Diabetes & Metabolism Journal

Original Articles

Relationship between Endothelial-dependent/-independent Vasodilation and Carotid Intimal- media Thickness in Newly-diagnosed Korean Type 2 Diabetic Patients.: Jung Ho Choi, Kyung Wan Min, Hyo Jeong Kim, Bo kyung Koo, Chae Young Lim, Hyun Jin Kim, Gang Seo Pak, Kyung Ah Han, Eung Jin Kim; Korean Diabetes J. 2007;31(6):498-506. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.498

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Abstract PDF: BACKGROUND
The relative effect of diabetes on the risk of cardiovascular disease in Asian population is much the same as that in Western populations. Although multiple atherosclerotic risk factors have been documented in Asia, precise estimates of vascular reactivity might provide more critical informations for the prevention and the control of diabetes-related cardiovascular mortality and morbidity. The aims of this study were to estimate the vascular reactivity directly and evaluate its relationship with other cardiovascular risk factors and carotid intimal-media thickness (IMT) in newly-diagnosed Korean type 2 diabetic patients. METHODS: We measured flow-mediated vasodilation (FMD) and endothelial-independent vasodilation (EID) of the brachial artery using high-resolution ultrasonography in total of 121 (M; N = 68, F; N = 53) diabetic patients. We assessed conventional cardiovascular risk factors such as age, smoking, obesity, hypertension, hyperlipidemia or family history of cardiovascular disease and analyzed the association among FMD/EID with cardiovascular risk factors, carotid IMT or the total number of risk factors. RESULTS: The mean values of age, smoking, BMI, waist, systolic blood pressure and diastolic blood pressure were 51.2 +/- 12.3 years, 11.0 +/- 15.8 pack years, 25.0 +/- 3.2 kg/m2, 86 +/- 9 cm, 123 +/- 16 mmHg and 79 +/- 12 mmHg. The mean values of HbA1c, fasting blood glucose, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol were 8.4 +/- 2.0%, 166 +/- 51 mg/dL, 187 +/- 37 mg/dL, 166 +/- 143 mg/dL, 114 +/- 30 mg/dL and 46 +/- 12 mg/dL. FMD and EID were estimated by 6.1 +/- 2.8% and 16.6 +/- 5.6% respectively. The mean/maximal carotid IMT were 0.63 +/- 0.12/0.76 +/- 0.16 mm and the number of risk factors besides diabetes mellitus were 2.3 +/- 1.3. After adjusting age, FMD was associated only with smoking, but EID was associated with smoking, systolic/diastolic blood pressure, mean/maximal carotid IMT and number of risk factors by partial correlations. Age, smoking and EID were independent risk variables for carotid IMT, analyzed by multiple regression test. CONCLUSION: These findings suggest that impaired vascular reactivity detected by EID is closely related to carotid IMT, an useful surrogate marker for atherosclerosis, in newly-diagnosed Korean type 2 diabetic patients.

Effects of Pioglitazone on Cerebral Hemodynamics in Patients of Type 2 Diabetes.: Jong Suk Park, You Jung Lee, Chul Sik Kim, Hai Jin Kim, Jina Park, Chul Woo Ahn, Kyung Yul Lee, Hyeong Jin Kim, Young Jun Won, Hun Ju Ha, Hae Sun Kwak, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(2):96-103. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.96

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Abstract PDF: BACKGROUND
Atherosclerosis is one of the major causes of morbidity and mortality in patients with type 2 diabetes and pioglitazone has been reported to have antiatherogenic effect. The aim of this study was to investigate whether pioglitazone affects carotid intima-media thickness (IMT) and pulsatility index (PI) in type 2 diabetic patients. METHODS: A total of 40 type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (pioglitazone 15 mg/day with gliclazide 80~320 mg/day for 12 weeks) (n = 20) and control group (gliclazide 80~320 mg/day for 12 weeks) (n = 20). The changes in lipid profile, insulin resistance, IMT, and PI were monitored to determine that pioglitazone improves cerebrovascular blood flow. RESULTS: The pioglitazone treatment significantly increased HDL-C, reduced triglyceride, insulin resistance and PI. IMT tended to decrease but the change was not significant. This study revealed that treatment with pioglitazone was associated with the improvement of cerebrovascular blood flow. CONCLUSIONS: Pioglitazone appears to be effective for the improvement of cerebrovascular blood flow in type 2 diabetic patients

Relationship of LDL Particle Size to IMT and Insulin Resistance in Non-Diabetic Adult.: Jina Park, Chul Sik Kim, Jong Suk Park, Dol Mi Kim, Min Ho Cho, Jee Hyun Kong, Hai Jin Kim, Jeong Ho Kim, Chul Woo Ahn, Kyung Rae Kim, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee; Korean Diabetes J. 2005;29(4):333-343. Published online July 1, 2005

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Abstract PDF: BACKGROUND
The aims of this study were to investigate the predictor of the low density lipoprotein(LDL) particle size and the relationship of the LDL particle size to the levels of insulin resistance and the carotid intima-media thickness (IMT) in healthy Koreans. METHODS: The subjects were 47 and 89 clinically healthy males and females, aged between 32 and 70years, without medications that could potentially alter glucose and lipid metabolisms. The mean LDL particle size was determined by polyacrylamide tube gel electrophoresis(Lipoprint(r) LDL, Quantimetrix), the insulin resistance using a short insulin tolerance test kit, and the subclinical atherosclerosis from the carotid intima-media thickness. RESULTS: The LDL particle size was found to be significantly correlated with insulin resistance using a simple Pearson's correlation(r=0.233, P<0.01), but the independent predictors of the LDL particle size, as determined by a multiple stepwise regression analysis, were serum triglyceride(TG), high density lipoprotein(HDL) cholesterol level and age(beta=-0.403, P=< 0.001; beta=0.309, P=0.003; beta=-0.219, P=0.016, respectively). Significant relationships were found between an increasing IMT and the traditional risk factors of atherosclerosis: age, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure(r=0.490, P<0.001; r=-0.251, P<0.01; r=0.211, P<0.05; r=0.298, P<0.01; r=0.263, P<0.01, respectively). However, no significant correlation was found between an increasing IMT and the LDL particle size (r=-0.172, P=0.075). CONCLUSION: The best predictors for the LDL particle size were the serum TG level, HDL cholesterol level and age. Insulin resistance was not found to be an independent predictor of the LDL particle size. Small dense LDL was not found to be a predictor of the IMT in healthy Koreans.

The Thickness of Carotid Artery Intima-Media Thickness in Hypertriglyceridemic Hyperapo B Type 2 Diabetes.: Ji Hyun Lee, Duck Soo Chung; Korean Diabetes J. 2005;29(1):57-64. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Atherosclerotic diseases such as cardiovascular disease and cerebrovascular disease are major causes of diabetes mellitus-related morbidity and mortality. The frequency of macrovascular disease in type 2 diabetic patients varies geographically, and this suggests that factors other than diabetes play an important role in the pathogenesis of their vascular disease. One such factor may be the dyslipoproteinemias that are common in diabetic patients. There were many studies showing that hypertriglyceridemia with an elevated apolipoprotein B (apo B) level was associated with an increased risk for coronary disease in type 2 diabetes patients. Meanwhile, an increase in the intima-media thickness (IMT) of the carotid artery has been previously reported in patients with type 2 diabetes, and this is related to the atherosclerotic risk factors. The aim of this study was to evaluate the relationship between the carotid artery IMT and lipoprotein and apolipoprotein, and we also wanted to assess the role of hypertriglyceridemic hyperapo B for the cardiovascular risk factors in the type 2 diabetic patients. METHODS: The carotid artery IMT was measured using high resolution B-mode ultrasono graphy in 117 type 2 diabetes. At the same time, we analyzed the patients characteristics including height, weight, body mass index, blood pressure, duration of diabetes and history of hypertension. Laboratory parameters such as fasting blood glucose, HbA1c, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, apolipoprotein A and B were included in this study. We defined hypertrigl yceridemic hyperapo B as when the triglyceride level was over 1.7 mmol/L and the apolipoprotein B level was over 1.20 g/L. RESULTS: Thirty-three patients (28%) were classified as having hypertriglyceridemic hyperapo B. Age (r = 348, P = 0.001), duration of diabetes (r = 0.438, P = 0.001), hypertension (P = 0.001), and LDL-cholesterol (r = 0.225, P = 0.018) were statistically significant for the carotid artery IMT values in diabetic patients. However, there were no correlations between carotid artery IMT and total cholesterol, triglyceride, HDL- cholesterol, and apolipoprotein A and B. Upon multiple regression analysis, age, duration of diabetes and LDL-cholesterol were statistically significant for the carotid artery IMT values in diabetic patients (R2 = 0.296). Hypertriglyceridemic hyperapo B diabetic patients didn't have higher carotid artery IMT values than the other patients. CONCLUSION: The increment of carotid artery IMT is affected by age, blood pressure, duration of diabetes and LDL-cholesterol. However, our study did not show any association between carotid artery IMT and hypertriglyceridemic hyperapo B

The Correlation Between Femoral Artery Intima-Media Thickness (IMT) and Atherosclerotic Risk Factors in Type 2 Diabetes Mellitus Patients.: Ji Hyun Lee, Ho Sang Shon, Duck Soo Chung; Korean Diabetes J. 2003;27(6):467-475. Published online December 1, 2003

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Abstract PDF: BACKGROUND
High resolution B-Mode ultrasound is increasingly used in epidemiological and clinical research to noninvasively study the atherosclerotic process in the carotid artery. An increase in the intimamedia thickness (IMT) of the carotid artery has previously been reported in patients with diabetes, compared with a control group, and is related to atherosclerotic risk factors. There have been few reports on the relationship between the IMT of the femoral artery, another large artery, and atherosclerotic risk factors in diabetic patients. The aim of the present investigation was to evaluate the relationship between the femoral artery IMT and the atherosclerotic risk factors in type 2 diabetics, and to assess if such a measurement might provide further information on the extent of the atherosclerotic disease in these patients. METHODS: The carotid and femoral IMT were measured using high resolution B-mode ultrasonography in 55 type 2 diabetes patients and 25 age- and sex-matched control subjects. The femoral artery was examined distal to the inguinal ligament, at the site the artery divides into the superficial femoral and the profound femoral arteries. At the same time, patient's characteristics, including height, weight, body mass index, blood pressure, duration of diabetes and histories of hypertension and smoking, were analyzed. Examinations of the laboratory parameters, such as serum glucose, HbA1C, lipid profile, blood urea nitrogen and serum creatinine, were included in this study. RESULTS: The carotid and femoral IMT values were significantly increased in the type 2 diabetes patients compared with the control subjects. There was a significant relationship between the IMT values of the two arteries in the diabetic patients (r=0.419, p< 0.001). In a simple regression analysis, age (r=0.534, p=0.001), systolic blood pressure (r=0.499, p=0.001), diastolic blood pressure (r=0.350, p=0.003), high density lipoprotein cholesterol (r=-0.262, p=0.037) and the serum creatinine level (r=0.280, p=0.020) were statistically significant for the femoral artery IMT value. In a multiple regression analysis, age, smoking and systolic blood pressure were statistically significant for the femoral artery IMT values in diabetic patients (R2=0.379). CONCLUSION: The femoral IMT values were significantly increased in the type 2 diabetes patients. Increases in the IMT of the femoral artery are affected by the atherosclerotic risk factors; age, smoking and blood pressure. Therefore, it is suggest that measurement of the femoral IMT, using high resolution B-mode ultrasonography, is also a useful method for the detection of macrovascular complications in type 2 diabetes patients.

Relationship between Serum Homocysteine Levels and Vascular Complications in Type 2 Diabetic Patients.: Seung Jin Choi, Jae Taek Kim, Yeon Sahng Oh, Soon Hyun Shinn; Korean Diabetes J. 2002;26(2):112-125. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Chronic complications in type 2 diabetic patients have microvascular and macrovascular components. Previous studies have shown that incidence of macrovascular complications correlates with the serum homocysteine levels, but the relationship is unclear. In addition, the connection between the microvascular complications and the serum homocysteine levels is still obscure and controversial. In this study, the relationship between the serum homocysteine levels and microvascular and macrovascular complications were evaluated in type 2 diabetic patients. METHODS: In 58 type 2 diabetic patients, the serum homocysteine levels, folic acid levels, Vit B12 levels, PAI-1 levels, the standard risk factors for macrovascular complications, the fasting serum glucose levels, the HbA1C levels, and the fasting insulin and C-peptide concentrations, the renal function tests, and the carotid intima-media thickness were measured and the relationship between them and the serum homocysteine level was analyzed according to the presence and absence of macrovascular and microvascular complications. RESULTS: 1) In type 2 diabetic patients, the mean serum homocysteine level was 9.9+/-.2 mol/L. The serum homocysteine level showed no relationship with the clinical and biochemical variables including the risk factors for atherosclerosis except the serum creatinine and creatinine clearance. 2) The maximum, minimum, and mean of the intima- media thickness of right carotid artery were 4.00+/-.20, 0.50+/-.04, 1.04+/-.62 mm, of left carotid artery were 3.54+/-.00, 0.31+/-.02, 1.03+/-.55 mm, and means were 3.77+/-.10, 0.44+/-.03, 1.03+/-.54 mm, and correlated with the serum homocysteine leve l (p=0.03), but only the serum LDL cholesterol level independently correlated with the intima-media thickness (p=0.04). 3) The serum homocysteine level (p=0.01) and intima-media thickness (p<0.01) was significantly higher in type 2 diabetic patients with macrovascular complications than without it. 4) The serum homocysteine level did not correlate with the incidence microvascular complications, but the intima-media thickness did correlate with diabetic nephropathy (p=0.03). CONCLUSIONS: The serum homocysteine level did not correlated with the incidence of diabetic microvascular complications. However, there was a small correlation with the risk factors of macrovascular complications. The intima- media thickness correlated with the incidence of macrovascular complications, and the relationship with diabetic nephropathy requires further study.

Relationship Between Intimal-Medial Thickness (IMT) of the Carotid Artery and Atherosclerotic Risk Factors in Patients with type 2 Diabets Mellitus.: Yu Bae Ahn, So Lyung Jung, Seung Hyun Ko, Ki Ho Song, 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(2):142-151. Published online April 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus is a major independent risk factor for atherosclerosis. In recent years non-invasive high resolution B-mode ultrasound methods have been developed to measure the IMT (intima-media thickness) of the carotid artery as an index for early atherosclerosis. The aims of this study were to measure IMT in type 2 diabetic patients, to investigate the relation of various cardiovascular risk factors to IMT, and to evaluate the difference in IMT according to presence of diabetic complication. METHODS: IMT was measured by ultrasound B-mode imaging in 300 subjects with type 2 diabetes mellitus (131 male, 169 female adults aged 53.4+/-9.5 years, duration of diabetes 7.4+/-6.3 years). All subjects underwent coronary artery disease (CAD) risk factors assessment and the presence of diabetic complications were evaluated. RESULT: There were positive correlations between IMT and age, duration of diabetes, LDL-C, systolic blood pressure and Lp (a) level. Multiple linear regression analysis demonstrated that in type 2 diabetic patients, the variables that interact independently with IMT were age, systolic blood pressure, levels of total cholesterol, HDL cholesterol and sex. IMT was significantly increased in type 2 diabetic patients with macrovascular complication regardless of presence of microvascular complication. But there was no significant difference in IMT according to Lp (a) level, presence of microalbuminuria, mode of treatment and glycemic control. CONCLUSION: The Intima-Media thickness of patients with type 2 diabetes mellitus was associated with age, systolic blood pressure, levels of total cholesterol, HDL-C and sex.

Dissociation of Microangiopathy and Macroangiopathy in Patients with Type 2 Diabetes.: C J Seo, K Y Lee, K S Song, Y S Jung, Hong Kyu Kim, H Y Park, W G Lee, M H Kang; Korean Diabetes J. 2001;25(2):133-141. Published online April 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes is a heterogeneous disease. As to its complications, microangiopathy predominantly develop in some patients while macroangiopathy is more predominant in others. Therefore, this study was performed to identify the factors associated with such dissociation. METHODS: Type 2 diabetic patients were classified into the macro and microangiopathy groups by carotid intima-medial thickness (IMT) and the presence of severe diabetic retinopathy. Patients with IMT

Intima-media Thickness of the Common Carotid Artery and Carotid Atherosclerotic Plaques as Predictors for Occurrence of Clinical Macrovascular Complication in Type 2 Diabetes.: Byoung Hyun Park, Chung Gu Cho; Korean Diabetes J. 2000;24(5):603-613. Published online January 1, 2001

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Abstract: BACKGROUND
This study was undertaken to investigate that intima-media thickness and plaque of the carotid artery, as measured by high resolution B-mode ultrasonography, can be used as predictors for occurrence of clinical macrovascular complication in type 2 diabetes patients. METHODS: High resolution B-mode ultrasonographic examination was performed in 39 type 2 diabetes, including 16 diabetes with macrovascular complication, and in 18 non-diabetic control subjects. Concurrently serum total cholesterol, HDL cholesterol, triglyceride, lipoprotein (a), HbA1c, C-peptide levels and body mass index (BMI) were measured and history of hypertension, smoking, duration of diabetes and occurrence of macrovascular complication during the last 6 months were investigated. RESULTS: 1) Significant differences in common carotid IMT (0.72+/-0.08 mm, vs 0.93+/- 0.26 mm), existence of atherosclerotic plaque (50%, vs 69%), plaque number (0.5+/- 0.86, vs 0.69+/-2.37) and carotid stenosis (0%, vs 18%) were found between control and type 2 diabetes (p<0.05). 2) Significant differences in age (67.63+/-4.30, vs 60.6+/-12.0), lipoprotein (a) (63.65+/- 32.2 mg/dL, vs 35.22+/-34.74 mg/dL), common carotid IMT (1.08+/-0.27 mm, vs 0.82+/- 0.20 mm), existence of atherosclerotic plaque (87.5%, vs 56.5%), plaque number (2.88+/-3.16, vs 0.91+/-1.02), end diastolic ventricular septal thickness (10.82+/-1.88 mm, vs 8.76+/-2.92 mm) and end diastolic left ventricular posterior wall thickness (10.79+/-1.60 mm, vs 9.1+/-2.56 mm) were found between type 2 diabetes patients with macrovascular complication and without macrovascular complication (p<0.05). 3) Age (r=0.363, p=0.023), hypertension (r=0.32, p=0.047), carotid plaque existence (r=0.377, p=0.018) and plaque number (r=0.662, p=0.000) showed a correlation with the IMT in type 2 diabetes. 4) Most common involving site of atherosclerotic plaques was carotid bulb and more extensive involvement was showed in type 2 diabetes with macrovascular complication than without macrovascular complication. 5) The sensitivity of common carotid IMT (> control mean IMT + 2 SD; >1.22 mm) for prediction of macrovascular complication in type 2 diabetes patients was 25%, the specificity 95.7%, the positive predictive value 80%, the negative predictive value 61.8%. 6) The sensitivity of existence of carotid plaque for prediction of macrovascular complication in type 2 diabetes patients was 87.5%, the specificity 60.9%, the positive predictive value 60.9%, the negative predictive value 87.5%. CONCLUSION: Increases in IMT and plaque of the carotid artery, as measured by high resolution B-mode ultrasonography, can be used as predictors for occurrence of clinical macrovascular complication in type 2 diabetes patients.

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