Diabetes & Metabolism Journal

Volume 23(3); June 1999

Original Articles

Associations of Carotid Intinma-Media Thickness Measured by High Resolution B-mode Ultrasonography and Atherosclerotic Risk Factors in NIDDM Patients.: Hyun Chul Lee, Jae Hyun Nam, Seong Kil Lim, Kap Bum Huh, Kyeong Rae Kim, Soo Yeon Nam, Seok Won Park, Churl Woo Ahn, Young Deuk Song, Dae Jung Kim, Young Guk Ko; Korean Diabetes J. 1999;23(3):234-242. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Atherosclerosis is more prevalent in diabetic patients, severe and wide spread than in non-diabetic subjects and clinically evident as macrovascular diseases such as coronary, cerebro- vascular and peripheral arterial diseases which are important causes of frequent morbidity and premature mortality. But atherosclerotic vascular lesions are not easily detectable, before they advanced and cause symptoms. Measurement of carotid Intima-Media thickness(IMT) by high- resolution B-mode ultrasonography is a useful, non-invasive method to detect early atherosclerotic vascular changes. In this study, we investigated associations of IMT with cardiovascular risk factors. METHODS: High-resolution B-mode ultrasonography was performed in 63 non-insulin-dependent diabetic patients in order to determine maximal and mean carotid IMT. Blood pressure, glucose, HbA total cholesterol, HDL cholesterol and triglyceride levels were measured on a regular basis in the last 12 months before the carotid ultrasonography. The mean and last values at the time of the carotid ultrasonography were analyzed in relationship to the IMT. RESULTS: Carotid IMT was increased in NIDDM patients with male sex, smoking habit and hypertension. Systolic blood pressure (r=0.252, p=0.050) and LDL cholesterol levels (r=0.273, p=0.031) at the time of carotid ultrasonography showed a correlation with the IMT. Mean triglyceride (r=0.368, p=0.018) and HbA1c>, levels (r=0.288, p=0.045) of the last 12 months were correlated with the IMT. CONCLUSION: Increased carotid IMT was associated with male sex, smoking, hypertension, systolic blood pressure, LDL cholesterol, mean HbA, and triglyceride levels.

Effect of Oxidezed LDL in Insulin Binding, Internalization and Recycling of Insulin Receptor in Cultured Bovine Aortic Endothelial Cells.: Sung Dae Moon, Bong Yun Cha, Hye Soo Kim, Sang Ah Jang, Yu Bae An, Ki Ho Song, Je Ho Han, Soon Jib You, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 1999;23(3):243-255. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Endothelial dysfunction is perhaps one of the earliest manifestations of atherosclerosis. This abnormality is in part due to altered membrane signal transduction in endothelial cells. Oxidized LDL that is atherogenic may induce endothelial dysfunction, and its presence has been documented in atherosclerotic vessels. Many studies have shown that oxidized LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi- protein). It is also known that G-protein is involved in insulin recycling on cultured human umbilical vein endothelial cells. Therefore, to determine the effect of oxidized LDL on endothelial cells: insulin binding, internalization, and the recycling of insulin receptors were assessed in cultured bovine aortic endothelial cells treated with native LDL, oxidized LDL, and in some cells pretreated with pertussis toxin before the incubation with oxidized LDL. METHOD: Native LDL (density 1.019 1.063 g/mL) was obtained from using the rapid single discontinuous density gradient ultracentrifugation of plasma samples from a single donor. Oxidized LDL was prepared by exposing samples of native LDL to CuSO4 (5 uM) at 37't for 24 hours. Endothelial cells at 80% confluence were treated with the indicated concentrations of native LDL, oxidized LDL, and some cells were pretreated with pertussis toxin for 6 hrs before the incubation with oxidized LDL. These cells were incubated for 24 72 hours. RESULTS: 1. Binding of (125)I-insulin(0.17nM) to endothelial cells treated with increasing concentrations of oxidized LDL shows dose-dependent decrease. There were significant differences in insulin binding between native LDL and oxidized LDL-treated cells (p<0.05). Binding of 'I-insulin (0.17 nM) to endothelial cells treated with increasing culture time of oxidized LDL shows more decreased than that of native LDL significantly (p<0.05). And oxidized LDL had additive effect, but not significant, with pertussis toxin on the specific (125)I-insulin binding to bovine aortic endothelial cells. 2. Internalization of insulin receptors reached rapidly to its maximal level around 30min at 37'C. At 60 min, oxidized-LDL treated cells was less increased in internalization of insulin receptors than that of native LDL treated cells [59.1+1.9% of total cell associated insulin (mean+SE) vs. 67.5+1.1%, p<0.05]. There were additive effects, but not significant differences, between oxidized LDL and pretreated with pertussis toxin before the incubation with oxidized LDL. 3. After 30 min of incubation with unlabeled insulin (33 nM), insulin binding in oxidized LDL treated cells was significantly higher compared to native LDL treated cells (69.0+2.5% of control values vs. 63.7+1.2%, p<0.05), suggesting that oxidized-LDL decreased internalization of insulin receptors. And during the process of recycling, there were significant differences in insulin receptor recycling between the oxidized LDL and native LDL treated cells, but oxidized LDL had an additive effect, but not significant, with pertussis toxin on insulin receptor recycling to the bovine aortic endothelial cells. CONCLUSION: 1. The findings in this study suggest that oxidized LDL may play a causative role to produce the insulin resistance by inhibiting insulin binding, internalization and recycling of insulin receptor in cultured bovine aortic endothelial cells 2. This study suggests that the effect of oxidized LDL to the bovine aortic endothelial cells in insulin binding and receptor-mediated transcytosis is caused by inhibiting pertussis toxin sensitive Gi-protein.

The Study of Alteration of Beta Cells in Pancreatic Islets, Glusoce Metabolism and Insulin Secretion in Low Dose Streptozotocin Indeced Type 2 Diabetic Rat Model.: Young Goo Shin, Hong Seung Kim, Mi Deok Lee, Young Uck Kim, Ho Suck Kang, Tae Sun Hwang, Choon Hee Chung; Korean Diabetes J. 1999;23(3):256-268. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Korean diabetes is different from western diabetes due to the racial differences in genetic factors and susceptability. It has recently been suggested that thrifty phenotype hypothesis is related to the recent increase in prevalence of Korean diabetes, but we have little evidence about that. We obtained basic materials in the animal model of type 2 diabetes mellitus and conducted a morphologic study of the beta cell change, insulin secreting capacity, and glucose metabolism. METHODS: To obtain the reference data of a non-insulin dependent diabetic animal model, we performed the intraperitoneal glucose tolerance test (IPGTT), hyperinsulinemic euglycemic clamp and immunobistochemical staining on the sacrificed pancreatic tissues on a Sprague-Dawley male rat into which streptozotocin (STZ) had been injected during the early neonatal period. The study groups consisted of a normal control group with citrate buffer injection, a group with injection of 50 ug STZ per kg of weight and a group with injection of 75 ug STZ per kg of weight. STZ was injected within 12 hours after birth. RESULTS: l. Although, STZ injected groups had lower body weight than the control group 7 weeks after birth, there were no differences during 14 weeks. 2. The IPGTT results showed that the average level of whole blood glucose concentration of the group with 50 ug STZ per kg of weight was higher than that of the control group at 7 and 14 weeks after birth. The mean serum insulin concentration of the 75 ug STZ per kg of weight injected group was lower than that of the control group at 7 weeks after birth, but it was higher than that of the control group at 14 weeks. 3. The hyperinsulinemic euglycemic clamp study showed that the average level of peripheral glucose disposal rate of the STZ injected groups was lower than the control group, but there were no differences in the study groups. 4. Pancreatic islet showed decreased beta cell mass and increased beta cell size in the STZ injected groups but the BrdU labelling index was not different between the control and study groups. CONCLUSION: STZ injection into neonatal Sprague-Dawley male rats may result in a diabetic status due to both decreased insulin secretion and increased insulin resistance, which gives us useful reference data for type 2 diabetes mellitus in the animal model.

Measurement of Anti-Phogrin Antibody in Korean Autoimmune Deabetes; Comparison to Anti-IA-2 Antibody.: Moon kyu Lee, Yong Ki Min, Myung Shik Lee, Sung Hoon Kim, Byoung Joon Kim, Dong Jun Kim, Jong Ryeal Hahm, Dong Kyu Jin, Kyoung Ah Kim, Kwang Won Kim; Korean Diabetes J. 1999;23(3):269-277. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Since the discovery of IA-2 as a major autoantigen in type 1 diabetes, the question arose as to whether other PTPs (protein tyrosine phosphatases) could act as diabetic autoantigens as well. A novel PTP, designated IA-2 B (phogrin; phosphatase homologue in granules of insulinoma) was isolated that has a high sequence similarity to IA-2. Since some studies suggested that auto- immunity to phogrin, rather than IA-2 may be more closely associated with the development of type 1 diabetes, we measured the frequency of anti-phogrin antibody in Korean patients with type 1 diabetes and compared it with that of anti-IA-2 antibody/ anti-GAD antibody. METHODS: The anti-phogrin antibody and the anti-IA-2 antibody were measured by radioligand binding assays using in vitro transcribed and translated S-labeled phogrin and IA-2, respectively. Anti-GAD antibody was measured using a commercial radioimmunoassay kit (RSR, Cardiff, U.K.). The subjects in this study consisted of 41 patients with classical type 1 diabetes, 22 with slowly progressive type 1 diabetes, and 39 with type 2 diabetes. Their average mean age was 16.9 years, 37.9 years and 45.3 years respectively. RESULTS: The prevalence of anti-phogrin antibody, anti-IA-2 antibody and anti-GAD antibody in classical type 1 diabetes was 24.4%, 26.8% and 51.2% respectively. That, in slowly progressive type 1 diabetes was 0%, 9.1% and 40.9% respectively. When the anti-GAD antibody assay and the anti-IA-2 antibody assay were combined, the prevalence of autoantibodies was 58.5% in classical type 1 diabetes and 50% in slowly progressive type I diabetes. However, the addition of the anti-phogrin antibody to the anti-GAD antibody/anti-IA-2 antibody measurement did not significantly increase the prevalence of autoantibody. The level of the antiphogrin antibody was positively correlated with that of the anti-IA-2 antibody. The presence of the anti-phogrin antibody and the anti-IA-2 antibody was negatively correlated with the age at diagnosis. One patient with type 1 diabetes had the anti-phogrin antibody without the anti-IA-2 antibody. CONCLUSION: Combined measurement of the anti-phogrin antibody with the anti-IA-2 antibody/ anti-GAD antibody did not significantly increase the prevalence of autoantibodies in Korean patients with type 1 diabetes. In the majority of Korean type 1 diabetes patients, the anti-phogrin antibody appears to share epitopes with the anti-IA-2 antibody. However, a small proportion of type 1 diabetes patients may have a specific autoimmune response to phogrin.

Mesurement of GAD Antibodies using Radioligand Binding Assay, IRMA and RIA in Patients with Tye 1 Diabetes Mellitus.: In Kyu Lee, Hyoung Woo Lee, Kyu Chang Won, Hyun Dae Yoon, In Ho Cho, Ji Sung Yoon, Sang Yiup Nam, Jung Hyun Oh, Jin Cheol Park, Jae Hong Kim; Korean Diabetes J. 1999;23(3):278-287. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include insulin autoantibodies (IAAs), cytoplasmic islet cell antibodies (ICA) and GAD antibodies. Recently, there has been increasing interest in the use of glutamic acid decarboxylase antibodies (GADA) for the identification of subjects with increased risk of developing type 1 diabetes. GAD antibodies were first discovered in 1982 and is detected persistently after long duration of type 1 diabetes, whereas ICA is transient. However, because the classic immunoprecipitation assays of GAD antibodies is still rather time-consuming, a more simple and reproducible radiolignad binding assay (RBA) is has been widely used recently. The RIA (radioimmunoassay) and IRMA (immunoradiome- tricassay) for GAD antibodies using (125)I-labelled human GAD has been developed, The aim of the present study is to evaluate the usefulness of each methods. METHODS: We measured GAD antibodies by RBA with in vitro spathesized recombinani S-methio- nine-labelled GAD65, and protein A-sepharose to separate free from antibody-bound ligand and radioimmunoassay and immunoradiometric assay using 'I-labelled human GAD kit, in addition to measurement of ICAs by standard indirect immunofluorescence technique in 26 patients with type 1 diabetes(male 10, female 16, mean age 14 years) and 10 normal controls(male 5, female 5, mean age 15 years). RESULTS: The overall prevalence of GAD antibodies by RBA and RIA in patients with type 1 diabetes was 38% (10/26), respectively. The prevalence of GAD antibodies by IRMA in patients with type 1 diabetes was 31% (8/26). The frequency of GAD antibodies by RBA,IRMA and RIA increased as the JDF unit of ICA increased. There is a significant correlation between the GAD index (by RBA) and GAD concentration (by RIAand IRMA). CONCLUSION: These results suggest that GAD antibodies (by RIA or RBA or IRMA) is useful for screening and diagnosis of type 1 diabetes in Korean, but long-term prospective studies on large cohorts of patients is necessary.

Floow-up Study of Clinical and Immunogenetic Chracteristics and Basal C-peptidein Korea Young Age Onset Diabetic Patients.: Hyun Chul Lee, Duk Hi Kim, Jae Hyun Nam, Chul Woo Ahn, Seong Kil Lim, Kap Bum Huh, Soo Yeon Nam, Seok Won Park, Young Deuk Song, Hyun Soo Kim, Jin Wook Kweon, Kyung Hee Chang, Kyung Rae Kim; Korean Diabetes J. 1999;23(3):288-298. Published online January 1, 2001

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Abstract PDF: BACKGROUND
This study was undertaken to observe the changes of basal C-peptide level and to compare the clinical and immunogenetic characteristics in newly dignosed young age-onset diabetics in Korea. We studied predictors effecting the change of insulin secretory capacity in these patients. METHODS: 82 newly diagnosed young diabetic patients (mean age; 23.0+7.1, M:F=46:36) were divided into 3 groups according to the initial fasting serum C-peptide level (Classification I, group 1; C-peptide < 0.6 ng/mL, group 2; 0.6 ng/mL C-peptide <1.2 ng/mL, and group 3; 1.2 ng/mL C-peptide) and reclassified by the follow-up (mean follow-up; 3.7 year) fasting serum C-peptide level. RESULTS: According to the initial fasting serum C-peptide level, 17.1% (14/82) of the patients were classified as group 1, 35.4% (29/82) as group 2, and 47.5%(39/82) as group 3. In group 3, body mass index (BMI, p<0.01) and maximal BMI (p<0.01) at onset, family history of diabetes (p=0.01) and stimulated C-peptide increment were significantly higher than those in group 1 and 2. Presence of urine ketone (p<0.01), history of diabetic keto- acidosis (p<0.01), and frequency of insulin therapy at diagnosis (p<0.01) were significantly lower than those in group 1 and 2. No significant differences in onset age, sex, weight loss at onset, HbA1c, anti GAD antibody and HLA-DR were found among the 3 groups. After certain follow-up periods, 37.8% (31/82) of the patients were reclassified as group 1, 24.4% (20/82) as group 2, and 37.8% (31/82) as group 3 according to the follow-up fasting serum C-peptide level(classification II). All of the patients in group 1 in classification I were reclassified as group 1 in classification II. In group 2, 44.8% were reclassified as group 1 and 17.3% were reclassified in group 3. In group 3, 15.4% (6/39) of patients showed a significant decrease in insulin secretory capacity and were reclassified as type I diabetes, and their predictors for decreased insulin secretory capacity were low BMI at onset, low slimulated C-peptide increment, and antiGAD antibody. CONCLUSION: Our study showed that classification of newly diagnosed young diabetics by fasting C-peptide level is not always easy. Therefore follow-up measurement of C-peptide and consideration of clinical characteristics are needed in discriminating the type of diabetes in these groups of diabetics in Korea.

The Prevalence of the Mitochondrial DNA 16189 Variant in Korean Adults and Its Association with Insulin Resistance.: 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; Korean Diabetes J. 1999;23(3):299-306. Published online January 1, 2001

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Abstract PDF: BACKGROUND
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.

Serum Levels of Sialic acid, CRP, and TNF-a in Type 2 Diabetin Patients with Syndrome X.: Dong Seop Choi, Sang Jin Kim, Se Hyeon Paek, Kyung Mook Choi, Nan Hee Kim, Jung Heon Oh, Young Hyun Kim; Korean Diabetes J. 1999;23(3):307-314. Published online January 1, 2001

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Abstract PDF: diabetic nephropathy and macro- vascular complications. Thus it is possible to conBACKGROUND: Type 2 diabetes is associated with increased blood concentrations of acute phase reactants including; sialic acid, ai-acid glycoprotein, serum amyloid A, and the main cytokine mediator of acute phase response, interleukin-6. Through the action of cytokines on many tissues, acute phase response could be a major contributor of biochemical and clinical features of metabolic syndrome X and type 2 DM. We investigated whether sialic acid, CRP, and TNF-a levels were elevated in type 2 diabetic patients who had features of syndrome X and whether they were correlated with diabetic vascular complications. METHODS: Group 1 was type 2 diabetic patients with any of 4 or 5 features of syndrome X (n=24). Group 2 was type 2 diabetic patients with 0 or 1 features of syndrome X (n=29), and group 3 was healthy nondiabetic control subjects (n=19). We compared the levels of sialic acid, CRP, and TNF-a in group 1, 2 and 3. We also observed the relationship between sialic acid, CRP, TNF-a levels and diabetic micro, macrovascular complications and studied the correlation between these markers and components of syndrome X. RESULTS: Group 1 had significantly higher sialic acid levels than group 2 (68.3+19 vs. 59.9+9.7 mg/dL, p=0.047). But the CRP, and TNF-a levels were similar in three groups. Serum sialic acid levels were signifieantly higher in proteinuria group than in normo- and microalbuminuria groups (81+27.6 vs. 59.9+7.1, 61.2+7.9 mg/dL, p=0.001, 0.005). Serum CRP levels were also higher in proteinuria groups (32.9+59.8 vs. 6.4+1.9, 6.0+3.1mg/L, p=0.017, p=0.037). Serum sialic acid levels were significantly higher in the macrovascular complication group (70.5 +21.3 vs. 60.5+ 6.8 mg/dL, p=0.015). Levels of sialic acid were correlated with urinary albumin excretion rate, log triglyceride, CRP, and fasting C-peptide. Levels of CRP were correlated with sialic acid and fasting C-peptide. CONCLUSION: Serum sialic acid levels were significantly elevated in type 2 diabetic patients who had features of syndrome X, and were also elevated in patients with sider that the mechanisms involved in the acute phase response can contribute to the pathophysiology of type 2 diabetes and syndrome X. Vascular complications do further increase stress reactions in type 2 diabetes.

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.

Prediction of Large for Gestational Age Infant in Women with Gestational Age Infant in Women with Gestational Diabetes Mellitus by Yltrasound Examination.: In Kwon Han, Hun Kee Min, Chang Hoon Yim, Ho Yeon Jeong, Hak Chul Chang, Ki Ok Han, Hyun Ku Yoon, Jeong Eun Park, Jae Eun Park, So Ra Park, Soo Young Lee, Young Ho Lee; Korean Diabetes J. 1999;23(3):326-335. Published online January 1, 2001

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Abstract PDF: BACKGROUND
In pregnancies complicated by diabetes, fetal hyperinsulinemia increases the deposition of fat, protein and glycogen in insulin-sensitive tissues leading to macrosomia, characterized by shoulder and truncal obesity. This may result in a shoulder dystocia, birth injury or fetal asphyxia. Thus, antenatal prediction of a large fetus for gestational age (LGA) can provide important information for the prevention of obstetric and perinatal complications. However, the measurement of materrml blood glucose concentration has yielded a low sensitivity for the prediction of LGA infants. This study was performed to determine whether fetal ultrasound examination could establish the onset of accelerated fetal growth in women with gestational diabetes mellitus (GDM) and to find the ultrasound indices for prediction of LGA infant. METHODS: The study subjects consisted of 77 women with GDM who had a singleton, and 156 women with a negative screen for GDM matched for age, height, and weight. All subjects had an early ultrasound examination before 14 weeks, assuring accurate dating and did not have any other medical condition that might affect fetal growth. Two ultrasound measurements including biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) were performed at the 2nd trimester (24.7+2.7 vs. 24.1+2.4 wks, p>0.05) and the 3rd trimester (35.0+1.9 vs. 35.3+1.3 wks,p>0.05, respectively). RESULTS: Although gestational age at delivery of GDM group was earlier than the control group (39.0 +1.4 vs. 39.7+1.1, p<0.01), birth weight and frequency of LGA infant were similar between two groups (3204+439 vs. 3288+371 g, p>0.05; 27.3% vs. 20.5%, p>0.05, respectively). However, the LGA subgroup of GDM had a larger AC and longer FL at the 3rd trimester compared to the appropriate gestational age (AGA) subgroup and control group. The AC of LGA subgroup of GDM appeared to be accelerated at 33 weeks gestation compared to the control group. When the upper limit of 95% confidential interval of AC of the control group was used for a cutoff value for predicting LGA in GDM at the 3rd trimester, sensitivity and specificity was 71% and 78%, respectively. CONCLUSION: The prediction of LGA infant in women with GDM might be achieved by an ultrasound examination of fetal AC at the 3rd trimester, especially after 33 weeks gestation.

The Appropriteness of New ADA Diagnostin Criteria for Diabetes Mellitus in Korean Population.: Moon kyu Lee, Myung Shik Lee, Young Ki Min, Sung Hoon Kim, Byoung Joon Kim, Dong Jun Kim, Jong Ryeal Hahm, Eun Young Oh, Yun Jae Chung, Kyoung Ah Kim, Jae Hoon Chung, Kwang Won Kim; Korean Diabetes J. 1999;23(3):336-351. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The ADA has proposed a new diagnostic criteria for diabetes based on fasting plasma glucose, redefining diabetes as fasting plasma glucose 7.0 mmol/L. Since only a few studies for the appropriateness of tbis new ADA criteria were undertaken in the Korean population, we examined the appropriateness of the new ADA criteria by analyzing the results of oral glucose tolerance tests done in our hospital. METHODS: 507 oral glucose tolerance tests were conducted. Cases with diabetes and diseases that could affect the glucose tolerance were excluded. Plasma glucose was measured by the hexokinase method. Three groups of NGT, IGT, and DM by the WHO criteria of 2 hour-plasma glucose were redivided at each level of fasting plasma glucose. We calculated the sensitivity and specificity of each level of fasting plasma glucose (FPG), and the FPG value of maximum accuracy to diagnose diabetes with reference to the WHO criteria of 2 hour-plasma glucose. RESULTS: Correlation between the levels of fasting plasma glucose and 2 hour-plasma glucose was relatively low (r=0.676). FPG of 7.0 mmol/L for diagnosing diabetes was relatively specific (specificity=0.934), but not sensitive (sensitivity= 0.552). FPG value of maximum accuracy for diagnosing diabetes was 6.8 mmol/L. 39 % of IFG (> 6.1mmol/L and < 7.0mmol/L) was reclassified as diabetes by the criteria of 2 hour plasma glucose 11.1 mmol/L and 34 % of NFG (<6.1mmol/L) was reclassified as impaired glucose tolerance by the criteria of 2 hour plasma glucose > 7.8 mmol/L. CONCLUSION: The fasting plasma glucose of 7.0 mmol/L was relatively specific for diagnosing diabetes. However, the new ADA criteria tended to underestimate the prevalence of diabetes and impaired glucose tolerance in the Korean population. Therefore, oral glucose tolerance test may be needed to diagnose diabetes in high risk subjects. Large-scale cross-sectional and prospective studies will be needed to clarify these points.

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