Diabetes & Metabolism Journal

Original Articles

The Prevalence of Chronic Complications in Non-Insulin Dependent Diabetic Patients.: Jick Hwa Nam, Soon Hee Lee, Hyun Jeong Lee, Jeung Hun Han, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 1999;23(5):702-714. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The chronic complications of diabetes mellitus are important prognostic factors of diabetics. The pathogenic mechanisms have not been known exactly and the prevalence is different according to the race and the reporter. In general, the development of diabetic microangiopathy depends on the duration and the severity of disease, while that of macroangiopathy does not. This study was undertaken to investigate the prevalence of diabetic chronic complications according to age and duration of diabetes and to elucidate associated factors and correlation of chronic complications. METHODS: We studied 1,270 patients with non- insulin dependent diabetes mellitus (NIDDM) who visited the Endocrine-metabolism clinic at Kyungpook National University during the period from February 1992 to September 1996. We investigated prevalence, severity, associated factors and correlation of chronic vascular complications, including micro- and macroangiopathy. RESULT: 1) The ratio of male to female was similar and the average duration was 7.8 years. Diabetes mellitus was most prevalent in the 6th decade and the 1-5 years of diabetes duration. 2) The prevalences of retinopathy, nephropathy and peripheral polyneuropathy were 47.8%, 31.9% and 41.0%, respectively. Macrovascular complications were found in 6.2% of patients and the prevalences of coronary artery disease, cerebrovas-cular disease and peripheral artery disease were 2.4%, 3.4%, 0.4%, respectively. Prevalence of diabetic foot was 4.4%. 3) The prevalence and severity of microvascular complications increased as the age and diabetic duration of patients increased. In the group of same age, the prevalence of microvascular complications increased as the duration of diabetes increased. However, prevalence of macrovascular complica-tions especially coronary artery disease depended on the age, but not the duration of diabetes (p<0.05). 4) In the group over 10 years of diabetes, the fasting blood glucose, age and serum creatinine levels were increased, while hemoglobin and total protein levels were decreased than other groups (p<0.05). 5) The development of diabetic retinopathy was related to the duration, fasting blood glucose, albumine excretion rate and serum creatinine. The nephropathy was related to the duration and systolic blood pressure. The peripheral polyneuropathy was related to the duration, fasting blood glucose and body mass index. Macrovascular complications-particularly, coronary artery disease-were related to the age of diabeties (p<0.05). 6) There was significant relation between development of retinopathy, nephropathy and neuropathy but no relation between development of micro and macrovascular complications (p<0.05). CONCLUSION : The prevalence of microvascular complications in non-insulin dependent diabetics increased as the duration and the age of diabetics increased. The development of microvascular complications was related to the duration of disease and the glycemic control. There was relation between development of retinopathy, nephropathy and neuropathy. The development of macrovascular complications, however, was related to the age of diabetics but not to the microvascular complications. Our results suggest that different pathogenic mechanisms may be involved in the development of micro- and macrovaseular complications of diabetes mellitus.

Clinical Study on Cerebral Infarction Complicated with CIDDM pateints.: Sang Jong Lee, Yoon Sang Choi, Seong Chun Shim, Hi Moo Lee, Kwon Choi, Hwa Young Lee; Korean Diabetes J. 1999;23(4):585-591. Published online January 1, 2001

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Abstract PDF: BACKGROUND
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.

Solyble ICAM-1 and BCAM-1 in Patients with NIDDM.: Young Min Kim, Yong Gi Kim, Seok Man Son, In Ju Kim, Seok Dong Yoo, Young Keun Choi, Chang Won Lee, Jun Hyup Ahn; Korean Diabetes J. 1999;23(3):315-325. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The development of vascular complications in diabetic patients changess their quality of life, as well as shortens their life expectancy. It has been recently discovered that the expressions of the cell adhesion molecules initiate vascular complications and have major effects on the progress of atherosclerosis. We measured soluble forms of intercelluar adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1), the immunoglobulin superfamily members of the cell adhesion molecules concerning firm adhesion and transendothelial migration during leukocyte- endothelial cell interactions to clarify their concentrations and their relation with glycemic control and plasma lipoproteins as well as differences in concentration according to the presence of diabetic microvascular complcations in non-insulin dependent diabetes mellitus (NIDDM) patients. METHODS: Serum sICAM-1and sVCAM-1 levels were measured by commercial ELISA kits in 35 NIDDM patients without overt macrovascular complications of diabetes or acute inflammation and 10 normal controls matched with body mass index and plasma lipoprotein levels. The mean age of the patient group and control group was 55.82+3.43 years and 46.30+15.15 years, respectively. Clinical characteristics and laboratory parameters such as fasting plasma glucose, HbAplasma lipoproteins and status of diabetic microvascular complications were evaluated and their relations with the levels of sICAM-1 and sVCAM-1 were analyzed. RESULTS: 1) The level of sICAM-1 in NIDDM patients was significantly higher than that of normal controls (15.79+6.21 ng/mL vs. 11.98+2.35, p<0.05). sVCAM-1 showed the trend in elevation in NIDDM patients, but had no statistical significance (p=0.053). 2) The level of soluble ICAM-1 was positively correlated with HbAlc>, and plasma triglyceride levels (r=0.38, p<0.05, r=0.36, p<0.05, respectively) and negatively correlated with HDL (r=-0.44, p<0.01) in the patient group. There were no differences in their age, sex, and the presence of hypertension with the levels of sICAM-1 and no relation between sICAM-1 level and body mass index, plasma total cholesterol, Lp (a), fasting plasma glucose, fasting plasma C-peptide levels. Plasma LDL was partially correlated with the level of sICAM-1, but failed to reveal statistical significance. sVCAM-1 level was not correlated with any parameters discussed above, but had a tendency of correlation with HbAlc level (r=0.31, p=0.06). 3) No significant correlation was noted between the levels of sICAM-1 or sVCAM-1 and the duration of diabetes. 4) Both sICAM-1 and sVCAM-1 levels were significantly higher in patients with diabetic nephropathy when compared to patients without nephropathy (21.58+7.11 ng/mL vs. 14.06+4.84 ng/mL, p<0.05, 37.51+16.91 ng/mL vs. 22.26+8.89 ng/mL, p<0.05, respectively, but such differences were not noted when patients were classifed according to the presence of retinopathy or neuropathy. 5) Both sICAM-1and sVCAM-1 levels did not correlate in the patient group or in the normal control group. CONCLUSION: These findings suggest that enhanced expression of the the endothelial cell adhesion molecules in diabetic patients can be explained by endothelial dysfunction caused by persistent hyperglycemia and dyslipidemia. Furthermore, it can be suggested that endothelial dysfunction may be initiated by diabetes itself and can be deteriorated by combined dyslipidemia. From the result of the elevated concentrations of sICAM-1 and sVCAM-1 in patients with diabetic nephropathy, we can suggest that the elevation of these cell adhesion molecules may be useful as markers in diabetic nephropathy. More selective and prospective studies are necessary in order to reveal thesignificance of these cell adhesion molecules in the pathogenesis of diabetic vascular complications.

Risk Factors for Peripheral Arterial Disease as Screened by Plethysmography in Patients with NIDDM.: Hyuk Jae Chang, Dae Jung Kim, Byoung Joo Choi, Young Guk Ko, Churl Woo Ahn, Dong Ryeol Ryu, Yong Seok Yun, Seol Hye Han, Jae Hyun Nam, Seok Won Park, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Won Heum Shim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1999;23(2):172-181. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Peripheral arterial disease (PAD) is one of the clinical manifestations of the atherosclerotic disease process. Early onset and rapid progression of PAD in diabetic patients has been well documented. PAD in diabetic patients has also been associated with an increased risk for total and cardiovascular mortality. Plethysmography is a noninvasive test to screen for the presence of PAD. Thus the aim of this study is to assess the risk factors for PAD screened by plethysmography in NII)DM patients. METHODS: A total of 289 NIDDM patients who undlerwent plethysmography were entered into our annlysis. Clinical characteristics of 38 patients with an ankle-brachial index of <0.9 (group B) were conapared with those of 231 patients with an ankle-brachial index of >1.0 (group A). RESULTS: Abnormalities in plethysmographic findings were found in 45.7% of diabetic patients. Age, duration of diabetes, hypertension, smoking, previous history of vascular diseases, HDL cholesterol, TC/HDL, and LDL/HDL appeared to be factors significantly related to PAD. Fasting sugar, HbAlc, total cholesterol, LDL cholestero1, trigly ceride, fibrinogen, lipoprotein(a), and waist-hip ratio were not significantly different between the two groups. The multiple logistic regression analysis showed the signficant contribution of the previous history of vascular disease (p=0.0028) and age (p-0.0115) to PAD in diabetic patients. CONCLUSION: The prevalence of PAD defined by plethysmography in our subjects was 45.7% higher than expected, suggests that efforts for early detection and prevention of PAD should be emphasized in diabetic patients.

The Risk Factors of Diabetic Retinopathy in NIDDM Patients.: Won Tae Seo, Seung O Song, Sy Young Kim, Yoon Sang Choi, Hye Ran Jang, Sang Jong Lee; Korean Diabetes J. 1999;23(2):162-171. Published online January 1, 2001

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Abstract PDF: BACKGROUND
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.

Plasma Concentrations of Plasminogen Activator Inhibitor-1(PAI-1) and Lipoprotein(a) in Non-Insulin-Dependent Diabetes Mellitus with Peripheral Vascular Disease.: Sung Jin Nam, Sung Rae Cho, Choo Sung Kim, Sang Gyun Woo, Hee Jin Choi, Sang Ki Kim, Jae Hong Park, In Kyu Lee, Seong Bum Han, Seung Yup Han, Chung Chul Kim; Korean Diabetes J. 1999;23(1):55-61. Published online January 1, 2001

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Abstract PDF: OBJECTIVES
The plasminogen activator inhibitor-1 (PAI-I) and lipoprotein(a) are considered as important fibrinolysis inhibitors. We evaluated PAI-1 and Lp(a) concentrations in Korean non-insulin- dependent diabetes mellitus (NIDDM) patients with or without peripheral vascular disorder. METHODS: By using National Diabetes Data Group (NDDG) criteria as a diabetes mellitus diagnostic criteria, a total of 127 Korean NIDDM patients were seleeted. The ankle brachial index was measured by segrnental volume plethysmography to diagnose peripheral vascular disease. We also examined clinical and biochemical parameters in NIDDM patients. RESULTS: The duration of diabetes, systolic and diastolic pressures was significantly higher in diabetic patients with peripheral vascular disease (Group 2) than in diabetic patients without peripheal vascular disease (Group 1). The 24 hour urine microalbumin and PAI-1 levels in Group 2 were also significantly higher and the HDL-cholesterol level was lower than in Group 1. There were significant correlations between the plasma level of PAI-1 and BMI (r=0.466, p=0,007) or C-peptide level(r=0.517, p=0.012). Multivariate logistic regression analysis showed that Lp(a) and PAI-1 are independent risk factors for peripheral vascular disease. CONCLUSION: In the light of these results, it seems reasonable to suggest that high levels of PAI-1 and Lp(a) in NlDDM patients may play a role in the pathogenesis of peripheral vascular disease.

Relationship between Circadian Mean Blood Pressure ( MBP ) Rhythm and Microvascular Complications in Normotensive NIDDM Patients.: 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; Korean Diabetes J. 1998;22(4):552-560. Published online January 1, 2001

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Abstract PDF: BACKGROUND
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

Lowering Effect of Voglibose, Monotherapy on Uncontrolled Postprandial Glucose in Patients with Non-Insulin Dependent Diabetes Mellitus (NIDDM) Being Treated with Strict Diet Control: Multicenter Open-Study.: Jeong Taek Woo, Young Seol Kim, Young Kil Choi, Jin Woo Kim, In Myung Yang, Sung Woon Kim, Deog Yoon Kim, Kwang Won Kim, Moon Kyu Lee, Myung Shik Lee, Jae Hoon Jung, Kyu Jeong Ahn, Hyun Chul Lee, Young Deuk Song, Bong Soo Cha, Jee Hyun Lee, Hyung Joon Won; Korean Diabetes J. 1998;22(3):419-428. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is sometimes very difficult to control the elevation of postprandial glucose with diet therapy only in patients with NIDDM partly because of their defective insulin response to glucose. Recently the alpha-glucosidase inhibitors which inhibit carbohydrate digestion and suppress or delay absorption of the final breakdown products, glucose and fructose when it is taken orally with meal have been widely used in the treatment of diabetes. The drugs, however, provoke the adverse effects e.g. flatulence, diarrhea etc. in some patients. Therefore we studied the efficacy of the more recently developed alpha glucosidase inhibitor, Voglibose (Basen, Cheiljedang) METHODS: Fifty five patients whose postprandial two hour serum glucose levels were more than 11.1 mmol/L despite the strict diet therapy during the 4 week observation period were assigned to receive Voglibose 0.2 mg before each meal t.i.d. for 8 weeks. Of 55 subjects, 41 were given Voglibose 0.3 mg t..i.d. for the last 4 weeks because of their poor glucose control, RESULTS: The postprandial one and two hour serum glucose levels significantly decreased after therapy; 1 hour: 17.5+4.4 mmol/L(prior to therapy), 15.4+3.8 mmol/L(4 week after), 14.8+5.1 mmol/L(8 week), p <0.00l, 2 hour: 16.7+4.5 mmol/L, 14.8+3.9 mmol/ L, 14.8+4.5 mmol/L, p<0.00 l, t-tests for paired samples. Total serum cholesterol and HDL cholesterol levels also significantly decreased(5.24+1.06 - 4.90+1.27 mmol/L, p=0.036, 1.34+0.66 1.16 +0.3l mmol/L, p=0.035 respectively) However, HbAlc, serum fructosamine, insulin and triglyceride levels were not significantly changed. The prevalence of the adverse effects due to Voglibose was 14%(10/71). All of them were less than grade II of WHO criteria and disappeared despite continuing therapy. CONCLUSION: Voglibose monotherapy is considered as having an glucose lowering effect in patients with NIDDM whose adequate postprandial blood glucose cannot be achieved with diet therapy only.

The Frequency of ICA and anti-GAD Antibody in Korean IDDM and NIDDM Patients.: Kyung Soo Ko, Sung Kwan Hong, Ki Up Lee, Nan Hee Kim, Dong Seop Choi, Sung Hee Ihm, Sung Woo Park, Chul Hee Kim, Dong Won Byun, Kyo Il Suh, Hak Chul Chang, Byoung Doo Rhee; Korean Diabetes J. 1998;22(3):312-319. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been suggested that the clinical and immunological characteristics of diabetes mellitus in Koreans are different from those of Caucasians. This study was undertaken to investigate the prevalence of autoimmune markers in Korean adults with IDDM and recent-onset NIDDM. METHODS: Seventy-seven Korean adults with IDDM and 245 recently(within 2 years) diagnosed NIDDM were included in the study. Islet cell cytoplasmic antibody was measured by immunohistochemical method, and anti-glutamic acid decarboxylase (anti-GAD) antibody was measured by radioimmunoassay. RESULTS: 1) The prevalence of ICA, anti-GAD antibody positivity was 27% and 40% in IDDM patients, and 5% and 4% in recent-onset NIDDM patients, respectively. 2) The prevalence of ICA positivity in IDDM patients decreased from 42% within one year to 21% over one year after clinical onset of disease. On the other hand, the positivity of anti-GAD antibody did not change according to the duration of diabetes. 3) The prevalence of ICA tends to be lower in IDDW patients with low serum C-peptide concentrations. In contrast, the prevalence of anti-GAD antibody was not different according to sernm C-peptide levels. CONCLUSION: These results suggested that the prevalence of ICA and antii-GAD antibody was lower in Korean adult IDDM and recent-onset NIDDM patients than that in Caucasians.

Effect of Troglitazone on Glucose Transport in Human Skeletal Muscle Cell Cultures from Obese Non-diabetic and Obese Non-insulin Dependent Diabetes Mellitus.: Theodore Ciaraldi, Robert R Henry, Kyong Soo Park, Hong Kyu Lee; Korean Diabetes J. 1998;22(2):164-172. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Skeletal muscle is the principal tissue of insulin resistance in obese non-diabetic and non-insulin dependent diabetic(NIDDM) subjects. Troglitazone(Tgz), a member of thiazolidinedione class of compounds, has been shown to improve glucose tolerance in insulin resistant state. At the celluar level, troglitazone has been shown to improve insulin action in skeletal muscle, liver and adipose tissue. However, there has been little knowledge about the mechanism of this drug in human skeletal muscle from insulin resistant subjects. METHODS: To determine the effect of troglitzone on glucose transport(GT) in skeletal muscle of obese non-diabetic and obese NIDDM patients, muscle cultures from 7 obese nondiabetic and 8 obese NlDDM subjects were grown for 4 weeks and then fused for 4 days either with or without Tgz (05ug/mL). At the end of fusion, GT activity was measured and cells were harvested for the measurement of glucose transporter protein expression. RESULTS: Tgz treatment(4 days) increased GT activity dose-dependently in skeletal muscle cell culture of both obese non-diabetic and obese NIDDM subjects. 5ug/mL troglitazone increased basal GT by 2.3 +0.3 fold in obese non-diabetic and 5.7+1.3 fold in obese NIDDM subjects (p <0.05, respectively) Absolute rate of insulin-stimulated GT was significantly increased following Tgz treatment with no enhancement of the incremental response above basal value in either group. Total memhrane GLUTl protein increased 1.7+0.3 fold(p<0.05) following troglitazone treatment(5ug/mL) in NIDDM but were unchhanged in obese non-diabetic cells. GLUT4 protein levels were not affected by Tgz treatment in either group. CONCLUSION: Troglitazone increased both basal and insulin-stimulated GT activity without enhancing the incremental insulin response above basal value in muscle cultures from insulin resistant subjects. These results indicate that troglitazone is not an insulin sensitizer in muscle cultures but acts primarily by mimicking insulin's ability to stimulate basal glucose metabolism in the insulin resistant state of obesity and NlDDM

Lipoprotein (a) Level and Vascular Complications in NIDDM.: Ji Youn Kim, Mung Su Kim, Joung Min Kim, Jai Hong Park, Joung Hun Lee, Seung Won Yang, Dong Jin Chung, Min Young Chung, Tai Hee Lee; Korean Diabetes J. 1998;22(1):65-73. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The risk of atherosclerosis is increased in subjects with diabetes mellitus. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic vascular disease in subjects without diabetes. The contribution of Lp(a) to the increased risk for atherosclerosis and diabetic complications in subjects with diabetes is not well known. In this report we examined the relationship between Lp(a) levels and development of vascular (macro- and microvascular) complications, and the relationship between Lp(a) and other risk factors for vascular complications in subjects with non-insulin-dependent diabetes mellitus(NIDDM), METHODS: For this study we evaluated 152 patients with NIDDM(72 women and 80 men). Lp(a) level was measured with N-Latex Lp(a) Reagent. Electrocardiography, coronary angiography, brain CT/MRI, doppler velocimetry and peripheral angiography were done for diagnosis of macravascular complieations, and fundus camera, nerve conduction velocity, BBV (beat to beat variation), VPT(vibration perception threshold) and 24-hour urine protein amount were examined for diagnosis of microvascular complications. RESULTS: Lp(a) levels in subjects with ischemic heart disease, cerebrovascular disease and diabetic retinopathy were significantly higher than those in subjects without above mentioned diseases. ApoB/ApoA1 ratio and LDL-cholesterol levels in subjects with Lp(a) level>30mg/dL were significantly higher than those in subjects with Lp(a) level 30mg/dL, and Lp(a) has a positive correlation with ApoB/ApoA1 ratio and LDL-cholesterol in NIDDM patients with vasculopathy. CONCLUSION: These results suggest that high Lp(a) levels seem to be associated with macrovascular and microvascular(especially with retinopathy) complications in subjects with NIDDM and Lp(a) level should be measured in the NIDDM with high level of ApoB/ApoA1 ratio and/or LDL-eholesterol.

Decreased Mitochondrial DNA Content in Peripheral Blood Leukocyte procedes the Development of Type 2 Diabetes Mellitus.: Jae Joon Koh, Jong Ho Ahn, Soon Ja Kwon, Ji Hyun Song, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 1998;22(1):56-64. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Mitochondrial mutations and deletions, have been implicated in the pathogenesis of diabetes mellitus. This can explain only a very small proportion of the patients with diabetes mellitus. Mitochondrial DNA(mtDNA) is vulnerable to oxidative stress, resulting in both qualitative and quantitative changes. We reported that the amount of mtBNA decreased in the peripheral blood leukocyte of patients with NIDDM. In this study, we examined that decreased mtDNA content preceded the development of NIDDM{Non-insulin dependent diabetes mellitus) and correlated with various insulin resistance parameters.In this study, we demonstrated that the amount of mtDNA decreased in peripheral blood leukocyte of patients with NIDDM. Furthermore, we found that lower mtDNA levels preceded the development of diabetes mellitus. METHODS: We utilized the stored blood samples from two community-based survey conducted in Yonchon County, Korea in 1993 and 1995. We selected 23 newly diagnosed diabetic patients and 22 age- and sex-matched control subjects. The buffy coats of peripheral blood samples were used for the competitive PCR and the products pairs were separated by gel EP. The content of mtDNA was calculated with the densitometry. RESULTS: There were no difference in the initial anthropometric parameters, blood pressure and lipid profiles between subjects who became diabetic converters and non converters. The mean quantity of mtDNA was lower in the converters, with 102.8+ 41.5 copies/pg template DNA compared to 137.8+ 67.7 copies/pg template DNA of the controls(p 0.05). The significant inverse correlations were noted between mtDNA content and WHR(r=0.31, p<0.05) in the first, and fasting glucose level(r=-0.35, p<0.05), diastolic blood pressures(r=-0.36, p<0.05), and WHR(r=-0.40, p<0.01) in the second survey. The correlations with the serum levels of total and high density cholesterol, triglyceride, insulin and proinsulin were not statistically significant. CONCLUSION: Although a relationship between diabetes and mitochondrial dysfunction has been suspected. This study showed that decreased mtDNA content in peripheral blood proceded the development of NIDDM. This is the first study to demonstrate that quantitative changes in mtDNA precede the development of NIDDM.

Elevated Levels of Soluble E-selectin and P-selectin in Patients with NIDDM.: Seok Dong Yoo, In Joo Kim, Yong Ki Kim; Korean Diabetes J. 1998;22(1):23-34. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although there is wide spread agreement that patients with NIDDM are at increased risk of the premature development of atherosclerosis, it is not totally clear why this is so. This may be related to the interaction of blood leukocytes with vascular endothelium resulting from a loss of normal metabolic control. The adherence of leukocytes to the endothelium is at least partly mcdiated by cell adhesion molecules. In this study, we evaluated the level of soluble E-selectin and P-selectin in blood of normal controls and patients with NIDDM, and studied its relation to glycemic control and identifiable factors influencing the level of soluble E-selectin and P-selectin. METHODS: Serum soluble E-selectin and plasma soluble P-selectin levels were measured by ELISA method in 24 NIDDM patients without macrovascullar disease and 14 normal controls matched with age, sex and body mass index. Clinical characteristics and laboratory findings such as fasting plasma glucose, HbA1c and lipid profile were evaluated, and their relation with the levels of E-selectin and P-selectin was analized. RESULTS: 1) The levels of E-selectin and P-selectin in NIDDM patients were significantly higher than those of normal controls(55.69+21.97 vs. 42.11+13.57ng/ mL, P<0.05 for E-selectin, 41.60+20.90 vs. 27.16 +7.12ng/mL, P 0.01 for P-selectin). 2) The levels of E-selectin and P-selectin were positively correlated with the fasting plasma glucose level(r=0.400 P<0,05 for E-selectin, r=0.456 P<0.01 for P-selectin). They were also positively correlated with the levels of serum triglyceride(r=0.531 P<0.01 for E-selectin, r=0.415 P =0.05 for P-selectin) but not with the levels of serum total cholesterol, LDL and HDL cholestrol in NIDDM patients. 3) No significant correlation was noted between the levels of E-selectin or P-selectin and the duration of NIDDM. And the levels were not different according to the type of treatment. 4) E-selectin level, not P-selectin level, was significantly higher in the patients with nephropathy when compared to the patients without nephropathy. But such difference was not noted when the patients were classified according to the presence of retinopathy or neuropathy. 5) E-selectin level was positively correlated with P-selectin level in both NIDDM patients and normal controls(r=0.52, P<0.01). CONCLUSION: These findings suggest that endothelial dysfunction, revealed by increased cellular adhesion molecules, could play a role in the pathogenesis of diabetic atherosclerotic vascular disorders in NIDDM patients with increased fasting plasma glucose control and hypertriglyceridemia. In addition, elevated soluble E-selectin and P-selectin level in blood might be used as a marker of diabetic nephropathy.

Randomized Controlled Trial

The Effect of Acarbose as an Adjuvant Therapy in Sulfonylurea-Treated NIDDM Patients.: Yun Yong Lee, Geon Sang Park, Jin Seong Kim, Byeong Sool Mun, Do Joon Park, Chan Soo Shin, Kyeong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 1997;21(4):484-492. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Acarbose-an aglucosidase inhibitor-is known to have a glucose lowering effect by delaying the digestion of complex carbohydrates in the small intestine. Acarbose especially prevents the abnormally high increment of postprandial blood glucose, reduces postprandial hyperinsulinemia and probably, alleviates insulin resistance. The aim of this study is to evaluate the glucose lowering effect of acarbose as an adjunt with a sulfonylurea in the treatment of NIDDM patients who have been poorly controlled with the use of sulfonylurea alone. METHODS: Forty NIDDM patients, who were poorly controlled with sulfonylurea alone, were randomly selected frorn outpatient diabetic clinic for study. For 16 weeks, they recieved either acarbose or placebo in additian to sulfonylurea under double blind method. RESULTS: 1) The metabohc parameters measured before initiation of either treatment regimen were similiar. 2) The HbAlc in placebo group increased from 8.9% to 9.0%. In contrast, in the acarbose group, HbAlc value decreased from 9.3% to 8.1%(p<0.05). 3) Mean fasting plasma glucose and 1-h postprandial glucose levels were reduced significantly in the acarbose group(p<0.001), especially in I-h postpandial glucose level in comparison with placebo group(p <0.0001). 4) Mean fasting, 1-h postprandial insulin levels decreased with time in the acarbose group in comparison with placebo group, but the decrease was not statistically significant. 5) Lipid profiles did not change during 16weeks of treatment period. 6) Adverse effects were observed in 3 patients on acarbose and 2 patients on placebo. CONCLUSION: Acarbose can be used as an effective adjuvant therapy to sulfonylurea in NIDDM patients who are poorly controlled with sulfonylurea alone.

Original Articles

Relationship between Carotid Artery Plaque Measured by Ultrasound and Cerebral infarction in Patients with Non-insulin Dependent Diabetes.: Kil Hong Rhee, Sang In Choi, Seung Ok Lee, Cheol Su Lim, Tae Sun Park, Hong Sun Baek; Korean Diabetes J. 1997;21(4):469-475. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The frequency of cerebral infarction is significantly increased in diabetic patients. Early detection of artherosclerotic lesions will be a useful to predict and delay the occurence of cerebral infarction in diabetic patients. The purpose of this study was to investigate the relationship between extracranial carotid artery plaque and cerebral infarction in NIDDM patients, who have cerebral infarction or not, using non-invasive B-mode ultrasonography. METHODS: Ultrasound high resolution B-mode imaging of carotid arteries was conducted on cerebral infaretion patients with NIDDM and non cerebral infaretion patients with NIDDM to determine the presence of the carotid artery plaque. RESULTS: The incidence rate of cerebral infarction was increased in relation to extracranial carotid artery plaquie existence. The exeistence of carotid artery plaque was higher in NIDDM patients with cerebral infarction than without cerebral infarction(p<01050). Multiple logistic regression analysis showed that development of cerebral infarction in NIDDM patients, who had carotid plaque, was 2.8 fold higher than NIDDM patients who had not carotid plaque(p<0.05), Conclusions: Existence of carotid plaque was closely related to cerebral infarction. Therefore, early detection of extraeranial carotid plaque by B-mode ultrasonography is very useful in predicting cerebral mfarction in NIDDM patients.

Visceral Fat Accumulation and the Fatty Acid Composition of Serum Phospholipids in Middle-Aged Women with Different Degrees of Glucose Tolerance.: Jee Young Yoon, Jong Ho Lee, Yang Cha Lee, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1997;21(4):444-456. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The aim of this study was to determine visceral fat accumulation and the fatty acid composition of serum phospholipids(PL) in middleaged female volunteers with different degrees of glucose tolerance and to analyze the factors that could be responsible for the observed differences between different degrees of glucose tolerance. METHODS: Anthropometric measurements and computed tomography measurements at umbilicus and thigh midway between the patella and pubis were performed in 125 subjects with normal glucose tolerance(NGT), 62 subjects with impaired glucose tolerance(IGT) and 50 subjects with non-insulin-dependent diabetes mellitus(NIDDM), Normal weight subjects were divided into 3 groups; NGT, IGT and long term NIDDM and overweight subjects into 4 groups; NGT, IGT, newly-onset NIDDM and long-term NIDDM. An oral glucose tolerance test(OGTT), the fatty acid composition of serum PL, fasting serum levels of IGF-1 were determined. RESULTS: Visceral fat area and visceral to subcutaneous fat ratio were higher in overweight control than normal weight control and higher in long-term NIDDM groups than controls. Thigh fat and muscle areas and serum levels of growth hormone and IGF-1 were lower in long-term NIDDM groups than controls. Insulin response area during OGTT was the highest in IGT groups and the lowest in NIDDM groups. The progression from the NGT group to the NGT and NlDDM groups was associated with an increase in glucose and free fatty acid areas during OGTT. Overweight long-term NIDDM group showed the lowest serum level of IGF-1 and the highest areas of glucose and FFA. The low ratio(about 0.64.~0.71) of polyunsaturated to saturated fatty acids in serum PL was found in diabetic groups. Long-term NIDDM groups showed an increase in proportions of palrnitic (C16:0), stearic(C18:0), dihomo-r-linolenic(C20:3w6) and docosapentaenoic(C22:3w6) and and a decrease in linoleic(C18:2w6), a-linolenic(C18;3w3), C20:4/20:3 (5-desaturase activity) and C18:1/18:0(9-desa-turase activity) in their serum PL compared with NGT groups. CONCLUSION: This study suggests that an increase in visceral fat and a decrease in thigh fat and muscle may be related to reduced secretion of growth hormone and insulin in long-term NIDDM subjects, These endocrine perturbations can be exacerbated by the prolonged exposure of hyperglycemia and high serum level of free fatty acid. In addition, lang term NIDDM may decrease 5-desaturase activity and 9-desaturase activity. Thus, the factors regulating fatty acid composition of serum PL in long-term NIDDM are affected by not only dietary fat but stored fat and serum concentrations of glucose and hormones, including insulin.

Changes of Glomerular Filtration Rate and Urinary Albumin Excretion Rate in NIDDM patients with Microalbuminuria.: Hyo Jung Kim, Jung Min Koh, Eun Sug Shin, Yun Ey Chung, Young Il Kim, Chul Hee Kim, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee; Korean Diabetes J. 1997;21(4):414-424. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We previously suggested that micro-albuminuria in the presence of retinopathy may represent a state of real incipient diabetic nephropathy with declining glomerular filtration rate(GFR), while the meaning of microalbuminuria in the absence of retinopathy may be more heterogeneous. This study was performed to further test this hypothesis. METHODS: We prospectively followed up the changes in GFR and urinary albumin excretinn rate (UAE) in microalbuminuric NIDDM patients with or without diabetic retinopathy for 3.1 years. RESULTS: 1) Among 45 patients who completed the followup, 27 had retinopathy from the baseline(group A), while 18 patients did not have retinopathy throughout the study(group B). 2) UAE at baseline was not statistically different between the group A and group B. During follow-up, VAE remained stable in the group B patients(40.0 [20.5 ~ 158.0) to 60.0[20.2 ~ 231.0] ug/min, NS). On the other hand, UAE significantly increased in the group A patients(47.9[20.0~186.0] to 140.0[24.5~2862.0] ug/min, P <0.001). 3) Thirty percent of the group A patients(8/27) progressed to overt proteinuria, while 11%(2/18) of the group B patients developed overt proteinuria(NS). 4) GFR significantly decreased both in the group A (113.0+21.2 to 89.1+24.0 mL/min/1.73 m, P < 0,001) and in the group B patients(134.1+27.2 to 121.5+27.3 mL/min/1.73 m, P<0.01). However, the magnitude of change in GFR was significantly higher in the group A than in the group B patients(7.7+7.6 vs 3.9+4.2 mL/min/1.73 m /year, P <0.05), 5) Multiple logistic regression analysis revealed that the presence of retinopathy was a independent risk factor for faster decline in GFR. CONCLUSION: It appears that clinical course is different in NIDDM patients with microalbuminuria, according to the presence or absence of diabetic retinopathy. Microalbuminuria in the presence of retinopathy predicts aggravation of albuminuria and decline in GFR. In contrast, the renal function in microalbuminuric NIDDM patients in the absence of retinopathy may remain stable for years.

Hyperfibrinogenemia as an Important Risk Factor for Microvascular Complications in NIDDM Patients.: Suk Kyeong Kim, Hyeong Kyu Park, Sun Wook Kim, Do Joon Park, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; Korean Diabetes J. 1997;21(4):406-413. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Abundant evidences have accumulated to suggest that atherosclerosis is accelerated in both type I and type Il diabetes but, traditional risk factors(hyperlipidemia, hypertension, smoking, age, obesity) do not account fully for the increased prevalence and severity of vascular diseases in diabetes. In this study, we examined the relationship of plasma fibrinogen to microvascular complications in NIDDM patients METHODS: In this cross-sectional study, 104 NIDDM patients were chosen from subjects who were attending the metabolic ward of Seoul National University Hospital. None of them were smokers, nor had any clinical evidences of acute infections, cancers or liver diseases. Arnong 104 patients, 55 patients (male 26, fernale 29) had no evidence of microvascular complications and 49(male 30, female 19) had one or moe microvascular complications. Their mean age(55.7+11.6 and 57.2+8.9 years old) and BMI (23.34+2.98 kg/m and 23.74+3.41 kg/m) were similar between two groups. This study defined microvascular complications as follows: 1) retinopathy classified based on fundoscopic and fluorescein angiographic assessmeot to background and proliferative, 2) nephropathy defined by 24 hour urine protein over 500mg, and 3) pheripheral neuropathy assessed by symptoms or NCV. RESULTS: 1) Clinically, there was no differences between two groups with respect to diastolic BP, C-peptide, HbA1c, and triglyceride level. However statistically significant differences were noted in systolic blood pressure, and total and LDL-cholesterol. Also mean fibrinogen level was more elevated significantly in diabetic patients with microvascular complications than those without microvascular complications. 2) Univariate analysis shows significant correlations between fibrinogen and the other variables such as duration of diabetes, total cholesterol level and systolic blood pressure. 3) However, fibrinogen concentration was higher in NIDDM patients with microvascuiar complications regardless of duration of diabetes, hypertension and HbA1c in multivariate logisric regression analysis (P=0.010). Conclusions: These results indicated that hyperfibrinogenemia were observed in NIDDM patient with microvascular complications regardless of duration of diabetes, systolic BP, and total cholesterol. Therefore our study suggests that hyperfibrogenemia may be one of the important missing links in the pathogenesis of diabetic microvascular diseases.

Angiotensin 1 Converting Enzyme ( ACE ) Gene Polymorphism According to Micro- and Mocro - angiopathy in non-insulin Dependent Diabetes Mellitus.: Moon Suk Nam, Hyun Chul Lee, Ji Hyun Lee, Bong Soo Cha, Su Youn Nam, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1997;21(4):397-405. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Chronic micro- and macro-angiopathy in diabetes are clinically significant complications that affect both quality and length of life in diabetic patients. Angiotensin 1 converting enzyme (ACE) is of key importance in regulating systemic and renal circulation by converting angiotensin-1 into -2 and inactivating bradykinin, Recent reports suggest that the ACE gene polymorphism is associated with susceptibility to micro- and macro-angiopathy in diabetes. But the results are diffetent according to the type of diabetes and complication. METHODS: We investigated the alleles of the ACE gene and measured the ACE activity in the 169 cases of non-insulin dependent diabetic patients and in the 95 cases of controls matched with age and BMI. RESULTS: The measured ACE activity was well correlated with the count of D allele. We found no differences of ACE alleles between in diabetes and control. No association was found between ACE gene polymorphism and diabetic microangiopathy(retinopathy or nephropathy). But DD genotypes (homozy-gotes for the deletion polymorphism) and D allele were found more frequently in diabetic patients with coronary artery obstructive diseases than in patients without coronary artery obstructive diseases in coronary angiography. CONCLUSION: These data indicate that ACE gene polymorphism in non-insulin dependent diabetes is associated with coronary artery obstructive diseases, but not with chronic microangiopathy.

Serum Fasting Proinsulin Level as a Predictor for Development of NIDDM in Korean Subjects.: Geon Sang Park, Chan Soo Shin, Kyong Soo park, Seong Yeon Kim, Hong Kyu Lee, Sun Ja Kwon, Yong Soo Park; Korean Diabetes J. 1997;21(4):365-371. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Proinsulin is raised in people with NIDDM. Hyperproinsulinemia is thought to be a predictor for the subsequent development of NIDDM. We studied to investigate whether hyperproinsulinemia can predict the development of NIDDM in Korean subjects. METHOD: This study was performed as a nested case-control study. The case group was 67 newly developed diabetic patients out of 1193 initially non-diabetic cohott in Yonchon county. We have also selected 66 age-sex-B541-WHR matched control group who remain non-diabetic for 2 years. We compared baseline insulin, proinsulin and proinsulin/insulin ratio between two groups, RESULTS: There was no significant difference in baseline fasting insulin levels[46,77+/-17.3 vs 42.87+/- 11.6(pmol/L)] between converters to diabetes and non-converters. However, the baseline proinsulin levels in converters to diabetes were higher than those in non-converters.[16.07+/-14.3 vs 8.72+/-5.2(pmol/L)) The baseline proinsulin/imulin ratio in converters was also higher than those in non-converters. [0.30+/-0.17 vs 0.20+/-0.10] CONCLUSION: The results suggest that fasting hyper-proinsulinemia may be a predictor for subsequent development of NIDDM in Korean subjects.

Serum Proinsulin Responses during Oral Glucose Tolerance Test in patients with Non-insulin Dependent Diabetes Mellitus.: Moon Suk Nam, Seong Bin Hong, Yeo Joo Kim, Mi Rim Kim, Yong Seong Kim, In Young Hyun, In Ho Kwak; Korean Diabetes J. 1997;21(4):356-364. Published online January 1, 2001

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Abstract PDF: BACKGROUND
When insulin is secreted from the pancreas, a small amount of proinsulin is also secreted at the same time. Pancreatic beta cell may release immature granules richer in proinsulin contents as well as mature granules in the over-stirnulated state. The significance of hyperproinsulinemia was recently reevaluated in the pathogenesis of non-insulin dependent diabetes mellitus(NIDDM). We studied proinsulin response at fasting and oral glucose tolerance test(OGTT) in NIDDM with a simple and sensitive human proinsulin radioimmunoassay system. METHODS: 22 new onset non-obese NIDDM patients and 11 matched healthy controls were selected for the study. The NIDDM group was divided into 3 groups(group 1; 7.8, group 2; 7.8~11, group 3; 11.0 mmol/L) according to the fasting plasma glucose level. After an overnight fast, a 75 g OGTT was performed and samples were analyzed with proinsulin and specific human insulin radioimmunoassay kits. RESULTS: The basal serum proinsulin level was reported as 9.29+/-4.19 pmol/L in normal control and as 18.09+/-9.32 pmol/L(p=0.04, compared with control) in diabetic group. The values in NIDDM group 1 and 2(18.07+/-9.D2; p=0.04, 21.60+/-6.98; p=0.03) were higher than in control. The molar ratia of the basal proinsulin to total insulin were also increased in NIDDM group 1 and 2(0.24, 0.28) than in control subjmts(0.13, p=0.03). The basal proinsulin and proineulin/total insulin ratio were highest in the group 2(p 0,05, than group 3). During oral glucose loading, the proinsulin response increased more slowly than total insulin response. The proinsulin and proinsulin/ total insulin ratio during oral glucose loading were higher in NIDDM group 1 and group 2 than cantrols. CONCLUSION: The basal proinsulin level in diabetic group was higher than in normal control. The proinsulin responses during oral glucose loading were higher in diabetic group 1 and 2 than controls. The proinlulin response increased more slowly than total insulin response during oral glucose loading. So we conclude that the proinsulin secretion frorn pancreatic beta cell is impaired in diabetic group. The mechanism about the metabolic pathway of the proinsulin secretion should be studied more.

The Effect of Metformin Monotherapy in Patients with NIDDM.: Yu Bae Ahn, Sung Dae Moon, Sang Ah Jang, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 1997;21(2):185-193. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We performed this study to investigate the effect of metformin on glycemia, insulin secretion and body weight in patients with non-insulin-dependent diabetes melltus(NIDDM) who could not aehieve satisfactory glycemic control by sulfonylurea or diet therapy. METHODS: A total of 167 patients with NIDDM were included in this study. At baseline the patients underwent anthropometry and a 75g oral glucose tolerance test. Jn addition, levels of hemoglobin Alc (HbAlc), setum lipids, fasting and postprandial 2hr glucose were measured. Metformin was given in an initial dose of 500mg twice daily and increased by 500mg every month as long as the fasting blood sugar(FBS) concentration exceeded 7.8mmol/L and the side effects were tolerable. After 3 rnonths of metformin therapy we defined a responder as a patient who experienced a FBS of under 7.8 mmol/L or a HbAlc of under 7%. Patients who failed to respond to metformin monotherapy were excluded in the study. Anthrapometric changes and results of a 75 g oral glucose tolerance test were reevaluated in the responder group after 6 months of metformin treatment. RESULTS: I) The overall response rate to metformin mono-therapy was 55.6%(79/142) in the study population. 2) There were significant changes in body weight (64.4+/-8.2 vs 62.9+/-8.4 kg, p(0.01) and body mass index(25.3+/-2.3 vs 24.6+/-2.3kg/m, p<0.01) during metformin treatment. 3) There were significant decreases in the fasting, postprandial 2hr serum glucose(10.1+/-2.8 vs 7.9+1.6, 15,2+/-5.0 vs 12.2+/-3.9 mmol/L, p 0.01) and HbAlc levels(8.4+/-1.7 vs 6.5+/-0.9%, p<0.05) after 6 months of metformin treatment. 4) There were significant decreases in the levels of AUC[g](59.2+/-15.5 vs 49.4+/-9.4mmol L-1. Min-1, p =C0.01) without changes of AUC[I] and AUC[I]/ AUC[g] ratio (558.0+486.0 vs 536.4+374.4 pmol.L-1. Min-1, p=0.71, 11.7+/-13.0 vs 11.8+/-10.0, p=0.89). 5) The incidence of side effects was 25% in the study population, but most of them were mild and fade away with continuous use of metformin, CONCLUSION: Metforrnin monotherapy improved glycemic control in NlDDM patients who failed to respond to diet or sulfonylurea therapy and may be a useful hypoglycemic agent for the treatment of NIBDM.

Urinary albumin excretion, von Willebrand factor and macrovascular disease in patients with NIDDM.: Sin Gon Kim, Soo Mi Kim, Dong Hyun Shin, Nan Hee Kim, Yoon Sang Choi, Ie Byung Park, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 1997;21(2):176-184. Published online January 1, 2001

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Abstract PDF: BACKGROUND
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.

Relationship between Angiotensin I Converting Enzyme Gene Polymorphism and Vascular complications in Non-Insulin Dependent Diabetic Patients.: Byoung Gue Na, Tae Geun Oh, Sang Moo Jung, Sang Woo Oh, Jae Hong Choi, Ji Hyun Lee, Seong Su Koong, Seung Taik Kim; Korean Diabetes J. 1997;21(2):138-146. Published online January 1, 2001

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Abstract PDF: No abstract available.

Disturbance of Cutaneous Microcirculation assessed by Laser Doppler Flowmetry in Non-Insulin Dependent Diabetic patients.: Jeong Hyun Park, Sang Hee Nam; Korean Diabetes J. 1997;21(1):56-64. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic microangiopathies are well-known long-term complication of diabetes mellitus, These are wide-spread phenomena, but little is known about the nature of cutaneous microcirculatory disturbance in diabetic patients which could be considered as cutaneous diabetic microangiopathy. To assess the cutaneous microcirculatory disturbance of diabetic patients, we performed this study. METHODS: We performed the laser Doppler flowmetry which has been known to be an accurate device for measuring cutaneous microcirculatory blood flow to 14 control subjects and 16 non-insulin dependent diabetic patients. We used thermal reactive hyperemic technique to the dorsum of right index finger and right great toe for measuring both baseline and maximum cutaneous microcirculatory blood flow. RESULTS: The baseline microcirculatory blood flow measured at 35C did not show any statistically significant differences between control subjects and diabetic patients, on both finger dorsum and toe dorsum. The maximurn microcirculatory blood flow measured at 44C showed statistically significant difference between control subjects and diabetic patients only at toe dorsum, but not at finger dorsum (p<0.05). CONCLUSION: From the above results, we conclude that cutaneous microcirculation is disturbed in noninsulin dependent diabetic patients, which was manifested at the toe dorsum in the condition of maximum blood flow induced by thermal stimulation. Further studies an exact pathophysiology and possible correlations with diabetic microangiopathies, diabetic duration and the level of glycemic control are needed along with more refinement of measurement techniques.

Significance of Serum Anticardiolipin Antibody in Non-Insulin Dependent Diabetes Mellitus.: Hee Jin Kim, Young Sun Hong, Yeon Ah Sung, Nan Ho Kyung; Korean Diabetes J. 1997;21(1):39-48. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The antiphospholipid antibodies have been characteristically found in the patients with autoimmune diseases. Some previous studies revealed that antiphospholipid antibodies are increased in the sera of patients with diabetes and correlate with the extent of neuropathy and measurements of amiphospholipid antibodies may constitute a marker for ongoing damage to nerves. We measured serum anticardiolipin antibodies(IgG, IgM) to assess the prevalence and significance of anticardiolipin antibodies in NIDDM patients. METHOD: Ninety NIDDM patients were screened for lgG/IgM isotypes of anticardiolipin antibodies by enzyme-linked immunosorbent assay and compared with 30 control subjects. RESULTS: 1) The titers and positivities of IgG anticardiolipin antibodies were significantly higher in the sera of NIDDM patients than those of control subjects(P<0.05). 2) In NIDDM patients with IgG anticardiolipin antibody, the titer of serum c-peptide was significantly lower(P<0.05) and the body mass index tended to be lower(P=0.08). 3) There were no significant differences of positivities of IgG anticardiolipin antibodies according to the state of chronic diabetic complications and the mode of treatment(P>0.05). 4) In the patients with NIDDM, no significant association was found between the titers of IgG anticardiolipin antibodies and age, diabetic duration, fasting blood glucose, HbAlc, total cholesterol and triglyceride. CONCLUSION: The titers and positivities of IgG anticardiolipin antibodies were elevated in NIDDM. In the NIDDM patients with IgG anticardiolipin antibody, the serum titers of c-peptide were significantly lower and the body mass index tended to be lower. It seems that serum IgG anticardiolipin antibodies might have autoimmune relationship with slowly progressive IDDM, but further prospective mass studies will be requird.

Comparison of the Antiproteinuric Effect to ACE Inhibitors in NIDDM Patients with Nephropathy According to Genotypes of ACE Gene.: Yong Mo Yang, Jeong Chul Seo, Kyoung Soo Lee, Won Joong Jeon, Hyun Hee Lee, Ji Bong Jeong, Seong Su Koong, Tae Geun Oh; Korean Diabetes J. 2000;24(4):476-484. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Albuminuria is a risk factor for progression of diabetic nephropathy. Antihypertensive treatment, especially angiotensin converting enzyme (ACE) inhibition, has been shown to reduce albuminuria and to ameliorate progression of diabetic nephropathy in IDDM patients. Recently, an insertion (I)/deletion (D) polymorphism of the ACE gene (ACE/ID) has been shown to influence the antiproteinuric efficacy of ACE inhibition in non-diabetic renal disease and the deterioration in kidney function in both non-diabetic and diabetic kidney disease. We evaluated the potential role of the ACE/ID polymorphism on the antiproteinuric responsiveness to ACE inhibition in NIDDM patients with nephropathy. METHODS: 35 NIDDM patients with overt proteinuria were included in this study. DNA amplified by PCR techniques was used to detect the two alleles of the ID polymorphism. Subjects were classified as II+ID group and DD group according to the presence (I) or absence (D) of a 270 base pair insertion. Ramipril was used for ACE inhibition. At a baseline and an end of the study(6 months later from baseline), arterial blood pressure, HbA1c, serum creatinine, creatinine clearance, and 24 hour urine protein amount were measured. The significant response to ACE inhibition was defined as a decline in proteinuria > or =30% of baseline. RESULTS: The MABP was decreased significantly in each groups, but the degree of BP reduction was not different between the groups. Twenty-four hour urine protein amount and creatinine clearance was not different in each groups and between CONCLUSION: Antiproteinuric effect of ACE inhibition was not associated with ACE/ID polymorphism in diabetic patients with nephropathy.

Alterations of Plasma Atrial Natriuretic Peptide and its mRNA in Non-insulin Dependent Diabetic Model of Rats.: Byeong Dae Yoo, Won Kyun Park, Young Su Hong, Dae Kyu Song, Jae Hoon Bae; Korean Diabetes J. 2000;24(4):421-430. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus has led to change in fluid and electrolyte balance and consequently affected blood volume and blood pressure. These changes can trigger the secretion and synthesis of atrial natriuretic peptide (ANP) from both atrial and extra-atrial tissues. ANP plays an important role in the regulations of body fluid balance and blood pressure. Therefore, this study was carried out to elucidate whether or not atrial and extra-atrial synthesis of ANP is influenced in experimental non-insulin dependent diabetes mellitus (NIDDM) rats. METHODS: Neonatal rats were induced into NIDDM rats by single injection of streptozotocin (80 mg/kg). Plasma ANP level was measured by the use of radioimmunoassay method and the ANP mRNA expressions from the right atrium, left ventricle, hypothalamus and kidney were analyzed by reverse transcription- polymerase chain reaction with [32P]-dCTP at 8 weeks after injection of streptozotocin or citrate buffer. RESULTS: Blood glucose was more significantly increased at 2 hours after glucose loading in NIDDM rats than control rats. Plasma concentration of ANP tended to significantly increase in NIDDM rats compared with control rats. The expressions of ANP mRNA from each tissue were observed in different patterns. Right atrial ANP mRNA expression revealed non-significant increasing trend in NIDDM rats, whereas left ventricular ANP mRNA did not have difference. However, both hypothalamic and renal ANP mRNA expressions in NIDDM rats were significantly increased. CONCLUSION: These results indicate that the enhanced expressions of hypothalamic and renal ANP mRNA act as an important regulator of electrolytes and body fluid volume in neonatally streptozotocin-induced NIDDM rats.

Devrease of Mitochondrial DNA Content in Non-Insulin Dependent Diabetic Rats.: Ji Hyun Song, Sun Hee Yim, Bok Ghee Han, Hong Kyu Lee, Young Mi Kim, Kyong Soo Park, S Suzuki; Korean Diabetes J. 2000;24(2):202-215. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although genetic disorder in diabetes mellitus (DM) is not well understood, it has been suggested that the maternally inherited mitochondrial DNA which does not follow the Mendel's laws is a genetic factor for DM. It was reported that the mitochondrial DNA contents in DM patients were decreased compared to the normal control. Similar decrease in mitochondrial DNA content before DM development was tested in animal models. METHOD: The mitochondrial DNA (mtDNA) content in various tissues obtained from two types of non-insulin dependent diabetic rats, Goto-Kakizaki (GK) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats at different ages were quantified. We also determined the quantity of hepatic COX subunit lll(COX III) mRNA, and the enzyme activities of succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) in mitochondria isolated from liver and skeletal muscle were measured. RESULTS: At 6 weeks, mtDNA content of GK rat liver was 20% decreased compared to the Wistar control, The mtDNA content of Wistar rat liver was decreased to aging from 6 weeks to 24 weeks while mtDNA in GK rat liver remains relatively constant. In case of skeletal muscle, however, mtDNA contents in GK rats were 50% decreased compared to the control at 12 and 24 week old, Similarly, OLETF and LETO control rats showed the age-dependent decrease of mtDNA content in liver and pancreas. Especially the mtDNA contents in OLETF rat tissues were reduced at the younger age than the LETO control content. That is, at 6 weeks old mtDNA contents in OLETF rat pancreas and liver were only 50% of the control. The level of mitochondrial coded hepatic CDX subunit III mRNA tends to decrease with age. Despite the decrease of mtDNA content, hepatic COX lll mRNA level and COX activities and SDH activities were not altered significantly, implying that the change of mtDNA contents did not damage the mitochondrial gene transcription and mitochondrial function dramatically. CONCLUSIONS: This results suggest that mtDNA contents in pancreas and liver decrease age-dependently but it occurs at younger age in NIDDM. The decrease of mtDNA content at young age may be a cause of NIODM.

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