- Two Cases of Autoantibody Negative Fulminant Type 1 Diabetes Mellitus.
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Hwa Young Cho, Young Min Cho, Myoung Hee Park, Mi Yeon Kang, Ki Hwan Kim, Yun Hyi Ku, Eun Kyung Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee
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Korean Diabetes J. 2007;31(4):372-376. Published online July 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.4.372
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- Autoantibody negative fulminant type 1 diabetes mellitus is a novel subtype of type 1 diabetes, which is characterized by a remarkably abrupt onset, metabolic derangement such as diabetic ketoacidosis at diagnosis, low HbA1c level at onset and a negative islet-related autoantibodies. The prevalence of fulminant type 1 diabetes has large difference between Japan and other countries. The precise reason for this regional variation remains to be clarified. One of the possible explanations is genetic background such as genotype of class II HLA molecule. In addition, environment factors including viral infection are suggested as possible pathogenesis of the disease. Only a few cases with fulminant type 1 diabetes have been reported outside Japan, and most of these cases with definite diagnosis have been reported in Korea. We report here on two Korean patients that met the criteria for diagnosis of fulminant type 1 diabetes in accordance with their HLA genotypes.
- Fetal Protein Deficiency Causes Long Term Changes in Mitochondrial DNA Content of Liver and Muscle in Female Sprague-Dawley Rats.
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Suk Kyeong Kim, Min Seon Kim, Youn Young Kim, Do Joon Park, Kyong Soo Park, Ki Up Lee, Hong Kyu Lee
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Korean Diabetes J. 2003;27(2):115-122. Published online April 1, 2003
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- BACKGROUND
Epidemiological data suggest a strong association between low birth weight and the increased risk of metabolic syndrome, including type 2 diabetes, hypertension and cardiovascular disease, in adult life. However, the underlying mechanisms are largely unknown. In our previous study, the mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes was decreased in patients with type 2 diabetes and insulin resistance. To test the hypothesis that mitochondrial changes may serve as a link between fetal under nutrition and insulin resistance in later life, the effects of fetal protein malnutrition on the mitochondria of the liver and skeletal muscle, the main sites of insulin action in adulthood, were investigated. METHODS: Eight-week old female rats were divided into 2 groups and fed on either a control diet (casein 180 g/kg diet) (n=5) or a low protein diet (casein 80 g/kg diet) (n=7) for 15 days prior to mating. They were mated with 10 week-old male Sprague Dawley rats that had been fed on the control diet. The female offspring, born to the mothers fed the low protein diet, were randomly divided into 2 groups 4 weeks after birth, and weaned on either the low protein (low protein group, n=48) or control diet (resuscitated group, n=48). As a control group, the offspring born to the mothers fed the control diet were weaned on the control diet (n=48). The animals in each group were again randomly divided into 4 groups, and sacrificed at 5, 10, 15 and 20 weeks of age, respectively (n=12 per group). The body weight, liver and muscle mtDNA content were measured at weeks 5, 10, 15 and 20. RESULTS: The mtDNA contents of the liver and skeletal muscle were reduced in fetal malnourished adult rats, and were not restored to normal levels even when proper nutrition was supplied after weaning. CONCLUSION: Our findings indicate that under nutrition in early life causes long lasting changes in the mitochondria DNA content of the liver and muscles, which may contribute to the development of insulin resistance in later life.
- Pancreatic beta-cell Function and Development in Male Offspring of Protein-Malnourished Rats.
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Hyeong Kyu Park, Cheng Ji Jin, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
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Korean Diabetes J. 2002;26(1):21-30. Published online February 1, 2002
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Nutritional deprivation of the fetus and infant may be associated with susceptibility to impaired glucose tolerance or type 2 diabetes in adult life. This association has been interpreted as a long-term effects of nutritional factors that reduce fetal growth and impair the development of tissues that regulate glucose metabolism. This study aimed to investigate the effect of protein malnutrition in a fetus and early life on the pancreatic beta-cell function and development. METHODS: Sprague-Dawley rats were fed a low-protein (8% casein) diet during pregnancy and lactation. Their male offspring were weaned onto either a control (18% casein) diet (recuperated group, R) or a low-protein diet (low-protein group, LP). The offspring of the rats fed control diet were weaned onto control diet (control group, C). Glucose tolerance tests and morphometry of the pancreas were performed to evaluate the pancreatic beta-cell function and development at the 25th week of age. RESULTS: Offspring of the protein-malnourished rats had a significantly lower body weights than the controls. The R and LP showed no major impairment in glucose tolerance, but the plasma insulin concentrations in the R (0.24+/-.03 nmol/L) and LP (0.28+/-.02 nmol/L) groups were lower at 20 min during IVGTT than the C (0.43+/-.05 nmol/L) groups. The areas under the curve for insulin (AUC insulin) during IVGTT were significantly lower in R and LP (0.39+/-.03 nmol/L/min, 0.43+/-.02 nmol/L/min) groups than the C (0.54+/-.03 nmol/L/min) group. In particular, the rats with fetal protein malnutrition showed severe impairment in late-phase insulin secretion to a glucose load. Both the pancreas weight and the proportion of the pancreas weight to the body weight were significantly lower in the R and LP groups than the C group. The proportion of beta-cells to pancreatic cells was lower in the LP (0.91+/-.14%) group than the C (2.19+/-.23%) and R (1.79+/-.25%) group. The relative beta-cell mass was significantly lower in the LP (by 62%) group that the C group. CONCLUSION: Rats with fetal protein malnutrition showed persistently impaired pancreatic beta-cell development and reduced insulin secretion capacity. These findings suggest that in utero protein malnutrition can contribute to the development of type 2 diabetes in adult life along with other deleterious environmental or genetic conditions.
- Comparison of Clinical Characteristics of Impaired Fasting Glucose with Impaired Glucose Tolerance in Yonchon County.
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In Kyong Jeong, Min Kyong Moon, Sang Wan Kim, Young Joo Park, Sun Yuk Kim, Chan Soo Shin, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Noe Kyeong Kim, Hong Kyu Lee
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Korean Diabetes J. 2000;24(1):71-77. Published online January 1, 2001
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To compare the clinical characteristics of 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) based on fasting plasma glucose (FPG) with World Health Organization (WHO) impaired glucose tolerance (IGT) based on oral glucose tolerance test (OGTT) in a Korean population. METHODS: The analyses were based on the data of 2,251 subjects aged 30-80 years obtained from the surveys of Yonchon County in Korea in 1993, and the data of 1084 subjects participated in the follow-up survey in 1995. Prevalence of glucose tolerance categories was obtained by using WHO and ADA criteria, and the level of agreement was estimated by index. Cardiovascular risk profile and the incidence of diabetes based on the ADA criteria after 2 years were compared by focusing on the discordant ctiagnostic categories namely IGT/NFS in which the subjects were diagnosed as IGT by WHO criteria but normal fasting glucose(NFG) by ADA criteria and NGT/IFG diagnosed as normal glucose tolerance(NGT) by WHO but IFG by ADA. Results The ADA criteria failed to diagnose 69% of IGT patients, that is 62% of them were considered normal and 7% as diabetes. The overall agreement was poor (x statistics = 0.32, p<0.05). Subjects classified into IGT/NFG or NGT/IFG showed the worse cardiovascular risk profile and higher incidence of diabetes than NGT/NFG. Especially, subjects with NGT/IFG exhibited higher incidence of diabetes than those with IGT/NFG. CONCLUSION: Although IFG predicts subsequent development of diabetes much better than IGT, the vast majority of the subjects with IGT will be missed according to ADA criteria based on FPG only. Consequently FPG alone could be an inadequate substitute for the OGTT.
- The Prevalence of the Mitochondrial DNA 16189 Variant in Korean Adults and Its Association with Insulin Resistance.
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Seong Yeun Kim, Hang Kyu Lee, Do Joon Park, Bo Yeon Cho, Suk Kyeong Kim, Geon Sang Park, Jae Hyun Kim, Kyong Soo Park, Bong Sun Kang
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Korean Diabetes J. 1999;23(3):299-306. Published online January 1, 2001
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Mutations in mitochondrial DNA (mtDNA) are of potential importance in the pathogenesis of diabetes mellitus. MtDNA 3243 mutation (G->A) is famous and associated with insulin secretory defect, but it is found in only 0.52% of type 2 diabetes mellitus and it can explain only a small proportion of the patients with diabetes mellitus. Recently Poulton et al. showed that the 16189 variant (T C transition) in mtDNA was associated with insulin resistance in Caucasians. They showed that the prevalence of the 16189 variant in the American was 11% and the people with the 16189 variant had higher fasting insulin and HOMA insulin resistance than the people without the 16l89 variant. In this study, we investigated the prevalence of the 161S9 variant in Korean adults and its association with insulin resistance. METHODS: We utilized the stored blood samples from community-based diabetes survey conducted in Yonchon County, Korea in 1993. We randomly selected 160 samples. We extracted the DNA from peripheral blood samples and examined the 16189 variant by PCR and restrictive enzyme digestion. We measured BMI, waist-hip ratio, blood pressure, fasting glucose, postprandial 2 hour glucose, fasting insulin, total cholesterol, triglyceride and HDL- cholesterol. HOMA insulin resistance and beta-cell function were calculated from fasting glucose and fasting insulin. RESULTS: The prevalence of the 16189 variant in Korean adults was 28.8% (46/160), higher than in the American, but the same as in the Japanese. The subjects with the 16189 variant had higher fasting glucose and BMI than the subjects without the 16189 variant, but fasting insulin, HOMA insulin resistance, beta-cell function, cholesterol and blood pressure were not different between the two groups. CONCLUSION: The prevalence of the 16189 variant in the Korean is higher than in the Caucasian but the same as in the Japanese. Our results support that a frequent mitochondrial variant may contribute to the phenotype related to insulin resistance. However, further detailed studies must be made in a large number of patients.
- Relationship of Insulin-like Growth Factor(IGF)-1, IGF-2, IGF Binding Protein(IGFBP)-3, and Mitochondrial DNA Amount in the Umbilical Cord Blood to Birth Weight.
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Yun Yong Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Hong Kyu Lee, Jong Kwan Jun, Boh Yun Yoon, Jih Yeun Song, Bong Sun Kang
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Korean Diabetes J. 1999;23(1):36-45. Published online January 1, 2001
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Reaven proposed a syndrome (syndrome X), consisting of glucose intolerance, hypertension, hyperinsulinemia, dyslipidemia, as a clinical entity. The fundamental metabolic defect of this syndrome was recognized as insulin resistance, but the pathophysiology of insulin resistance is not clarified as of yet. Recent evidence, suggests that non-insulin dependent diabetes mellitus (NIDDM) ancl lipid and cardiovascular abnormalities-syndrome X-are associated with intrauterine growth retar- dation (IUGR). Recently Shin reported that the amounts of mitochondrial DNA (mtDNA) in a given amount of genomic DNA were lower in NIDDM patients than in healthy controls, and the amount of mtDNA is negatively correlated with blood pressure ancl waist-hip ratio. Birth weight is known to be correlated with levels of insulin-like growth factors (IGFs). The purpose of this study was to identify the correlation of low birth weight with reduced mtDNA and syndrome X. We investigated the relationship of birth weight to IGFs and the amount of mtDNA METHODS: 72 singleton pregnancy babies and their mathers admitted in Seoul National University Hospital from March to May, 1997 were studied. After delivery, the cord blcxxl and maternal venous blood sampling was done. Using the imnnmoradiometric assay (IRMA) the IGF-l, IGF-2, IGFBP-3 was measured from cord and maternal plasma. Among them only 27 pairs samples were measured mtDNA amount with competitive PCR method in their buffy coat. Then statistical analysis was done within these paratneters. RESULTS: Birth weight is correlated significantly with cord plasma IGF-1 (r=0.32, p<0.01), IGFBP-3 (r=0.44, p<0.01), prepregnancy maternal body weight (r=0.45, p<0.01), maternal mtDNA amount (r=0.63, p<0.01). Cord blood mtDNA is correlated with maternal mtDNA amount (r=0.55, p<0,01). In multiple regression analysis, the maternal mtDNA was found to be the only independent factor related to birth weight (p<0.01). COMCLUSION: We have found the correlation between birth weight and maternal prepregnancy body weight and mtDNA amount. The clinical implications of this result remain yet to be deiermined.
- The Characteristics of Insulin-resistance Syndrome in the Korean Population.
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Jin Sung Kim, Gun Sang Park, Yun Yong Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hyeon Kyu Kim, Yong Soo Park, Soon Ja Kwon
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Korean Diabetes J. 1998;22(1):84-92. Published online January 1, 2001
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Insulin-resistance syndrome or syndrome X which includes diabetes mellitus, hypertension, dyslipidemia, and obesity has been regarded as one of the mechanisms involved in the atherosclerotic disease. This study was performed to evaluate the prevalence of each camponent of insulin-resistance syndrome. We have also analyzed the clustering of insulin-resistance syndrome according to fasting insulin levels in subjects who participated in the Younchon county diabetes prevalence study in 1993. METHOD: One thousand, eight hundred and eleven subjects among 2520 subjects over 30 years-old were enrolled, We investigated the prevalence of 5 metabolic syndromes: glucose intolerance(impaired glucose tolerance and diabetes mellitus by WHO criteria), hypertension(diastolic blood pressure >95 mmHg), Hypertriglyceridemia(triglyceride >2.26 mmol/L), low HDL cholesterolemia(HDL cholesterol <0.91 mmol/ L) and obesity(body mass index >25 kg/m) according to fasting serum insulin level. RESULTS: The prevalence of glucose intolerance (diabetes mellitus and impaired glueose tolerance), hypertension, hypertriglyceridemia, low HDI, cholesterolemia and obestiy were 18.2%, 21.3%, 10.9%, 45.6% and 36.3%, respectively. According to the four quartiles(quartile 1, 2, 3, 4) of fasting serum insulin level, the prevalence rate of each metaboic syndrome was as follows: 9.5%, 15.6%, 22.8% and 25.0% for glucose intolerance; 18.7%, 17.5%, 21.1% and 27.9% for hypertension; 5.0%, 8.1%, 13 8% and 16.9% for hypertriglyceridemia; 37.9%, 46.6%, 46.5% and 51.6% for low HDL cholesterolemia; 19.2%, 30.1%, 40.8% and 55.4% for obesity. As the fasting insulin levels increase, the clustering of 2 or more disease increase. CONCLUSION: Metabolic syndromes associated with insulin-resistance are relatively common disorders in the Korean population. The prevalence and clustering of metabolic abnormalities also increase as serum insulin level increases in Korean population.
- Decreased Mitochondrial DNA Content in Peripheral Blood Leukocyte procedes the Development of Type 2 Diabetes Mellitus.
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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
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Korean Diabetes J. 1998;22(1):56-64. Published online January 1, 2001
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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.
- The Effect of Acarbose as an Adjuvant Therapy in Sulfonylurea-Treated NIDDM Patients.
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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
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Korean Diabetes J. 1997;21(4):484-492. Published online January 1, 2001
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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.
- Hyperfibrinogenemia as an Important Risk Factor for Microvascular Complications in NIDDM Patients.
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Suk Kyeong Kim, Hyeong Kyu Park, Sun Wook Kim, Do Joon Park, Chan Soo Shin, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee
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Korean Diabetes J. 1997;21(4):406-413. Published online January 1, 2001
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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.
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