| 61. |
- Lewerin, Catharina, 1961, et al.
(författare)
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High plasma osteocalcin is associated with low blood haemoglobin in elderly men: the MrOS Sweden Study
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:4, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been suggested that osteoblasts are involved in the regulation of haematopoietic stem cells. Whether osteocalcin, which is derived from osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels is not known. OBJECTIVE: To determine whether plasma osteocalcin is a determinant of Hb in elderly men. METHODS: A total of 993 men (mean age 75.3 +/- 3.2 years) participated in the population-based MrOS (osteoporotic fractures in men) study. Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments were made for potential confounders (i.e. age, body mass index, erythropoietin, total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C). RESULTS: Hb correlated (age adjusted) negatively with osteocalcin in the total study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men (r = -0.16, P < 0.001). In nondiabetic men with higher osteocalcin levels, it was more likely that Hb would be in the lowest quartile (odds ratio per SD decrease in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men (47/812) (Hb <130 g L-1 ) had significantly higher mean osteocalcin levels than nonanaemic men (33.9 vs. 27.1 mug L-1 , P < 0.001). In multiple stepwise linear regression analyses (adjusted for age, body mass index, total oestradiol, adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and holotranscobalamin), osteocalcin was an independent predictor of Hb concentration in nondiabetic men (P < 0.05). CONCLUSIONS: These data add further support to the evidence indicating that the bone-specific protein osteocalcin has several endocrine functions targeting the pancreas, testes, adipocytes, brain. An additional novel finding is that osteocalcin may also have a paracrine function as a regulator of haematopoiesis.
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| 62. |
- Mardinoglu, Adil, 1982, et al.
(författare)
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Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes
- 2018
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Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 27, s. 151-155
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Tidskriftsartikel (refereegranskat)abstract
- Branched-chain amino acids (BCAAs) metabolite, 3-Hydroxyisobutyric acid (3-HIB) has been identified as a secreted mediator of endothelial cell fatty acid transport and insulin resistance (IR) using animal models. To identify if 3-HIB is a marker of human IR and future risk of developing Type 2 diabetes (T2D), we measured plasma levels of 3-HIB and associated metabolites in around 10,000 extensively phenotyped individuals. The levels of 3-HIB were increased in obesity but not robustly associated with degree of IR after adjusting for BMI. Nevertheless, also after adjusting for obesity and plasma BCAA, 3-HIB levels were associated with future risk of incident T2D. We also examined the effect of 3-HIB on fatty acid uptake in human cells and found that both HUVEC and human cardiac endothelial cells respond to 3-HIB whereas human adipose tissue-derived endothelial cells do not respond to 3-HIB. In conclusion, we found that increased plasma level of 3-HIB is a marker of future risk of T2D and 3-HIB may be important for the regulation of metabolic flexibility in heart and muscles.
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| 63. |
- Roos, Vendela, et al.
(författare)
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Alterations in multiple lifestyle factors in subjects with the metabolic syndrome independently of obesity
- 2017
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Ingår i: Metabolic Syndrome and Related Disorders. - : Mary Ann Liebert Inc. - 1540-4196 .- 1557-8518. ; 15:3, s. 118-123
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors.METHODS: BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire.RESULTS: Prevalent MetS (23% in the sample) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes.CONCLUSIONS: This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.
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| 64. |
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| 65. |
- Toschke, Audré M., et al.
(författare)
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Paternal smoking is associated with a decreased prevalence of type 1 diabetes mellitus among offspring in two national British birth cohort studies (NCDS and BCS70)
- 2007
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Ingår i: Journal of Perinatal Medicine. - Berlin : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 35:1, s. 43-7
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Tidskriftsartikel (refereegranskat)abstract
- AB Aims: An association between paternal age and type 1 diabetes (IDDM) among their offspring was recently reported as well as transgenerational responses in humans. This paper aims to assess the association of markers for prenatal exposures with IDDM. Methods: We analysed data from two birth cohorts in Great Britain on 5214 cohort members from the National Child Development Study (NCDS) and 6068 members of the 1970 British Birth Cohort Study (BCS70) with full information on IDDM and explanatory variables using multivariate logistic regression. Results: IDDM prevalence was 0.7% (95% CI 0.5-1.0%; n = 38) in the NCDS and 0.4% (95% CI 0.3-0.6%; n = 27) in the BCS70 cohort. Paternal age was not associated with IDDM possibly due to lack of sample power. Unex-pectedly, a lowered prevalence of IDDM was observed among offspring of smoking fathers in both cohorts, with a combined odds ratio of 0.44 (95% CI 0.25-0.75). This association could not be explained by maternal smoking prior to, during or after pregnancy, number of siblings, parental social class, maternal and paternal age, or cohort. Maternal smoking in pregnancy did not alter the IDDM prevalence among offspring. Conclusions: This unexpected finding may be explained by germ-line mutations or other mechanisms associated with paternal smoking. This phenomenon should be investigated and these results should not be used as a justification for smoking. Paternal exposures may be important in determining IDDM risk.
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| 66. |
- Piltonen, Terhi T, et al.
(författare)
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Utility of Serum Anti-Müllerian Hormone Measurement as Part of Polycystic Ovary Syndrome Diagnosis.
- 2024
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Ingår i: Seminars in reproductive medicine. - 1526-4564. ; 42:1, s. 49-59
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Forskningsöversikt (refereegranskat)abstract
- The 2023 international evidence-based guideline update for the assessment and management of polycystic ovary syndrome (PCOS) recommends using the Rotterdam criteria for the diagnosis of PCOS. The updated guideline has evidence-based recommendation for the diagnosis, and it now also includes serum anti-Müllerian hormone (AMH) measurement as an alternative tool for gynecological ultrasound to diagnose polycystic ovary morphology (PCOM). The aim of this new recommendation was to facilitate PCOS diagnostic workup in primary care and other disciplines, as currently most diagnosing is done in gynecology and infertility clinics. Here, we review factors affecting AMH levels as well as the utility of AMH in PCOS diagnosis. We identified relevant studies that report different cut-offs for AMH to diagnose PCOM as part of PCOS diagnosis. There are, however, some limitations when using AMH that should be acknowledged. These include physiological aspects like age, ethnicity, and obesity and iatrogenic causes like hormonal medication and ovarian surgery. Also reference ranges are different depending on AMH assay used. As a summary, we conclude that AMH is a usable tool in PCOM diagnostics, but it does not have a single cut-off. Therefore, further studies are needed to establish age and assay-based reference ranges.
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| 67. |
- Teede, Helena J, et al.
(författare)
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Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.
- 2023
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Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 108:10, s. 2447-2469
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Tidskriftsartikel (refereegranskat)abstract
- What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS.The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist.The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout.This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC).The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management.Overall, recommendations are strengthened and evidence is improved, but remain generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation programme supports the Guideline with an integrated evaluation program.This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and the European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
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| 68. |
- Alesi, Simon, et al.
(författare)
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Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.
- 2023
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Ingår i: EClinicalMedicine. - 2589-5370. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS.We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640.From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n=961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens+lifestyle were superior to metformin+lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]:-1.59 [-3.06,-0.12], p=0.03; I2=74%), SHBG (7.70nmol/l [0.75, 14.66], p=0.03; I2=0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97,-0.26], p=0.03; I2=0% and-1.12 [-1.44,-0.79], p<0.0001, I2=0%, respectively), but were not superior to placebo+lifestyle for hirsutism (-0.93, [-3.37, 1.51], p=0.45; I2=76%) or SHBG (9.72nmol/l [-0.71, 20.14], p=0.07; I2=31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58,-2.39], p<0.0001, I2=1%), and resulted in lower androstenedione levels (-0.30ng/ml [-0.50,-0.10], p=0.004; I2=0%). Combination treatment with anti-androgens+metformin+lifestyle resulted in lower testosterone compared with metformin+lifestyle (-0.29nmol/l [-0.52,-0.06], p=0.01; I2=61%), but there were no differences in hirsutism when anti-androgens+metformin+lifestyle were compared with either anti-androgens+lifestyle or metformin+lifestyle. In limited meta-analyses (n=2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP±placebo, with no differences in other outcomes.Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics.National Health and Medical Research Council (NHMRC) of Australia Monash University.
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| 69. |
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| 70. |
- Belda, E., et al.
(författare)
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Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism
- 2022
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:12
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. Design We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. Results Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. Conclusion Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.
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