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71.
One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes 总被引:8,自引:0,他引:8
Hanefeld M Brunetti P Schernthaner GH Matthews DR Charbonnel BH;QUARTET Study Group 《Diabetes care》2004,27(1):141-147
OBJECTIVE: The goal was to assess the 1-year efficacy and safety of the addition of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: In this multicenter, double-blind study, patients were randomized to receive either pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA(1c) at week 52. Fasting plasma glucose, insulin, and lipid profiles were also measured. RESULTS: HbA(1c) was reduced by 1.20% in the SU plus pioglitazone group and 1.36% in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and 2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml). There were no significant between-treatment differences in these three parameters. Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9%; P = 0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with metformin addition. LDL cholesterol was increased 2% by the addition of pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001). Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017). Both combinations were well tolerated with no evidence of hepatic or cardiac toxicity in either group. CONCLUSIONS: Clinically equivalent improvements in glycemic control were observed for both combinations. Compared with metformin plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels. Metformin plus SU was associated with a significant reduction in LDL cholesterol. SU plus pioglitazone is an effective and well-tolerated combination regimen that may provide additional beneficial effects for patients with type 2 diabetes. 相似文献
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Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice 总被引:1,自引:0,他引:1 下载免费PDF全文
Nikolova V Leimena C McMahon AC Tan JC Chandar S Jogia D Kesteven SH Michalicek J Otway R Verheyen F Rainer S Stewart CL Martin D Feneley MP Fatkin D 《The Journal of clinical investigation》2004,114(3):357-369
Laminopathies are a group of disorders caused by mutations in the LMNA gene that encodes the nuclear lamina proteins, lamin A and lamin C; their pathophysiological basis is unknown. We report that lamin A/C-deficient (Lmna(-/-)) mice develop rapidly progressive dilated cardiomyopathy (DCM) characterized by left ventricular (LV) dilation and reduced systolic contraction. Isolated Lmna(-/-) myocytes show reduced shortening with normal baseline and peak amplitude of Ca(2+) transients. Lmna(-/-) LV myocyte nuclei have marked alterations of shape and size with central displacement and fragmentation of heterochromatin; these changes are present but less severe in left atrial nuclei. Electron microscopy of Lmna(-/-) cardiomyocytes shows disorganization and detachment of desmin filaments from the nuclear surface with progressive disruption of the cytoskeletal desmin network. Alterations in nuclear architecture are associated with defective nuclear function evidenced by decreased SREBP1 import, reduced PPARgamma expression, and a lack of hypertrophic gene activation. These findings suggest a model in which the primary pathophysiological mechanism in Lmna(-/-) mice is defective force transmission resulting from disruption of lamin interactions with the muscle-specific desmin network and loss of cytoskeletal tension. Despite severe DCM, defects in nuclear function prevent Lmna(-/-) cardiomyocytes from developing compensatory hypertrophy and accelerate disease progression. 相似文献
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Strohmer B Schernthaner C Iglseder B Paulweber B Pichler M 《Wiener klinische Wochenschrift》2007,119(17-18):544-552
INTRODUCTION: The metabolic syndrome is a matter of immense public concern for atherosclerosis prevention. Key features are visceral obesity, dyslipidemia, hyperglycemia in the non-diabetic range, and arterial hypertension. Subclinical atherosclerosis is the clinical consequence of metabolic syndrome, which may influence the QT interval. The aim was to investigate the rate corrected QT interval in subjects with metabolic syndrome in comparison to those without cardiometabolic risk factor clusters, and to explore gender differences in cardiac repolarization between the two groups. PATIENTS, MATERIALS AND METHODS: Heart rate and QT interval were automatically measured from surface ECG in 1086 participants (767 men, 319 women) from the Salzburg-Atherosclerosis-Prevention-program-in-subjects-at-High-Individual-Risk (SAPHIR). To omit the QT adjustment bias inherent in Bazett's formula we used a QT adjustment method with linear scaling as described by Rautaharju. RESULTS: The prevalence of metabolic syndrome was 13.8% among males and 10% among females. Mean rate adjusted QT (QTa) intervals were longer in women than in men. Presence of metabolic syndrome, however, was associated with significantly prolonged QTa only in men but not in women. Adjustment for relevant confounders reduced the difference of mean QTa in men from 9.24 to 5.83 ms (95% CI 0.9-10.8), but this difference was still statistically significant (p = 0.021). The effect of metabolic syndrome on QTa was only partly mediated by hypertension and insulin resistance. In females, however, no relevant differences were detected for QTa interval between subjects categorized by presence or absence of metabolic syndrome. CONCLUSIONS: The findings indicate a significant association between metabolic syndrome and rate-invariant QT in middle-aged men after adjustment for other risk factors. QT measurement may provide additive diagnostic and prognostic information in populations undergoing cardiovascular risk screening. However, the effect of metabolic and hormonal factors on ventricular repolarization seems to differ between the sexes. 相似文献
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Eva-Christina Krzizek Johanna Maria Brix Carsten Thilo Herz Hans Peter Kopp Gerit-Holger Schernthaner Guntram Schernthaner Bernhard Ludvik 《Obesity surgery》2018,28(3):643-648
Background
Postoperative micronutrient deficiency is a known side effect of bariatric surgery. In this study, we examined the prevalence of micronutrient deficiency in patients with morbid obesity (MO) preoperatively.Methods
A total of 1732 patients with MO wishing to undergo bariatric surgery (age: 40 ± 12 years, mean BMI: 44 ± 9 kg/m2, means ± SD, 77.3% female) were analyzed in this cross-sectional examination. Iron state, vitamin B12, folic acid, 25hydroxy(OH)-vitamin D, PTH, vitamin A, and vitamin E levels were determined. Subsequently, patients underwent nutritional counseling and were substituted accordingly.Results
A total of 63.2% (n = 1094) of the patients had a deficit in folic acid (< 5.3 ng/ml), 97.5% (n = 1689) in 25OHvitamin D (< 75 nmol/l), and 30.2% (n = 523) had a PTH elevation (> 56.9 pg/ml). A total of 5.1% (n = 88) of the patients presented with a deficit in vitamin B12 (< 188 pg/ml) and 6.2% (n = 107) in vitamin A (< 1.05 μmol/l). A total of 9.6% (n = 166) exhibited iron deficiency (ferritin < 15 μg/l). None of the patients had a deficit in vitamin E. There were no gender differences except for ferritin deficiency (women 11.8% vs. men 1.5%, p < 0.001). Patients in the highest BMI tertile had significantly more often a deficit in vitamin D (p = 0.033) and folic acid (p < 0.001). Patients in the lowest age tertile had significantly more often a deficit in folic acid (p < 0.001).Conclusions
Our data show a high prevalence of micronutrient deficiency in patients with morbid obesity preoperatively and emphasize the importance of exact preoperative evaluation and adequate substitution as well as postoperative surveillance.77.
Imig JD Dimitropoulou C Reddy DS White RE Falck JR 《Microcirculation (New York, N.Y. : 1994)》2008,15(2):137-150
The epoxygenase metabolite, 11, 12-epoxyeicosatrienoic acid (11, 12-EET), has renal vascular actions. 11, 12-EET analogs have been developed to determine the structure activity relationship for 11, 12-EET and as a tool to investigate signaling mechanisms responsible for afferent arteriolar dilation. We hypothesized that 11, 12-EET mediated afferent arteriolar dilation involves increased phosphoprotein phosphatase 2A (PP2A) and large-conductance calcium activated K+ (KCa) channels. We evaluated the chemically and/or metabolically table 11, 12-EET analogs: 11, 12-EET-N-methylsulfonimide (11, 12-EET-SI), 11-nonyloxy-undec-8(Z)-enoic acid (11, 12-ether-EET-8-ZE), and 11, 12-trans-oxidoeicosa-8(Z)-eonoic acid (11, 12-tetra-EET-8-ZE). Afferent arteriolar responses were assessed. Activation of KCa channels by 11, 12-EET analogs were established by single cell channel recordings in renal myocytes. Assessment of renal vascular responses revealed that 11, 12-EET analogs increased afferent arteriolar diameter. Vasodilator responses to 11, 12-EET analogs were abolished by K+ channel or PP2A inhibition. 11, 12-EET analogs activated renal myocyte large-conductance KCa channels. 11, 12-EET analogs increased cAMP by 2-fold and PP2A activity increased 3-8 fold in renal myocytes. PP2A inhibition did not significantly affect the 11, 12-EET analog mediated increase in cAMP and PP2A increased renal myocyte KCa channel activity to a much greater extent than PKA. These data support the concept that 11, 12-EET utilizes PP2A dependent pathways to activate large-conductance KCa channels and dilate the afferent arteriole. 相似文献
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Jordana Muroff Ph.D. M.S.W. Gail Steketee Ph.D. M.S.W. Jessica Rasmussen M.A. Amanda Gibson M.A. Christiana Bratiotis Ph.D. M.S.W. Cristina Sorrentino Ph.D. M.S.W. 《Depression and anxiety》2009,26(7):634-640
Background: Time‐limited group cognitive behavioral treatments (GCBT) for obsessive–compulsive disorder have demonstrated improvement in target symptoms. One small sample study of GCBT specifically for hoarding problems also showed benefit. This study examines the efficacy of a specialized GCBT for compulsive hoarding on a larger sample. Methods: Thirty‐two clients diagnosed with hoarding participated in five groups. Four groups met once weekly for 2 hour over 16 weeks (n=27) and one group met for 20 weeks (n=5). All participants had two individual 90‐min home sessions. Self‐report assessments were completed at baseline, mid‐treatment, and post‐treatment about hoarding behavior and related symptoms (e.g., depression). The sample was predominantly female, White, highly educated, unemployed, and not partnered/married; mean age was 53. A majority was diagnosed with major depressive disorder and obsessive–compulsive personality disorder. Results: Participants showed significant improvement from pre‐ to post‐treatment on the Saving Inventory Revised, Saving Cognitions Inventory, Clutter Image Rating, and Clinical Global Severity. The most recent group (n=8) that used a more formalized treatment and research protocol improved significantly more than did earlier members. Conclusion: This study demonstrates the feasibility and modest success of GCBT methods in improving hoarding symptoms. Group treatment may be especially valuable because of its cost‐effectiveness, greater client access to trained clinicians, and reduction in social isolation and stigma linked to this problem. Further research is needed to improve the efficacy of GCBT methods for hoarding and to examine durability of change, predictors of outcomes, and processes that influence change. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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