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Comparative study on hemoglobin A1c, glycated albumin and glycosylated serum protein in aplastic anemia patients with Type 2 diabetes mellitus.
Suo, M, Wen, D, Wang, W, Zhang, T
Bioscience reports. 2020;(5)
Abstract
OBJECTIVE To differentiate the value of hemoglobin A1c (HbA1c), glycated albumin (GA) and glycosylated serum protein (GSP) in monitoring blood glucose of patients with aplastic anemia. METHODS 42 patients with aplastic anemia (AA) and 30 patients with AA and Type 2 diabetes mellitus (T2DM) were enrolled in the study, in comparison with 114 healthy subjects and 88 subjects with T2DM. HbA1c, GA, GSP, fasting plasma glucose (FPG), hemoglobin (Hb) and albumin (ALB) were measured, and group comparison and correlation analysis were carried out. RESULTS Compared with the non-diabetes patients while ALB were <30 g/l or 30-40 g/l, the HbA1c and GSP values in AA, T2DM and AA+T2DM patients were significantly higher while the GA values were lower. Moreover, no differences in FPG levels. The AA+T2DM patients with ALB >40 g/l had higher HbA1c level, with no difference in GA, GSP and FPG levels. There was a positive correlation between HbA1c and GA in healthy group (ALB ≥ 40 g/l), AA patients (ALB 30-40 g/l and ≥40 g/l), T2DM patients (ALB 30-40 g/l and ≥40 g/l) and AA+T2DM patients (ALB 30-40 g/l and ≥40 g/l) but not in those with ALB < 30 g/l. CONCLUSION The HbA1c results were affected by moderate-to-severe anemia, but not mild anemia. HbA1c is not recommended to detect blood glucose levels in AA patients (Hb < 90 g/l) or AA patients (ALB < 30 g/l). FPG and GSP are not suitable for AA patients.
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Association of serum C1q/TNF-Related Protein-9 (CTRP9) concentration with visceral adiposity and metabolic syndrome in humans.
Hwang, YC, Woo Oh, S, Park, SW, Park, CY
International journal of obesity (2005). 2014;(9):1207-12
Abstract
BACKGROUND C1q/TNF-Related Protein (CTRP) family members are novel adipokines that have anti-inflammatory, immunomodulatory, glucose-regulating and vascular effects. However, the metabolic effects of CTRP9 remain unclear in humans. OBJECTIVES The aims of this study were to investigate whether serum CTRP9 concentrations are associated with glucose tolerance, metabolic parameters and abdominal fat accumulation. In addition, the authors investigated whether the aforementioned effects of CTRP9 are independent of serum adiponectin levels. METHODS A total of 221 subjects (140 men and 81 women), 25-72 years of age (mean age 46.0 years), were randomly selected from two different study populations. The normal glucose tolerance group (n=120) was selected from one study population and the prediabetes/type 2 diabetes group (n=101) was selected from the other study population. Serum CTRP9, total adiponectin concentrations and abdominal fat via computed tomography scan were measured in all subjects. RESULTS Subjects in the lower serum CTRP9 tertile were older, had metabolically unhealthy profiles and had lower serum total adiponectin levels when compared with subjects in the middle or upper serum CTRP9 tertiles. In addition, serum CTRP9 concentration were inversely correlated with age, blood pressure, fasting glucose, homeostasis model assessment for insulin resistance, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels (all P<0.01) and positively correlated with serum total adiponectin levels (P=0.03). In terms of abdominal fat accumulation, serum CTRP9 concentrations were inversely correlated with visceral fat amount (P<0.01), but no correlation was observed with subcutaneous fat amount. Finally, serum CTRP9 was inversely associated with the presence of metabolic syndrome, independent of age, sex, body mass index, smoking status, total cholesterol, visceral fat and serum total adiponectin concentrations (odds ratio per 1 s.d. 0.47; 95% confidence interval 0.32-0.70; P<0.01). CONCLUSIONS Serum CTRP9 concentrations were positively associated with favorable glucose or metabolic phenotypes and absence of metabolic syndrome, independent of serum total adiponectin concentrations.
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The effect of somatostatin, ulinastatin and Salvia miltiorrhiza on severe acute pancreatitis treatment.
Wang, G, Wen, J, Wilbur, RR, Wen, P, Zhou, SF, Xiao, X
The American journal of the medical sciences. 2013;(5):371-6
Abstract
BACKGROUND The aim of this study was to evaluate the efficacy of somatostatin, ulinastatin and Salvia miltiorrhiza for treatment of severe acute pancreatitis. METHODS Three hundred six patients with severe acute pancreatitis were divided randomly into 5 groups: basic treatment, somatostatin, somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza. Amount of time for resolution of abdominal pain/distention, recovery to normal heart and respiratory rates, amylase and blood glucose levels, Acute Physiology and Chronic Health Evaluation II scores, and levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-10 were analyzed and recorded for all 5 subgroups. RESULTS Tumor necrosis factor-α and IL-6 levels on the fourth and seventh days, and Acute Physiology and Chronic Health Evaluation II scores on the seventh day after treatment showed significant decrease in the somatostatin, somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup. IL-10 levels on the fourth and seventh days were significantly improved in the somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup. The incidences of pancreatic sepsis, multiple organ dysfunction syndrome and mortality were lower in the somatostatin, somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup. CONCLUSIONS Somatostatin is effective for the treatment of acute pancreatitis and both ulinastatin and S miltiorrhiza demonstrate improvement in therapeutic benefits.
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Comparative structure analyses of cystine knot-containing molecules with eight aminoacyl ring including glycoprotein hormones (GPH) alpha and beta subunits and GPH-related A2 (GPA2) and B5 (GPB5) molecules.
Alvarez, E, Cahoreau, C, Combarnous, Y
Reproductive biology and endocrinology : RB&E. 2009;:90
Abstract
BACKGROUND Cystine-knot (cys-knot) structure is found in a rather large number of secreted proteins and glycoproteins belonging to the TGFbeta and glycoprotein hormone (GPH) superfamilies, many of which are involved in endocrine control of reproduction. In these molecules, the cys-knot is formed by a disulfide (SS) bridge penetrating a ring formed by 8, 9 or 10 amino-acid residues among which four are cysteine residues forming two SS bridges. The glycoprotein hormones Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Thyroid-Stimulating Hormone (TSH) and Chorionic Gonadotropin (CG) are heterodimers consisting of non-covalently associated alpha and beta subunits that possess cys-knots with 8-amino-acyl (8aa) rings. In order to get better insight in the structural evolution of glycoprotein hormones, we examined the number and organization of SS bridges in the sequences of human 8-aa-ring cys-knot proteins having 7 (gremlins), 9 (cerberus, DAN), 10 (GPA2, GPB5, GPHalpha) and 12 (GPHbeta) cysteine residues in their sequence. DISCUSSION The comparison indicated that the common GPH-alpha subunit exhibits a SS bridge organization resembling that of DAN and GPA2 but possesses a unique bridge linking an additional cysteine inside the ring to the most N-terminal cysteine residue. The specific GPHbeta subunits also exhibit a SS bridge organization close to that of DAN but it has two additional C-terminal cysteine residues which are involved in the formation of the "seat belt" fastened by a SS "buckle" that ensures the stability of the heterodimeric structure of GPHs. GPA2 and GPB5 exhibit no cys residue potentially involved in interchain SS bridge and GPB5 does not possess a sequence homologous to that of the seatbelt in GPH beta-subunits. GPA2 and GPB5 are thus not expected to form a stable heterodimer at low concentration in circulation. SUMMARY The 8-aa cys-knot proteins GPA2 and GPB5 are expected to form a heterodimer only at concentrations above 0.1 microM: this would be consistent with a short-term paracrine role but not with an endocrine role after dilution in circulation. Consequently, GPA2 and GPB5 could exert separate endocrine roles either during development and/or during adult life of both vertebrates and invertebrates.
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Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers.
Young-Min, S, Cawston, T, Marshall, N, Coady, D, Christgau, S, Saxne, T, Robins, S, Griffiths, I
Arthritis and rheumatism. 2007;(10):3236-47
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Abstract
OBJECTIVE To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis (RA). METHODS One hundred thirty-two patients with early RA were treated with nonbiologic therapies for 2 years and studied longitudinally. Genomic DNA was analyzed for presence of the shared epitope. Levels of matrix metalloproteinases (matrix metalloproteinase 1 [MMP-1], MMP-13, and MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), and cartilage oligomeric matrix protein (COMP) were assessed in serially obtained serum samples. The presence of pyridinoline (Pyr), deoxypyridinoline, glycosylated Pyr (Glc-Gal-Pyr), and C-telopeptide of type II collagen (CTX-II) was assessed in urine samples. Radiographs obtained at entry and at 2 years were evaluated using the modified Larsen score. RESULTS Baseline and 2-year radiographs were available from 118 patients. Larsen scores worsened during the 2 years in 50 patients, while 68 patients had no radiographic progression. Levels of a variety of biochemical markers, i.e., MMP-3, CTX-II, COMP, TIMP-1, Pyr, and Glc-Gal-Pyr, correlated significantly with radiographic progression at entry and longitudinally as assessed by area under the curve (AUC). By multivariate analysis, a model including MMP-3 and CTX-II was identified as providing the best prediction of radiographic progression at entry (predictive accuracy by receiver operating characteristic [ROC] AUC = 0.76 [95% confidence interval 0.66-0.85]), while a combination of MMP-3, CTX-II, and swollen joint count formed the best longitudinal AUC model (predictive accuracy by ROC AUC = 0.81 [95% confidence interval 0.73-0.89]). Patient-reported measures (Health Assessment Questionnaire, pain scores) were of limited use. In a subset of 50 patients who were treated with methotrexate (MTX) during the followup period, median serum MMP-3 levels decreased after the initiation of MTX therapy (P = 0.0003). CONCLUSION These results indicate that biochemical markers are useful predictors of radiographic progression in RA and that serum MMP-3 levels decrease significantly with MTX therapy. Multivariate models that include MMP-3 and CTX-II perform better than existing traditional markers in predicting radiographic outcome in RA.
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Hydrophobic cluster analysis and modeling of the human Rh protein three-dimensional structures.
Callebaut, I, Dulin, F, Bertrand, O, Ripoche, P, Mouro, I, Colin, Y, Mornon, JP, Cartron, JP
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine. 2006;(1-2):70-84
Abstract
Rh (Rhesus) is a major blood group system in man, which is clinically significant in transfusion medicine. Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein, that shared a common predicted structure with 12 transmembrane a-helices (M0 to M11). Non erythroid homologues of these proteins have been identified (RhBG and RhCG), notably in diverse organs specialized in ammonia production and excretion, such as kidney, liver and intestine. Phylogenetic studies and experimental evidence have shown that these proteins belong to the Amt/Mep/Rh protein superfamily of ammonium/methylammonium permease, but another view suggests that Rh proteins might function as CO2 gas channels. Until recently no information on the structure of these proteins were available. However, in the last two years, new insight has been gained into the structural features of Rh proteins (through the determination of the crystal structures of bacterial AmtB and archeaebacterial Amt-1. Here, models of the subunit and oligomeric architecture of human Rh proteins are proposed, based on a refined alignment with and crystal structure of the bacterial ammonia transporter AmtB, a member of the Amt/Mep/Rh superfamily. This alignment was performed considering invariant structural features, which were revealed through Hydrophobic Cluster Analysis, and led to propose alternative predictions for the less conserved regions, particularly in the N-terminal sequences. The Rh models, on which an additional Rh-specific, N-terminal helix M0 was tentatively positioned, were further assessed through the consideration of biochemical and immunochemical data, as well as of stereochemical and topological constraints. These models highlighted some Rh specific features that have not yet been reported. Among these, are the prediction of some critical residues, which may play a role in the channel function, but also in the stability of the subunit structure and oligomeric assembly. These results provide a basis to further understand the structure/function relationships of Rh proteins, and the alterations occurring in variant phenotypes.
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Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet.
Fiore, CE, Pennisi, P, Ferro, G, Ximenes, B, Privitelli, L, Mangiafico, RA, Santoro, F, Parisi, N, Lombardo, T
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2006;(6):417-22
Abstract
Skeletal demineralization and mineral metabolism derangement are well-recognized features of untreated celiac disease (CD). Although treatment with a gluten-free diet appears to prevent bone loss while correcting skeletal demineralization in childhood, there is evidence that bone mineral density does not return to normal in celiacs diagnosed in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, and ligand of receptor activator of NFkB (RANKL) are involved in the process of bone turnover and have been implicated in the pathogenesis of osteoporosis and other metabolic bone diseases. We measured OPG, RANKL, bone mineral density (BMD), and biochemical markers of bone turnover in 32 adult female premenopausal celiac patients on a gluten-free diet, and thirty age-matched healthy women. We correlated the OPG/RANKL ratio with the severity of bone loss. Celiac patients had a mean BMD lower than controls in lumbar spine and in the femoral neck. Serum levels of bone alkaline phosphatase (BAP, marker of bone formation), and urinary excretion of telopeptides of type I collagen (a marker of bone resorption) were significantly higher than in controls. Serum OPG and RANKL levels were significantly higher in CD patients than in controls, while the OPG/RANKL ratio was significantly lower in CD patients than in controls and was positively correlated with BMD at the spine. The role of elevated OPG in CD patients is unclear, but it might represent a compensatory mechanism against other factors that promote bone damage. Further studies are required to assess a possible therapeutic potential of osteoprotegerin in optimally treated celiacs with persistent osteopenia.
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Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes.
Pratley, RE, Jauffret-Kamel, S, Galbreath, E, Holmes, D
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2006;(6):423-8
Abstract
UNLABELLED Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones, improving glycemic control in subjects with type 2 diabetes. This twelve-week randomized, double-masked, placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor, vildagliptin (25 mg, bid, n=70) VS. placebo (bid, n=28) in previously diet-treated subjects with type 2 diabetes. Standardized meal tests were performed at baseline and endpoint. The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 +/- 0.2 % (p=0.0012) for the whole cohort (baseline 8.0 %) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 %. Fasting glucose and mean prandial glucose were reduced by 1.1 +/- 0.4 (p=0.0043) and 1.9 +/- 0.5 mmol/l (p <0.0001), respectively. The between-group differences in corrected insulin response at peak glucose and mean prandial C-peptide were + 0.06 +/- 0.02 (p=0.0258) and + 0.10 +/- 0.03 nmol/l (p=0.0031), respectively. Vildagliptin had no effect on fasting lipid levels or body weight. The incidence of adverse events was similar in subjects receiving placebo (71.4 %) and vildagliptin (55.7 %). CONCLUSION monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes. Concomitant improvements in beta-cell function were also observed. Subjects with higher baseline HbA1c levels showed greater response.
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Effects of short-term caloric restriction on circulating free IGF-I, acid-labile subunit, IGF-binding proteins (IGFBPs)-1-4, and IGFBPs-1-3 protease activity in obese subjects.
Rasmussen, MH, Juul, A, Kjems, LL, Hilsted, J
European journal of endocrinology. 2006;(4):575-81
Abstract
OBJECTIVE Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease activity in relation to 24-h GH release before and after a short-term very low-calorie diet (VLCD). DESIGN Six obese subjects before weight loss, five after an average weight loss of 36.1 kg, and five age-and sex-matched lean controls underwent a 4-day VLCD. All subjects were studied on two occasions, once during normal basic diet and again during the last day of the VLCD (1.6 MJ). METHODS Free IGF-I was determined by a non-competitive immunoradiometric assay. RESULTS Free IGF-I levels decreased in concert with increased ALS and unchanged blunted GH release after a VLCD in the obese subjects. IGFBPs-1-3 proteolytic activity was found to be unchanged by hypocaloric diet in all groups. CONCLUSIONS We conclude that free IGF-I decreases after a short-term hypocaloric diet in obese subjects with no concomitant change in 24-h GH release. Circulating free IGF-I per se cannot be the main mechanism of the attenuated GH release in dieting obese subjects.
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[Genetic variation of the cholesterol ester transfer protein gene and the prevalence of coronary artery disease. The AtheroGene case control study].
Blankenberg, S, Tiret, L, Bickel, C, Schlitt, A, Jungmair, W, Genth-Zotz, S, Lubos, E, Espinola-Klein, C, Rupprecht, HJ
Zeitschrift fur Kardiologie. 2004;:IV16-23
Abstract
BACKGROUND Various functional polymorphisms of the cholesteryl ester transfer protein ( CETP) gene influence CETP activity and the concentration of high-density lipoprotein (HDL) cholesterol. Beside other functional variants mainly the promoter polymorphism CETP/C-629A is currently discussed as a risk factor of coronary artery disease (CAD). We evaluated in a large case-control study the impact of various CETP genotypes and haplotypes on HDL concentration and the prevalence of CAD. METHODS AND RESULTS In 1214 patients with documented CAD as well as 754 population controls we determined the CETP/C-629A, TaqIB, I405V, R451Q, and A373P polymorphisms. All genotypes have an impact on the HDL concentration; univariate genotype and haplotype analyses demonstrate a significant effect of A-allel carriers on the elevation of HDL concentration. In addition, among all genotypes determined, the C-629A polymorphism is associated with the prevalence of CAD in a codominant fashion. Homozygous A-allel carriers reveal a relative risk of 0.6 (95% CI 0.44-0.82; P = 0.005) compared to the wild type. Adjustment for classical risk factors did not alter this association significantly, whereas after controlling for HDL concentration no independent significance between CETP/C-629A genotype and prevalence of CAD was observed anymore. CONCLUSION CETP genotypes have an significant but moderate impact on systemic HDL-cholesterol concentration. The A-allel of the CETP/C-629A polymorphism is associated with a reduced CAD risk. This risk reduction is probably mediated by elevated HDL-concentration. Whether genotyping of the CETP/C-629A polymorphism provides information over and above that obtained by HDL-cholesterol measurement has to be further investigated in various prospective studies.