. CONCLUSION: As a marker of chronic inflammation, the serum CRP level was independently associated with the components of MS and IRS. Also, the serum CRP and E2 levels were positively correlated. These results suggest that estrogen and CRP might play some independent roles in chronic inflammation which is a part of MS and IRS.

Relative Hyperglucagonemia and Its Related Factors in Patients with Type 2 Diabetes.: Kang Hyun Choi, Ki Ho Song, Sang Hoon Lee, Seong Hoon Chung, Eun Jung Kim, Seung Hyun Ko, Hyuk Sang Kwon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(4):338-345. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Excessive secretion of glucagon contributes to metabolic disturbance in type 2 diabetes. A hyperglucagonemic state is likely to be involved in increased hepatic glucose output resulting from both gluconeogenesis and glycogenolysis. The mechanism of hyperglucagonemia, though still unclear, is explained, in part, by the decreased sensitivity of cells to insulin or glucose and disturbances of the normal oscillatory secretory pattern of insulin. The aim of the study was to determine the extent of glucagon excess and its related factors in Korean patients with type 2 diabetes. METHODS: The subjects of this study were 21 controls and 102 type 2 diabetic patients. The blood glucose, glucagon and insulin concentrations were measured at 0, 30, 60, 90 and 120 min after ingestion of 75 g of glucose, and the areas under the curve (AUC) calculated. RESULTS: The AUC of plasma glucose (AUCgc) was significantly higher in the type 2 diabetic patients than in the controls (2,026.1585.8 vs. 854.8190.3 mmol/min, P<0.01), but there was no difference in the AUC of plasma glucagon (AUCgn) between the two groups. The AUCgn in the type 2 diabetic patients was positively correlated with the duration of diabetes (r=0.202, P<0.05) or HbA1c (r=0.208, P<0.05). The AUC of serum insulin (AUCin) was negatively correlated with the duration of diabetes (r=-0.291, P<001). AUCgn, AUCgc and HbA1c in long-term diabetic patients (duration of diabetes 10 years, n=32) were significantly higher compared with recently diagnosed patients (duration of diabetes <1 year, n=38) (11,362.35,981.9 vs. 9,097. 22,990.4 ng/min; 2,119.9519.0 vs. 1,832.2477.6 mmol/min; 9.52.0 vs. 8.32.1%, P<0.05). In addition, the AUCin and insulinogenic index in long-term patients were significantly lower compared with recently diagnosed patients. (Eds note: the highlighted figures are confusing, due to your various uses of commas and period marks, olease clarify?) CONCLUSIONS: Our results suggest that duration of diabetes and poor glycemic control might be closely associated with relative hyperglucagonemia in Korean type 2 diabetic paticnts.

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