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1.
  • Teede, Helena J, et al. (author)
  • Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.
  • 2023
  • In: Fertility and sterility. - 1556-5653. ; 120:4, s. 767-793
  • Journal article (peer-reviewed)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 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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2.
  • Björkman, Kristoffer, et al. (author)
  • Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
  • 2022
  • In: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
  • Conference paper (other academic/artistic)abstract
    • Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
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3.
  • Svedbo Engström, Maria, 1980, et al. (author)
  • A disease-specific questionnaire for measuring patient-reported outcomes and experiences in the Swedish National Diabetes Register: Development and evaluation of content validity, face validity, and test-retest reliability
  • 2018
  • In: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 101:1, s. 139-146
  • Journal article (peer-reviewed)abstract
    • Objective: To describe the development and evaluation of the content and face validity and test-retest reliability of a disease-specific questionnaire that measures patient-reported outcomes and experiences for the Swedish National Diabetes Register for adult patients who have type 1 or type 2 diabetes. Methods: In this methodological study, a questionnaire was developed over four phases using an iterative process. Expert reviews and cognitive interviews were conducted to evaluate content and face validity, and a postal survey was administered to evaluate test-retest reliability. Results: The expert reviews and cognitive interviews found the disease-specific questionnaire to be understandable, with relevant content and value for diabetes care. An item-level content validity index ranged from 0.6-1.0 and a scale content validity/average ranged from 0.7-1.0. The fourth version, with 33 items, two main parts and seven dimensions, was answered by 972 adults with type 1 and type 2 diabetes (response rate 61%). Weighted Kappa values ranged from 0.31-0.78 for type 1 diabetes and 0.27-0.74 for type 2 diabetes. Conclusions: This study describes the initial development of a disease-specific questionnaire in conjunction with the NDR. Content and face validity were confirmed and test-retest reliability was satisfactory. Practice implications: With the development of this questionnaire, the NDR becomes a clinical tool that contributes to further understanding the perspectives of adult individuals with diabetes. (c) 2017 Elsevier B.V. All rights reserved.
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5.
  • Pourhamidi, Kaveh, et al. (author)
  • Evaluation of clinical tools and their diagnostic use in distal symmetric polyneuropathy
  • 2014
  • In: Primary care diabetes. - : Elsevier. - 1878-0210 .- 1751-9918. ; 8:1, s. 77-84
  • Journal article (peer-reviewed)abstract
    • AIMS: To compare the diagnostic usefulness of tuning fork, monofilament, biothesiometer and skin biopsies in peripheral neuropathy in individuals with varying glucose metabolism.METHODS: Normoglycaemic, impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) individuals were recruited. Nerve conduction studies (NCS) and thermal threshold tests were performed. Vibrotactile sense was tested with a biothesiometer and a 128-Hz tuning fork. Touch/pressure perception was examined with a 10-g monofilament. Skin biopsies were performed and intraepidermal nerve fibres were quantified. Distal symmetric polyneuropathy (DSPN) was defined as neuropathy disability score ≥2 and abnormal NCS. Thermal threshold tests were used to define small nerve fibre neuropathy (sDSPN) in cases where NCS (large nerve fibres) were normal.RESULTS: The prevalence of DSPN and sDSPN in the whole group (n=119) was 18% and 23%, respectively. For the biothesiometer, a cut-off of ≥24.5V had a sensitivity of 82% and specificity of 70% (AUC=0.81, 95% CI 0.71-0.91) when evaluating DSPN. An intraepidermal nerve fibre density cut-off of ≤3.39fibres/mm showed a sensitivity of 74% and specificity of 70% in the detection of sDSPN, whereas the sensitivity of the tuning fork and the biothesiometer were relatively low, 46% and 67%, respectively. When combining skin biopsies with the tuning fork, 10 more sDSPN cases were identified. Adding skin biopsy to the combination of the tuning fork and biothesiometer increased the sensitivity of finding sDSPN cases, but not DSPN, from 81% to 93%.CONCLUSION: Using a biothesiometer in clinical routine might be a sensitive method to detect large nerve fibre dysfunction in the lower extremity, whereas skin biopsies in combination with methods measuring vibrotactile sense could increase the diagnostic sensitivity of detecting peripheral neuropathy at an early stage.
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6.
  • Lindahl, Bernt, et al. (author)
  • A randomized lifestyle intervention with 5-year follow-up in subjects with impaired glucose tolerance : pronounced short-term impact but long-term adherence problems
  • 2009
  • In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 37:4, s. 434-442
  • Journal article (peer-reviewed)abstract
    • AIMS: To compare data on cardiovascular risk factor changes in lipids, insulin, proinsulin, fibrinolysis, leptin and C-reactive protein, and on diabetes incidence, in relation to changes in lifestyle. METHODS: The study was a randomized lifestyle intervention trial conducted in northern Sweden between 1995 and 2000, in 168 individuals with impaired glucose tolerance (IGT) and body mass index above 27 at start. The intensive intervention group (n = 83) was subjected to a 1-month residential lifestyle programme. The usual care group (n = 85) participated in a health examination ending with a single counselling session. Follow-up was conducted at 1, 3 and 5 years. RESULTS: At 1-year follow-up, an extensive cardio-metabolic risk factor reduction was demonstrated in the intensive intervention group, along with a 70% decrease of progress to type 2 diabetes. At 5-year follow-up, most of these beneficial effects had disappeared. Reported physical activity and fibre intake as well as high-density lipoprotein cholesterol were still increased, and fasting insulin and proinsulin were lower. CONCLUSIONS: The intervention affected several important cardio-metabolic risk variables beneficially, and reduced the risk for type 2 diabetes, but the effects persisted only as long as the new lifestyle was maintained. Increased physical activity seemed to be the behaviour that was most easy to preserve.
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7.
  • Lodefalk, Maria, 1968-, et al. (author)
  • Food habits, energy and nutrient intake in adolescents with Type 1 diabetes mellitus
  • 2006
  • In: Diabetic Medicine. - Oxon, United Kingdom : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 23:11, s. 1225-1232
  • Journal article (peer-reviewed)abstract
    • AIMS: The aims were to describe the food habits of adolescents with Type 1 diabetes (Type 1 DM) and to compare them with healthy control subjects; to describe the distribution of energy-providing nutrients in patients and compare it with current recommendations and previous reports; and finally, to investigate associations between dietary intake and glycaemic control. METHODS: One hundred and seventy-four adolescents with Type 1 DM and 160 age- and sex-matched healthy control subjects completed a validated food frequency questionnaire, and 38 randomly chosen patients completed a prospective 4-day food record. RESULTS: Patients ate more regularly, and more often ate fruit and fruit juice, potatoes and root vegetables, meat, fish, egg, offal and sugar-free sweets than control subjects. Control subjects more often ate ordinary sweets and snacks. Patients chose coarse rye bread and dairy products with less fat to a greater extent than control subjects. Patients were heavier than control subjects. The intake of saturated fat was higher in patients compared with recommendations and, for boys with diabetes, the intake of protein was higher than recommended. Patients with poorer glycaemic control ate vegetables, fruit and fish less often than patients with better control. CONCLUSIONS: The food habits of adolescents with Type 1 DM were healthier than those of control subjects. The intake of energy-providing nutrients was in line with current recommendations and showed improvements compared with previous reports, with the exception of fibre intake. The association between dietary intake and glycaemic control needs further investigation in prospective studies.
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8.
  • Hoey, Hilary, et al. (author)
  • Parent and health professional perspectives in the management of adolescents with diabetes : development of assessment instruments for international studies
  • 2006
  • In: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 15:6, s. 1033-1042
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Assessment of quality of life (QOL) in adolescents with diabetes requires patient, parent and health professional input. Psychometrically robust instruments to assess parent and professional perspectives are required. RESEARCH DESIGN AND METHODS: Questionnaires concerning adolescent QOL were developed for completion by parents and health professionals. In an international study assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10-18; from 17 countries including Europe, Japan and North America), parents and health professionals completed their respective questionnaires between March and August 1998. RESULTS: Feasibility and acceptability of the new questionnaires were indicated by high questionnaire completion rates (adolescents 92%; parents 89%; health professionals 94%). Internal consistency was confirmed (Cronbach's alpha coefficients 0.80 parent; 0.86 health professional). Correlations of Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and health professional global QOL ratings were generally low (r ranging from 0.12 to 0.36). Parent-rated burden decreased incrementally across adolescence, particularly for girls. Professional-rated burden followed a similar profile but only after age 15 years. Until then, burden was rated as uniformly high. Clinically relevant discrepancies in parent and professional burden scores were noted for one-parent families and families where adolescents had been referred for psychological help. In both cases, health professionals but not one-parent families perceived these as high burden situations. The clinical significance of this relates to the significantly poorer metabolic control recorded for adolescents in both situations. CONCLUSIONS: Parent and health professional questionnaires were found to have adequate internal consistency, and convergent and discriminant validity in relation to key clinical and QOL outcomes. The questionnaires are brief, easy to administer and score. They may also enable comparisons across countries and languages to facilitate development of international health outcome parameters. The inclusion of the parent and health professional perspectives completes a comprehensive assessment of adolescent QOL relevant to diabetes.
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9.
  • Tejedor, Sandra, et al. (author)
  • The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice : An Ex Vivo and In Vivo Investigation
  • 2024
  • In: Cells. - : MDPI. - 2073-4409. ; 13:5
  • Journal article (peer-reviewed)abstract
    • Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.
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10.
  • Lewerin, Catharina, 1961, et al. (author)
  • Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden.
  • 2014
  • In: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 131-140
  • Journal article (peer-reviewed)abstract
    • In a population-based study on cobalamin status and incident fractures in elderly men (n=790) with an average follow-up of 5.9years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.
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11.
  • Backman, Olof, et al. (author)
  • Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels : A Nationwide Cohort Study From Sweden
  • 2019
  • In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 269:5, s. 895-902
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.SUMMARY OF BACKGROUND DATA: Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.METHODS: The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.RESULTS: Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67-0.89; P < 0.001).CONCLUSIONS: Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetes but also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.
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12.
  • Elfström, Peter, 1974-, et al. (author)
  • Risk of primary adrenal insufficiency in patients with celiac disease
  • 2007
  • In: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3595-3598
  • Journal article (peer-reviewed)abstract
    • Objectives: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD).Wehave here investigated the risk of AD in individuals with CD from a general population cohort.Methods: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964–2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.Results: There was a statistically significantly positive association between CD and subsequent AD [HR _ 11.4; 95% confidence interval (CI) _ 4.4 –29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI _ 1.9 –11.4). Individuals with prior AD were at increased risk of CD (odds ratio _ 8.6; 95% CI _ 3.4 –21.8).Conclusions: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.
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13.
  • Johansson, Karin, et al. (author)
  • Patients' experiences of support for learning to live with diabetes to promote health and well-being : A lifeworld phenomenological study
  • 2016
  • In: International Journal of Qualitative Studies on Health and Well-being. - : Taylor & Francis. - 1748-2623 .- 1748-2631. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Learning to live with diabetes in such a way that the new conditions will be a normal and natural part of life imposes requirements on the person living with diabetes. Previous studies have shown that there is no clear picture of what and how the learning that would allow persons to incorporate the illness into their everyday life will be supported. The aim of this study is to describe the phenomenon of support for learning to live with diabetes to promote health and well-being, from the patient's perspective. Data were collected by interviews with patients living with type 1 or type 2 diabetes. The interviews were analysed using a reflective lifeworld approach. The results show that reflection plays a central role for patients with diabetes in achieving a new understanding of the health process, and awareness of their own responsibility was found to be the key factor for such a reflection. The constituents are responsibility creating curiosity and willpower, openness enabling support, technology verifying bodily feelings, a permissive climate providing for participation and exchanging experiences with others. The study concludes that the challenge for caregivers is to create interactions in an open learning climate that initiates and supports reflection to promote health and well-being.
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14.
  • Stogianni, Anna, et al. (author)
  • Obstetric and perinatal outcomes in pregnancies complicated by diabetes, and control pregnancies, in Kronoberg, Sweden
  • 2019
  • In: BMC Pregnancy and Childbirth. - : BioMed Central. - 1471-2393 .- 1471-2393. ; 19
  • Journal article (peer-reviewed)abstract
    • BackgroundDiabetes during pregnancy is an increasingly common metabolic disorder, associated with significantly increased risks for both mother and child. Aim of this study was to compare maternal and perinatal outcomes in women with pregestational (PDM) type 1 (T1DM), type 2 diabetes (T2DM), gestational diabetes mellitus (GDM) and compare these to pregnancies not complicated with diabetes. This study also evaluated a specifically organized care-model mostly involving specialist diabetes nurses.MethodsRetrospective population-based records review 2009-2012. Rates of maternal (preeclampsia, pre-term delivery, cesarean section (CS)) and fetal outcomes (large for gestational age (LGA), macrosomia, congenital malformations/intrauterine death) were assessed and potential predisposing or contributing factors as maternal age, ethnicity, obesity, weight gain, parity, HbA1c levels, insulin types and doses.ResultsAmong 280 pregnancies 48 were PDM, 97 GDM and 135 without diabetes. Within the group with diabetes, early-pregnancy BMI was higher (p=0.0001), pregnancy weight gain lower (11.16.7kg vs 13.1 +/- 7.1kg, p=0.005), more delivered preterm (p=0.0001), by CS (p=0.05), and had more LGA neonates (p=0.06) than the group without diabetes. Among pregnancies with diabetes, GDM mothers gained less weight (9.9kg vs 13.5kg) (p=0.006), and rates of CS (p=0.03), preterm deliveries (p=0.001) and LGA (p=0.0001) were not increased compared to PDM; More T1DM infants were LGA, 60% vs. 27% in T2DM. In pregnancies with diabetes obesity, excessive weight gain and multiparity were associated with increased risk of LGA neonates, and mother's type of diabetes and gestational week were associated with higher rates of CS.Conclusion p id=Par4 Weight gain during pregnancy was lower in pregnancies with diabetes and prevalence of LGA, CS and preterm deliveries in GDM was not elevated, also for T2DM, except increased prevalence of LGA in T1DM that warrants increased clinical attention, indicating that this model of antenatal diabetes care may have contributed to improved maternal and fetal outcomes.
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15.
  • Jansson, Stefan P.O. 1959-, et al. (author)
  • Mortality trends in subjects with and without diabetes during 33 years of follow up
  • 2009
  • In: Diabetes Care. - Alexandria, USA : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 33:3, s. 551-556
  • Journal article (peer-reviewed)abstract
    • Objective: Mortality rates have declined substantially over the past decades in the general population, but the situation among diabetic subjects is less clear. The aim of this study was to analyze mortality trends in diabetic and nondiabetic subjects during 1972–2004.Research design and methods: Since 1972, all patients with diabetes are entered in a diabetes register at Laxå Primary Health Care Center; 776 incident cases were recorded up to 2001. The register has been supplemented with a nondiabetic population of 3,880 subjects and with data from the National Cause of Death Register during 1972 to 2004.Results: During the 33-year follow-up period, 233 (62.0%) diabetic women and 240 (60.0%) diabetic men and 995 (52.9%) nondiabetic women and 1,082 (54.1%) nondiabetic men died. The age-adjusted hazard ratio (HR) for all-cause mortality among diabetic and nondiabetic subjects was 1.17 (P < 0.0021) for all, 1.22 (P < 0.007) for women, and 1.13 (P = 0.095) for men. The corresponding cardiovascular disease (CVD) mortality HRs were 1.33 (P < 0.0001), 1.41 (P < 0.0003), and 1.27 (P < 0.0093), respectively. The CVD mortality reduction across time was significant in nondiabetic subjects (P < 0.0001) and in men with diabetes (P = 0.014) but not in diabetic women (P = 0.69). The results regarding coronary heart disease (CHD) were similar (P < 0.0001, P < 0.006, and P = 0.17, respectively). The CVD and CHD mortality rate change across time was fairly linear in all groups.Conclusions: Diabetic subjects had less mortality rate reduction during follow-up than nondiabetic subjects. However the excess mortality risk for diabetic subjects was smaller than that found in other studies.
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16.
  • Lindqvist, A, et al. (author)
  • Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients
  • 1997
  • In: Clinical Physiology. - : Wiley. - 1365-2281 .- 0144-5979. ; 17:2, s. 159-169
  • Journal article (peer-reviewed)abstract
    • Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n = 23, age 35 +/- 9 years; mean +/-SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n = 18, 38 +/- 13 years), with AN but no cardiovascular drugs (group 2a: n = 7, 44 +/- 11 years) and with both AN and cardiovascular drugs (group 2b: n = 10, 47 +/- 7 years). Systolic and diastolic overshoot were similar in the control (15 +/- 13/15 +/- 11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (-1 +/- 9 mmHg; P < 0.03), whereas artery blood pressure still overshot in diastole (8 +/- 7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (-22 +/- 22 mmHg; P < 0.0006) and diastolic overshoot disappeared in 60% of these patients (-6 +/- 16 mmHg; P = 0.0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P < 0.006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for chi 2 < 0.001, n = 58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r > or = 0.76; P < or = 0.001). In conclusion, baroreceptor reflex-dependent overshoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.
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17.
  • Boman, Åse, 1957-, et al. (author)
  • Health care to empower self-care in adolescents with type 1 diabetes mellitus and an immigrant minority background
  • 2017
  • In: Sage Open medicine. - : SAGE Publications. - 2050-3121 .- 2050-3121. ; 5
  • Journal article (peer-reviewed)abstract
    • Background: The pediatric diabetes team aims to support health, quality of life, and normal growth and development among adolescents with type 1 diabetes mellitus. Adolescents with an immigrant background have been found less successful in self-care. Previous research indicated that adolescents who had integrated the disease as a part of their self-image reasoned differently about their self-care to those who had not. Objective: The aim of this study was to identify elements in the patient–pediatrician consultations that might influence such integration of the disease among adolescents with type 1 diabetes mellitus. Methods: A total of 12 pediatrician–adolescent consultations were video-recorded and analyzed. The adolescents all had an immigrant background. Results: Integration of the disease appeared enabled when responsibility was shared; when hope, autonomy, and emotions were confirmed; and when the pediatrician asked probing questions. Letting objective data dominate the adolescent’s experiences, using risk as a motivator, neutralizing emotions in relation to having diabetes, and confirming forgetfulness, may instead inhibit disease integration. Conclusion: An extended person-centered approach with focus on the adolescent’s experiences of everyday life with a chronic disease and less attention on physical parameters in the pediatrician–adolescent consultations may increase integration of the disease.
  •  
18.
  • Solinas, Giovanni, et al. (author)
  • An adipoincretin effect links adipostasis with insulin secretion.
  • 2024
  • In: Trends in endocrinology and metabolism: TEM. - 1879-3061. ; 35:6, s. 466-477
  • Research review (peer-reviewed)abstract
    • The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretins, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect.
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19.
  • Albertsson-Wikland, Kerstin, 1947, et al. (author)
  • Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
  • 2008
  • In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
  • Journal article (peer-reviewed)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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20.
  • Herlitz, Anders, 1981, et al. (author)
  • The Counseling, Self-care, Adherence Approach to Person-centered Care and Shared Decision Making: Moral Psychology, Executive Autonomy, and Ethics in Multi-dimensional Care Decisions
  • 2016
  • In: Health Communication. - : Informa UK Limited. - 1041-0236 .- 1532-7027. ; 31:8, s. 964-973
  • Journal article (peer-reviewed)abstract
    • This article argues that standard models of person-centred care (PCC) and shared decision making (SDM) rely on simplistic, often unrealistic assumptions of patient capacities that entail that PCC/SDM might have detrimental effects in many applications. We suggest a complementary PCC/SDM approach to ensure that patients are able to execute rational decisions taken jointly with care professionals when performing self-care. Illustrated by concrete examples from a study of adolescent diabetes care, we suggest a combination of moral and psychological considerations to support the claim that standard PCC/SDM threatens to systematically undermine its own goals. This threat is due to a tension between the ethical requirements of SDM in ideal circumstances and more long-term needs actualized by the context of self-care handled by patients with limited capacities for taking responsibility and adhere to their own rational decisions. To improve this situation, we suggest a counseling, self-care, adherence approach to PCC/SDM, where more attention is given to how treatment goals are internalized by patients, how patients perceive choice situations, and what emotional feedback patients are given. This focus may involve less of a concentration on autonomous and rational clinical decision making otherwise stressed in standard PCC/SDM advocacy.
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21.
  • Paterson, R W, et al. (author)
  • A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.
  • 2016
  • In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6:11
  • Journal article (peer-reviewed)abstract
    • Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.
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22.
  • Hellstrand Tang, Ulla, 1956, et al. (author)
  • Exploring the Role of Complexity in Health Care Technology Bottom-Up Innovations : Multiple-Case Study Using the Nonadoption, Abandonment, Scale-Up, Spread, and Sustainability Complexity Assessment Tool
  • 2024
  • In: JMIR Human Factors. - : JMIR Publications. - 2292-9495. ; 11:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: New digital technology presents new challenges to health care on multiple levels. There are calls for further research that considers the complex factors related to digital innovations in complex health care settings to bridge the gap when moving from linear, logistic research to embracing and testing the concept of complexity. The nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework was developed to help study complexity in digital innovations.OBJECTIVE: This study aims to investigate the role of complexity in the development and deployment of innovations by retrospectively assessing challenges to 4 digital health care innovations initiated from the bottom up.METHODS: A multicase retrospective, deductive, and explorative analysis using the NASSS complexity assessment tool LONG was conducted. In total, 4 bottom-up innovations developed in Region Västra Götaland in Sweden were explored and compared to identify unique and shared complexity-related challenges.RESULTS: The analysis resulted in joint insights and individual learning. Overall, the complexity was mostly found outside the actual innovation; more specifically, it related to the organization's readiness to integrate new innovations, how to manage and maintain innovations, and how to finance them. The NASSS framework sheds light on various perspectives that can either facilitate or hinder the adoption, scale-up, and spread of technological innovations. In the domain of condition or diagnosis, a well-informed understanding of the complexity related to the condition or illness (diabetes, cancer, bipolar disorders, and schizophrenia disorders) is of great importance for the innovation. The value proposition needs to be clearly described early to enable an understanding of costs and outcomes. The questions in the NASSS complexity assessment tool LONG were sometimes difficult to comprehend, not only from a language perspective but also due to a lack of understanding of the surrounding organization's system and its setting.CONCLUSIONS: Even when bottom-up innovations arise within the same support organization, the complexity can vary based on the developmental phase and the unique characteristics of each project. Identifying, defining, and understanding complexity may not solve the issues but substantially improves the prospects for successful deployment. Successful innovation within complex organizations necessitates an adaptive leadership and structures to surmount cultural resistance and organizational impediments. A rigid, linear, and stepwise approach risks disregarding interconnected variables and dependencies, leading to suboptimal outcomes. Success lies in embracing the complexity with its uncertainty, nurturing creativity, and adopting a nonlinear methodology that accommodates the iterative nature of innovation processes within complex organizations.
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23.
  • Sundbom, Magnus, et al. (author)
  • Substantial Decrease in Comorbidity 5 Years After Gastric Bypass: A Population-based Study From the Scandinavian Obesity Surgery Registry.
  • 2017
  • In: Annals of Surgery. - Philadelphia PA, USA : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 265:6, s. 1166-1171
  • Journal article (peer-reviewed)abstract
    • Objective: To evaluate effect on comorbid disease and weight loss 5 years after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity in a large nationwide cohort. Background: The number patients having surgical procedures to treat obesity and obesity-related disease are increasing. Yet, population-based, long-term outcome studies are few. Methods: Data on 26,119 individuals [75.8% women, 41.0 years, and body mass index (BMI) 42.8 kg/m2] undergoing primary RYGB between May 1, 2007 and June 30, 2012, were collected from 2 Swedish quality registries: Scandinavian Obesity Surgery Registry and the Prescribed Drug Registry. Weight, remission of type 2 diabetes mellitus, hypertension, dyslipidemia, depression, and sleep apnea, and changes in corresponding laboratory data were studied. Five-year follow-up was 100% (9774 eligible individuals) for comorbid diseases. Results: BMI decreased from 42.8 ± 5.5 to 31.2 ± 5.5 kg/m2 at 5 years, corresponding to 27.7% reduction in total body weight. Prevalence of type 2 diabetes mellitus (15.5%–5.9%), hypertension (29.7%–19.5%), dyslipidemia (14.0%–6.8%), and sleep apnea (9.6%–2.6%) was reduced. Greater weight loss was a positive prognostic factor, whereas increasing age or BMI at baseline was a negative prognostic factor for remission. The use of antidepressants increased (24.1%–27.5%). Laboratory status was improved, for example, fasting glucose and glycated hemoglobin decreased from 6.1 to 5.4 mmol/mol and 41.8% to 37.7%, respectively. Conclusions: In this nationwide study, gastric bypass resulted in large improvements in obesity-related comorbid disease and sustained weight loss over a 5-year period. The increased use of antidepressants warrants further investigation. Studies with long-term results after bariatric surgery are surprisingly rare, 1–5 especially in the light of the large number of procedures performed worldwide. In most studies there is a 1 to 2-year follow-up, 6 and at such an early point in time, it is impossible to evaluate the true effect of gastric bypass, because patients have just reached their nadir in weight. Moreover, for this group of patients, the longstanding remission of obesity-related comorbidities, for example, diabetes mellitus, hypertension, dyslipidemia, and sleep apnea, are of utmost importance. The Scandinavian Obesity Surgery Registry (SOReg) was launched in 2007 as a quality registry for the expanding number of bariatric surgeries in Sweden. 7 In 2015, SOReg contained more than 50,000 bariatric procedures (>98% national coverage), with all 43 operating centers reporting to the registry. There has been an expansion of bariatric surgery, with 3300 bariatric procedures performed in 2008, 4800 in 2009, 7800 in 2010, and 8600 in 2011. There has been a slight decrease in procedures, and currently approximately 7000 performed annually, and approximately 95% of the reported procedures have been primary laparoscopic gastric bypass. 8 Perioperative complication rates (eg, 1.2% leaks) and mortality are low (0.04%), the latter validated with the Swedish Population Register. Regular audits are performed by randomly comparing data in SOReg with patient charts at the surgical centers, demonstrating a high validity with less than 2% incorrect values. 7 Furthermore, by cross-linkage with the national Prescribed Drug Registry (PDR), a 100% follow-up of the occurrence of comorbid disease (defined as medical treatment) can be achieved. The present study reports outcome in weight and obesity-related comorbid disease in a nationwide cohort of 26,119 individuals over 5 years after primary Roux-en-Y gastric bypass (RYGB) in Sweden, using the prospective SOReg database with cross-linkage with the PDR.
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24.
  • Schlesinger, S, et al. (author)
  • Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort
  • 2013
  • In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:9, s. 2449-2455
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.
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25.
  • Åkerman, Linda, 1983- (author)
  • Aspects of the Pre-Diabetic Period in Type 1 Diabetes
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.
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26.
  • Toschke, Audré M., et al. (author)
  • 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
  • In: Journal of Perinatal Medicine. - Berlin : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 35:1, s. 43-7
  • Journal article (peer-reviewed)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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27.
  • Brundin, Peik M. A., 1975- (author)
  • Sex differences in immune response and sex hormone receptor expression in healthy individuals and during viral infection
  • 2021
  • Doctoral thesis (other academic/artistic)abstract
    • There is sex-bias in morbidity and mortality from infectious diseases. Infections kill more men than women and several studies have pointed out differences in the immune system as a reason. The sex hormones estrogen, progesterone and testosterone all shape the effect of the immune response on multiple levels. Women at fertile age have been suggested to have higher proinflammatory responses from inflammatory stimuli compared to men and post-menopausal women, which has been ascribed to their higher estrogen levels. This could possibly lead to a more active pathogen response but may also result in a detrimental immunopathology to infections or development of autoimmune reaction.The overall aim of this thesis is to study the contribution of sex hormones and sex hormone receptors (SHR) to sex differences in immune response. We focus on peripheral blood mononuclear cells (PBMCs) to study such relationships in healthy individuals, as well as in individuals with asymptomatic Torque Teno Virus infection, and individuals with acute Puumala virus infection.In Paper I, we investigated expression of SHR and immune response genes in PBMC from healthy premenopausal (pre-MP) women during the menstrual cycle. The expression levels were estimated using a qPCR Array (Taqman low-density array, TLDA). SHR expression did not change significantly during the menstrual cycle, but several key immune regulatory genes were significantly more expressed during the ovulatory and mid luteal phase. Further, we separated PBMC into cell subsets (CD4+ T-cells, CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) and analyzed the expression through qPCR of estrogen receptors (ERs), ERα, ERβ1 (wildtype) and the isoform ERβ2. For the first time and unexpectedly, we demonstrate that the isoform ERβ2 was more abundant than wildtype ERβ1. The data from this paper provides new knowledge on the contribution of the menstrual cycle on immune response.In Paper II, we explored the use of Torque Teno Virus as a secondary functional immune marker in men and women. Expression of viral TTV DNA in PBMCs was estimated using a qPCR kit from Argene (R-gene) and analyzed in relation to serum sex hormone levels. The results showed that 50% of the men, 25% the post-MP women, and 18% of the pre-MP women were TTV+. Interestingly, all pre-MP women that were TTV+ had hormonal aberrances and were either anovulatory and/or hypothyroid. TTV+ pre-MP women also had significantly lower progesterone levels than TTV- pre-MP women. This paper indicates that the prevalence of TTV in PBMC differs between men, pre-MP and post-MP women. Furthermore, hormonal aberrances (at least in pre-MP women) will lead to increased prevalence of TTV.In Paper III we investigated the expression of ERα, ERβ1 and ERβ2 in PBMC from patients with Nephropathia epidemica, the viral zoonotic disease caused by Puumala virus, a Hanta virus known to affect more men than women. Expression of ERs in PBMCs and clinical laboratory results during the acute and convalescent phases were analyzed using a principal component analysis (PCA). The results show differences in ER expression and support previous findings that men and women have a different clinical pictureIn conclusion, the results in this thesis reveal distinct patterns of immune response related to sex hormone levels, SHR expression and the phases of the menstrual cycle supporting that there a link between sex hormone levels and immune responses. Further, we show that the ER isoform ERβ2 is more abundant in PBMCs than what was previously described. The data in this thesis adds to the knowledge to the sex differences in immune response and exemplifies the importance of taking these differences into account in the clinic.
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28.
  • Holmer, Helene, et al. (author)
  • Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
  • 2007
  • In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
  • Journal article (peer-reviewed)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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29.
  • Taddei, C, et al. (author)
  • Repositioning of the global epicentre of non-optimal cholesterol
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
  • Journal article (peer-reviewed)abstract
    • High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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30.
  • Decker, Ralph, 1968, et al. (author)
  • Case report of a girl with secondary amenorrhea associated with aurantiasis cutis
  • 2016
  • In: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826.
  • Conference paper (other academic/artistic)abstract
    • Introduction: --- Aurantiasis cutis is a condition of yellowish or golden skin discoloration that can result from eating excessive amounts of foods containing carotene leading to hypercarotenemia(1), described causing secondary amenorrhea(2). Objective & hypothesis: --- Hypercarotenemia can cause secondary amenorrhea without overconsumption of excessive quantities of carotene. Results: --- Laboratory tests showed a ß-Carotene level more than the 2-fold above the upper reference level. Hyperbilirubinemia could be excluded. Hypogonadotropic hypogonadism was not present. There was no evidence for adrenal dysfunction. Liver function tests were normal. Material/ Methods: --- A 16-year-old girl presented to our endocrine outpatient clinic with a 2-year history of varying yellow discoloration of her skin and secondary amenorrhea. The findings of the general physical examination were normal, but there was a marked yellow discoloration of the palms, soles, and nasolabial folds. A dietary history revealed a low carotene diet, but also a low carbohydrate diet. BMI was 19.9 kg/m² (-0.2 SDS) without signs of anorexia. Discussion: --- In this girl we observed hypercarotenemia associated with secondary nonhypothalamic amenorrhea in absence of excess external intake of carotenes. This suggests an intrinsic reason due to a polymorphism(3) in ß-carotene 15,15'-monooxygenase (BCO)(4), an enzyme breaking down carotenes to vitamin A(5). Phenotype-genotype association studies are needed to confirm this hypothesis. Conclusion: --- Secondary non-hypothalamic amenorrhea can be associated with hypercarotenemia. References: --- 1. Tanikawa K, Seta K, Machii A, Itoh S 1961 [Aurantiasis cutis due to overeating of dried laver (nori): a case report]. Jpn J Med Sci Biol 50:414-419 2. Kemmann E, Pasquale SA, Skaf R 1983 Amenorrhea associated with carotenemia. JAMA 249:926-929 3. Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G 2009 Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB j 23:1041-1053 4. Frumar AM, Meldrum DR, Judd HL 1979 Hypercarotenemia in hypothalamic amenorrhea. Fertil Steril 32:261-264 5. Lindqvist A, Andersson S 2002 Biochemical properties of purified recombinant human beta-carotene 15,15'-monooxygenase. J Biol Chem 277:23942-23948
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31.
  • Türkmen, Sahruh, et al. (author)
  • Tolerance development to Morris water maze test impairments induced by acute allopregnanolone
  • 2006
  • In: Neuroscience. - : Elsevier Inc.. - 0306-4522 .- 1873-7544. ; 139:2, s. 651-659
  • Journal article (peer-reviewed)abstract
    • The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.
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32.
  • Nowak, Christoph, 1986- (author)
  • Insulin Resistance : Causes, biomarkers and consequences
  • 2017
  • Doctoral thesis (other academic/artistic)abstract
    • The worldwide increasing number of persons affected by largely preventable diseases like diabetes demands better prevention and treatment. Insulin is required for effective utilisation of circulating nutrients. Impaired responsiveness to insulin (insulin resistance, IR) is a hallmark of type 2 diabetes and independently raises the risk of heart attack and stroke. The pathophysiology of IR is incompletely understood. High-throughput measurement of large numbers of circulating biomarkers may provide new insights beyond established risk factors.The aims of this thesis were to (i) use proteomics, metabolomics and genomics methods in large community samples to identify biomarkers of IR; (ii) assess biomarkers for risk prediction and insights into aetiology and consequences of IR; and (iii) use Mendelian randomisation analysis to assess causality.In Study I, analysis of 80 circulating proteins in 70-to-77-year-old Swedes identified cathepsin D as a biomarker for IR and highlighted a tentative causal effect of IR on raised plasma tissue plasminogen activator levels. In Study II, nontargeted fasting plasma metabolomics was used to discover 52 metabolites associated with glycaemic traits in non-diabetic 70-year-old men. Replication in independent samples of several thousand persons provided evidence for a causal effect of IR on reduced plasma oleic acid and palmitoleic acid levels. In Study III, nontargeted metabolomics in plasma samples obtained at three time points during an oral glucose challenge in 70-year-old men identified associations between a physiologic measure of IR and concentration changes in medium-chain acylcarnitines, monounsaturated fatty acids, bile acids and lysophosphatidylethanolamines. Study IV provided evidence in two large longitudinal cohorts for causal effects of type 2 diabetes and impaired insulin secretion on raised coronary artery disease risk.In conclusion, the Studies in this thesis provide new insights into the pathophysiology and adverse health consequences of IR and illustrate the value of combining traditional epidemiologic designs with recent molecular techniques and bioinformatics methods. The results provide limited evidence for the role of circulating proteins and small molecules in IR and require replication in separate studies and validation in experimental designs.
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33.
  • Pourhamidi, Kaveh, 1985-, et al. (author)
  • Association between symptoms of neuropathy, nerve conduction and levels of heat shock protein 27 in type 2 diabetes
  • 2010
  • Conference paper (peer-reviewed)abstract
    • Background and aims: Increased levels of serum HSP27 (sHSP27) are associated with distal symmetric polyneuropathy (DSPN) in type 1 diabetic patients. However, the association between nerve function and sHSP27 has not been studied in subjects with type 2 diabetes (T2D) and impaired glucose tolerance (IGT). Thus, our objectives were to investigate the association between nerve conduction in the legs, symptoms of distal polyneuropathy and sHSP27 levels. Methods: Subjects were consecutively recruited from the population-based Västerbotten Intervention Program; controls (n=39, m/f=19/20, mean age=61± 0.6 years), IGT (n=29, m/f=15/14, mean age=61± 0.8 years), T2D (n=51, m/f=30/21, mean age=61± 1.3 years). Nerve conduction studies were performed. Z-scores for motor conduction velocity (CV) of the peroneal nerve, and the sensory CV and amplitude of the sural nerve were measured and compiled into a composite Z-score of the right leg (Z-score leg). Neurological Disability Score (NDS), including examination of sensory perception, reflexes and muscle strength, were used to evaluate symptoms of neuropathy in the leg. NDS and Z-score leg were categorized into tertiles, respectively. sHSP27 levels were measured and divided into low and high levels. Results: Subjects in the highest NDS tertile had lower sHSP27 levels (328 ± 287 pg/mL) compared to subjects in the lowest NDS tertile (558 ± 404 pg/mL, p=0.04). Subjects in the lowest tertile of Z-score leg were in the lowest sHSP27 group (63%) compared to the subjects in the highest group (38%, p=0.034). The highest tertile of Z-score leg was associated with high levels of sHSP27 (OR 3.8, 95% CI 1.2; 11.5, p=0.02); adjusted for age and sex. However, this association was attenuated when adjusted for T2D status (OR 3.1, 95% CI 0.9; 9.9, p=0.06). Conclusion: In summary, increased sHSP27 levels were associated with an increasing Z-score of the leg; thus, a better nerve conduction, and fewer symptoms using the whole study population. The attenuation of the association when including diabetic status indicates an altered HSP27 production in T2D patients compared to controls and subjects with IGT.
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34.
  • Xu, H., et al. (author)
  • Excess protein intake relative to fiber and cardiovascular events in elderly men with chronic kidney disease
  • 2016
  • In: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 26:7, s. 597-602
  • Journal article (peer-reviewed)abstract
    • Background and aims: The elevated cardiovascular (CVD) risk observed in chronic kidney disease (CKD) may be partially alleviated through diet. While protein intake may link to CVD events in this patient population, dietary fiber has shown cardioprotective associations. Nutrients are not consumed in isolation; we hypothesize that CVD events in CKD may be associated with dietary patterns aligned with an excess of dietary protein relative to fiber. Methods and Results: Prospective cohort study from the Uppsala Longitudinal Study of Adult Men. Included were 390 elderly men aged 70-71 years with CKD and without clinical history of CVD. Protein and fiber intake, as well as its ratio, were calculated from 7-day dietary records. Cardiovascular events were registered prospectively during a median follow-up of 9.1 (inter-quartile range, 4.5-10.7) years. The median dietary intake of protein and fiber was 66.7 (60.7-71.1) and 16.6 (14.5-19.1) g/day respectively and the protein-to-fiber intake ratio was 4.0 (3.5-4.7). Protein-to-fiber intake ratio was directly associated with serum C-reactive protein levels. During follow-up, 164 first-time CVD events occurred (incidence rate 54.5/1000 per year). Protein-fiber intake ratio was an independent risk factor for CVD events [adjusted hazard ratio, HR per standard deviation increase (95% confidence interval, CI) 1.33 (1.08, 1.64)]. Although in opposing directions, dietary protein [1.18 (0.97, 1.44)], dietary fiber alone [0.81 (0.64, 1.02)], were not significantly associated with CVD events. Conclusions: An excess of dietary protein relative to fiber intake was associated with the incidence of cardiovascular events in a homogeneous population of older men with CKD.
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35.
  • Xu, H., et al. (author)
  • Lipophilic index, kidney function, and kidney function decline
  • 2016
  • In: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 31, s. 177-177
  • Journal article (peer-reviewed)abstract
    • Background and aims: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Methods and results: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended reexamination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction >= 30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m(2) 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m(2), p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). Conclusions: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.
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36.
  • Janelidze, Shorena, et al. (author)
  • Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
  • 2017
  • In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 104-112
  • Journal article (peer-reviewed)abstract
    • Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF bio-markers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage. (C) 2016 The Authors. Published by Elsevier Inc.
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37.
  • Teede, Helena J., et al. (author)
  • Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome
  • 2023
  • In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 189
  • Journal article (peer-reviewed)abstract
    • Study question: 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? Summary answer: 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. What is known already: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from 6 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, the evidence quality was low, and evidence-practice gaps persist. Study design, size, and duration: The 2023 International Evidence-based Guideline update re-engaged 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. Participants/materials, setting, and methods: This summary should be read in conjunction with the full guideline for detailed participants and methods. Governance included a 6-continent international advisory and management committee, 5 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 5 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 5 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. Main results and the role of chance: The evidence in the assessment and management of PCOS has generally improved in the past 5 years but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpin 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include the following: (1) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm, and inclusion of anti-Müllerian hormone levels as an alternative to ultrasound in adults only; (2) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnoea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; (3) 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; (4) maintained emphasis on healthy lifestyle, emotional well-being, and quality of life, with awareness and consideration of weight stigma; and (5) emphasizing evidence-based medical therapy and cheaper and safer fertility management. Limitations and reasons for caution: Overall, recommendations are strengthened and evidence is improved but remains 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. Wider implications of the findings: 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 programme.
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38.
  •  
39.
  • Löfgren, Magnus, 1979- (author)
  • Behavioral effects of female sex steroid hormones : models of PMS and PMDD in Wistar rats
  • 2009
  • Doctoral thesis (other academic/artistic)abstract
    • Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors. Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids. Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA). Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior. Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats.
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40.
  • Guo, Jie, et al. (author)
  • Differential impacts of fat and muscle mass on cardiovascular and non-cardiovascular mortality in individuals with type 2 diabetes.
  • 2024
  • In: Journal of Cachexia, Sarcopenia and Muscle. - : John Wiley & Sons. - 2190-5991 .- 2190-6009.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The distribution of fat and muscle mass in different regions of the body can reflect different pathways to mortality in individuals with diabetes. Therefore, we investigated the associations between whole-body and regional body fat and muscle mass with cardiovascular disease (CVD) and non-CVD mortality in type 2 diabetes (T2D).METHODS: Within the National Health and Nutrition Examination Survey 1999-2006, 1417 adults aged ≥50 years with T2D were selected. Dual-energy X-ray absorptiometry was used to derive whole-body, trunk, arm, and leg fat mass and muscle mass indices (FMI and MMI). Mortality data until 31 December 2019 were retrieved from the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models.RESULTS: A total of 1417 participants were included in this study (weighted mean age [standard error]: 63.7 [0.3] years; 50.5% female). Over a median follow-up of 13.6 years, 797 deaths were recorded (371 CVD-related and 426 non-CVD deaths). Higher FMI in the arm was associated with increased risk of non-CVD mortality (fourth quartile [Q4] vs. first quartile [Q1]: HR 1.82 [95% CI 1.13-2.94]), whereas higher FMI in the trunk or leg was not significantly associated with CVD or non-CVD mortality. Conversely, higher arm MMI was associated with a lower risk of both CVD (Q4 vs. Q1: HR 0.51 [95% CI 0.33-0.81]) and non-CVD (Q4 vs. Q1: HR 0.56 [95% CI 0.33-0.94]) mortality. There was a significant interaction between smoking status and arm FMI on non-CVD mortality (P for interaction = 0.007). Higher arm FMI was associated with a higher risk of non-CVD mortality among current or former smokers (Q4 vs. Q1: HR 2.67 [95% CI 1.46-4.88]) but not non-smokers (Q4 vs. Q1: HR 0.85 [95% CI 0.49-1.47]).CONCLUSIONS: Fat mass and muscle mass, especially in the arm, are differently associated with CVD and non-CVD mortality in people with T2D. Our findings underscore the predictive value of body compositions in the arm in forecasting mortality among older adults with T2D.
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41.
  • Jendle, Johan, 1963-, et al. (author)
  • Swedish recommendations on recreational diving and diabetes mellitus.
  • 2012
  • In: Diving and hyperbaric medicine : the journal of the South Pacific Underwater Medicine Society. - Melbourne, Australia : South Pacific Underwater Medicine Society Inc.. - 1833-3516. ; 42:4, s. 231-3
  • Journal article (peer-reviewed)abstract
    • Divers from many countries travel to explore various diving sites worldwide. In 2005, the Divers Alert Network (DAN) wrote guidelines for recreational diving and diabetes mellitus, but there is no up-to-date consensus or adoption of international guidelines on diabetes and diving. There are also large differences between the regulations in different countries. This is potentially both a medical and an insurance problem for a diver with diabetes. We present the current Swedish recommendations for recreational divers with Type 1 diabetes mellitus.
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42.
  • Mortensen, Henrik B., et al. (author)
  • New definition for the partial remission period in children and adolescents with type 1 diabetes
  • 2009
  • In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 32:8, s. 1384-1390
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual beta-cell function. RESULTS By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient -0.21, P < 0.001) and insulin dose (-0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C < or =9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C < or =9 had a significantly higher agreement (P < 0.001) with residual beta-cell function than use of a definition of A1C < or =7.5%. Between 6 and 12 months after diagnosis, for IDAA1C < or =9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C < or =7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose < or =0.5 units . kg(-1) . 24 h(-1) 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual beta-cell function and has better stability compared with the conventional definitions.
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43.
  • Hartvigsson, Thomas, 1985, et al. (author)
  • Error trawling and fringe decision competence: Ethical hazards in monitoring and addressing patient decision capacity in clinical practice
  • 2018
  • In: Clinical Ethics. - : SAGE Publications. - 1477-7509 .- 1758-101X. ; 13:3, s. 126-136
  • Journal article (peer-reviewed)abstract
    • This article addresses how health professionals should monitor and safeguard their patients’ ability to participate in making clinical decisions and making subsequent decisions regarding the implementation of their treatment plan. Patient participation in clinical decision-making is essential, e.g. in self-care, where patients are responsible for most ongoing care. We argue that one common, fact-oriented patient education strategy may in practice easily tend to take a destructive form that we call error trawling. Illustrating with empirical findings from a video study of consultations between clinicians and adolescent patients with diabetes, we argue on independent grounds that this strategy not only risks to overlook significant weaknesses in patient decision competence, but also to undermine patient capacity for decision-making and implementing care. In effect, this strategy for clinically monitoring and addressing the problem of fragile decision-making capacity brings hazards in need of address. We close by suggesting complementary and alternative strategies, and comment on how these may call for broadened competency among clinical health professionals.
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44.
  • Herlitz, Anders, 1981, et al. (author)
  • Family-Centeredness as Resource and Complication in Outpatient Care with Weak Adherence, Using Adolescent Diabetes Care as a Case in Point
  • 2019
  • In: What about the family? : practices of responsibility in care / edited by Marian A. Verkerk, Hilde Lindemann, and Janice McLaughlin.. - Oxford : Oxford University Press. - 9780190624880 ; , s. 137-146
  • Book chapter (peer-reviewed)abstract
    • Care for adolescent patients with diabetes type 1 is a recognized challenge, with known adherence problems in a context where home-/self-care and continuous vital need of day-to-day life-style adjustment. The recommended care regimen often gives rise to conflicts with broader personal and social needs and desires, and in case of weak adherence negative spirals of undermined self-confidence and/or emotional denial further deteriorating the situation may result. The need to adjust care to the specific situation is accepted within the pediatric diabetes professional community, accepting a commitment to person centeredness involving alliance with the family as a critical part. Yet, families can be involved in different ways and the issue of how to involve families and what ethical tensions that may actualize is largely unexplored. Standard models of person- and family-centeredness tell us little about how to involve family members in care similar to that of diabetes. We have elsewhere proposed an alternative approach more attuned to such circumstances, aiming at empowering patients' long-term capacities to manage their condition domestically. This “counselling, self-care, adherence (CSA) approach” offers a look at the role that family can play to improve these types of care. We will illustrate how family members can assist in the care of teenagers with diabetes, but that there are also serious risks actualized by such involvement. In particular, we will highlight ethical complications that arise when the role of a family member is changed from “parent” to “care provider.”
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45.
  • Carlsson, Axel C., et al. (author)
  • Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes
  • 2016
  • In: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15
  • Journal article (peer-reviewed)abstract
    • AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.
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46.
  • Mejaddam, Ala, et al. (author)
  • Comorbidity and quality of life in obesity–a comparative study with the general population in Gothenburg, Sweden
  • 2022
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:10
  • Journal article (peer-reviewed)abstract
    • Context Obesity is considered to have a detrimental impact on health-related quality of life (HRQoL). Objective To compare HRQoL in a well-defined group of people with obesity with a population-based control group from the general public. Design Observational cross-sectional cohort study with a reference population. Setting The Regional Obesity Center at the Department of Medicine at Sahlgrenska University Hospital, Gothenburg, Sweden. Participants People with obesity (n = 1122) eligible for surgical and non-surgical obesity treatment in routine care were included consecutively between 2015 and 2017 into the BASUN study. Men and women from the WHO-MONICA-GOT project were used as a reference population (n = 414). Main outcome measures HRQoL was measured with the RAND-36/Short Form-36 questionnaire (SF-36) and a Visual Analogue Scale (VAS) for self-related health (SRH). Prescription drugs for hypertension, diabetes mellitus, depression, and anxiety were taken as a proxy for these conditions. Results People with obesity rated their overall HRQoL lower than the reference population according to the SRH-VAS. Lower scores were reported on physical and social functioning, vitality, general and mental health after adjustment for age and use of prescription drugs (considered a proxy for burden of disease, or comorbidities) using the RAND-36/SF-36 questionnaire. Use of some psychopharmacological agents was more common in patients with obesity. Conclusion People with obesity seeking help with weight reduction are more likely to have lower physical and mental self-reported HRQoL than the general population.
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47.
  • Li, Peishun, 1988, et al. (author)
  • Metabolic Alterations in Older Women With Low Bone Mineral Density Supplemented With Lactobacillus reuteri
  • 2021
  • In: JBMR Plus. - : Wiley. - 2473-4039. ; 5:4
  • Journal article (peer-reviewed)abstract
    • JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Osteoporosis and its associated fractures are highly prevalent in older women. Recent studies have shown that gut microbiota play important roles in regulating bone metabolism. A previous randomized controlled trial (RCT) found that supplementation with Lactobacillus reuteri ATCC PTA 6475 (L.reuteri) led to substantially reduced bone loss in older women with low BMD. However, the total metabolic effects of L. reuteri supplementation on older women are still not clear. In this study, a post hoc analysis (not predefined) of serum metabolomic profiles of older women from the previous RCT was performed to investigate the metabolic dynamics over 1 year and to evaluate the effects of L. reuteri supplementation on human metabolism. Distinct segregation of the L. reuteri and placebo groups in response to the treatment was revealed by partial least squares-discriminant analysis. Although no individual metabolite was differentially and significantly associated with treatment after correction for multiple testing, 97 metabolites responded differentially at any one time point between L. reuteri and placebo groups (variable importance in projection score >1 and p value <0.05). These metabolites were involved in multiple processes, including amino acid, peptide, and lipid metabolism. Butyrylcarnitine was particularly increased at all investigated time points in the L. reuteri group compared with placebo, indicating that the effects of L. reuteri on bone loss are mediated through butyrate signaling. Furthermore, the metabolomic profiles in a case (low BMD) and control population (high BMD) of elderly women were analyzed to confirm the associations between BMD and the identified metabolites regulated by L. reuteri supplementation. The amino acids, especially branched-chain amino acids, showed association with L. reuteri treatment and with low BMD in older women, and may serve as potential therapeutic targets. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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48.
  • Hernestål-Boman, Jenny, et al. (author)
  • Long-term stability of fibrinolytic factors stored at-80 degrees C
  • 2010
  • In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 125:5, s. 451-456
  • Journal article (peer-reviewed)abstract
    • Introduction: Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits. Materials and Methods: Plasma samples stored at -80 degrees C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n=1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n=1558) and re-analysed 2001 (n=78) and 2005 (n=828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1. Results: Long-term storage for a median time of 11.6 years (range 5 to 20) showed an effect of time on tPA antigen R-2=0.01, PAI-1 antigen R-2=0.01 and tPA-PAI-1 complex R-2=0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R-2 0.47-0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R-2 0.67-0.93). Conclusions: This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect. (C) 2009 Elsevier Ltd. All rights reserved.
  •  
49.
  • Borg, Henrik, et al. (author)
  • High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age
  • 2001
  • In: Journal of Clinical Endocrinology and Metabolism. - 1945-7197. ; 86:7, s. 3032-3038
  • Journal article (peer-reviewed)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.
  •  
50.
  • Tancredi, Mauro, et al. (author)
  • Prevalence of primary aldosteronism among patients with type 2 diabetes
  • 2017
  • In: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 87:3, s. 233-241
  • Journal article (peer-reviewed)abstract
    • Context: Diabetes and hypertension coexist in 40%-60% of individuals with type 2 diabetes. The coexistence of these two conditions is associated with increased risk of retinopathy, nephropathy and cardiovascular disease. Objective: To investigate the prevalence of primary aldosteronism (PA) in a general cohort of persons with type 2 diabetes. Design: Cross-sectional study involving six diabetes outpatient clinics in Sweden. Patients: were enrolled individuals with type 2 diabetes between February 2008 and December 2013. Measurements: Plasma aldosterone concentrations (PAC pmol/L) and direct renin concentrations (DRC mIU/L) were measured. Patients with increased aldosterone renin ratios (ARR) > 65 were further evaluated for PA. Results: Of 578 consecutively screened patients with type 2 diabetes, 27 were treated with mineralocorticoid receptor antagonists (MRA) and potassium-sparing diuretics not further evaluated. Among the remaining 551 patients, 38 had increased ARR, including 22 who were clinically indicated for PA tests and 16 who were not further evaluated due to severe comorbidities and old age. There were five (0.93%) patients with confirmed PA after computerized tomography and adrenal venous sampling. Patients with PA had higher systolic blood pressure (P=.032) and lower potassium levels (P=.027) than those without PA. No significant association was found between plasma aldosterone and diabetic complications. Conclusions: The prevalence of PA in an unselected cohort of patients with type 2 diabetes is relatively low, and measures of plasma aldosterone are not strong risk factors for micro-and macrovascular diabetic complications.
  •  
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