- Relationship Among Urinary Glycosaminoglycan (GAG) Excretion Rates, Urinary Albumin Excretion and Macrovascular Disease in Patients with Type 2 Diabetes Mellitus.
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Yoon Sang Choi, Sang Hoon Kim, Hyang Kim, Yun Kyung Cho, Hyun Ju Um, Si Yong Kim, Byong Ik Kim, Yoo Lee Kim, Hwa Young Lee, Sang Jong Lee
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Korean Diabetes J. 2000;24(2):245-255. Published online January 1, 2001
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- BACKGROUND
Increased loss of proteoglycan (PG) from glomerular basement membrane (GBM) has been postulated to alter glomerular charge selectivity which contributes to urinary loss of albumin. The glycosaminoglycan (GAG) is the degradation products of PG. Recently, one of the hypothesis suggested that urinary albumin execretion(UAE) reflects not only merely a glomerular manifes-tation but also a macrovascular disease (by Deckert et al), Wasty et al. reported a significant decrease in total GAG concentration and marked changes in their distribution in atherosclarotic plaques in human. Thus, the alterations in the metabolism of GAG might play a role in the pathogenesis of diabetic macroangiopathy. Therefore, we investigated the relationship among urinary GAG execretion rates, UAE and macrovascular disease in patients with type 2 diabetes mellitus. METHODS: We measured urinary excretion rates of GAS in type 2 diabetic patients with and without macrovascular disease ( cerebrovascular disease, ischemic heart disease and other peripheral vascular disease ) and investigated the relationships among urinary execretion of GAG, UAE and macrovascular disease in 103 patients with type 2 diabetes mellitus. RESULTS: 1) Among total 103 patients, 66 patients (64.0%) showed normoal-buminuria, 18 patients (17.5%) showed microabluminuria and 19 paitents (18.4%) showed macro albuminuria respectively. The duration of diabetes mellitus and the prevalence of hypertension, diabetic retinopathy and macrovascular disease were increased according to the degree of UAE. 2) The urinary excretion rates of GAG in type 2 diabetes mellitus with normo-, microand macro-albuminuria were 6.72+/-4.05, 9.17+/-3.26 and 14.20+/-6.13 microgram glucuronic acid/min respectively (p<0.05). The urinary GAG levels were significantly correlated with UAE (r=0.43, p<0.05). 3) The urinary excretion rates of GAG in type 2 diabetes mellitus with (n=26) and without (n=77) macrovascular disease were 6.21+/-2.75 and 9,31+/-5.59 ug glucuronic acid/min, respectively (p<0.05). CONCLUSION: 1) The urinary excretion rates of GAG were decreased in patients with macro vascular complications of type 2 diabetes mellitus. 2) The urinary excretion rates of GAG may be a possible marker of macrovascular disease in type 2 diabetes mellitus. Yet, further large prospective studies are necessary to confirm our findings.
- The Comparison between Doppler Ultrasonography and Digital Infrared Thermographic Imaging (DITI) in Detecting the Diabetic Peripheral Angiopathy.
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Yoon Sang Choi, Hyun Ju Um, Seung Oh Song, Si Yong Kim, Byong Ik Kim, Young Uk Lee, Seok Won Park, Yoo Lee Kim, Hwa Young Lee, Yong Wook Cho, Sang Jong Lee
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Korean Diabetes J. 1999;23(5):686-694. Published online January 1, 2001
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- BACKGROUND
The frequency of nontraumatic lower extremities amputation has significantly increased in patients with type 2 diabetes (DM). Digital Infrared Thermographic (DITI) has been used to demonstrate the skin temperature and its change. mellitus Imaging regional Doppler ultrasonography was developed to show excellent images of superficial arteries. In this study, we observed the relationship between DITI and doppler ultrasonography for detection or evaluation of diabetic peripheral angiopathy. METHODS: 71 patients with type 2 DM were divided to groups with and without peripheral arterial obliteration (PAO) by ankle pressure index (API). For all patients, doppler ultrasonography of lower extremities was performed in measuring inner diameter, wall thickness and calcification of femoral, popliteal and dorsalis pedis artery. DITI was done also. We analized the result of doppler ultrasono-graphy and DITI findings. RESULT: 1) In clinical characteristics of patients between nonperipheral arterial obliteration (NPAO) and PAO : there was no significant differences between two groups with respect to age, sex, smoking, BMI (body mass index), FPG (fasting plasma glucose)/2HPG (2 hour plasma glucose), HbA(1C), serum lipid profile and/or the frequency of NPDR (nonproliferative diabetic retinopathy). However, the number of patients with hypertension and 24hr urine total protein amount were significantly increased in PAO group. 2) The results of doppler ultrasonographic imaging of lower extremities: In PAO group, inner diameters of common femoral artery and dorsalis pedis artery were significantly narrower than in those of NPAO group. However, no difference was detected in respect to vessel wall thickness. The numbers of calcified vessel wall have significantly increased in all vessels in PAO group 3) The results of DITI patterns of big toes after cold stimulus: (1) In 49 patients with NPAO: 11 showed as normal, 14 an increased, 15 a decreased, and 9 flat patterns, respectively. (2) All of 22 patients with PAO showed abnormal patterns. Among them, 2 showed a decreased, but 20 a flat pattern. 4) The comparison between the results of doppler ultrasonography and DITI: In all groups, inner diameter of common femoral artery, which was measured by doppler ultrasonography, were narrow in the flat pattern. Also, the number of calcified vessel walls in common femoral artery and dorsalis pedis artery increased more in the same patterns. No significant difference of vessel wall thickness was found between both groups. CONCLUSION : Vasoreaction of lower extremities after cold stimulus was mainly related to PAO of the common femoral artery and dorsalis pedis artery. DITI is a useful method used in detecting the early state of artherosclerosis. As a result, it can be employed in early prevention and treatment of diabetic angiopathy. If DITI is combined with doppler ultrasonography, we can practice more precise diagnosis and follow-up in diabetic peripheral angiopathy.
- Effect of Protein Kinase C Inhibitors on Expression of TGF-betamRNA in Cultured Mesangial Cells Under High Glucose Concentration.
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Yoon Sang Choi, Dong Seop Choi
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Korean Diabetes J. 1999;23(5):635-646. Published online January 1, 2001
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Diabetic nephropathy is characterized by hypertrophy of both glomerular and tubular elements, thickening of the glomerular and tubular basement membranes, progressive accumulation of extracellular matrix components in mesangium, and tubulointerstitial fibrosis. Hyperglycemia increases the level of diacylglycerol (DAG) and activates protein kinase C (PKC) in mesangial cells and other vascular tissues. PKC activation regulates a number of vascular functions such as vascular permeability, contractility, cellular proliferation, basement membrane synthesis, signal transduction mechanisms for hormones and growth factors, In addition, glomerular mesangial cells play an important role in the development of diabetic nephropathy. Mesangial cells have many functions such as contractile properties, phagocytosis of macromolecules, synthesis of matrix proteins, and production of and response to growth factors (e.g., PDGF, TGF beta). Also, these growth factors play important roles for mesangial cell proliferation and in pathophysiology of diabetic nephropathy. Specifically, TGF beta is a key mediator in development of diabetic nephropathy. This study was performed to evaluate the relationship between PKC activation and TGF f3 production in mesangial cells under high glucose condition. METHODS: The expression of the TGF beta mRNA was evaluated in cultured human mesangial cells by semiquantitive RT-PCR, under varying degree of glucose concentrations (5 mM, 10 mM, 30 mM) with and without treatment of PKC inhibitors (calphostin C, Vitamin-E). RESULT: In control group (no treatment), ratio of TGF beta/beta-aetin mRNA in 5mM, 10mM, 30mM glucose were 1.694+/-0.223, 3.383+/-2.089, 5,474+/-1.74S, respectively. In calphostin C treated group, ratio of TGF beta/beta-actin mRNA in 5mM, 10mM, 30mM glucose were 1.457+/-0,322, 1.379+/-0.138, 1.205+/-0.050, respectively. In vitamin E treated group, ratio of TGF beta/beta-actin mRNA in 5mM, 10rnM, 30mM glucose were 1.198+/-0.081, 1.995+/-1.625, O.S04+/-0.570, respectively. In 10mM glucose concentration, ratios of TGF beta/beta-actin mRNA were reduced in calphostin C and vitamin E treated groups, compared with those in control group. But, there were no statistical significancies (p=0.191, 0.208). In high glucose concentration (30mM), ratios of TGF /3/f3-actin mRNA were significantly reduced in calphostin C and vitamin E treated groups compared with those in control group (p<0.05), respectively. CONCLUSIONS: These results indicate that high glucose concentration induce TGF beta expression in eultured mesangial cells through PKC activation. This suggests that selective PKC beta isoform inhibitors may be useful for treatment and prevention of diabetie nephropathy.
- Clinical Study on Cerebral Infarction Complicated with CIDDM pateints.
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Sang Jong Lee, Yoon Sang Choi, Seong Chun Shim, Hi Moo Lee, Kwon Choi, Hwa Young Lee
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Korean Diabetes J. 1999;23(4):585-591. Published online January 1, 2001
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Diabetes mellitus increases the risk of cardiovascular disease by two-fold and ischemic cerebrovascular disease by two to four-fold compared with the risk for non-diabetic patients. In patients with NIDDM, the risk of athero- thromboembolic cerebral infarction is known to be increased. We evaluated the significance of clinical variables with respect to the risk of cerebral infarction in NIDDM patients. METHODS: We assessed clinical variables retrospectively in 170 patients (90 men, 80 women) from April 1, 1991 through March 31, 1996, divided into 3 groups;100 NIDDM patients with cerebral infarction (58 men, 42 women), 40 NIDDM patients (17 men, 23 women) and 30 non-diabetic patients with cerebral infarction(15 men, 15 women). We evaluated 130 patients with cerebral infarction employing brain CT or MRI. RESULTS: 1) The mean values of age, serum total cholesterol, LDL, TG, HbA1C, systolic and diastolic BP were significantly higher in patients with NIDDM complicated by cerebral infarction than in those without cerebral infarction. 2) There were no statistically significant differences in body mass index (BMI), duration of DM and HDL between the two groups, respectively. 3) Diabetic retinopathy (especially, proliferative retinopathy) andmacroproteinuria(550 mg/day) were found significantly higher in diabetic patients with cerebral infarction than in those without cerebral infarction. 4) Multiple lacunar infarctions were more frequently observed in patients with NIDDM than non-diabetic patients with cerebral infarction. However, there were no statistically significant differences between the two groups. Conclusion: We suggest that increased age and HbAlC, hypertension, dyslipidemia, macroproteinuria and proliferative diabetic retinopathy could be associated with the risk of cerebral infarction in patients with NIDDM. The results showed that multiple lacunar infarctions were more frequent in patients with NIDDM than in non-diabetic patients. However, there were no statistical significances between the two groups.
- The Risk Factors of Diabetic Retinopathy in NIDDM Patients.
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Won Tae Seo, Seung O Song, Sy Young Kim, Yoon Sang Choi, Hye Ran Jang, Sang Jong Lee
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Korean Diabetes J. 1999;23(2):162-171. Published online January 1, 2001
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Diabetic retinopathy, which is one of the microvascular complications, has been shown to be related to visual disturbance and blindness. In this report we examined the risk factors for diabetic retinopathy in NIDDM patients and investigate the relationship between the prevalence of diabetic retinopathy and other risk factors. METHODS: Clinical characteristics and laboratory findings such as HbAlc, fasting plasma glucose, hemoglobin, BUN, creatinine and lipid profile and treatment modality were evaluated and their relation with diabetic retinopathv were analyzed. Fundoscopic examinations of the retina were performed using direct/indirect opthalmoscopy and fundus photograph. The grade of retinopathy was judged from the results of opthalmological examinations and were elassified into non-proliferative retinopathy and proliferative retinopathy. RESULTS: A total of 163 patients with NIDDM (M/F=59:104) were evaluated. Of these patients, 80 of them developed diabetic retinopathy. 71 patients were detected to have non-proliferatie and 9 patients to have proliferative retinopathy. The presence of proteinuria, the long diabetic duration, hypertension, anemia, the high plasma glucose levels, the high level of HbA1c, old age were all associated with the development of diabetic retinopathy. I-lowever, sex, body mass index, type of therapy, lipid profile, C-peptide levels, insulin levels had little impact on the development of retinopathy. CONCLUSIONS: The presence of proteinuria, the long diabetic duration, hypertension, anemia, high plasma glucose levels, high HbA., and old age are important risk factors for the development of rc;tinopathy in patients with NIDDM.
- Relationship between Circadian Mean Blood Pressure ( MBP ) Rhythm and Microvascular Complications in Normotensive NIDDM Patients.
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Hyang Kim, Seong Chun Shim, Dae Jung Shim, Hi Moo Lee, Yoon Sang Choi, Jin Ho Kang, Byung Ik Kim, Sang Jong Lee, Yoo Lee Kim, Yoon Kyung Cho
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Korean Diabetes J. 1998;22(4):552-560. Published online January 1, 2001
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Thanks to ambulatory 24-h blood pressure monitoring device, it became possible to investigate circadian pressure rhythm under variable physiologic and pathologic conditions. Moreover, ambulatory 24-h blood pressure has allowed us to detect in diabetic patients unsuspected abnormalities of the blood pressure circadian rhythm and to relate them to autonomic or renal dysfunction. This study was designed to evaluate the relationship between circadian rhythm of mean blood pressure (MBP) and microvascular complications in patients with noninsulin-dependent diabetes mellitus (NIDDM). METHODS: 24hr blood pressure monitoring was applied to 63 normotensive NIDDM patients(mean age 55.3+7.2 year, male: 35, female: 28) who have been hospitalized at our hospital from March 1993 to December 1994 to measure systolic, diastolic and hourly mean pressure of daytime, night time and 24hr. In addition, NIDDM patients were divided into 2 groups according to 24 hour circadian blood pressure rhythm by measuring hourly mean pressure. These 2 groups, group 1 who had a circadian MBP rhythm, with a peak value in the afternoon and group 2 who had an absent or reversed circadian rhythm with a peak value during the night time, were observed to evaluate the frequency of diabetic microvascular complication. RESULTS: The mean systolic and diastolic ambulatory BP values were significantly higher in the group 2 NIDDM during night-time compared with control group and group 1(systolic pressure: F=12.53 p<0.05 diastolic pressure: F:=15.159 p<0.05). Although there was no significant differences in day-time heart rate between three groups, 1 and 2 group showed significant higher level of night-time heart rate comparing with that of control group (F=3.444 p<0.05). Group 2 diabetes patients showed, both systolic and diastolic, higher night-time and day-time blood pressure ratio(systolic pressure: F=35.958 p<0.05> diastolic pressure F=40.126 p<0.05). Observing the night-time and day-time heart rate ratio, group 1 and 2 patients showed significantly higher level compared with that of cantrol group(F=12.144 p<0.05). Regarding the retmopathy, group 1 patient.; showed mild degree retinopathy or normal finding(X =3.65 p<0.05). However, many group 2 patients showed moderate 2 degree nonproliferative retinopathy(X =3.23 p<0.05). The prevalence of overt nepkuopathy (24-hour urine protein>500mg) and autonomic neuropathy (postural and abnormal E:I ratio during deep breathing test) was significantly higher in group 2 (overt nephropathy: X'=3.23 p
- QTc Interval and QT Dispersion Prolongation in NIDDM Patients with Diabetic Autonomic Neuropathy.
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Yong Kyun Cho, Seung Won Lee, Won Tae Seo, Yoon Sang Choi, Jin Ho Kang, Man Ho Lee, Sang Jong Lee
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Korean Diabetes J. 1998;22(1):93-102. Published online January 1, 2001
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It has been reported that QTc interval and QT dispersion prolongation on 12 lead EKG reflects predictability and diagnosis of cardiovascular complications induced by autonomic nervous system abnormalities. We have investigated in NIDDM patients whether severity of cadiovascular autonomic neuropathy(CAN) evaluated by conventional standard cardiovascular autonomic function test is correlated with prolongation of QT, QTc interval and QT dispersion. In addition, whether these prolonagtion can reflect CAN and if any other clinical variables related to pralongatian exist. METHODS: Eighty patients(39 male, 41 female) treated with oral hypoglycemic agents or insulin after diagnosis of NIDDM in our hospital were included in the study. These patients were devided into three groups (Group I, 13 subjects: No CAN, Group II, 20 subjects: Borderline CAN, Group III, 47 subjects: Definite CAN) according to the score of standard catdiovascular autonomic function test(Deep breathing test, Lying to standing test, Heart ration on Valsalva manuever, Postural BP drop test). The measured QT, QTc interval and QT disp rsion of eaeh diabetic group and control group were analyzed. RESULTS: l. Statistically significant prolongation of QT,QTc, QT dispersion was observed in NIDDM tients as compared with those of control group(p=0.015, 0,021, 0.001). 2. Severity of autonomic neuropathy has shown positive correlation with only prolongation of QT dispersion(p<0.05) in three diabetic subgroups. 3. Statistically significant difference was not ob::rved in HbAlc and BMI between each patients groups of NIDDM(p>0.05) but both HbAlc and BMI showed weak positive correlation with prologation of QT dispersion(r=0.262, r=0.267 repectively). CONCLUSION: QTc interval and QT dispersion are considered easily accessible factors to predict and evaluate the degree of cardiovascular autonomic function abnormalities in NIDDM patients, yet further long term follow up and study in large group should be carried out to decide if these factor can predict and reflect severity of cardiovascular abnormalities such as ventricular arrhythmia, and sudden cardiac death. In additian, prolonged QT dispersion has shown weak positive correlation with both HbAlc and BMI and some other influential factors are suggested to play a role in autonomic neuropathy in NIDDM patients.
- Urinary albumin excretion, von Willebrand factor and macrovascular disease in patients with NIDDM.
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Sin Gon Kim, Soo Mi Kim, Dong Hyun Shin, Nan Hee Kim, Yoon Sang Choi, Ie Byung Park, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 1997;21(2):176-184. Published online January 1, 2001
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Increased urinary albumin excretion (UAE) is not only an independent predictor of progressive renal disease but also an important marker of atherosclerotic disease in patients with NIDDM. However, the pathaphysiologic basis of this observation is poorly understood. Recently, one interesting hypothesis suggested: UAE rnerely reflects a glomerular manifestation of an otherwise generalized vascular dysfunction(hyperpermeable state), and Stehouwer et al. Reported a strong relationship between plasma von Willebrand factor level(a measure of endothelial dysfunction), UAE and cardiovascular diseases. Therefore, we studied the relationship between UAE, plasma vWF and macrovascular disease in patients with NIDDM. METHODS: We measured UAE and plasma vWF levels in 102 patients with NIDDM, and investigated the telationship between these values and macrovascular diseses. Also, we assesed the risk factars for macrovascular disease. RESULTS: 1) Among total of 102 patients, nonnoalbuminuria, microalbuminuria and macroalbuminuria group were 58 patients(56.9%), 28 patients(27.5%) and 16 patients(15.6%), respectively. 2) The prevalencies of hypertension, diabetic retinopathy and macrovascular diseases were the highest in macroalbuminuria group, followed by microalbuminuria and norrnoalbuminuria group in order of frequency. 3) Plasma vWF and UAE levels were significantly correlated(r=0.44). 4) Plasma vWF concentrations were higher in patients with macrovascular diseases than in those without macrovascular diseases, and also higher in patients with retinopathy compared with those without retinopathy. 5) Multivariate logistic regression analysis showed that age, smoking and vWF were independent risk factors for macrovascular diseases. CONCLUSION: 1) As plasma vWF and UAE values were increased, more macrovascular diseases were observed in patients with NIDDM. 2) Plasma vWF may be used as an indicator of macrovascular disease in patients with NIDDM.
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