| 1. |
- Borg, Henrik, et al.
(författare)
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High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 1945-7197. ; 86:7, s. 3032-3038
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.
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| 2. |
- Holmer, Helene, et al.
(författare)
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Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
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Tidskriftsartikel (refereegranskat)abstract
- Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
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| 3. |
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| 5. |
- Melin, Johanna, et al.
(författare)
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Metformin and combined oral contraceptive pills in the management of polycystic ovary syndrome: a systematic review and meta-analysis.
- 2024
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Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 109:2, s. e817-e836
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is affecting more than every tenth woman.As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin and combination treatment were evaluated.Ovid Medline, Embase, PsycINFO, All EBM and CINAHL were searched.Women with PCOS included in randomized controlled trials (RCT).We calculated mean differences (MD) and 95% confidence intervals (CI) regarding anthropometrics, metabolic and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE was performed.The search identified 1660 publications, 36 RCTs were included. For hirsutism no differences were seen when comparing metformin versus COCP, nor when comparing COCP versus combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08, 95% CI 4.81; 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/l, 95% CI -174.46; -62.75) and testosterone (0.48 nmol/l,95% CI 0.32; 0.64) compared with COCP. COCP was inferior for FAI (0.58, 95% CI 0.36; 0.80) and SHBG (-16.61 nmol/L, 95% CI -28.51; -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/l, 95%CI -40.65; -13.59) and triglycerides (-0.15 mmol/l, 95%CI -0.29; -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/l, 95%CI 7.79; 26.26) and insulin resistance (0.44, 95%CI 0.17; 0.70) compared with combination treatment.The choice of metformin or COCP treatment should be based on symptoms, noting that there are some biochemical benefits from combination treatment, targeting both major endocrine disturbances seen in PCOS; hyperinsulinemia and hyperandrogenism.
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| 6. |
- Nethander, Maria, 1980, et al.
(författare)
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BMD-Related Genetic Risk Scores Predict Site-Specific Fractures as Well as Trabecular and Cortical Bone Microstructure
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:4
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: It is important to identify patients at highest risk of fractures. OBJECTIVE: To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately. DESIGN, SETTING, AND PARTICIPANTS: Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs). Associations between these GRSs and forearm (ncases = 1020; ncontrols = 2838), hip (ncases = 1123; ncontrols = 2630) and vertebral (ncases = 288; ncontrols = 1187) fractures were evaluated in 3 Swedish cohorts. Associations between the GRSs and trabecular and cortical bone microstructure parameters (n = 426) were evaluated in the MrOS Sweden cohort. RESULTS: We found that eBMDGRS was the only significant independent predictor of forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS were significant independent predictors of hip fractures. The eBMDGRS was the major GRS contributing to prediction of trabecular bone microstructure parameters while both FN-BMDGRS and eBMDGRS contributed information for prediction of cortical bone microstructure parameters. CONCLUSIONS: The eBMDGRS independently predicts forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS contribute independent information for prediction of hip fractures. We propose that eBMDGRS captures unique information about trabecular bone microstructure useful for prediction of forearm and vertebral fractures. These findings may facilitate personalized medicine to predict site-specific fractures as well as cortical and trabecular bone microstructure separately.
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| 7. |
- 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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| 8. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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| 9. |
- Aschim, Elin L, et al.
(författare)
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The RsaI polymorphism in the ER{beta} gene is associated with male infertility.
- 2005
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:Jul 5, s. 5343-5348
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Tidskriftsartikel (refereegranskat)abstract
- Context: Hypospadias, cryptorchidism, testicular cancer, and low semen quality have been proposed as being parts of the testicular dysgenesis syndrome (TDS) hypothetically due to changes in the androgen- estrogen balance in utero. Estrogens and estrogen receptors (ERs) play a role in regulating testicular function. ER beta contains two silent polymorphisms, RsaI (G1082A) and AluI (G1730A). Objective: We investigated the significance of these polymorphisms in the etiology of disorders being part of TDS. Setting: The patients were recruited consecutively through university hospital clinics. Participants: Four groups of Caucasian patients were included: 106 men from infertile couples with a sperm concentration less than 5 x 106 spermatozoa/ ml, 86 testicular cancer patients, 51 boys with hypospadias, and 23 cases with cryptorchidism. Military conscripts (n = 186) with sperm concentration higher than 5 x 10(6) spermatozoa/ ml served as controls. Main Outcome Measures: ER beta polymorphisms RsaI and AluI were determined by allele-specific PCR. In addition, reproductive hormone analyses were performed in controls and infertile men. Results: Compared with the controls, the frequency of the heterozygous RsaI AG-genotype was three times higher in infertile men (13.2 vs. 4.3%; P = 0.01). The heterozygous RsaI AG-genotype was associated with an approximately 20% reduction in LH concentration, compared with the wild-type RsaI GG genotype in both controls and infertile men. Subjects with testicular cancer, hypospadias, or cryptorchidism did not differ from controls regarding the frequency of any of the polymorphisms. Conclusions: Polymorphisms in ER beta may have modulating effects on human spermatogenesis. The phenotype of TDS seems to be, at least partly, determined by the genotype.
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| 10. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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