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Fractures negatively impact quality of life and survival. We hypothesized that recipient frailty score and genetic profile measured before transplant would predict risk of fracture after lung transplant. We conducted a retrospective cohort study of bone mineral density (BMD) and fracture among lung transplant recipients at a single center. The association between predictors and outcomes were assessed by multivariable time-dependent Cox models or regression analysis. Among the 284 participants, osteoporosis and fracture were highly prevalent. Approximately 59% of participants had posttransplant osteopenia, and 35% of participants developed at least 1 fracture. Low BMD was associated with a polygenic osteoporosis risk score, and the interaction between genetic score and BMD predicted fracture. Pretransplant frailty was associated with risk for spine and hip fracture, which were not associated with chronic lung allograft dysfunction or death. Chest fractures were the most frequent type of fracture and conferred a 2.2-fold increased risk of chronic lung allograft dysfunction or death (time-dependent P < .001). Pneumonia, pleural effusions, and acute rejection frequently occurred surrounding chest fracture. Pretransplant frailty and recipient genotype may aid clinical risk stratification for fracture after transplant. Fracture carries significant morbidity, underscoring the importance of surveillance and osteoporosis prevention.

Коморбидное течение сахарного диабета и сердечно-сосудистых заболеваний является одним из патологических состояний, с которым часто встречаются в своей практике врачи терапевтического профиля всех звеньев. Ассоциируясь, заболевания отягощают друг друга, приводят к более быстрому и тяжелому поражению органов-мишеней, сердечно-сосудистым осложнениям, инвалидизации и смерти и требуют современных медикаментозных подходов к лечению. В статье приведены данные касательно основных положений современных рекомендаций по лечению сердечно-сосудистых заболеваний, протекающих в сочетании с сахарным диабетом, основанные на последних документах европейских и американских экспертов в области диабетологии и кардиологии.

This review presents the applications of artificial intelligence for the study of the mechanisms of diabetes development and generation of new technologies of its prevention, monitoring and treatment. In recent years, a huge amount of molecular data has been accumulated, revealing the pathogenic mechanisms of diabetes and its complications. Data mining and text mining open up new possibilities for processing this information. Analysis of gene networks makes it possible to identify molecular interactions that are important for the development of diabetes and its complications, as well as to identify new targeted molecules. Based on the big data analysis and machine learning, new platforms have been created for prediction and screening of diabetes, diabetic retinopathy, chronic kidney disease, and cardiovascular disease. Machine learning algorithms are applied for personalized prediction of glucose trends, in the closed-loop insulin delivery systems and decision support systems for lifestyle modification and diabetes treatment. The use of artificial intelligence for the analysis of large databases, registers, and real-world evidence studies seems to be promising. The introduction of artificial intelligence systems is in line with global trends in modern medicine, including the transition to digital and distant technologies, personification of treatment, high-precision forecasting and patient-centered care. There is an urgent need for further research in this field, with an assessment of the clinical effectiveness and economic feasibility.

Background We present the results of the pilot study of a multinational “Diabetes Know‐Me” project investigating knowledge regarding diabetes of medical students. This is the first collaborative project of the ISPAD JENIOUS group. Methods Students of the final year of medical studies from six countries answered a 25‐question survey regarding basic knowledge concerning diabetes (1091 surveys handed out, response rate 86%). Results Among the responders (58% female) 90% confirmed attending diabetology classes; 11% planned to specialize in diabetology. There were significant differences between countries in the median score of correct answers ranging from 10/25 to 22/25. Attending diabetes classes (20 vs. 13/25, p

Introduction. Adherence to physician recommendations and the principles of healthy lifestyle is the key to avoid diabetic complications. Daily physical activity, a healthy diet and adherence to drug therapy can delay the development of the disease and its complications, leading to an increased life expectancy. The aim of the study was to evaluate the adherence to physician recommendations among patients with diagnosed diabetes mellitus type 2 (DM2). Material and methods. We studied 57 patients, including 27 women (47.4%) and 30 men (52.6%) diagnosed with DM2. The patients were hospitalized in the Department of Diabetology and Internal Diseases at the Independent Public Central Clinical Hospital in Warsaw in April–August 2019. The average age was 57 years in women and 58 years in men. We analyzed the answers obtained from the respondents in response to the original questionnaire developed by the authors. Results. We found that 70% of respondents did not follow dietary recommendations, 52% regularly consumed fast foods, 82% consumed sweets, 15% consumed the recommended amount of vegetables, 92% consumed meat at least once a day, and 39% were physically inactive. Among those declaring any physical activity, the most commonly reported type of activity was walking (32 patients or 56%). Conclusions. The adherence to physician recommendations in patients with diagnosed DM2 is unsatisfactory. The available solutions lack cooperation within multi-specialist teams.

Pharmaceutical care for diabetic patients in the field of podiatry Author: Anna Mazánková Tutor: PharmDr. Eliška Kolmanová Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University in Prague Introduction and objective: Diabetic foot syndrome (DFS) is one of the most common chronic complications of diabetes mellitus (DM), which significantly reduces the quality of life of patients. Emphasis on the prevention of DFU development is essential to care of diabetic patients, and pharmacists can play an important role in achieving this goal, especially in the education of regime measures and glycemic self-monitoring. The aim of this work is to analyze the attitudes of pharmacists in the Czech Republic to the provision of pharmaceutical care for diabetic patients in the field of podiatry. Methods: The data were colected by a questionnaire survey from September 2021 to November 2021. The electronic anonymous questionnaire was distributed by e-mail to members of 4 District Pharmacists' Associations (OSL Kurná Hora, OSL Jičín, OSL Beroun, OSL Mělník) and to members of the closed group Mladí lékárníci via the social network Facebook. The questionnaire consisted of 23 questions focusing on the pharmacist confidence in providing professional information to the...

Zusammenfassung. Die Initiative für die Arbeiten, welche in Toronto 1921 zur Entdeckung des Insulins führten, ging von Frederik G. Banting aus. Er arbeitete unter der Leitung von John J. R. Macleod im Institut für Physiologie der Universität Toronto. In seinem Versuchsprogramm unterstützte ihn der Student Charles H. Best. An Hunden mit experimentellem Diabetes demonstrierten sie den blutzuckersenkenden Effekt von Pankreasextrakten. Dank Zusammenarbeit mit Macleod und James B. Collip, einem Biochemiker der Universität Alberta, der in Toronto ein Sabbatical absolvierte, waren die Arbeiten rasch von Erfolg gekrönt und erste klinische Anwendungen der Extrakte wurden anfangs 1922 möglich. Bereits 1923 erhielten Banting und Macleod den Nobelpreis für Physiologie oder Medizin. Banting teilte seine Hälfte des Preises mit Best, während Macleod seine Hälfte mit Collip teilte. Dass gerade ihre Untersuchungen von Erfolgt gekrönt waren, dürfte zu einem grossen Teil auf Bantings Fähigkeiten als Chirurg, Bests Enthusiasmus als Student, Collips Fähigkeiten als Biochemiker und Macleods Umsicht, die Gruppe zusammenzubringen und mit den notwendigen Ressourcen auszustatten, zurückzuführen sein. In den nächsten zwei Jahrzehnten wurden erste Depotinsulinpräparate verfügbar. In den 1950er Jahren gelangen in der Insulinforschung wichtige Fortschritte, welche die weitere Forschung in der Diabetologie beflügeln sollten. Dies betraf zum einen die Klärung der Insulinstruktur und zum andern die Möglichkeit der Insulinmessung im Blut. Diese beiden Entdeckungen wurden mit dem Nobelpreis für Chemie ausgezeichnet (siehe Kasten 1). In den 1960er und 70er Jahren entwickelten die Insulinhersteller immer bessere Reinigungsmethoden, die schliesslich zu Präparaten mit sehr guter Verträglichkeit und nur sehr seltenen Allergien führten. Später, in den 1980er Jahren, führte die Möglichkeit der biotechnologischen Herstellung von Insulin zu einer immer stärkeren Verbreitung des Humaninsulins. Auf der Grundlage derselben Technologie wurden in den 1990er Jahren und dann im neuen Jahrtausend Insulinanaloga hergestellt, die sozusagen als «Designer-Insuline» neue, klinisch interessante Wirkprofile ermöglichten. Die heutige Vielfalt der verfügbaren Insuline, moderne Formen der Insulinapplikation (Insulinpens, Insulinpumpen) sowie die Blutzuckerselbstkontrolle beziehungsweisen das kontinuierliche Glukosemonitoring bilden heute die Grundlage der modernen intensivierten Insulintherapie.

Introduction. The history of recommendations by the Polish Federation for Education in Diabetology dates back to 2006, when guidelines for nurses/midwifes working with diabetic patients were first drawn up. However, the development of nurses and midwifes? competences requires stronger actions that foster a transition from experience-based towards evidence-based practice. Aim. The aim of this publication is to present a set of procedures describing nursing interventions in diabetes care, including currently available scientific evidence and clinical experience of specialists involved in the care of diabetic patients. Material and methods. The study involved a literature review of selected areas of nursing practice in diabetes care. When compiling the material, the priority was to use data from (in order of significance): randomized controlled clinical trials and their meta-analyses, observational studies and other studies with an adequate scientific status. Results. This joint study yielded 11 procedures describing selected aspects of nursing interventions in diabetic patients. Each of the procedures details key recommendations on diabetes care, arranged in accordance of the significance ascribed to the scientific evidence analyzed. Conclusions. The 2020 PFED guidelines on nursing and midwifery diabetes care are the effect of the evaluation of the previous versions and comprise a considerably more extensive, comprehensive and evidence-based set of practices. The major asset of these guidelines is their interdisciplinarity, reflected in the fact that the final version of the publication was approved by consultants in numerous nursing fields, a consultant in diabetology, and the President of the Polish Federation for Education in Diabetology, who all represent the medical community. The authors experience gained during work on international recommendations (New Insulin Delivery Recommendations) played an important role when formulating the present guidelines.

Aim/background To assess the effectiveness of mobile SMS as a tool for behavior and life style modification in management of diabetes. Methods This interventional study was conducted from July 2014 to April 2015 at Baqai Institute of Diabetology and Endocrinology (BIDE). Demographical and clinical information of subjects (patients and relatives) along with their knowledge and beliefs regarding diabetes was recorded using questionnaire. In Short Message Service (SMS) and non-SMS groups, education regarding diabetes was given. Two messages per day were sent to SMS group for two months. Results Total 648 subjects, SMS (n = 376) and non-SMS (n = 276) groups, were included in study. Mean age of patients and relatives was 45.41 ± 15.13 and 34.58 ± 11.91 in SMS group, while 47.06 ± 14.83 and 31.02 ± 11.51 in non-SMS group, respectively. No significant difference regarding level of knowledge and beliefs among both groups was observed at baseline. After SMS intervention, level of knowledge (p ≤ 0.0001) and beliefs (p ≤ 0.0001) were found to be significantly higher in SMS groups Non-SMS group. Conclusion Mobile SMS are an effective tool to deliver behavior and lifestyle modification advice and support for better management of diabetes and its prevention in people who are at high risk. Education intervention through SMS is found to be an important variable which enhances the knowledge and beliefs of the subjects.

In modern clinical practice, the assessment of the state of blood microcirculation and the diagnosis of microcirculatory disorders are extremely relevant in a variety of diseases: in cardiology, diabetology, oncology, dermatology, dentistry, surgery and resuscitation. Microcirculatory disorders are very diverse both in their pathogenesis and in clinical manifestations. Therefore, in the pattern of various diseases and extreme conditions, as well as in the correction of microcirculatory disorders the methods are needed for both operative assessment of the state of blood flow at tissue level and for its long-term monitoring. The interest in the study of the microvascular bed of the circulatory system is sparked by the significant role of capillaries in the implementation of the basic processes of the body's vital activity, in the trophic support of organs and their direct participation in tissue and cellular respiration. The health and life expectancy of a person depend on the coordinated work of the heart, large blood lines, and microcirculation vessels. The authors have studied modern optical methods for diagnosing microcirculation. The feasibility of using the speckle imaging method for noninvasive rapid assessment of the state of the microvasculature of human surface biological tissues has been substantiated. To implement the speckle-visualization method, methodological and software have been developed. The processing parameters that are most optimal from the point of view of the ratio of spatiotemporal resolution and computation time have been experimentally substantiated. The purpose of this work is the experimental testing of the developed methodological and hardware speckle imaging for the diagnosis of microcirculation of human surface biological tissues. The authors have carried out the studies of the state of microcirculation in the superficial blood vessels of the skin during physiotherapeutic procedures and in the imitation of pathology. The results of the studies have proved the feasibility of using the developed software for a high-quality diagnosis of the state of microcirculation of human surface biological tissues: primary changes in microcirculation are revealed, further changes to occur during physiotherapeutic procedures are visualized.

To assess the health-related quality of life of Pakistani adolescents with type 1 diabetes mellitus and their parents. This cross-sectional study of adolescents with T1DM and their parents was conducted at Baqai Institute of Diabetology and Endocrinology, a tertiary care hospital, Karachi Pakistan from April 2017 to September 2018. Diabetes Quality of Life for Youths (DQOLY) questionnaire (assess possible problems in six dimensions of impact) and WHO QOL-BREF instrument was used to assess quality of life of adolescents with type 1 diabetes and their parents respectively. The data was entered and analyzed using IBM Statistical Package for Social Sciences version 20. Adolescents with T1DM had adverse impact on their quality of life (QOL); overall QOL score was found 20.76 ± 0.83, the maximally reported adverse impact was related to symptoms of diabetes 24.35 ± 1.92 and impact of treatment 24.59 ± 2.12. Females had more adverse impact on QOL score, i.e. 22.49 ± 1.2 (p value = 0.015). Adverse effect on QOL score is strongly correlated with increasing age (p value = 0.006). Overall QOL score of parents/care takers was 56.3 ± 0.98. The worst overall QOL score was noted to be of care takers 53.75 ± 3.4 followed by mothers 54.52 ± 1.25 and fathers 60.56 ± 1.61 respectively (p value = 0.015); the environment domain was associated with statistically significance adverse impact on QOL of mothers (p value = 0.008). It is imperative for health care professionals to be aware of the effect of diabetes on QOL as timely screening is important for better health care outcomes.

The aim of this paper is to present the most relevant clinical applications of positron emission tomography/computed tomography, scintigraphy and single photon emission tomography with different radiotracers allowing to visualize e.g. glucose metabolism, amino acids metabolism, receptor density or inflammation and infections in diabetology.

Introduction. Due to high prevalence of diabetes mellitus all over the world it is essential for students who will become doctors of different specialties to possess a basic knowledge of it in this field. This pilot surveybased study was designed to assess diabetes related knowledge among faculty of medicine students from all of the medical universities in Poland. Materials and methods. Students were invited to fulfill the questionnaire during Students’ Diabetology Conference and via the Internet (social media). The survey consisted of questions about respondent’s age and personal history of diabetes and diabetes related knowledge (etiology, symptoms, risk factors, complications and treatment of diabetes mellitus and additionally a section concerning gestational diabetes). Results. A total number of 1200 medical students from Poland (70% women; mean age [SD] 22.12 [1.83] years of age) completed the survey. Mean test result was 66.62%. The best score was observed in the group of students enrolled in the 5th and 6th year of study, and those with diabetes mellitus type 1. Conclusions. The study outcome proves that knowledge about diabetes mellitus among surveyed medical students in Poland is insufficient, therefore persistent improvement in transmitting it during the course of medical education is essential.

Introduction COVID-19 pandemic suddenly affected all countries and health care systems from different perspectives including severe disruption of chronic disease services including diabetes. Diabetes is a serious condition and highly present in Bosnia and Herzegovina population, so provision of diabetes care is a important part of good control. Countries had different responses to adopt diabetes care under new circumstances as well as Bosnia and Herzegovina. Aim To investigate and evaluate the impact of the COVID-19 pandemic on the provision of diabetology care in Bosnia and Herzegovina from the perspective of patients and diabetologists. Methods Online survey for diabetologists and patient organizations have been developed with adopted question for different perspectives. The survey has been conducted online early September 2020. Collected data were analyzed in SPSS software for descriptive statistics. Results 25 diabetologists and 24 diabetes patient organizations responded. 72% of diabetologists believe that pandemic has partially altered work with patients and 56% believe that the organization of diabetes care has successfully responded to the new circumstances but 80% believe that the diabetes care system should change. 75% of patient organizations thought that the organization of diabetes care did not adequately respond and 87.5% believe system should change. Conclusion No significant differences found between RS and FBiH when it comes to majority of questions. Both diabetologists and patients consider that system of diabetes care in Bosnia and Herzegovina should be improved in future. It has been also found that diabetologists in Bosnia and Herzegovina responded and adopted their practices similar to other countries.

Hypertension and diabetes are, after smoking, obesity and hypercholesterolemia, the most important cardiovascular risk factors. It is common for these diseases to coexist, which leads to a poorer prognosis. There are differing medical association guidelines regarding the values of blood pressure when treatment should start, but instructions are consistent with the goals of treatment for diabetic patients. The guidelines published in 2017 by the American College of Cardiology/American Heart Association (ACC/AHA) suggest a value of 130/80 mm Hg for both diagnosis and starting treatment. The European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines published in 2018 recommend a value of 140/90 mm Hg when we should start therapy, with the goal of treatment below 130/80 mm Hg, but only if drug tolerance is good. The exception is patients aged over 65, for whom we should maintain systolic blood pressure in the range 130–140 mm Hg. The new Polish 2019 guidelines from the Polish Diabetology Association (PTD, Polskie Towarzystwo Diabetologiczne ) and the Polish Society of Hypertension (PTNT, Polskie Towarzystwo Nadciśnienia Tetniczego ) have been adjusted to align with the ESC/ESH guidelines. In this article, we look at changes in the guidelines over the last 20 years. We also look back at the clinical trials which have had the biggest impact on the guidelines. We describe the optimal treatment of hypertension in diabetic patients. Among all the hypotensive drugs recommended as a first choice are angiotensin-converting enzyme inhibitors or angiotensin AT 1 receptor blockers, together with calcium channel blockers and/or diuretics. There is increasing evidence regarding the positive influence of diabetic drugs on blood pressure, especially sodium-glucose cotransporter 2 inhibitors.

Summary Crosstalk between immunity and the thermogenic program has provided insight into metabolic energy regulation. Here, we generated thermogenic program-accelerating mice (T-QKO), in which Foxo1 is knockout and Foxo3 is hetero-knockout in CD4+ T cells. T-QKO exhibit lean phenotype under HFD due to increased energy expenditure. Cold exposure significantly increased expression of the thermogenic genes (Ppargc1a and Ucp1), Th2 cytokines (Il4 and Il13), and Th2 marker gene (Gata3) in subcutaneous adipose tissue (SC) of T-QKO. Furthermore, Ccr4 expression was significantly increased in Th2 cells of T-QKO, and cold exposure induced Ccl22 expression in SC, leading to increased accumulation of Th2 cell population in SC of T-QKO. These data reveal a mechanism by which cold exposure induces selective recruitment of Th2 cells into SC, leading to regulation of energy expenditure by generating beige adipocyte and suggest that inhibition of Foxo in T cells may support a strategy to prevent and treat obesity., Graphical Abstract, Highlights • T-QKO increases Gata3 and Ccr4 expression in CD4+ T cells • Cold exposure increases Ccl22 expression in subcutaneous adipose tissue • Cold exposure increases SC-specific recruitment of Th2 cells in T-QKO • Recruited Th2 cells secrete IL-4 and IL-13 and increase beiging of adipocytes, Molecular Mechanism of Behavior; Immunology; Immune Response; Diabetology

First and last of my vivid memories of Fred Whitehouse are actually tied to Davida Kruger. Shortly after I moved to Detroit in 1986 to establish a comprehensive diabetes center at Wayne State University and the Detroit Medical Center I made an appointment to see Fred to pay him homage as the giant of diabetology. Upon my entrance he stopped my compliments and said, with his usual dry humor, “Oh, I don’t really do anything here. My job is just to hold the doors open so Davida does not run into closed ones….” More sadly, it was on 1 March 2019, while flying to Houston for a meeting, when Davida, who happened to sit next to me on the plane, received the call about Fred’s passing. She was clearly shaken by that awful news. Ironically, the night before, at the meeting of the Endocrine Club of the Michigan chapter of the American Association of Clinical Endocrinologists (AACE), the past officers of AACE took a picture together to deliver it to Fred upon learning that he was in a local hospice. Another classic “Fred” recollection: We were caught in the epic snowstorm of 2003 at the Washington, DC, Mandarin Oriental Hotel (where we were preparing educational efforts for the anticipated approval of insulin glulisine) and the nation’s capital was shut down. All airports were closed, our flights canceled, and streets became impassable with the huge amount of snow. Fred approached me and said, “Let’s go and see if the Freer Art Gallery is open.” And so we went out into the blizzard, trudging the half mile through more than a foot of snow, the only crazy ones out in the street. I had a hard time keeping up with his long strides, but we made it and were the only people …

Summary Secretagogin (SCGN) is a β-cell enriched, secretory/cytosolic Ca2+-binding protein with unknown secretory regulation and functions. Recent findings suggest that SCGN deficiency correlates with compromised insulin response and diabetes. However, the (patho)physiological SCGN-insulin nexus remains unexplored. We here report that SCGN is an insulin-interacting protein. The protein-protein interaction between SCGN and insulin regulates insulin stability and increases insulin potency in vitro and in vivo. Mutagenesis studies suggest an indispensable role for N-terminal domain of SCGN in modulating insulin stability and function. SCGN supplementation in diabetogenic-diet-fed mice preserves physiological insulin responsiveness while relieving obesity and cardiovascular risk. SCGN-insulin interaction mediated alleviation of hyperinsulinemia by increased insulin internalization, which translates to reduced body fat and hepatic lipid accumulation, emerges as a plausible mechanism for the preservation of insulin responsiveness. These findings establish SCGN as a functional insulin-binding protein (InsBP) with therapeutic potential against diabetes., Graphical Abstract, Highlights • SCGN is an insulin-interacting calcium sensor protein • SCGN binding protects insulin from aggregation • SCGN potentiates insulin action in vivo • SCGN administration into HFD-fed animals impedes insulin resistance, Molecular Interaction; Endocrinology; Diabetology; Specialized Functions of Cells

Summary Orexins are hypothalamic neuropeptides that regulate feeding, energy expenditure, and sleep. Although orexin-deficient mice are susceptible to obesity, little is known about the roles of the orexin receptors in long-term energy metabolism. Here, we performed the metabolic characterization of orexin receptor-deficient mice. Ox1r-deficient mice were resistant to diet-induced obesity, and their food intake was similar between chow and high-fat food. Ox2r-deficient mice exhibited less energy expenditure than wild-type mice when fed a high-fat diet. Neither Ox1r-deficient nor Ox2r-deficient mice showed body weight gain similar to orexin-deficient mice. Although the presence of a running wheel suppressed diet-induced obesity in wild-type mice, the effect was weaker in orexin neuron-ablated mice. Finally, we did not detect abnormalities in brown adipose tissues of orexin-deficient mice. Thus, each orexin receptor signaling has a unique role in energy metabolism, and orexin neurons are involved in the interactive effect of diet and exercise on body weight gain., Graphical Abstract, Highlights • Food intakes of Ox1r-deficient mice are similar between chow and high-fat food • Ox2r-deficient mice exhibit less energy expenditure when fed a high-fat diet • Orexin neurons are involved in the interactive effect of diet and exercise • Orexin-deficient mice have normal brown adipose tissue, Physiology; Cellular Physiology; Endocrinology; Diabetology

Aims Type-2 diabetes mellitus (T2DM) is a common health condition which prevalence increases with age. Besides lifestyle modifications, passive heating could be a promising intervention to improve glycemic control. This study aimed to assess the efficacy of passive heat therapy on glycemic and cardiovascular parameters, and body weight among patients with T2DM. Methods A systematic review and meta-analysis were reported according to PRISMA Statement. We conducted a systematic search in three databases (MEDLINE, Embase, CENTRAL) from inception to 19 August 2021. We included interventional studies reporting on T2DM patients treated with heat therapy. The main outcomes were the changes in pre-and post-treatment cardiometabolic parameters (fasting plasma glucose, glycated plasma hemoglobin, and triglyceride). For these continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Study protocol number: CRD42020221500. Results Five studies were included in the qualitative and quantitative synthesis, respectively. The results showed a not significant difference in the hemoglobin A1c [WMD −0.549%, 95% CI (−1.262, 0.164), p = 0.131], fasting glucose [WMD −0.290 mmol/l, 95% CI (−0.903, 0.324), p = 0.355]. Triglyceride [WMD 0.035 mmol/l, 95% CI (−0.130, 0.200), p = 0.677] levels were comparable regarding the pre-, and post intervention values. Conclusion Passive heating can be beneficial for patients with T2DM since the slight improvement in certain cardiometabolic parameters support that. However, further randomized controlled trials with longer intervention and follow-up periods are needed to confirm the beneficial effect of passive heat therapy.

Summary The rs58542926C >T (E167K) variant of the transmembrane 6 superfamily member 2 gene (TM6SF2) is associated with increased risks for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). Nevertheless, the role of the TM6SF2 rs58542926 variant in glucose metabolism is poorly understood. We performed a sex-stratified analysis of the association between the rs58542926C >T variant and T2D in multiple cohorts. The E167K variant was significantly associated with T2D, especially in males. Using an E167K knockin (KI) mouse model, we found that male but not the female KI mice exhibited impaired glucose tolerance. As an ER membrane protein, TM6SF2 was found to interact with inositol-requiring enzyme 1 α (IRE1α), a primary ER stress sensor. The male Tm6sf2 KI mice exhibited impaired IRE1α signaling in the liver. In conclusion, the E167K variant of TM6SF2 is associated with glucose intolerance primarily in males, both in humans and mice., Graphical abstract, Highlights • The TM6SF2 E167K variant is significantly associated with T2D, primarily in males • Male, but not female, Tm6sf2 KI mice exhibited impaired glucose tolerance • IRE1α signaling is attenuated in the liver of male Tm6sf2 KI mice • IDE and LIPIN1 were dysregulated in the liver of male KI mice but not the females, Physiology; Molecular physiology; Diabetology; Genomics

Summary Pancreatic islets are essential for maintaining physiological blood glucose levels, and declining islet function is a hallmark of type 2 diabetes. We employ mass spectrometry-based proteomics to systematically analyze islets from 9 genetic or diet-induced mouse models representing a broad cross-section of metabolic health. Quantifying the islet proteome to a depth of >11,500 proteins, this study represents the most detailed analysis of mouse islet proteins to date. Our data highlight that the majority of islet proteins are expressed in all strains and diets, but more than half of the proteins vary in expression levels, principally due to genetics. Associating these varied protein expression levels on an individual animal basis with individual phenotypic measures reveals islet mitochondrial function as a major positive indicator of metabolic health regardless of strain. This compendium of strain-specific and dietary changes to mouse islet proteomes represents a comprehensive resource for basic and translational islet cell biology., Graphical abstract, Highlights • Most comprehensive mouse islet proteome library generated to date • Quantification of islet proteomic changes across 6 strains of mice on 2 diets • Islet mitochondrial function revealed as strain-independent regulator of metabolic health, Animal physiology; Diabetology; Proteomics.

Summary The capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that following icv FGF1 injection, hypothalamic signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family, is induced for at least 24 h. Further, we show that this prolonged response is required for the sustained antidiabetic action of FGF1 since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, fails to mimic the sustained glucose lowering induced by FGF1. These data identify sustained activation of hypothalamic MAPK/ERK signaling as playing an essential role in the mechanism underlying diabetes remission induced by icv FGF1 administration., Graphical abstract, Highlights • FGF1 action in the brain induces remission of diabetic hyperglycemia • FGF1 induces sustained activation of hypothalamic MAPK/ERK signaling • Blockade of hypothalamic MAPK/ERK signaling abolishes the antidiabetic action of FGF1 • FGF1 increases hypothalamic astrocyte-neuron interaction by transcriptomic analysis, Molecular biology; Molecular neuroscience; Diabetology

Summary Skeletal muscle insulin resistance is a central defect in the pathogenesis of type 2 diabetes (T2D). Here, we analyzed skeletal muscle proteome in 148 vastus lateralis muscle biopsies obtained from men covering all glucose tolerance phenotypes: normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D. Skeletal muscle proteome was analyzed by a sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics technique. Our data indicate a downregulation in several proteins involved in mitochondrial electron transport or respiratory chain complex assembly already in IFG and IGT muscles, with most profound decreases observed in T2D. Additional phosphoproteomic analysis reveals altered phosphorylation in several signaling pathways in IFG, IGT, and T2D muscles, including those regulating glucose metabolic processes, and the structure of muscle cells. These data reveal several alterations present in skeletal muscle already in prediabetes and highlight impaired mitochondrial energy metabolism in the trajectory from prediabetes into T2D., Graphical abstract, Highlights • Skeletal muscle proteome from men with all stages of glucose tolerance was analyzed • Phosphoproteomics reveal altered phosphorylation in IFG, IGT, and T2D muscles • OXPHOS proteins are decreased in prediabetic muscles, with most decrease in T2D, Molecular biology; Diabetology; Proteomics