SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Frystyk J.) "

Sökning: WFRF:(Frystyk J.)

  • Resultat 1-10 av 22
  • [1]23Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Christiansen, J. S., et al. (författare)
  • Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
  • 2016
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 174:6, s. C1-C8
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
  •  
2.
  • Johannsson, Gudmundur, 1960, et al. (författare)
  • Growth Hormone Research Society perspective on biomarkers of GH action in children and adults
  • 2018
  • Ingår i: Endocrine Connections. - 2049-3614. ; 7:3, s. R126-R134
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
  •  
3.
  • Ingelsson, E, et al. (författare)
  • Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity
  • 2009
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 94:3, s. 953-957
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Skeletal muscle morphology and function are strongly associated with insulin sensitivity.Objective: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity.Design, Settings, and Participants: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study.Main Outcome Measures: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies.Results: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (β, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (β, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (β, −0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (β difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (β difference, −0.053; 95% confidence interval −0.107, −0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models.Conclusions: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.Circulating adiponectin concentrations are associated with skeletal muscle morphology and could be involved in the relations between muscle morphology and insulin sensitivity.
  •  
4.
  • Chen, Weena J Y, et al. (författare)
  • Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men
  • 2011
  • Ingår i: Cardiovascular Diabetology. - 1475-2840 .- 1475-2840. ; 10, s. 67-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease. Negative associations exist between circulating OPG and cardiac function. The adipocytokine adiponectin (ADPN) is downregulated in type 2 diabetes mellitus (T2DM) and coronary artery disease and shows an inverse correlation with insulin sensitivity and cardiovascular disease risk. We assessed the relationship of plasma OPG and ADPN and arterial function, cardiac function and myocardial glucose metabolism in T2DM.METHODS:We included 78 asymptomatic men with uncomplicated, well-controlled T2DM, without inducible ischemia, assessed by dobutamine-stress echocardiography, and 14 age-matched controls. Cardiac function was measured by magnetic resonance imaging, myocardial glucose metabolism (MMRglu) by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography. OPG and ADPN levels were measured in plasma.RESULTS:T2DM patients vs. controls showed lower aortic distensibility, left ventricular (LV) volumes, impaired LV diastolic function and MMRglu (all P < 0.05). In T2DM men vs. controls, OPG levels were higher (P = 0.02), whereas ADPN concentrations were decreased (P = 0.04). OPG correlated inversely with aortic distensibility, LV volumes and E/A ratio (diastolic function), and positively with LV mass/volume ratio (all P < 0.05). Regression analyses showed the associations with aortic distensibility and LV mass/volume ratio to be independent of age-, blood pressure- and glycated hemoglobin (HbA1c). However, the associations with LV volumes and E/A ratio were dependent of these parameters. ADPN correlated positively with MMRglu (P < 0.05), which, in multiple regression analysis, was dependent of whole-body insulin sensitivity, HbA1c and waist.CONCLUSIONS:OPG was inversely associated with aortic distensibility, LV volumes and LV diastolic function, while ADPN was positively associated with MMRglu. These findings indicate that in asymptomatic men with uncomplicated T2DM, OPG and ADPN may be markers of underlying mechanisms linking the diabetic state to cardiac abnormalities.TRIAL REGISTRATION:Current Controlled Trials ISRCTN53177482.
  •  
5.
  •  
6.
  • Younis, Shady, et al. (författare)
  • The ZBED6-IGF2 axis has a major effect on growth of skeletal muscle and internal organs in placental mammals
  • 2018
  • Ingår i: ; 115:9, s. E2048-E2057
  • Tidskriftsartikel (refereegranskat)abstract
    • A single nucleotide substitution in the third intron of insulin-like growth factor 2 (IGF2) is associated with increased muscle mass and reduced subcutaneous fat in domestic pigs. This mutation disrupts the binding of the ZBED6 transcription factor and leads to a threefold up-regulation of IGF2 expression in pig skeletal muscle. Here, we investigated the biological significance of ZBED6-IGF2 interaction in the growth of placental mammals using two mouse models, ZBED6 knock-out (Zbed6(-/-)) and Igf2 knock-in mice that carry the pig IGF2 mutation. These transgenic mice exhibit markedly higher serum IGF2 concentrations, higher growth rate, increased lean mass, and larger heart, kidney, and liver; no significant changes were observed for white adipose tissues. The changes in body and lean mass were most pronounced in female mice. The phenotypic changes were concomitant with a remarkable up-regulation of Igf2 expression in adult tissues. Transcriptome analysis of skeletal muscle identified differential expression of genes belonging to the extracellular region category. Expression analysis using fetal muscles indicated a minor role of ZBED6 in regulating Igf2 expression prenatally. Furthermore, transcriptome analysis of the adult skeletal muscle revealed that this elevated expression of Igf2 was derived from the P1 and P2 promoters. The results revealed very similar phenotypic effects in the Zbed6 knock-out mouse and in the Igf2 knock-in mouse, showing that the effect of ZBED6 on growth of muscle and internal organs is mediated through the binding site in the Igf2 gene. The results explain why this ZBED6 binding site is extremely well conserved among placental mammals.
  •  
7.
  • Ekstrom, Klas, et al. (författare)
  • Tissue IGF-I Measured by Microdialysis Reflects Body Glucose Utilization After rhIGF-I Injection in Type 1 Diabetes
  • 2015
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 100:11, s. 4299-4306
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Type 1 diabetes is associated with portal insulin deficiency and disturbances in the GH-IGF axis including low circulating IGF-I and GH hypersecretion. Whether peripheral hyperinsulinemia and GH hypersecretion, which are relevant to the development of vascular complications, result in elevated tissue IGF-I remains unknown. Objective: The purpose of this study was to determine the relationship between whole-body glucose uptake and tissue IGF-I measured by microdialysis. Design: This was a single-blind placebo-controlled crossover study. Setting: The setting was a tertiary pediatric endocrine referral center. Participants: The participants were seven young male adults with type 1 diabetes. Intervention: After an overnight fast, a 6-h lasting euglycemic clamp was performed (constant insulin infusion at 0.5mU/kg x minute and variable glucose infusion rate [GIR]) and a subcutaneous injection of recombinant human (rh) IGF-I (120 mu g/kg) or saline was given after 2 hours. In parallel, tissue IGF-I levels were determined by microdialysis (md-IGF-I). Main Outcome Measures: md-IGF-I levels in muscle and subcutaneous fat, and GIR were determined. Results: md-IGF-I levels were detectable but unchanged after saline. After rhIGF-I, muscle and subcutaneous fat md-IGF-I increased during the second and third hour and then reached a plateau up to 10-fold higher than baseline (P less than .001). GIR was unchanged after saline, whereas it increased 2.5-fold concomitantly with the increase in md-IGF-I (P less than .0001). In contrast, serum IGF-I was increased already at 30 minutes after rhIGF-I and reached a plateau 2-fold above baseline (P less than .0001). Conclusion: We demonstrate that md-IGF-I measurements are valid and physiologically relevant by reflecting rhIGF-I-induced glucose uptake. Future studies should be conducted to elucidate the role of local tissue IGF-I in diabetic vascular complications.
  •  
8.
  •  
9.
  • Khalili, P., et al. (författare)
  • Total adiponectin does not predict cardiovascular events in middle-aged men in a prospective, long-term follow-up study
  • 2010
  • Ingår i: Diabetes & Metabolism. - : Elsevier Masson SAS. - 1878-1780 .- 1262-3636. ; 36:2, s. 137-143
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim. Plasma total adiponectin is a marker of insulin resistance, but its role in predicting cardiovascular events is unclear. We aimed to investigate the role of adiponectin as a predictor of cardiovascular risk in middle-aged men, and to describe the association between adiponectin and glucose metabolism. Methods. In this population-based prospective study of middle-aged men (n=3885), total adiponectin was analyzed. All individuals had undergone an oral glucose tolerance test (OGTTs), and the mean follow-up duration was 27 years. Regression analyses were carried out for indices of glucose metabolism in relation to quintiles (Q1-Q5) of total aliponectin levels. After stratification for smoking or not, the association between total adiponectin and the first incidence of fatal or non-fatal cardiovascular disease (CVD) was analyzed, using Cox's proportional-hazards regression model. Results. In a separate multiple-regression analysis and after adjusting for possible confounders, the relationship between adiponectin levels and markers of glucose metabolism were found to be significant (P<0.05). However, adiponectin did not independently predict the risk of stroke, coronary events, or a combination of these two outcomes. Conclusion. Levels of total plasma adiponectin are not useful for predicting long-term cardiovascular events in middle-aged men, but are strongly associated with glucose metabolism and markers of insulin resistance. (c) 2010 Elsevier Masson SAS. All rights reserved.
  •  
10.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 22
  • [1]23Nästa
 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy