Diabetes & Metabolism Journal

Original Articles

Association Between Impaired Vascular Endothelial Function and High Sensitivity C-reactive Protein, a Chronic Inflammatory Marker, in Patients with Type 2 Diabetes Mellitus.: Jang Yel Shin, Mi Young Lee, Jang Hyun Koh, Jang Young Kim, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2005;29(5):469-478. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Eighty percents of diabetes-related mortalities are due to atherosclerotic vascular complications. The accelerated atherosclerosis in type 2 diabetic patients is partly due to the increased incidences of cardiovascular risk factors, such as hypertension, obesity, dyslipidemia, insulin resistance and oxidative stress. Endothelial dysfunction is known as an early marker of cardiovascular disease and a predictor of cardiovascular events. The flow mediated dilation (FMD) of the brachial artery has been documented as being reduced in type 2 diabetic patients. Inflammatory markers, such as C-reactive protein(CRP) and interleukin-6(IL-6), are associated with the risk of cardiovascular disease. Endothelial dysfunction has a direct correlation with the levels of CRP, which are elevated in patients with diabetes compared with non-diabetic subjects. In this study, the FMD in diabetic and non-diabetic subjects were compared, and the association of cardiovascular risk factors and endothelial function examined in type 2 diabetic patients. METHODS: 57 consecutive diabetic subjects and 29 non-diabetic subjects, aged 35 to 69(54.0+/-1.0 years), without proven macrovascular complications, were enrolled in this study. Cardiovascular risk factors, such as body weight, height, waist and hip circumference, fasting plasma glucose and insulin levels, lipid profiles, inflammatory and coagulation markers were measured. The FMD of the brachial artery and the intima-media thickness(IMT) of the carotid artery were determined using high-resolution B-mode ultrasound. RESULTS: The FMD values were significantly lower in the diabetic compared with the non-diabetic subjects(7.6+/-0.2% vs. 8.9+/-0.4%, P=0.004). The homocysteine levels were significantly higher in the diabetic than non-diabetic subjects(12.4+/-0.4micromol/L vs. 9.5+/-0.6micromol/L, P<0.0001). In diabetic subjects, the FMD was shown to be significantly negatively correlated with high sensitivity C-reactive protein(hsCRP)(P=0.006), fibrinogen(P=0.024) and homocysteine (P=0.038). A multiple regression analysis, after adjusted for age, sex, body mass index(BMI), hypertension, and smoking, showed that hsCRP(beta=-0.424, P=0.002) and fibrinogen(beta=-0.324, P=0.025) had significant inverse association with the FMD in diabetic subjects. CONCLUSION: Diabetic subjects have an impaired endothelial function compared with the non-diabetic subjects, and the vascular endothelial function has a significant negative correlation with hsCRP and fibrinogen. These findings suggest that hsCRP might be an independent predictor of endothelial dysfunction and atherosclerosis, and chronic inflammation might play a pivotal role in the impairment of the endothelial function in diabetic patients.

The Relationship Between the C1818T Polymorphism in Exon 4 of the klotho Gene with Fasting Glucose and Insulin Levels in Korean Women.: Ki Won Oh, Eun Joo Yun, Eun Jung Rhee, Won Young Lee, Ki Hyun Baek, Kun Ho Yoon, Moo Il Kang, Seong Gyun Kim, Cheol Young Park, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park; Korean Diabetes J. 2005;29(3):189-197. Published online May 1, 2005

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Abstract PDF: BACKGROUND
A novel gene, termed klotho has been identified as a suppressor of several aging phenotypes, and a genetic defect of klotho in mice resulted in a syndrome resembling human aging, i.e., a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis, and pulmonary emphysema. Since klotho mice also showed an abnormal glucose metabolism, we investigated the relationship between the C1818T polymorphism in exon 4 of the klotho gene and fasting glucose and insulin resistance in Korean women to observe its contribution to glucose metabolism. METHODS: The weight, height, blood pressure, fasting blood glucose, insulin, and lipid profiles were measured in 241 women(mean age, 51.2+/-7.0yr) by using the standard methods. Homeostasis model assessment(HOMA)-insulin resistance(IR), the quantitative insulin sensitivity check index(QUICKI) and HOMAbeta-cell were calculated. The genotyping of the C1818T polymorphism in exon 4 of the klotho gene was performed by allelic discrimination with using a 5' nuclease polymerase chain reaction assay. RESULTS: The allele frequencies were 0.805 for the C allele and 0.195 for the T allele, and they were in Hardy-Weinberg equilibrium(P=0.290). The mean fasting blood glucose(P= 0.005) and HOMA IR(P=0.035) were significantly higher in the T allele carriers compared with the non-carriers. After adjustment was made for age, fasting blood glucose was persistently significant(P=0.015), but the HOMA-IR became marginally significant(P=0.063). In the premenopausal women, the T allele carriers showed a higher mean fasting blood glucose(P=0.038), insulin(P=0.024), HOMA-IR(P=0.010), total cholesterol(P=0.039), and triglyceride levels(P=0.031) than in the non-carriers. After adjustment was made for age, the fasting blood glucose, insulin, HOMA-IR and triglyceride were persistently significant(P= 0.043, P=0.026, P=0.011, P=0.040). Also, the QUICKI, total cholesterol and low-density ilpo-protein cholesterol became marginally significant(P=0.073, P=0.061, P=0.098). For the postmenopausal women, the T allele carriers showed a tendency for higher mean fasting blood glucose levels(P=0.065) and lower HOMA beta-cell levels(P=0.085) than in the noncarriers. These differences became non-significant after adjustment was made for age. CONCLUSION: We observed that the C1818T polymorphism in exon 4 of the klotho gene was partly associated with glucose metabolism in Korean women. Also, these data suggest that the C1818T polymorphism is related with some cardiovascular risk factors in Korean women. The mechanism linking this gene with glucose metabolism warrants further study

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.

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