Carotid Intimal-Medial Thickness Is Not Increased in Women with Previous Gestational Diabetes Mellitus

BackgroundGestational diabetes mellitus (GDM) is known to increase the risk of cardiovascular diseases. Measuring the carotid artery intimal-medial thickness (CIMT) is a non-invasive technique used to evaluate early atherosclerosis and to predict future cardiovascular diseases. We examined the association between CIMT and cardiovascular risk factors in young Korean women with previous GDM.MethodsOne hundred one women with previous GDM and 19 women who had normal pregnancies (NP) were recruited between 1999 and 2002. At one year postpartum, CIMT was measured using high-resolution B-mode ultrasonography, and oral glucose tolerance tests were performed. Fasting glucose, glycated hemoglobin A1c (HbA1c), insulin levels and lipid profiles were also measured. CIMTs in the GDM and NP groups were compared, and the associations between CIMT and cardiovascular risk factors were analyzed in the GDM group.ResultsCIMT results of the GDM group were not significantly different from those of the NP group (GDM, 0.435±0.054 mm; NP, 0.460±0.046 mm; P=0.069). In the GDM group, a higher HbA1c was associated with an increase in CIMT after age adjustment (P=0.011). CIMT results in the group with HbA1c >6.0% were higher than those of the normal HbA1c (HbA1c ≤6.0%) (P=0.010). Nine of the patients who are type 2 diabetes mellitus converters within one year postpartum but showed no significant difference in CIMT results compared to NP group.ConclusionHigher HbA1c is associated with an increase in CIMT in women with previous GDM. However, CIMT at one year postpartum was not increased in these women compared to that in NP women

Differential Proteome Profiling Using iTRAQ in Microalbuminuric and Normoalbuminuric Type 2 Diabetic Patients

Diabetic nephropathy (DN) is a long-term complication of diabetes mellitus that leads to end-stage renal disease. Microalbuminuria is used for the early detection of diabetic renal damage, but such levels do not reflect the state of incipient DN precisely in type 2 diabetic patients because microalbuminuria develops in other diseases, necessitating more accurate biomarkers that detect incipient DN. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify urinary proteins that were differentially excreted in normoalbuminuric and microalbuminuric patients with type 2 diabetes where 710 and 196 proteins were identified and quantified, respectively. Some candidates were confirmed by 2-DE analysis, or validated by Western blot and multiple reaction monitoring (MRM). Specifically, some differentially expressed proteins were verified by MRM in urine from normoalbuminuric and microalbuminuric patients with type 2 diabetes, wherein alpha-1-antitrypsin, alpha-1-acid glycoprotein 1, and prostate stem cell antigen had excellent AUC values (0.849, 0.873, and 0.825, resp.). Moreover, we performed a multiplex assay using these biomarker candidates, resulting in a merged AUC value of 0.921. Although the differentially expressed proteins in this iTRAQ study require further validation in larger and categorized sample groups, they constitute baseline data on preliminary biomarker candidates that can be used to discover novel biomarkers for incipient DN

Rosiglitazone increases endothelial cell migration and vascular permeability through Akt phosphorylation

Abstract Background Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, exhibit anti-inflammatory and antioxidant properties and inhibit endothelial inflammation and dysfunction, which is anti-atherogenic. However, fluid retention, which may lead to congestive heart failure and peripheral edema, is also a concern, which may result from endothelial cell leakage. In the current study, we examined the effects of PPAR-γ agonists on vascular endothelial cell migration and permeability in order to determine its underlying mechanisms. Methods We used rosiglitazone and conducted cell migration assay and permeability assay using HUVEC cells and measured vascular permeability and leakage in male C57BL/6 mice. Results Rosiglitazone significantly promoted endothelial cell migration and induced permeability via activation of phosphatidylinositol-3-kinase (PI3K) – Akt or protein kinase C (PKC)β. In addition, rosiglitazone increased vascular endothelial growth factor (VEGF) expression and suppressed expression of tight junction proteins (JAM-A and ZO-1), which might promote neovascularization and vascular leakage. These phenomena were reduced by Akt inhibition. Conclusions Vascular endothelial cell migration and permeability change through Akt phosphorylation might be a mechanism of induced fluid retention and peripheral tissue edema by TZD

Preoperative Localization and Intraoperative Parathyroid Hormone Assay in Korean Patients with Primary Hyperparathyroidism

BackgroundThe intraoperative parathyroid hormone (IOPTH) assay is widely used in patients with primary hyperparathyroidism (PHPT). We investigated the usefulness of the IOPTH assay in Korean patients with PHPT.MethodsWe retrospectively reviewed the data of 33 patients with PHPT who underwent parathyroidectomy. Neck ultrasonography (US) and 99mTc-sestamibi scintigraphy (MIBI scan) were performed preoperatively and IOPTH assays were conducted.ResultsThe sensitivity of neck US and MIBI scans were 91% and 94%, respectively. A 50% decrease in parathyroid hormone (PTH) levels 10 minutes after excision of the parathyroid gland was obtained in 91% (30/33) of patients and operative success was achieved in 97% (32/33) of patients. The IOPTH assay was 91% true-positive, 3% true-negative, 0% false-positive, and 6% false-negative. The overall accuracy of the IOPTH assay was 94%. In five cases with discordant neck US and MIBI scan results, a sufficient decrease in IOPTH levels helped the surgeon confirm the complete excision of the parathyroid gland with no additional neck exploration.ConclusionThe IOPTH assay is an accurate tool for localizing hyperfunctioning parathyroid glands and is helpful for evaluating cases with discordant neck US and MIBI scan results

A Relationship Between Alzheimer`s Disease and Type 2 Diabetes Mellitus Through the Measurement of Serum Amyloid-beta Autoantibodies

Increasing evidence suggests that type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimer`s disease (AD). To examine the relationship between T2DM and AD, autoantibodies against amyloid-A beta were measured in the serum of T2DM patients and age-matched controls. Levels of A beta autoantibody were measured by ELISA in serum samples of T2DM patients (n = 92) and age-matched control group (n = 106). A beta autoantibody levels were increased in T2DM compared with age-matched controls by 45.4 +/- 8.1% (p < 0.001). Females had higher A beta autoantibody levels than males in both T2DM and control group. A beta autoantibody levels in the T2DM group were positively correlated with the levels of cholesterol (p = 0.011), low density lipoprotein cholesterol (p = 0.020), and triglycerides (p = 0.039). In conclusion, the level of A beta autoantibody is dramatically elevated in patient serum of T2DM, and, as such, might be used as a possible biomarker for T2DM.Gotz J, 2009, CELL MOL LIFE SCI, V66, P1321, DOI 10.1007/s00018-009-9070-1Sohn JH, 2009, FRONT BIOSCI, V14, P3879, DOI 10.2735/3496Rubinstein R, 2008, CLIN EXP IMMUNOL, V154, P235, DOI 10.1111/j.1365-2249.2008.03742.xLi L, 2007, BRAIN RES REV, V56, P384, DOI 10.1016/j.brainresrev.2007.09.001Sohn JH, 2007, BIOCHEM BIOPH RES CO, V361, P800, DOI 10.1016/j.bbrc.2007.07.107de la Monte SM, 2006, J ALZHEIMERS DIS, V10, P89Lester-Coll N, 2006, J ALZHEIMERS DIS, V9, P13Dickstein DL, 2006, FASEB J, V20, P426, DOI 10.1096/fj.05-3956comMoir RD, 2005, J BIOL CHEM, V280, P17458, DOI 10.1074/jbc.M414176200Steen E, 2005, J ALZHEIMERS DIS, V7, P63Sakowicz M, 2005, INT IMMUNOL, V17, P145, DOI 10.1093/intimm/dxh195Krentz AJ, 2003, DIABETES OBES METAB, V5, pS19, DOI 10.1046/j.1462-8902.2003.0310.xSilvius JR, 2003, BBA-BIOMEMBRANES, V1610, P174, DOI 10.1016/S0005-2736(03)00016-6Pan WH, 2002, EXP BIOL MED, V227, P609Weksler ME, 2002, EXP GERONTOL, V37, P943DeMattos RB, 2002, SCIENCE, V295, P2264PELIA R, 2002, DIABETES, V51, P1256Bard F, 2000, NAT MED, V6, P916Refolo LM, 2000, NEUROBIOL DIS, V7, P321Ott A, 1999, NEUROLOGY, V53, P1937Schenk D, 1999, NATURE, V400, P173Alberti KGMM, 1998, DIABETIC MED, V15, P539Alexiewicz JM, 1997, AM J KIDNEY DIS, V30, P98Yankner BA, 1996, NEURON, V16, P921CLARK A, 1988, DIABETES RES CLIN EX, V9, P151COOPER GJS, 1987, P NATL ACAD SCI USA, V84, P8628

Regulatory Effect of Common Promoter Polymorphisms on the Expression of the 11 beta-Hydroxysteroid Dehydrogenase Type 1 Gene

Background/Aims: Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to active cortisol, has become an emerging therapeutic target for type 2 diabetes mellitus and obesity. In this study, we examined the association between HSD11B1 polymorphisms and type 2 diabetes and metabolic phenotypes in Koreans. Methods: We sequenced all exons including exon-intron boundaries and the promoter region of the HSD11B1 gene. Of 8 polymorphisms identified, we selected 4 common single-nucleotide polymorphisms (g.-19835G>A, g.-19609A>G, g.+27447G>C and g.+27810C>T) based on location, linkage disequilibrium and frequency and which were genotyped in 757 subjects with type 2 diabetes and 644 nondiabetic subjects. Results: There was no association between the 4 common polymorphisms of HSD11B1 and type 2 diabetes. g.-19835G>A and g.-19609A>G showed modest associations with fasting plasma glucose and body mass index but the significance of these associations was lost after adjustment for multiple comparison. With regard to promoter polymorphisms in the HSD11B1 gene, a haplotype construct carrying both g.-19835A and g.-19609G showed significantly decreased promoter activity compared to other common haplotype constructs. Conclusion: The variations in HSD11B1 were not associated with susceptibility to type 2 diabetes or metabolic phenotypes in Koreans. However, the common promoter variants of the gene might exert a polymorphic regulatory effect on HSD11B1 expression. Copyright (C) 2009 S. Karger AG, BaselThis work was supported by the Korea Health 21 R & D Project, Korean Ministry of Health, Welfare and Family Affairs (Grant No. 00-PJ3-PG6-GN07-001).Smit P, 2007, J CLIN ENDOCR METAB, V92, P359, DOI 10.1210/jc.2006-1349Hermanowski-Vosatka A, 2005, J EXP MED, V202, P517, DOI 10.1084/jem.20050119Robitaille J, 2004, OBES RES, V12, P1570Nair S, 2004, DIABETOLOGIA, V47, P1088, DOI 10.1007/s00125-004-1407-6Stulnig TM, 2004, DIABETOLOGIA, V47, P1, DOI 10.1007/s00125-003-1284-4Alberts P, 2003, ENDOCRINOLOGY, V144, P4755, DOI 10.1210/en.2003-0344Westerbacka J, 2003, J CLIN ENDOCR METAB, V88, P4924, DOI 10.1210/jc.2003-030596Storey JD, 2003, P NATL ACAD SCI USA, V100, P9440, DOI 10.1073/pnas.1530509100Gelernter-Yaniv L, 2003, INT J OBESITY, V27, P983, DOI 10.1038/sj.ijo.0802327Lindsay RS, 2003, J CLIN ENDOCR METAB, V88, P2738, DOI 10.1210/jc.2002-030017Tomlinson JW, 2002, J CLIN ENDOCR METAB, V87, P5630, DOI 10.1210/jc.2002-020687Draper N, 2002, J CLIN ENDOCR METAB, V87, P4984, DOI 10.1210/jc.2001-011375Paulmyer-Lacroix O, 2002, J CLIN ENDOCR METAB, V87, P2701Masuzaki H, 2001, SCIENCE, V294, P2166Hedrick P, 2001, EUR J HUM GENET, V9, P969Sandeep TC, 2001, TRENDS ENDOCRIN MET, V12, P446Morton NM, 2001, J BIOL CHEM, V276, P41293Stephens M, 2001, AM J HUM GENET, V68, P978Seckl JR, 2001, ENDOCRINOLOGY, V142, P1371Rask E, 2001, J CLIN ENDOCR METAB, V86, P1418, DOI 10.1210/jc.86.3.1418Kerstens MN, 2000, CLIN ENDOCRINOL, V52, P403Eberle MA, 2000, GENET EPIDEMIOL, V19, pS29Bujalska IJ, 1999, ENDOCRINOLOGY, V140, P3188Livak KJ, 1999, GENET ANAL-BIOMOL E, V14, P143Alberti KGMM, 1998, DIABETIC MED, V15, P539Ricketts ML, 1998, J CLIN ENDOCR METAB, V83, P1325Walker BR, 1998, HYPERTENSION, V31, P891Phillips DIW, 1998, J CLIN ENDOCR METAB, V83, P757Napolitano A, 1998, J STEROID BIOCHEM, V64, P251Hautanen A, 1997, J INTERN MED, V241, P451