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Using in vivo magnetic resonance spectroscopy, our study is the first one indicating fluid balance-dependent properties of glycerophosphocholine concentrations in human skeletal muscle. In vivo examination of GPC as organic osmolyte in human skeletal muscle marks a novel approach, which might give further insight on how water and electrolyte balance affect muscle tissue. Beside this main finding, glycerophosphocholine of both calf and thigh muscle correlated remarkably with blood laboratory parameters of lipid metabolism in our study population.

The prevalence of type 2 diabetes mellitus is increasing in both sexes, but men are usually diagnosed at a younger age and lower body fat mass than women. Worldwide, an estimated 17.7 million more men than women have diabetes mellitus. Women appear to bear a greater risk factor burden at the time of their type 2 diabetes diagnosis, especially obesity. Moreover, psychosocial stress might play a more prominent role in diabetes risk in women. Across their lifespan, women experience greater hormone fluctuations and body changes due to reproductive factors than men. Pregnancies can unmask pre-existing metabolic abnormalities, resulting in the diagnosis of gestational diabetes, which appears to be the most prominent risk factor for progression to type 2 diabetes in women. Additionally, menopause increases women’s cardiometabolic risk profile. Due to the progressive rise in obesity, there is a global increase in women with pregestational type 2 diabetes, often with inadequate preconceptual care. There are differences between men and women regarding type 2 diabetes and other cardiovascular risk factors with respect to comorbidities, the manifestation of complications and the initiation of and adherence to therapy. Women with type 2 diabetes show greater relative risk of CVD and mortality than men. Moreover, young women with type 2 diabetes are currently less likely than men to receive the treatment and CVD risk reduction recommended by guidelines. Current medical recommendations do not provide information on sex-specific or gender-sensitive prevention strategies and management. Thus, more research on sex differences, including the underlying mechanisms, is necessary to increase the evidence in the future. Nonetheless, intensified efforts to screen for glucose metabolism disorders and other cardiovascular risk factors, as well as the early establishment of prophylactic measures and aggressive risk management strategies, are still required for both men and women at increased risk of type 2 diabetes. In this narrative review we aim to summarise sex-specific clinical features and differences between women and men with type 2 diabetes into risk factors, screening, diagnosis, complications and treatment. Graphical abstract

ZusammenfassungBereits vor mehr als 30 Jahren forderte die St. Vincent Deklaration, dass Schwangere mit vorbestehendem Diabetes mellitus vergleichbare Schwangerschaftsergebnisse wie gesunde Frauen erreichen sollen. Dennoch bestehen bei Frauen mit konzeptionell manifestem Diabetes nach wie vor höhere Komplikationsraten und eine höhere perinatale Morbidität und Mortalität. Eine fehlende oder zumindest unzureichende Schwangerschaftsplanung und präkonzeptionelle Betreuung mit Optimierung der Stoffwechsellage vor Konzeption ist dafür verantwortlich. Alle Frauen mit Diabetes sollen im Selbstmanagement der Insulintherapie mit Anpassungen der Insulindosis geschult sein und eine stabile Stoffwechsellage vor Schwangerschaftsbeginn aufweisen. Eine Schilddrüsendysfunktion, Hypertonie oder diabetische Komplikationen vor der Konzeption sollten ausgeschlossen bzw. adäquat behandelt sein, um das Risiko einer möglichen Progression der Komplikationen und Begleiterkrankungen sowie insgesamt mütterliche und fetale Risiken zu minimieren. Ein Ziel der mütterlichen Stoffwechselkontrolle ist das Erreichen von Normoglykämie und normalen HbA1c-Werten, falls dies ohne Risiko für Hypoglykämien möglich ist, da eine schlechte Blutzuckereinstellung mit diabetischer Embryopathie und diabetischer Fetopathie assoziiert ist. Das Hypoglykämierisiko ist speziell bei Typ 1 Diabetes mellitus in der Frühschwangerschaft deutlich erhöht, nimmt aber mit den hormonellen Veränderungen und der Zunahme der Insulinresistenz im Schwangerschaftsverlauf deutlich ab. Eine weltweit steigende Adipositasprävalenz führt zusätzlich zu einem Anstieg von Müttern mit Typ 2 Diabetes. Dieser Trend ist auch bei Frauen mit Typ 1 Diabetes zu beobachten und aggraviert die Metabolik und die perinatalen Ergebnisse. Eine funktionelle, intensivierte Insulintherapie mit multiplen täglichen Insulininjektionen oder eine Insulinpumpentherapie tragen neben dem vermehrten Einsatz des kontinuierlichen Glukosemonitorings zum Erreichen einer guten mütterlichen Stoffwechselkontrolle vor und während der Schwangerschaft bei. Orale Antidiabetika (Metformin) können vor allem bei Typ 2 Diabetes und Adipositas helfen die Insulinsensitivität zu verbessern und dadurch den Insulinbedarf zu vermindern, sollten jedoch aufgrund der Plazentagängigkeit und ungewissen Langzeitergebnissen bei den Nachkommen mit Bedacht (shared decision making) verordnet werden. Aufgrund des erhöhten Präeklampsierisikos bei Frauen mit Diabetes in der Schwangerschaft ist hier ein frühes Screening zu empfehlen. Regelmäßige und engmaschige geburtshilfliche Kontrollen in einem spezialisierten Zentrum und bei spezialisierten Fachärzt:innen sowie interdisziplinäre Zusammenarbeit werden empfohlen um eine gute Stoffwechseleinstellung und gesunde Entwicklung des Kindes zu sichern.

ZusammenfassungMetabolische Erkrankungen beeinflussen das Leben von Männern und Frauen in den verschiedenen Lebensabschnitten in unterschiedlicher und vielfältiger Weise und stellen eine große Herausforderung für das Gesundheitssystem dar. Die behandelnden Ärztinnen und Ärzte sind mit den unterschiedlichen Bedürfnissen von Männern und Frauen im klinischen Alltag konfrontiert. Geschlechtsspezifische Unterschiede beeinflussen die Pathophysiologie, das Screening und die Diagnose von Krankheiten, sowie Behandlungsstrategien und die Entwicklung von Komplikationen und die Mortalitätsraten. Veränderungen im Glukose- und Lipidstoffwechsel, die Regulation von Energiehaushalt und Körperfettverteilung sowie damit assoziierte kardiovaskuläre Erkrankungen werden stark von Steroid- und Sexualhormonen beeinflusst. Zusätzlich spielen Erziehung, Einkommen und psychosoziale Faktoren eine wichtige Rolle bei der Entstehung von Adipositas und Diabetes und müssen bei geschlechtsspezifischer Betrachtung mitberücksichtigt werden. Männer weisen im jüngeren Alter und bei niedrigerem BMI ein höheres Risiko für Typ 2 Diabetes auf als Frauen, die wiederum von einem starken Anstieg im Risiko für Diabetes-assoziierte kardiovaskuläre Erkrankungen nach der Menopause betroffen sind. Frauen dürften durch Diabetes auch etwas mehr Lebensjahre verlieren als Männer, wobei die höhere Mortalität hauptsächlich auf vaskuläre Komplikationen zurückgeführt werden kann. Bei Männern mit Diabetes scheint dafür der Mortalitätsanstieg durch Krebs gewichtiger als bei Frauen zu sein. Bei Frauen sind Prädiabetes und Diabetes meist mit mehr vaskulären Risikofaktoren assoziiert wie erhöhte Inflammationsparameter, prothrombotische Veränderungen und höherem Blutdruck. Sie weisen deshalb ein relativ höheres vaskuläres Risiko auf. Frauen sind öfter stark übergewichtig und weniger körperlich aktiv, obwohl sie sogar noch mehr als Männer von einem höheren Bewegungsausmaß in ihrer Gesundheit und Lebenserwartung profitieren dürften. In Gewichtsreduktionsprogrammen verlieren Männer häufig mehr Gewicht als Frauen. Frauen und Männern profitieren gleich gut von Präventionsprogrammen mit etwa 40 % Risikoreduktion für Typ 2 Diabetes nach 3 Jahren. Langzeitdaten konnten bisher eine Reduktion der allgemeinen und kardiovaskulären Mortalität nur bei Frauen zeigen. Frauen weisen öfter eine gestörte Glukosetoleranz, Männer hingegen erhöhte Nüchternblutzuckerspiegel auf. Eine Anamnese eines Gestationsdiabetes oder polyzystischen Ovarsyndroms (PCOS) sowie höhere Androgenspiegel, und erniedrigte Östrogenspiegel stellen bei Frauen, das Vorhandensein einer erektilen Dysfunktion oder erniedrigter Testosteronspiegel bei Männern, wichtige geschlechtsspezifische Diabetesrisikofaktoren dar. Viele Studien zeigen des Weiteren, dass Frauen in der Therapie weniger oft die Zielwerte für HbA1c, LDL-Cholesterin oder Blutdruck erreichen, wobei die Ursachen unklar sind. Generell sollen in der medikamentösen Behandlung geschlechtsspezifische Unterschiede in der Wirkung, Pharmakokinetik und in den Nebenwirkungen mehr Beachtung finden.

ZusammenfassungDiabetes mellitus und Osteoporose zählen zu den häufigsten chronischen Erkrankungen und kommen deshalb beide häufig in ein und demselben Individuum vor. Da die Prävalenz beider mit steigendem Alter zunimmt, wird in Anbetracht der Altersstruktur unserer Bevölkerung deren Häufigkeit zunehmen.Patient:innen mit Diabetes haben ein erhöhtes Risiko für Fragilitätsfrakturen. Die Pathophysiologie ist unklar und vermutlich multifaktoriell.Longitudinale Studien haben den Nachweis erbracht, dass das Fracture Risk Assessment Tool (FRAX) und die Knochendichte (BMD) mittels DXA (T-score) Messungen und einem eventuell vorhandenen Trabecular Bone Score (TBS) das individuelle Frakturrisiko vorhersagen können. Hierfür muss allerdings eine Adjustierung vorgenommen werden, um das Risiko nicht zu unterschätzen.Es gibt derzeit aus osteologischer Sicht noch nicht den optimalen Ansatz, da es keine Studien mit rein diabetischen Patient:innen und Osteoporose gibt.Patient:innen mit Diabetes mellitus und einem erhöhten Frakturrisiko sollten genauso wie Patient:innen ohne Diabetes und einem erhöhten Frakturrisiko behandelt werden.Der Vitamin-D-Spiegel sollte auf jeden Fall immer optimiert werden und auf eine ausreichende Kalziumaufnahme (vorzugsweise durch die Nahrung) ist zu achten.Bei der Wahl der antihyperglykämischen Therapie sollten Substanzen mit nachgewiesen negativem Effekt auf den Knochen weggelassen werden. Bei Vorliegen einer Fragilitätsfraktur ist auf jeden Fall – unabhängig von allen vorliegenden Befunden – eine langfristige spezifische osteologische Therapie indiziert.Zur Prävention von Fragilitätsfrakturen sind antiresorptive Medikamente die erste Wahl, entsprechend den nationalen Erstattungskriterien auch anabole Medikamente. Das Therapiemonitoring soll im Einklang mit der nationalen Osteoporose Leitlinie erfolgen.

ZusammenfassungDie Hyperglykämie ist wesentlich an der Entstehung der Spätkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten/Patientinnen beteiligt. Während Lebensstilmaßnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benötigen im Verlauf die meisten Patienten/Patientinnen mit Typ 2 Diabetes eine medikamentöse Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit, die Effektivität sowie substanzspezifische, kardiovaskuläre Effekte der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten für die klinische Praxis zusammengestellt.

ZusammenfassungEpidemiologische Untersuchungen zeigen, dass etwa 2–3 % aller Österreicher*innen einen Diabetes mellitus mit Nierenbeteiligung aufweisen. Dies betrifft somit in Österreich etwa 250.000 Menschen. Das Risiko des Auftretens und Fortschreitens der diabetischen Nierenerkrankung kann durch Lebensstilinterventionen und Optimierung des arteriellen Blutdrucks, Blutzuckers und spezielle Medikamentenklassen vermindert werden. In diesem gemeinsamen Artikel der Österreichischen Gesellschaften für Nephrologie und Diabetologie werden die entsprechende Diagnostik und therapeutische Strategien bei diabetischer Nierenerkrankung vorgeschlagen.

ZusammenfassungDiabetes mellitus ist häufig mit psychischen Erkrankungen assoziiert. Depressive Störungen kommen bei diabetischen Patient:innen doppelt so häufig vor wie in der nicht-diabetischen Population. Andere psychische Erkrankungen, die gehäuft mit Prädiabetes und Diabetes mellitus vorkommen, sind kognitive Dysfunktionen bis zur Demenz, auffälliges Essverhalten, Angststörungen, Schizophrenie, bipolare Störungen und Borderline-Persönlichkeitsstörungen. Die ungünstigen Auswirkungen dieser Koinzidenz auf den Stoffwechsel sind nachhaltig und manifestieren als schlechtere metabolische Kontrolle und vermehrte mikro- und makroangiopathische Komplikationen. Ziel dieses Positionspapieres ist die Sensibilisierung aller involvierten medizinischen Fachkolleg:innen sowie aller anderen mit dem Thema Diabetes befassten Berufsgruppen und Organisationen, um eine Intensivierung der komplexen therapeutischen Interventionen bei Patient:innen zu erreichen.Positive Auswirkungen wären die Verringerung der Inzidenz von Diabetes mellitus bei Patient:innen mit psychischen Erkrankungen, sowie die Reduktion von Spätfolgen des Diabetes mellitus, insbesondere der kardiovaskulären Morbidität und Mortalität und eine verbesserte Lebensqualität der Betroffenen.

ZusammenfassungDiese Leitlinie repräsentiert die Empfehlungen der Österreichischen Diabetes Gesellschaft (ÖDG) zur Nutzung von Diabetes-Technologie (Insulinpumpentherapie; kontinuierliche Glukosemesssysteme, CGM; Hybrid Closed Loop Systeme, HCL; Automated Insulin Delivery Systeme, AID, Diabetes-Apps) und den Zugang zu diesen technologischen Innovationen für Menschen mit Diabetes mellitus. Die Leitlinie wurde basierend auf aktueller wissenschaftlicher Evidenz erstellt.

ZusammenfassungJe nach Diabetesform und -therapie sollen alle Menschen mit Diabetes eine individuelle ernährungsmedizinische Beratung und Schulung durch Fachpersonal erhalten. Im Vordergrund sollte eine patientinnen- und patientenzentrierte, individualisierte Beratung stehen, angepasst an die jeweiligen Bedürfnisse und Lebensumstände der Menschen mit Diabetes. Neben der Unterstützung zur Umsetzung einer ausgewogenen Ernährung gilt es, gemeinsam mit Patient:innen individuelle Stoffwechselziele und Gewichtsziele zu definieren, um mithilfe der Ernährung den Krankheitsverlauf positiv zu beeinflussen und mögliche Spätfolgen zu vermeiden. Dabei sollten vor allem praxisbezogene Empfehlungen unter Berücksichtigung der persönlichen Nahrungsmittel-Präferenzen ausgesprochen werden und Hilfsmittel zur Planung von geeigneten Portionsgrößen und der geeigneten Mahlzeitenzusammenstellung zum Einsatz kommen. Entsprechend aktueller internationaler und nationaler Standards sollen Menschen mit Diabetes im Diabetes-Selbstmanagement unterstützt werden (DSMES) und erlernen, die postprandiale Reaktion auf Speisen und Getränke besser einschätzen und durch die geeignete Lebensmittel- und Getränkeauswahl positiv beeinflussen zu können. Alle Menschen mit Diabetes sollten regelmäßig, je nach individuellem Bedarf, die Möglichkeit haben, eine ernährungstherapeutische Beratung oder Schulung in Anspruch nehmen zu können.Diese Praxisempfehlung stellt eine Zusammenfassung der aktuellen Literatur zu ernährungsrelevanten Aspekten bei Diabetes dar.

ZusammenfassungGestationsdiabetes (GDM) wird als Glukosetoleranzstörung definiert, die erstmals in der Schwangerschaft festgestellt wird. GDM ist mit einer erhöhten feto-maternalen Morbidität sowie Langzeitkomplikationen bei Mutter und Kind assoziiert. Frauen, die die Kriterien eines manifesten Diabetes mellitus bereits in der Frühschwangerschaft erfüllen (Nüchternplasmaglukose ≥ 126 mg/dl, Spontanglukosemessung ≥ 200 mg/dl oder HbA1c ≥ 6,5 % vor der 20. Schwangerschaftswoche) sollen als Schwangere mit manifestem Diabetes klassifiziert und ebenso behandelt werden. Ein Screening auf unerkannten Typ 2 Diabetes bei der ersten pränatalen Kontrolle wird besonders bei Frauen mit hohem Risiko (Anamnese eines GDM/Prädiabetes, Fehlbildungen, Totgeburt, wiederholte Aborte oder Geburtsgewicht über 4500 g in früheren Schwangerschaften, Adipositas, metabolisches Syndrom, Alter > 35 Jahre, bei Gefäßerkrankungen, Auftreten von Diabetessymptomen wie Glukosurie, ethnische Zugehörigkeit zu Gruppen mit hohem Risiko [arabisch, S und SO-asiatisch, lateinamerikanisch]) empfohlen. GDM wird durch einen oralen Glukosetoleranztest (oGTT, 120 min; 75 g Glukose) oder durch Nüchternplasmaglukose ≥ 92 mg/dl diagnostiziert. Bei hohem Risiko kann ein oGTT bereits im ersten Trimenon sinnvoll sein, zwischen der 24.–28. Schwangerschaftswoche muss dieser Test aber in jedem Fall bei allen Schwangeren mit bis dahin unauffälligen Glukosewerten im Rahmen der Mutter-Kind-Pass-Untersuchung durchgeführt werden. Nach WHO Empfehlungen basierend auf der „Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study“ liegt ein GDM vor, wenn die Plasmaglukose nüchtern 92 mg/dl, nach 60 min 180 mg/dl oder nach 120 min 153 mg/dl überschreitet (Internationale Konsensuskriterien). Ein einziger erhöhter Wert ist für die Diagnose ausreichend und bedarf bereits einer strikten Stoffwechselkontrolle. Nach bariatrischer Operation wird aufgrund der Gefahr einer postprandialen Hypoglykämie die Durchführung eines oGTT nicht empfohlen. Alle Frauen mit GDM müssen eine Ernährungsberatung erhalten und ihre Blutzuckerwerte (4 Messzeitpunkte) regelmäßig kontrollieren. Ebenso sollte, falls nicht kontraindiziert, die körperliche Aktivität erhöht werden. Falls die Blutzuckerspiegel nicht im Therapiezielbereich liegen (nüchtern 1c oder oGTT) erfolgen (Evidenzklasse B). Alle Frauen sollen über ihr deutlich erhöhtes Risiko für Typ 2 Diabetes, das höhere kardiovaskuläre Risiko, sowie über entsprechende Präventionsmaßnahmen, informiert werden. Dazu gehören Lebensstilmaßnahmen, wie Gewichtsreduktion bei Übergewicht, gesunde Ernährung und ausreichend körperliche Aktivität (Evidenzklasse A). Auch die Kinder sollen hinsichtlich einer unauffälligen Entwicklung regelmäßig nachuntersucht werden, da in rezenten Untersuchungen höheres Risiko für Übergewicht und Adipositas sowie erhöhte Glukoseparameter festgestellt wurden. Wenn möglich sollte die gesamte Familie über Lebensstilmaßnahmen zur Aufrechterhaltung/Verbesserung der Gesundheit informiert werden.

ZUSAMMENFASSUNGSchwangerschaften mit präkonzeptionell bekanntem Typ-1- und Typ-2-Diabetes sind Hochrisiko-Schwangerschaften und bedürfen einer interdisziplinären Betreuung. Kinder diabetischer Mütter haben ein im Mittel 1,5- bis 3-fach erhöhtes Risiko für angeborene Fehlbildungen, Frühgeburtlichkeit, Hypertrophie, Atemstörungen, Plexusparese und Asphyxie. Das Risiko für Totgeburt und Tod in den ersten 7 Lebenstagen ist bei prägravidem Diabetes erhöht. Die mit Abstand häufigste Komplikation bei Neugeborenen diabetischer Mütter ist die postnatale Hypoglykämie. Diabetesassoziierte Begleiterkrankungen und maternale Adipositas sind unabhängige Risikofaktoren für Schwangerschaftskomplikationen und ein ungünstiges fetales Outcome. Für die Blutglukoseeinstellung während der Schwangerschaft wurde ein klarer Zusammenhang höherer Werte mit ungünstigen fetalen und maternalen Ereignissen gezeigt. Analoginsuline sind mittlerweile die Insuline der Wahl. Darüber hinaus konnte eine Überlegenheit einer CGM-Versorgung während der Schwangerschaft gegenüber der konventionellen Blutglukosemessung gezeigt werden. Die Rate an Sektiones ist bei Frauen mit Diabetes nach wie vor gegenüber der Grundgesamtheit in der Perinatalstatistik deutlich erhöht. Evidenzbasierte Erkenntnisse zum intrapartalen Vorgehen liegen nicht vor. Die Einstellungsziele orientieren sich daher an den während der Schwangerschaft geltenden Zielen.

ZusammenfassungSchilddrüsenhormone steuern direkt und indirekt viele metabolische Vorgänge, welche für Wachstum, Entwicklung und Stoffwechsel entscheidend sind. Ein essenzieller Mikronährstoff für die Schilddrüsenhormonproduktion ist Jod, welches einen Bestandteil der Schilddrüsenhormone Triiodthyronin (T3) und Thyroxin (T4) bildet. Österreich ist aufgrund der geografischen Lage für Jodmangel prädisponiert. Jodmangel kann speziell in der Schwangerschaft und Stillzeit problematisch sein, weshalb in dieser Population eine Jodsupplementation empfohlen wird. Selen trägt in der Form der Aminosäure Selenocystein als Bestandteil von Dejodinasen einen maßgeblichen Teil zur Funktion der Schilddrüse, zum Beispiel bei der Umwandlung zwischen aktiven und inaktiven Formen von Schilddrüsenhormonen, bei. Die bisher vorhandenen klinischen Daten deuten insgesamt auf ein beachtliches Potenzial von Selensupplementation bei Hypothyreose oder Autoimmunerkrankungen der Schilddrüse hin. Für andere Vitamine und Mineralstoffe wie Zink, Magnesium, Eisen, Vitamin D und C ist die derzeitige Studienlage unzureichend, um eine Empfehlung auszusprechen. Zusammenfassend ist neben der bereits in Leitlinien empfohlenen Behandlung von Jodmangelzuständen auch eine gezielte Selensupplementation für bestimmte Patientenpopulationen möglicherweise sinnvoll.

This study aims to quantify whether age and sex groups in Austrian regions are equally affected by the rise of type 2 diabetes. Population-wide medical claims data was obtained for citizens in Austria aged above 50 year, who received antihyperglycemic treatments or underwent HbA1c monitoring between 2012 and 2017. Diabetes incidence was measured using an epidemiological diabetes progression model accounting for patients who discontinued antihyperglycemic therapy; the erratic group. Out of 746,184 patients, 268,680 (140,960 females) discontinued their treatment and/or monitoring for at least one year. Without adjusting for such erratic patients, incidence rates increase from 2013 to 2017 (females: from 0·5% to 1·1%, males: 0·5% to 1·2%), whereas they decrease in all groups after adjustments (females: − 0·3% to − 0·5%, males: − 0·4% to − 0·5%). Higher mortality was observed in the erratic group compared to patients on continued antihyperglycemic therapy (mean difference 12% and 14% for females and males, respectively). In summary, incidence strongly depends on age, sex and place of residency. One out of three patients with diabetes in Austria discontinued antihyperglycemic treatment or glycemic monitoring for at least one year. This newly identified subgroup raises concern regarding adherence and continuous monitoring of diabetes care and demands further evaluation.

Roux-en-Y gastric bypass operations (RYGB-OP) and pregnancy alter glucose homeostasis and the adipokine profile. This study investigates the relationship between adipokines and glucose metabolism during pregnancy post-RYGB-OP. (1) Methods: This is a post hoc analysis of a prospective cohort study during pregnancy in 25 women with an RYGB-OP (RY), 19 women with obesity (OB), and 19 normal-weight (NW) controls. Bioimpedance analysis (BIA) was used for metabolic characterization. Plasma levels of adiponectin, leptin, fibroblast-growth-factor 21 (FGF21), adipocyte fatty acid binding protein (AFABP), afamin, and secretagogin were obtained. (2) Results: The phase angle (φ) was lower in RY compared to OB and NW. Compared to OB, RY, and NW had lower leptin and AFABP levels, and higher adiponectin levels. φ correlated positively with leptin in RY (R = 0.63, p < 0.05) and negatively with adiponectin in OB and NW (R = −0.69, R = −0.69, p < 0.05). In RY, the Matsuda index correlated positively with FGF21 (R = 0.55, p < 0.05) and negatively with leptin (R = −0.5, p < 0.05). In OB, FGF21 correlated negatively with the disposition index (R = −0.66, p < 0.05). (3) Conclusions: The leptin, adiponectin, and AFABP levels differ between RY, OB, and NW and correlate with glucose metabolism and body composition. Thus, adipokines might influence energy homeostasis and maintenance of cellular health during pregnancy.

Purpose Sodium-glucose cotransporter 2 inhibitor (SGLT2i) regulation, developed as treatment for patients with type 2 diabetes, can be imaged with the glucose analogue alpha-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me4FDG), a positron emission tomography (PET) tracer with a high affinity for SGLT1 and SGLT2 proteins. With regard to therapy effectiveness, we aimed to investigate whether clinical parameters or Me4FDG excretion could predict response to SGLT2i in patients with type 2 diabetes. Methods In a longitudinal, prospective study, 19 patients with type 2 diabetes underwent Me4FDG combined PET and magnetic resonance imaging (PET/MRI) scans at baseline and 2 weeks after initiation of therapy with SGLT2i, accompanied by the collection of blood and urine samples. Me4FDG-excretion was determined from the Me4FDG uptake in the bladder. Long-term response was determined by HbA1c level after 3 months; a strong response to the therapy was defined as a reduction of HbA1c by at least 10% from baseline. Results SGLT2i resulted in significantly increased Me4FDG excretion (4.8 vs. 45.0, P P r = 0.55 (P P = 0.005, OR 1.9). Conclusions Using Me4FDG-PET, we demonstrated for the first time renal SGLT2-related excretion before and after short-term SGLT2i treatment. In contrary to other clinical parameters, SGLT2-related excretion before treatment was a robust predictor of long-term HbA1c response in patients with type 2 diabetes, suggesting that therapy effectiveness is only dependent of endogenous SGLT2 processes.

Context Non-alcoholic fatty liver disease (NAFLD) is a leading causes of liver-related morbidity and mortality. While data on acromegaly, a state of chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess, suggest an inverse relationship with intrahepatic lipid (IHL) content, less is known about the impact of the GH/IGF-I axis on IHL, lipid composition, and phosphor metabolites in individuals without disorders of GH secretion. Objective The aim was to investigate the relation between activity of the GH/IGF-I axis and IHL content and phosphor metabolism. Methods We performed a cross-sectional study in 59 otherwise metabolically healthy individuals (30 females), of which 16 met the criteria of NAFLD with IHL of ≥5.6%. The GH/IGF-I axis was evaluated in a fasting state and during an oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by validated indices. IHL, lipid composition (unsaturation index), and phosphate metabolites were analyzed by using 1H/31P magnetic resonance spectroscopy. Results In the overall cohort (40.6 ± 15 years; body mass index: 24.5 ± 3 kg/m2; IGF-I: 68.0 ± 17% upper limit of normal), fasting GH (R = −0.31; P = .02), GH during oral glucose tolerance test (R = −0.51; P < .01), and IGF-I (R = −0.28; P = .03) inversely correlated with IHL. GH levels during OGTT were significantly lower in NAFLD than in controls (47.7 [22; 143] ng/mL/min vs 16.8 [7; 32] ng/mL/min; P = .003). GH/IGF-I axis activity correlated with lipid composition and with phosphor metabolites. In multiple regression analysis, the GH/IGF-I axis activity was a strong predictor for IHL and lipid composition independent from insulin sensitivity. Conclusion GH/IGF-I axis activity impacts hepatic lipid and phosphate metabolism in individuals without disorders in GH secretion. Lower GH axis activity is associated with higher IHL and an unfavorable lipid composition, probably mediated by changes in hepatic energy metabolism.

This is an updated preprint of our Delphi study to develop a person-centered outcome set for routine diabetes care in Europe: Objective: Standardised patient-reported outcomes (PRO) data can contextualise clinical outcomes enabling precision diabetes monitoring and care. Comprehensive outcome sets can guide this process, but their implementation in routine diabetes care has remained challenging and has not been successful at the international level. We aimed to address this with a person-centred outcome set for Type 1 and 2 diabetes that can be feasibly implemented and sustained in international healthcare settings. Methods: A questionnaire-based Delphi study consisting of three consecutive survey rounds and based on previously identified outcomes was undertaken to reach consensus on the outcome set. Participants included patients (N=94), health professionals (N=65), representatives of industry (N=22) and health authorities (N=3). Subsequent consensus meetings were held to finalise the outcome set. Results: The list of preliminary person-centred outcomes presented in the Delphi study included 64outcomes and was shortlisted via the consensus process to 46 outcomes (27 clinical outcomes and 19 PROs). Two main collection times were recommended: 1) linked to a medical visit (e.g., diabetes-specific well-being, symptoms, and psychological health) and 2) annually (e.g., clinical data, general well-being, and diabetes self-management-related outcomes). Conclusions: PROs are often considered in a non-standardised way in routine diabetes care. We propose a person-centred outcome set for diabetes, specifically considering psychosocial and behavioural aspects, which was agreed by four international key stakeholder groups. It guides standardised patient-important outcome collection at scale to support individual and population level healthcare decision-making. It will be implemented and tested in Europe as part of the H2O project. &nbsp

AimsThe aim of this study was to elucidate whether sex and gender factors influence access to health care and/or are associated with cardiovascular (CV) outcomes of individuals with diabetes mellitus (DM) across different countries.MethodsUsing data from the Canadian Community Health Survey (8.4% of respondent reporting DM) and the European Health Interview Survey (7.3% of respondents reporting DM), were analyzed. Self-reported sex and a composite measure of socio-cultural gender was constructed (range: 0–1; higher score represent participants who reported more characteristics traditionally ascribed to women). For the purposes of analyses the Gender Inequality Index (GII) was used as a country level measure of institutionalized gender.ResultsCanadian females with DM were more likely to undergo HbA1c monitoring compared to males (OR = 1.26, 95% CI: 1.01–1.58), while conversely in the European cohort females with DM were less likely to have their blood sugar measured compared to males (OR = 0.88, 95% CI: 0.79–0.99). A higher gender score in both cohorts was associated with less frequent diabetes monitoring. Additionally, independent of sex, higher gender scores were associated with higher prevalence of self-reported heart disease, stroke, and hospitalization in all countries albeit European countries with medium-high GII, conferred a higher risk of all outcomes and hospitalization rates than low GII countries.ConclusionRegardless of sex, individuals with DM who reported characteristics typically ascribed to women and those living in countries with greater gender inequity for women exhibited poorer diabetes care and greater risk of CV outcomes and hospitalizations.

Pre-print of asystematic literature review toidentify candidate patient reported outcomes with potential to inform individual patient care and service development for inclusion in a digital outcome set to be collected in routine diabetes care.

We aim to comprehensively identify typical life-spanning trajectories and critical events that impact patients' hospital utilization and mortality. We use a unique dataset containing 44 million records of almost all inpatient stays from 2003 to 2014 in Austria to investigate disease trajectories. We develop a new, multilayer disease network approach to quantitatively analyse how cooccurrences of two or more diagnoses form and evolve over the life course of patients. Nodes represent diagnoses in age groups of ten years; each age group makes up a layer of the comorbidity multilayer network. Inter-layer links encode a significant correlation between diagnoses (p $$ 1.5), while intra-layers links encode correlations between diagnoses across different age groups. We use an unsupervised clustering algorithm for detecting typical disease trajectories as overlapping clusters in the multilayer comorbidity network. We identify critical events in a patient's career as points where initially overlapping trajectories start to diverge towards different states. We identified 1,260 distinct disease trajectories (618 for females, 642 for males) that on average contain 9 (IQR 2-6) different diagnoses that cover over up to 70 years (mean 23 years). We found 70 pairs of diverging trajectories that share some diagnoses at younger ages but develop into markedly different groups of diagnoses at older ages. The disease trajectory framework can help us to identify critical events as specific combinations of risk factors that put patients at high risk for different diagnoses decades later. Our findings enable a data-driven integration of personalized life-course perspectives into clinical decision-making.

Purpose Bariatric surgery has a favorable effect on fertility in women. However, due to a lack of data regarding children’s outcomes, the ideal time for conception following bariatric surgery is unknown. Current guidelines advise avoiding pregnancy during the initial weight loss phase (12–24 months after surgery) as there may be potential risks to offspring. Thus, we aimed to analyze health outcomes in children born to mothers who had undergone bariatric surgery. The surgery-to-delivery interval was studied. Materials and Methods A nationwide registry belonging to the Austrian health insurance funds and containing health-related data claims was searched. Data for all women who had bariatric surgery in Austria between 01/2010 and 12/2018 were analyzed. A total of 1057 women gave birth to 1369 children. The offspring’s data were analyzed for medical health claims based on International Classification of Diseases (ICD) codes and number of days hospitalized. Three different surgery-to-delivery intervals were assessed: 12, 18, and 24 months. Results Overall, 421 deliveries (31%) were observed in the first 2 years after surgery. Of these, 70 births (5%) occurred within 12 months after surgery. The median time from surgery to delivery was 34 months. Overall, there were no differences noted in frequency of hospitalization and diagnoses leading to hospitalization in the first year of life, regardless of the surgery-to-delivery interval. Conclusion Pregnancies in the first 24 months after bariatric surgery were common. Importantly, the surgery-to-delivery interval had no significant impact on the health outcome of the children. Graphical Abstract

Je nach Diabetesform und -therapie sollen alle Menschen mit Diabetes eine individuelle ernährungsmedizinische Beratung und Schulung durch Fachpersonal erhalten. Im Vordergrund sollte eine patientinnen- und patientenzentrierte, individualisierte Beratung stehen, angepasst an die jeweiligen Bedürfnisse und Lebensumstände der Menschen mit Diabetes. Neben der Unterstützung zur Umsetzung einer ausgewogenen Ernährung gilt es, gemeinsam mit Patient:innen individuelle Stoffwechselziele und Gewichtsziele zu definieren, um mithilfe der Ernährung den Krankheitsverlauf positiv zu beeinflussen und mögliche Spätfolgen zu vermeiden. Dabei sollten vor allem praxisbezogene Empfehlungen unter Berücksichtigung der persönlichen Nahrungsmittel-Präferenzen ausgesprochen werden und Hilfsmittel zur Planung von geeigneten Portionsgrößen und der geeigneten Mahlzeitenzusammenstellung zum Einsatz kommen. Entsprechend aktueller internationaler und nationaler Standards sollen Menschen mit Diabetes im Diabetes-Selbstmanagement unterstützt werden (DSMES) und erlernen, die postprandiale Reaktion auf Speisen und Getränke besser einschätzen und durch die geeignete Lebensmittel- und Getränkeauswahl positiv beeinflussen zu können. Alle Menschen mit Diabetes sollten regelmäßig, je nach individuellem Bedarf, die Möglichkeit haben, eine ernährungstherapeutische Beratung oder Schulung in Anspruch nehmen zu können.Diese Praxisempfehlung stellt eine Zusammenfassung der aktuellen Literatur zu ernährungsrelevanten Aspekten bei Diabetes dar. All patients with diabetes require individual and personalized nutritional consultation with professionals. The patient’s needs should be the primary focus of the dietary therapy, taking their lifestyle and the type of diabetes into consideration. With the recommendations to the patient’s diet, there need to be specific metabolic goals to reduce the disease’s progression and to avoid long term health effects. Therefore, practical guidelines such as portion size and meal planning tips should be the main focus.According to the latest national and international standards, patients suffering from diabetes should have access to nutrition consulting and nutritional training. During consultation they can be supported on- how to manage their health condition and choosing food and beverage to improve their health.These practical recommendations sum up the latest literature on nutritional aspects of diabetes treatment. Version of record

Die Hyperglykämie ist wesentlich an der Entstehung der Spätkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten/Patientinnen beteiligt. Während Lebensstilmaßnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benötigen im Verlauf die meisten Patienten/Patientinnen mit Typ 2 Diabetes eine medikamentöse Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit, die Effektivität sowie substanzspezifische, kardiovaskuläre Effekte der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten für die klinische Praxis zusammengestellt. Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals. Version of record

This Guideline represents the recommendations of the Austrian Diabetes Association (ÖDG) on the use of diabetes technology (insulin pump therapy; continuous glucose monitoring, CGM; hybrid closed-loop systems, HCL; diabetes apps) and access to these technological innovations for people with diabetes mellitus based on current scientific evidence.

Sociocultural gender is a complex construct encompassing different aspects of individuals’ life, whereas sex refers to biological factors. These terms are often misused, although they impact differently on individuals’ health. Recognizing the role of sex and gender on health status is fundamental in the pursuit of a personalized medicine. Aim of the current study was to investigate the awareness in approaching clinical and research questions on the impact of sex and gender on health among European internists. Clinicians affiliated with the European Federation of Internal Medicine from 33 countries participated to the study on a voluntary basis between January 1st, 2018 and July 31st, 2019. Internists’ awareness and knowledge on sex and gender issues in clinical medicine were measured by an online anonymized 7-item survey. A total of 1323 European internists responded to the survey of which 57% were women, mostly young or middle-aged (78%), and practicing in public general medicine services (74.5%). The majority (79%) recognized that sex and gender are not interchangeable terms, though a wide discrepancy exists on what clinicians think sex and gender concepts incorporate. Biological sex and sociocultural gender were recognized as determinants of health mainly in cardiovascular and autoimmune/rheumatic diseases. Up to 80% of respondents acknowledged the low participation of female individuals in trials and more than 60% the lack of sex-specific clinical guidelines. Internists also express the willingness of getting more knowledge on the impact of sex and gender in cerebrovascular/cognitive and inflammatory bowel diseases. Biological sex and sociocultural gender are factors influencing health and disease. Although awareness and knowledge remain suboptimal across European internists, most acknowledge the underrepresentation of female subjects in trials, the lack of sex-specific guidelines and the need of being more informed on sex and gender-based differences in diseases.

We evaluated possible mediators underlying lifestyle intervention effects on neonatal adiposity, assessed with sum of skinfolds and cord blood leptin. This is a secondary analysis of the DALI study, a randomised controlled trial in nine European countries. Pregnant women with a pre-pregnancy body mass index of ≥29 kg/m2 were randomly assigned to counselling for healthy eating (HE), physical activity (PA), HE&PA combined, or to usual care. We considered five maternal metabolic factors at 24–28 and 35–37 weeks of gestation, and four cord blood factors as possible mediators of the effect of combined HE&PA counselling on neonatal adiposity. From all potential mediators, the intervention only affected cord blood non-esterified fatty acids (NEFA), which was higher in the HE&PA group compared to UC (0.068 (mmol/L), 95% CI: 0.004 to 0.133). Cord blood NEFA did not mediate the HE&PA intervention effects on neonatal sum of skinfolds or cord blood leptin, based on an indirect effect on skinfolds of 0.018 (mm), 95% CI: −0.217 to 0.253 and an indirect effect on leptin of −0.143 (μg/l), 95% CI: −0.560 to 0.273. The Dali study observed reductions in neonatal adiposity in pregnant women with obesity, but we were not able to identify the underlying metabolic pathway.

Purpose Bariatric surgery reduces mortality in patients with severe obesity and is predominantly performed in women. Therefore, an analysis of sex-specific differences after bariatric surgery in a population-based dataset from Austria was performed. The focus was on deceased patients after bariatric surgery. Materials and Methods The Austrian health insurance funds cover about 98% of the Austrian population. Medical health claims data of all Austrians who underwent bariatric surgery from 01/2010 to 12/2018 were analyzed. In total, 19,901 patients with 107,806 observed years postoperative were eligible for this analysis. Comorbidities based on International Classification of Diseases (ICD)-codes and drug intake documented by Anatomical Therapeutical Chemical (ATC)-codes were analyzed in patients deceased and grouped according to clinically relevant obesity-associated comorbidities: diabetes mellitus (DM), cardiovascular disease (CV), psychiatric disorder (PSY), and malignancy (M). Results In total, 367 deaths were observed (1.8%) within the observation period from 01/2010 to 04/2020. The overall mortality rate was 0.34% per year of observation and significantly higher in men compared to women (0.64 vs. 0.24%; p p p = 0.034), whereas malignant diseases (36%) were more frequent in women (30 vs. 41%; p = 0.025). Conclusion After bariatric surgery, short-term mortality as well as long-term mortality was higher in men compared to women. In deceased patients, diabetes was more common in men, whereas malignant diseases were more common in women. Graphical abstract

Obesity is associated with increasing cardiometabolic morbidity and mortality rates worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested to be a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in people with severe obesity, a population at high cardiometabolic risk. In this cross-sectional study, we included 40 individuals with World Health Organization class II-III obesity (BMI ≥35 kg/m2). Using a 150-min personalized cooling protocol and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography, cold-activated BAT was detectable in 14 of the participants (35%). Cold-induced thermogenesis was significantly higher in participants with detectable BAT compared with those without. Notably, individuals with obesity and active BAT had 28.8% lower visceral fat mass despite slightly higher total fat mass compared with those without detectable BAT 18F-FDG uptake. The lower amount of visceral fat mass was accompanied by lower insulin resistance and systemic inflammation and improved nonalcoholic fatty liver disease parameters, all adjusted for age, sex, and percent body fat. Contrary to previous assumptions, we show here that a significant fraction of individuals with severe obesity has active BAT. We found that decreased BAT 18F-FDG uptake was not associated with adiposity per se but with higher visceral fat mass. In summary, active BAT is linked to a healthier metabolic phenotype in obesity.

Collecting patient-reported outcomes (PROs) in a standardised way and integrating them with clinical data can empower patients and support diabetes care. We sought to develop a patient-centred core outcome set (COS) to be used in routine diabetes care employing an international multi-stakeholder consensus process focusing on outcome relevance, feasibility and measurement frequency. The three-round Delphi study and subsequent consensus meeting led to a comprehensive outcome set and recommendations for frequency of measurement for each included outcome. The outcome set allows for collecting patient-reported and clinical data in a standardised way to sustainably support diabetes management on the international level and inform research and policy making., {"references":["Walker RJ, Garacci E, Campbell JA, Egede LE. The influence of daily stress on glycemic control and mortality in adults with diabetes. J Behav Med. 2020;43(5):723-31","Hermanns N, Ehrmann D, Shapira A, Kulzer B, Schmitt A, Laffel L. Coordination of glucose monitoring, self-care behaviour and mental health: achieving precision monitoring in diabetes. Diabetologia. 2022","Nano J, Carinci F, Okunade O, Whittaker S, Walbaum M, Barnard-Kelly K, et al. A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach. Diabet Med. 2020;37(12):2009-18","Skovlund SE, Troelsen LH, Klim L, Jakobsen PE, Ejskjaer N. The participatory development of a national core set of person-centred diabetes outcome constructs for use in routine diabetes care across healthcare sectors. Res Involv Engagem. 2021;7(1):62","Terwee CB, Zuidgeest M, Vonkeman HE, Cella D, Haverman L, Roorda LD. Common patient-reported outcomes across ICHOM Standard Sets: the potential contribution of PROMIS®. BMC Med Inform Decis Mak. 2021;21(1):259","Svedbo Engström M, Leksell J, Johansson UB, Borg S, Palaszewski B, Franzén S, et al. New Diabetes Questionnaire to add patients' perspectives to diabetes care for adults with type 1 and type 2 diabetes: nationwide cross-sectional study of construct validity assessing associations with generic health-related quality of life and clinical variables. BMJ Open. 2020;10(11):e038966","Stamm T, Bott N, Thwaites R, Mosor E, Andrews M, Borgdorff J, et al. Building a Value-Based Care Infrastructure in Europe: The Health Outcomes Observatory. NEJM Catalyst. 2021;2"]}

Combining mouse experiments with big data analysis of the Austrian population, we investigated the association between high-dose statin treatment and bone quality.The bone microarchitecture of the femur and vertebral body L4 was measured in male and ovariectomized female mice on a high-fat diet containing simvastatin (1.2 g/kg). A sex-specific matched big data analysis of Austrian health insurance claims using multiple logistic regression models was conducted (simvastatin 60-80 mg/day vs. controls; males: n = 138,666; females: n = 155,055).High-dose simvastatin impaired bone quality in male and ovariectomized mice. In the trabecular femur, simvastatin reduced bone volume (µmHigh-dose simvastatin dramatically reduces bone quality in obese male and ovariectomized female mice, suggesting that direct drug action accounts for the association between high dosage and increased risk of osteoporosis as observed in comparable human cohorts. The underlying pathophysiological mechanisms behind this relationship are presently unknown and require further investigation.

World's population is exponentially aging as people reaching 100 years old has increased. The number of areas with the highest centennial population rates (Blue Zones), are significantly higher. Are there any determinant factors that favor this situation in Spain? The goal of this study was to determine the possible influence of sex, rurality and socioeconomic factors (Gross Domestic Product (GDP)) on the prevalence of the centennial population of the Spanish society. The Spanish register of inhabitants was published in 2017 by the National Statistics Institute. The analysis was carried out both by Autonomous Communities and by provinces in phases: a first descriptive analysis, followed by an inferential analysis, based on statistical tests (independent T- Student test, Pearson correlation and ANOVA). There were significant interactions between: i) sex and longevity (in favor of the female population); ii) female and rural housing and iii) female, GDP and urban areas. Feminization was proven in the longevity revolution, but, in general, GDP per Capita was not a significant survival factor on its own. This study was the first step of further analysis related to extreme longevity in Spain, which will include other dependent variables such as state of health and well-being as well as social factors.

In this SARS-COV2-pandemic, diabetes mellitus (DM) soon emerged as one of the most prominent risk factors for a severe course of corona virus disease-2019 (COVID-19) and increased mortality due to hyperglycemia/insulin resistance, obesity, inflammation, altered immune status, and cardiovascular complications. In general, men are at a higher risk of severe or fatal COVID-19 disease irrespective of age, region and despite comparable infection rates in both sexes. In COVID-19, there is also a male predominance among hospitalized patients with diabetes, however, overall, data among patients with diabetes are ambiguous so far. Of note, similar to cardiovascular complications, women with type 2 diabetes (DM2) appear to lose their biological female advantage resulting in comparable death rates to those of men. The complex interplay of biological and behavioral factors, which may put men at greater risk of a severe or fatal course of COVID-19, and gender-related psychosocial factors, which may cause disadvantage to women concerning the infection rates, might explain why sex-disaggregated data among infected patients with diabetes are conflicting. Better knowledge on biological factors leading to functionally different immune responses and of gender-sensitive sociocultural determinants of COVID-19 infection rates may help to optimize prevention and management in the high-risk groups of men and women with diabetes.

Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p p = 0.02). Conclusions In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

Summary Background The incidence and the comorbidities, such as infectious diseases (e.g. pneumonia or influenza) of diabetes mellitus are increasing. Therefore, the purpose of this study is to investigate immunization status and preventive care in diabetes mellitus patients. Methods Two groups from the Austrian health interview survey 2014 were identified, a cohort of diabetes mellitus (DM) individuals (n = 678) and a non-diabetes mellitus (non-DM) cohort (n = 15,093). The frequencies of doctors’ visits, preventive care and immunization status were compared. Furthermore, the study population was divided by age (> 50 years, 50 years old DM with 50 years old DM and > 50 years old Non-DM cohort were investigated. Results In the DM cohort a higher frequency of influenza immunization (13.3% vs. 7.1%, p p p p 50 years DM cohort has similar frequencies of colonoscopy, hemoccult test and immunization against influenza and TBE (tick-borne encephalitis) compared to > 50 years Non-DM. Although the > 50 years old DM cohort had a higher frequency of doctors’ visits, they still had lower frequencies of mammography and dentists’ visits compared to > 50 years old Non-DM. In comparison to the 50 years DM cohort was related to lower intact immunization status of tetanus, diphtheria, Polio and TBE. Still a higher frequency of intact immunization of pneumococcus, influenza and doctors’ visits in the > 50 years old DM cohort compared to the Conclusion Preventive care and immunization status in the DM cohort just differ slightly from the general cohort but still should be improved.

Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women

Sex and gender can affect diabetes outcomes. Evidence suggests this is mediated by various biological and sociocultural factors, including hormones and behaviour. We set out to find out about gender-related differences in health (outcome) priorities. In an exploratory analysis the voting results of a previously conducted Delphi study, undertaken to reach consensus on a person-centred diabetes outcome set, were stratified according to the indicated gender of participating patients. Our results provide initial evidence that men and women prioritise self-reported diabetes outcomes differently: e.g., we saw that feeling in control was a major concern for men, while women felt it was important to be mindful of side effects. Clinicians may want to consider this to measure outcomes in a personalised, gender-conscious way and provide gender-specific diabetes care that supports the achievement of personal treatment goals., Gender, Gender medicine, Diabetes, Diabetes outcomes, Health outcomes, Patient-reported outcomes, Person-centred care, {"references":["Guidance for Industry - Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. (2009). https://www.fda.gov/media/77832/download","Himmelstein, M. S., & Puhl, R. M. (2021). At multiple fronts: Diabetes stigma and weight stigma in adults with type 2 diabetes. Diabet Med, 38(1), e14387. https://doi.org/10.1111/dme.14387","Kautzky-Willer, A., Harreiter, J., & Pacini, G. (2016). Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus. Endocr Rev, 37(3), 278-316. https://doi.org/10.1210/er.2015-1137","Markey, C. N., Markey, P. M., Schneider, C., & Brownlee, S. (2005). Marital Status and Health Beliefs: Different Relations for Men and Women. Sex Roles, 53(5), 443-451. https://doi.org/10.1007/s11199-005-6767- y","Mauvais-Jarvis, F., Berthold, H. K., Campesi, I., Carrero, J. J., Dakal, S., Franconi, F., Gouni-Berthold, I., Heiman, M. L., Kautzky-Willer, A., Klein, S. L., Murphy, A., Regitz-Zagrosek, V., Reue, K., & Rubin, J. B. (2021). Sex- and Gender-Based Pharmacological Response to Drugs. Pharmacol Rev, 73(2), 730-762. https://doi.org/10.1124/pharmrev.120.000206","Samulowitz, A., Gremyr, I., Eriksson, E., & Hensing, G. (2018). \"Brave Men\" and \"Emotional Women\": A Theory- Guided Literature Review on Gender Bias in Health Care and Gendered Norms towards Patients with Chronic Pain. Pain Res Manag, 2018, 6358624. https://doi.org/10.1155/2018/6358624","Stamm, T., Bott, N., Thwaites, R., Mosor, E., Andrews, M., Borgdorff, J., Cossio-Gil, Y., Portu, S., Ferrante, M., Fischer, F., Hameed, F., Hazelzet, J., Hopkins, D., Kalra, D., Metcalfe, T., Molero, E., Newson, R., Patalano, F., Prasser, F., & Styliadou, M. (2021). Building a Value-Based Care Infrastructure in Europe: The Health Outcomes Observatory. NEJM Catalyst, 2. https://doi.org/10.1056/CAT.21.0146"]}

Introduction: Gendered-psycho-socio-cultural factors have been shown to play a significant role in disease manifestation, control and management of hypertension (HTN), and their relationship varies in males and females. We investigated the role of sex and gender in HTN prevalence and country-level differences in Canadian and European populations. Methods: Data from the Canadian Community Health Survey (CCHS, 2015-16, N=109,659, Females:56.6%) and the European Health Interview Survey (E-HIS, 2013-2015, N=316,333, females: 51.3%) were analyzed. Primary endpoint was defined as having a diagnosed HTN made by a health professional in the past 12 months. Relationship between gender variables and HTN prevalence and interaction with sex was assessed in a multivariable model. Federated analysis was conducted using the R package and DataShield which allows international data pooling by only exposing aggregated results. Results: The prevalence of HTN was greater in Canada compared with Europe (CCHS: 30.1% vs EHIS: 22.4%, P Conclusion: The findings of the study demonstrate the importance of gender related factors and particularly the differences amongst various countries.

Background Sex and gender-based differences in cardiovascular health (CVH) has been explored in the context of high-income countries. However, these relationships have not been examined in low- and middle-income countries. There is an upsurge of cardiovascular diseases (CVDs) in sub-Saharan Africa (SSA). Irrespective of biological sex, gender-related factors could be the precursor of these conditions. Purpose To examine the associations between biological sex, gender-related variables, and CVH risk factors in SSA countries. Methods We conducted a retrospective analysis of the World Health Organization's “STEPwise approach to surveillance of risk factors for non-communicable disease” or “STEPS” survey, conducted in adults aged 18–69 years from Ghana, Gambia, Mali, Guinea, and Botswana. The surveys were conducted between 2006 and 2014. The main outcome was CVH, as measured by a composite measure of STEPS-HEART health index (smoking, hypertension, diabetes, obesity/overweight, and daily consumption of fruits and vegetables), values ranging from 0 (worst) to 5 (best or ideal). Multivariable logistic regression was applied to determine the gender-related factors related to poorer CVH (index less than 4). Two-way interaction between the sex and gender-related factors were tested by including an interaction term in bivariate models. Results Data included 15,356 adults (61.4% females, mean age 36.9 years). The prevalence of hypertension (21.6% vs. 13.8%) and overweight/obesity (48.3% vs. 27.5%) was higher among females as compared to males. Females were more likely to be unemployed (17.3% vs. 9.7%) or reported unpaid work (36.8% vs. 15.2%). Overall, females showed worse CVH than males (OR female = 0.95, 95% CI: 0.91–0.99). Being married was associated with better CVH compared with being single, more so for males (OR male = 1.09, 95% CI: 0.96–1.24, p interaction Conclusion This study highlights an alarmingly high prevalence of CVD risk factors, mainly overweight/obesity and hypertension among females in SSA population. Being female was associated with poorer CVH given the disproportionate burden of hypertension and overweight/obesity. Gender-related factors such as marital status and unpaid work were associated with better CVH in males compared to females. With the rising prevalence of CVDs in SSA, it will be important to consider the gender-related factors while implementing preventive programs and creating effective health policies. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The GENDER– NET Plus ERA-NET Initiative (project ref. number: GNP-78): The Canadian Institutes of Health Research (GNP-161904)