No abstract available.
Adult ; Humans ; Lung ; Male

No abstract available.
Adult ; Humans ; Lung ; Male

BACKGROUND: Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) generates inorganic pyrophosphate, a solute that serves as an essential physiological inhibitor of calcification. Inactivating mutations of ENPP1 are associated with generalized calcification in infancy and an increased risk of developing type 2 diabetes mellitus (T2DM). We hypothesized that the ENPP1 K121Q variant may be associated with increased coronary artery calcification in T2DM patients. METHODS: The study subjects were aged 34 to 85 years and showed no evidence of clinical cardiovascular disease prior to recruitment. A total of 140 patients with T2DM were assessed for their coronary artery calcium (CAC) scores and ENPP1 K121Q polymorphisms were identified. RESULTS: The prevalence of subjects carrying the KQ genotype was 12.9% (n = 18). There were no 121QQ homozygotes. Patients with the KQ genotype did not show a significantly higher CAC score (122 vs. 18; P = 0.858). We matched each patient with the KQ genotype to a respective control with the KK genotype by gender, age, and duration of diabetes. When compared to matched controls, we observed no significant difference in CAC score (P = 0.959). CONCLUSIONS: The ENPP1 K121Q polymorphism does not appear to be associated with coronary artery calcification in patients with T2DM.
Aged ; Calcium ; Cardiovascular Diseases ; Coronary Vessels ; Diabetes Mellitus, Type 2 ; Diphosphates ; Genotype ; Homozygote ; Humans ; Lifting ; Phosphoric Diester Hydrolases ; Prevalence ; Pyrophosphatases

BACKGROUND: The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression. METHODS: The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter. RESULTS: The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression. CONCLUSIONS: This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.
Blotting, Northern ; Blotting, Western ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Gene Expression ; Humans ; Insulin ; Insulin-Secreting Cells ; RNA, Messenger ; Thapsigargin ; Transfection ; Tunicamycin

BACKGROUND: Identification of dietary patterns is important for glycemic management in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: Elderly T2DM patients (> 65 years of age, n = 48) were categorized based on their concentration of glycated hemoglobin (HbA1c). Subjects with HbA1c levels below 7% were placed in the good control (GC) group and those with HbA1c levels equal to or above 8% were placed in the poor control (PC) group. Anthropometric data, blood parameters, and dietary intake records were compared between the groups. Statistical analysis included Student's t-test, chi-square test, and Pearson correlation coefficient test. RESULTS: Anthropometric data, including body mass index (24.7 +/- 2.9 kg/m2), did not differ between the GC and PC groups. Significant abnormalities in blood glucose levels (P < 0.01), lean body mass (P < 0.01), and plasma protein and albumin levels (P < 0.05, P < 0.01) were found in the PC group. In contrast to the GC group, the PC group depended on carbohydrate (P = 0.014) rather than protein (P = 0.013) or fat (P = 0.005) as a major source of energy, and had a lower index of nutritional quality for nutrients such as protein (P = 0.001), and all vitamins and minerals (P < 0.001, 0.01, or 0.05 for individual nutrients), except vitamin C, in their usual diet. Negative correlations between HbA1C levels and protein (r = -0.338, P < 0.05) or fat (r = -0.385, P < 0.01) intakes were also found. CONCLUSIONS: Healthcare professionals should encourage elderly diabetic patients to consume a balanced diet to maintain good glycemic control.
Aged ; Ascorbic Acid ; Blood Glucose ; Body Mass Index ; Delivery of Health Care ; Diabetes Mellitus, Type 2 ; Diet ; Hemoglobins ; Humans ; Micronutrients ; Minerals ; Nutritive Value ; Plasma ; Vitamins

BACKGROUND: We examined the prevalence and clinical characteristics of aspirin resistance in the Korean patients with type 2 diabetes mellitus. METHODS: We studied 181 Korean patients with type 2 diabetes mellitus who were taking aspirin (100 mg/day for > or = 3 months) and no other antiplatelet agents. The VerifyNow System was used to determine aspirin responsiveness. Aspirin resistance was defined as an aspirin reaction unit (ARU) > or = 550. We measured the cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) to evaluate arteriosclerosis. The anthropometric parameters, electrocardiogram, blood pressure, fasting plasma glucose, lipid profiles, hemoglobin A1c, highly sensitive C-reactive protein (hsCRP), homocysteine, and microalbuminuria were measured in each patient. RESULTS: The prevalence of aspirin resistance in type 2 diabetic patients was 9.4% (17 of 181). Those who had aspirin resistance were older than those without aspirin resistance (64.6 +/- 10.6 vs. 59.8 +/- 8.1, P = 0.024). Aspirin resistance was not associated with fasting plasma glucose, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, hemoglobin A1c, hsCRP, homocysteine, microalbuminuria, ABI, CAVI, and body mass index. CONCLUSION: Prevalence of aspirin resistance in the Korean patients with type 2 diabetes mellitus was 9.4%. Although aspirin resistance was associated with old age, we could not find any good clinical parameter to predict it. Therefore, aspirin resistance should be evaluated in diabetic patients taking aspirin for prevention of cardiovascular complications.
Ankle Brachial Index ; Arteriosclerosis ; Aspirin ; Blood Pressure ; C-Reactive Protein ; Cholesterol ; Diabetes Mellitus, Type 2 ; Electrocardiography ; Fasting ; Glucose ; Hemoglobins ; Homocysteine ; Humans ; Plasma ; Platelet Aggregation Inhibitors ; Prevalence

BACKGROUND: Vascular Endothelial Growth Factor (VEGF) and Advanced Glycation End products (AGEs) have been implicated in the development of diabetic retinopathy. In this study, we examined the expression of VEGF and AGEs in the retina and serum, apoptosis in the retina, and lens opacities in streptozotocin (STZ)-induced diabetic rats. METHODS: The localization of VEGF and AGEs in the retina of STZ-induced diabetic rats was determined by immunohistochemical analysis, and apoptotic cell death was assessed using the TUNEL assay. In the serum, STZ-induced diabetic rats were assayed for VEGF and AGEs by ELISA. Lenses were also isolated to detect the opacity. RESULTS: Expression of VEGF and accumulation of AGEs were significantly increased in the retinal ganglion cell layers (GCL) and nuclear cell layers (NCL) of STZ-induced diabetic rats compared to normal control rats. In addition to cellular expression, serum VEGF and AGEs levels were also increased significantly in STZ-diabetic rats compared to normal rats (both P < 0.001) and there was a significant correlation between the serum VEGF and AGEs levels (r = 0.504). The lens opaque density of STZ-induced diabetic rats were significantly higher than in normal rats (P < 0.001). CONCLUSIONS: AGEs could be involved in the development of diabetic retinopathy through the induction of VEGF. One could possibly correlate this lens opaque formation with elevation of AGE induced VEGF level. Thus, this study should be considered as a basic research for studying pathology of the retina and lens in diabetic experimental models.
Animals ; Apoptosis ; Cataract ; Cell Death ; Diabetic Retinopathy ; Enzyme-Linked Immunosorbent Assay ; Glycosylation End Products, Advanced ; In Situ Nick-End Labeling ; Models, Theoretical ; Rats ; Retina ; Retinal Ganglion Cells ; Streptozocin ; Vascular Endothelial Growth Factor A

BACKGROUNDS: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first detection during pregnancy and mostly caused by insulin resistance and beta-cell dysfunction like type 2 diabetes. However, autoimmune or monogenic diabetes can contribute to GDM. Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by an early age of onset and an autosomal dominant pattern of inheritance. Most MODY cases are attributable to mutations in HNF-1alpha gene, also known as MODY3. We investigated whether mutations in HNF-1alpha gene are present in Korean women with GDM. METHODS: A total of 96 Korean women with GDM who have a family history of DM were screened for mutations in the HNF-1alpha gene. We evaluated the clinical characteristics of GDM women with HNF-1alpha gene mutations. RESULTS: Five of 96 patients (5.2%) were found to have a mutation in HNF-1alpha gene. Four of those (-23C > G, 833G > A (Arg278Gln), 923C > T, IVS5 + 106A > G) were novel and one (-124G > C) in promoter region was reported in previous study. The mean age of GDM women with mutations of HNF-1alpha gene was 34 years. Four women with MODY3 gene mutations required insulin therapy during pregnancy. GDM women with MODY3 gene mutations appeared to be decreased insulin secretion (HOMA-%B) than those without mutations. CONCLUSIONS: We have found the existence of MODY3 as well as novel HNF-1alpha gene mutations in Korean women with GDM.
Age of Onset ; Diabetes Mellitus, Type 2 ; Diabetes, Gestational ; Female ; Glucose Intolerance ; Hepatocyte Nuclear Factor 1-alpha ; Humans ; Insulin ; Insulin Resistance ; Mass Screening ; Pregnancy ; Promoter Regions, Genetic ; Wills

BACKGROUND: Increased prevalence of diabetes in recent years is linked with increased cardiovascular morbidity and mortality. Apolipoprotein E (apo E) polymorphism is well known to be related to hyperlipidemia and coronary heart disease, but only a few studies investigated the association between apo E polymorphism and diabetes or insulin resistance. In Korea, two studies with relatively small subjects reported controversial results. Therefore, we investigated the association between apo E polymorphism and diabetes in elderly community population. METHODS: 982 elderly people aged 65 or over in Seongnam city were enrolled. We measured anthropometric variables and blood pressure and performed biochemical tests including fasting glucose, fasting insulin, HbA1c, and lipid profiles. Apo E polymorphism was determined by PCR-RFLP method. RESULTS: Frequencies of apo E isoforms and alleles were similar to those of other reports. Subjects with e4 allele had significantly higher total and LDL-cholesterol levels. However, there were no differences in cholesterol levels between normal subjects and diabetes. Diabetes was not related to apo E polymorphism. CONCLUSION: In Korean aged 65 or over, subjects with diabetes didn't have increased total or LDL-cholesterol, triglyceride, and decreased HDL-cholesterol levels. Diabetes and apo E polymorphism were not related.
Aged ; Alleles ; Apolipoproteins ; Apolipoproteins E ; Blood Pressure ; Cholesterol ; Coronary Disease ; Fasting ; Glucose ; Humans ; Hyperlipidemias ; Insulin ; Insulin Resistance ; Korea ; Prevalence ; Protein Isoforms

BACKGROUND: It is well known that renal TGFbeta expression is related to the development of diabetic nephropathy. Alpha-lipoic acid (ALA), a potent antioxidant and cofactor of mitochondrial respiratory enzymes, can improve the insulin resistance and the vascular endothelial dysfunction, and suppresses the development of diabetic vascular complications. This study was undertaken to investigate whether ALA could reduce urinary protein excretion and renal TGFbeta protein expression in obese type 2 diabetes mellitus animal model, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHODS: Obese 30 male OLETF rats were randomly divided to 3 groups at the age of 30 weeks. The rats in the Control group fed normal rat chow while the rats in the ALA group were fed with rat chow containing ALA (0.5% of food weight). Ten rats in the Pair-fed group were fed with normal rat chow, but were given the same amount of food as consumed by the ALA group. During 5 weeks of ALA feeding, food intake and body weight were checked in metabolic chamber. Blood glucose levels, HbA1c and urinary protein excretion were measured at 30 weeks and 35 weeks of age, and renal TGFbeta protein expression at 35 weeks of age was measured by Western blot and represented by relative unit (RU). Immunohistochemical staining for TGFbeta protein in renal tissue was also examined at 35 weeks of age. RESULTS: Food intake, body weight, blood glucose levels, HbA1c and urinary protein excretion among the Control, ALA and Pair-fed groups at 30 weeks of age were not different. At 35 weeks of age, food intake was significantly decreased in the ALA group than the Control group (Control group vs. ALA group, 27.7 +/- 1.1 g/day vs. 22.4 +/- 1.4 g/day, P < 0.001), and body weight was significantly decreased in the ALA group than the Control and Pair-fed groups (Control group: 694.4 +/- 10.3 g, ALA group: 600.4 +/- 7.4 g, Pair-fed group: 685.4 +/- 11.6 g, P < 0.001). Blood glucose levels were significantly decreased in the ALA group than the Control and Pair-fed groups (Control group: 157.7 +/- 4.6 mg/dL, ALA group: 130.7 +/- 4.8 mg/dL, Pair-fed group: 153.7 +/- 3.3 mg/dL, P < 0.001) although blood glucose levels from 30 weeks to 34 weeks of age and HbA1c at 35 weeks of age were not different among the groups. Urinary protein excretion and renal TGFbeta protein expression were significantly decreased in the ALA group than the Control and Pair-fed groups (urinary protein excretion, Control group: 5.033 +/- 0.254 mg/mgCr, ALA group: 3.633 +/- 0.303 mg/mgCr, Pair-fed group: 4.977 +/- 0.339 mg/mgCr, P < 0.001; renal TGFbeta protein expression, Control group: 7.09 +/- 0.17 RU, ALA group: 4.14 +/- 0.26 RU, Pair-fed group: 7.00 +/- 0.29 RU, P < 0.001). In the ALA group at 35 weeks of age, urinary protein excretion and renal TGFbeta protein expression were positively related in the Control, ALA and Pair-fed groups (Control group, r = 0.847, P = 0.002; ALA group, r = 0.954, P < 0.001; Pair-fed group, r = 0.858, P = 0.002). TGFbeta staining in glomeruli was observed in all groups but was decreased in the ALA group at 35 weeks of age. CONCLUSION: These results suggest that ALA may prevent the increase of food intake, body weight, blood glucose, urinary protein excretion and renal TGFbeta protein expression in obese type 2 diabetic rat model. The effect of ALA on diabetic nephropathy presented as proteinuria and renal TGFbeta expression in diabetic patients needs to be further clarified.
Animals ; Blood Glucose ; Blotting, Western ; Body Weight ; Diabetes Mellitus, Type 2 ; Diabetic Angiopathies ; Diabetic Nephropathies ; Eating ; Humans ; Insulin Resistance ; Male ; Models, Animal ; Proteinuria ; Rats ; Rats, Inbred OLETF ; Thioctic Acid ; Transforming Growth Factor beta