snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis.

Adipose tissue is usually classified on the basis of its function as white, brown or beige (brite)1. It is an important regulator of systemic metabolism, as shown by the fact that dysfunctional adipose tissue in obesity leads to a variety of secondary metabolic complications2,3. In addition, adipose tissue functions as a signalling hub that regulates systemic metabolism through paracrine and endocrine signals4. Here we use single-nucleus RNA-sequencing (snRNA-seq) analysis in mice and humans to characterize adipocyte heterogeneity. We identify a rare subpopulation of adipocytes in mice that increases in abundance at higher temperatures, and we show that this subpopulation regulates the activity of neighbouring adipocytes through acetate-mediated modulation of their thermogenic capacity. Human adipose tissue contains higher numbers of cells of this subpopulation, which could explain the lower thermogenic activity of human compared to mouse adipose tissue and suggests that targeting this pathway could be used to restore thermogenic activity.

Mental Health Among Medical Professionals During the COVID-19 Pandemic in Eight European Countries: Cross-sectional Survey Study.

BACKGROUND: The death toll of COVID-19 topped 170,000 in Europe by the end of May 2020. COVID-19 has caused an immense psychological burden on the population, especially among doctors and nurses who are faced with high infection risks and increased workload. OBJECTIVE: The aim of this study was to compare the mental health of medical professionals with nonmedical professionals in different European countries during the COVID-19 pandemic. We hypothesized that medical professionals, particularly those exposed to COVID-19 at work, would have higher levels of depression, anxiety, and stress. We also aimed to determine their main stressors and most frequently used coping strategies during the crisis. METHODS: A cross-sectional online survey was conducted during peak COVID-19 months in 8 European countries. The questionnaire included demographic data and inquired whether the participants were exposed to COVID-19 at work or not. Mental health was assessed via the Depression Anxiety Stress Scales32 (23.53)-21 (DASS-21). A 12-item checklist on preferred coping strategies and another 23-item questionnaire on major stressors were completed by medical professionals. RESULTS: The sample (N=609) consisted of 189 doctors, 165 nurses, and 255 nonmedical professionals. Participants from France and the United Kingdom reported experiencing severe/extremely severe depression, anxiety, and stress more often compared to those from the other countries. Nonmedical professionals had significantly higher scores for depression and anxiety. Among medical professionals, no significant link was reported between direct contact with patients with COVID-19 at work and anxiety, depression, or stress. "Uncertainty about when the epidemic will be under control" caused the most amount of stress for health care professionals while "taking protective measures" was the most frequently used coping strategy among all participants. CONCLUSIONS: COVID-19 poses a major challenge to the mental health of working professionals as a considerable proportion of our participants showed high values for depression, anxiety, and stress. Even though medical professionals exhibited less mental stress than nonmedical professionals, sufficient help should be offered to all occupational groups with an emphasis on effective coping strategies.

Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.

Importance: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. Objective: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. Design, Setting, and Participants: Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes. Interventions: A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. Main Outcomes and Measures: The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). Results: Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). Conclusions and Relevance: Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT03548987.

Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial.

AIM: To investigate the long-term efficacy and safety of dapagliflozin as an adjunct to adjustable insulin in adults with type 1 diabetes (T1D) and inadequate glycaemic control. MATERIALS AND METHODS: Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-2) was a placebo-controlled, double-blind, multicentre, phase III study of adults with T1D (HbA1c 7.5%-10.5%) randomized (1:1:1) to receive dapagliflozin 5, 10 mg, or placebo. The efficacy and safety of dapagliflozin over 52 weeks were exploratory endpoints in this extension to DEPICT-2. RESULTS: Of 813 participants randomized, 88.2% completed the study. From baseline to 52 weeks, dapagliflozin 5 and 10 mg were associated with reduction in HbA1c (difference [95% CI] vs. placebo: -0.20% [-0.34, -0.06] and -0.25% [-0.38, -0.11], respectively) and adjusted mean percentage change in body weight (difference [95% CI] vs. placebo: -4.42% [-5.19, -3.64] and -4.86% [-5.63, -4.08], respectively). Serious adverse events were reported in the dapagliflozin 5, 10 mg, and placebo groups (32 [11.8%], 19 [7.0%] and 16 [5.9%], respectively). The proportion of hypoglycaemic events was similar across groups; severe hypoglycaemia was uncommon. More participants with events adjudicated as definite diabetic ketoacidosis (DKA) were in the dapagliflozin 5 and 10 mg groups versus placebo (11 [4.1%], 10 [3.7%] and 1 [0.4%], respectively); the majority of events were mild or moderate in severity and all were resolved with treatment. CONCLUSIONS: Dapagliflozin led to long-term reductions in HbA1c and body weight in adults with T1D, but increased DKA risk compared with placebo.

BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer.

Radioiodine refractoriness in differentiated thyroid cancer remains an unsolved therapeutic problem. Response to retinoids might depend on specific genetic markers. In this retrospective analysis, associations between BRAF V600E and clinical outcomes after redifferentiation with retinoic acid (RA) and radioiodine therapy (RIT) were investigated. Thirteen patients with radioiodine-refractory (RAI-R) papillary thyroid cancer (PTC) were treated with 13-cis-RA followed by iodine-131 treatment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. DNA sequencing was performed in formalin-fixed paraffin-embedded tissue. Clinical outcome parameters were tumor size, thyroglobulin, and radioiodine uptake in correlation to mutational status. Differences of each parameter were compared before and after RA/RIT. Initial response showed no difference in patients with BRAF V600E compared to patients with wild type. However, after a median follow-up of 2 and a half years, 2 out of 3 patients with BRAF V600E showed response compared to 5 out of 9 with wild type under consideration of all 3 parameters. In this small cohort, more RAI-R PTC patients with BRAF V600E receiving redifferentiation therapy showed response. Verification in a larger study population analyzing mutational status in patients with RAI-R PTC might be helpful to identify patients where redifferentiation therapy might lead to an improved outcome.

In obesity even young women suffer from urogynecological symptoms.

PURPOSE: To evaluate the occurrence of urogynecological symptoms in obese women treated in a university outpatient clinic for obesity, setting a focus on younger women. METHODS: In this explorative, prospective, cross-sectional, single-center, multidisciplinary clinical trial, all consecutively recruited women received the Prolapse Quality of Life questionnaire (P-QOL) for data acquisition. The total study population (TSP) and a subgroup (SG) aged 18-49 years were evaluated descriptively regarding symptom demonstration. RESULTS: Of the TSP (n = 166, mean age 40.2, standard deviation (SD) 12.98, mean body mass index (BMI) 45 kg/m2, SD 8.44) 105 (63%) and of the SG (n = 125, mean age 34.6, SD 9.29, mean BMI 44.9 kg/m2, SD 8.26) 72 (58%) women suffered from urinary incontinence (UI) being most impaired by stress urinary incontinence (SUI; TSP: 25%; SG: 27%) and least by urge urinary incontinence (UUI; TSP: 15%; SG: 11%). A significant correlation in the TSP between UI and age was detectable (p < 0.001, r φ = 0.37), but not between UI and BMI (p = 0.296, r φ = 0.08). The highest QOL impairment is detected for the domain general health perceptions [GHP; TSP & SG score >50 (score scale 0-100)]. Women with UI are significantly more affected than women with pelvic organ prolapse (GHP UI: TSP p = 0.04, SG p = 0.037; GHP POP: TSP p = 0.081, SG p = 0.659). CONCLUSIONS: A remarkable number of young obese women mentioned urogynecological symptoms and quality-of-life impairment. The P-QOL questionnaire proved to be an easily applicable tool to scan for concerned obese women. Its use in non-urogynecological departments, as performed, enables an early introduction of symptomatic women to urogynecologists, possibly preventing future growing urogynecological health issues.

The effect of lifestyle intervention in obesity on the soluble form of activated leukocyte cell adhesion molecule.

BACKGROUND: The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters. METHODS: Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined. Oral glucose tolerance test (OGTT) was performed when indicated. RESULTS: At baseline, the serum concentration of sALCAM was increased and correlated positively with HOMA-IR and negatively with age. At the end of the program, sALCAM concentrations decreased significantly. Multivariate analysis showed that sALCAM significantly correlated with age, glucose concentration after 2 h OGTT and the HOMA-IR. A higher decrease of HOMA-IR during the study was observed in subjects with higher concentration of sALCAM at baseline. CONCLUSIONS: sALCAM might be a novel biomarker in obesity that correlates and predicts insulin sensitivity improvement and that can be affected by lifestyle intervention.

Autotransplantation of parathyroid grafts into the tibialis anterior muscle after parathyroidectomy: a novel autotransplantation site.

BACKGROUND: Surgical management of renal secondary hyperparathyroidism (sHPT) is varying. Total parathyroidectomy with heterotopic autotransplantation (TPTX + AT) is one of the standard surgical procedures in sHPT, but there is no consensus about the optimal site for graft insertion. At the surgical department of the University Hospital of Heidelberg we prefer the autotransplantation into the tibialis anterior muscle. The aim of this study was to assess the long-term function of the auto-transplanted parathyroid tissue in this type of surgical procedure. METHODS: The function of the autograft of 42 patients was assessed 8.2 ± 2.5 years after surgery, using a modified Casanova-test of the leg bearing the parathyroid tissue. Ischemic blockage was induced by tourniquet and the levels of parathyroid hormone (PTH) were assessed during the test. RESULTS: At the point of assessment, the ischemic blockage led to a significant reduction in the concentration of PTH (≥50% of the baseline value) in 19 patients (45%) indicating well-functioning autografts. In 11 patients (26%), ischemic blockage did not cause any change in the concentration of PTH (≤20% of the baseline value), indicating functioning residual parathyroid tissue from another site. The source of PTH production was classified as unidentifiable in five patients (12%). Two patients had developed graft-dependent recurrent HPT (5%) without therapeutic consequences and three patients suffered from persistent symptomatic hypoparathyroidism (7%). CONCLUSIONS: These results indicate that TPTX + AT into the tibialis anterior muscle is a successful surgical treatment for renal HPT and that the modified Casanova-test is a suitable diagnostic tool for autografts function.

Pilot study to assess the influence of an enhanced medication plan on patient knowledge at hospital discharge.

PURPOSE: This study assessed the effect of providing an enhanced medication plan (EMP) to patients during patient-physician conversation at hospital discharge and evaluated its immediate impact on patient knowledge on pharmacotherapy. METHODS: We observed patient-physician conversations at hospital discharge in three internal medicine wards of the University Hospital Heidelberg before and after the EMP was integrated into the discharge process, and documented how and to what extent physicians provided the patients with drug information. After the conversation, the patients' knowledge was evaluated by three standardized questions about their pharmacotherapy. RESULTS: We observed 90 conversations (50 before EMP-implementation, 40 after). In both phases, the conversation duration was 5.6-6 min (p = 0.56). However, the time spent on drug information increased significantly by 61.7% after EMP-implementation (+63 s, p = 0.02). Before implementation, physicians gave at least one drug administration recommendation for 75.1% of all drugs, compared to 84.6% after implementation (p = 0.02). The EMP provided information for almost all drugs (98.9%; p < 0.01) after implementation. Three times more patients answered all questions correctly after EMP-implementation (p < 0.01). CONCLUSION: The provision of an EMP improves information transfer and therefore increases the patients' knowledge of their individual drug treatment without prolonging the overall discharge process.

Difficulties in emotion regulation across the spectrum of eating disorders.

Theoretical models consider difficulties in emotion regulation (ER) as central trans-diagnostic phenomena across the spectrum of eating disorders (ED). However, there is a lack of studies directly comparing ED subtypes regarding ER problems. Furthermore, patients with anorexia nervosa-restricting type (AN-R) and patients with AN-binge/purge type (AN-BP) have usually been merged into one overall AN group in previous research on ER. In order to overcome these limitations of previous studies, the present study investigated specific ER difficulties in 120 patients with different ED subtypes, including AN-R, AN-BP, bulimia nervosa (BN), and binge-eating disorder (BED). As compared to 60 healthy normal-weight controls (NWC) and 29 healthy over-weight controls (OWC), all ED subtypes reported greater difficulties in ER. ED subtypes did not differ regarding most domains of ER except BED showing less severe ER difficulties in some domains. In addition, AN-BP but not BN reported greater impulse control difficulties than AN-R and BED. The findings underscore the relevance of ER difficulties in ED and support the trans-diagnostic view of ER difficulties being present across the whole spectrum of ED. In addition, the present results suggest that certain domains of ER may be linked more closely to certain ED subtypes than to others.

Real-World Use of Oral Semaglutide in Adults with Type 2 Diabetes: The PIONEER REAL Switzerland Multicentre, Prospective, Observational Study.

INTRODUCTION: Real-world data provide insight into how medications perform in clinical practice. The PIONEER REAL Switzerland study aimed to understand clinical outcomes with oral semaglutide in adults with type 2 diabetes (T2D). METHODS: PIONEER REAL Switzerland was a 34-44-week, multicentre, prospective, non-interventional, single-arm study of adults with T2D naïve to injectable glucose-lowering medication who were initiated on oral semaglutide in routine clinical practice. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS); secondary endpoints included change in body weight (BW) from BL to EOS and the proportion of participants achieving HbA1c < 7.0% and the composite endpoints HbA1c reduction ≥ 1%-points with BW reduction ≥ 3% or ≥ 5% at EOS. Safety was assessed in participants who received ≥ 1 dose of oral semaglutide. RESULTS: Of the 185 participants (female/male, n = 67/118) initiating oral semaglutide, 168 (90.8%) completed the study and 143 (77.3%) remained on treatment with oral semaglutide at EOS. At BL, participants had a mean age of 62 years, diabetes duration of 6.4 years, HbA1c of 7.7%, BW of 95.6 kg and body mass index of 33.2 kg/m2; 56.2% of participants were receiving glucose-lowering medications. Significant reductions were observed for HbA1c (estimated change - 0.91%; 95% confidence interval [CI] - 1.10, - 0.71; p < 0.0001) and BW (estimated change - 4.85%; 95% CI - 5.70, - 4.00; p < 0.0001). In total, 139 adverse events (AEs) were reported in 65 (35.1%) participants; most were mild or moderate. The most frequent AEs were gastrointestinal disorders (27.0%); 31 AEs in 20 (10.8%) participants led to discontinuation of oral semaglutide. Six serious AEs were reported; all were considered unlikely to be related to oral semaglutide. CONCLUSION: People living with T2D treated with oral semaglutide in Switzerland achieved clinically significant reductions in HbA1c and BW, with no new safety signals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04537624. A graphical abstract is available for this article.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

BACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Regulation of adipocyte formation by GLP-1/GLP-1R signaling.

Increased nutrient intake leads to excessive adipose tissue accumulation, obesity, and the development of associated metabolic disorders. How the intestine signals to adipose tissue to adapt to increased nutrient intake, however, is still not completely understood. We show here, that the gut peptide GLP-1 or its long-lasting analog liraglutide, function as intestinally derived signals to induce adipocyte formation, both in vitro and in vivo. GLP-1 and liraglutide activate the GLP-1R, thereby promoting pre-adipocyte proliferation and inhibition of apoptosis. This is achieved at least partly through activation of ERK, PKC, and AKT signaling pathways. In contrast, loss of GLP-1R expression causes reduction in adipogenesis, through induction of apoptosis in pre-adipocytes, by inhibition of the above mentioned pathways. Because GLP-1 and liraglutide are used for the treatment of type 2 diabetes, these findings implicate GLP-1 as a regulator of adipogenesis, which could be an alternate pathway leading to improved lipid homeostasis and controlled downstream insulin signaling.

Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy.

Whereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed to a positive selection pressure (eg, resulting from reduced blood loss or improved survival in sepsis). The consequences of enhanced coagulation activation, as observed in FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated the role of FVL in diabetic nephropathy. In heterozygous or homozygous diabetic FVL mice, albuminuria and indices of diabetic nephropathy were reduced compared with diabetic wild-type mice. This was associated with reduced glomerular apoptosis and preservation of podocytes in diabetic FVL-positive mice. In vitro, low-dose thrombin (50pM) prevented, whereas high-dose thrombin (20nM) aggravated, glucose-induced apoptosis in podocytes. In diabetic patients, the FVL mutation, but not the plasminogen activator inhibitor-1 4G/5G polymorphism, is associated with reduced albuminuria, which is consistent with a nephroprotective role of low but sustained thrombin generation. Consistently, anticoagulation of diabetic FVL-positive mice with hirudin abolished the nephroprotective effect. These results identify a nephroprotective function of low but sustained thrombin levels in FVL carriers, supporting a dual, context-dependent function of thrombin in chronic diseases.

Development of a standardized knowledge base to generate individualized medication plans automatically with drug administration recommendations.

AIMS: We aimed to develop a generic knowledge base with drug administration recommendations which allows the generation of a dynamic and comprehensive medication plan and to evaluate its comprehensibility and potential benefit in a qualitative pilot study with patients and physicians. METHODS: Based on a literature search and previously published medication plans, a prototype was developed and iteratively refined through qualitative evaluation (interviews with patients and focus group discussions with physicians). To develop the recommendations for safe administration of specific drugs we screened the summary of product characteristics (SmPC) of different exemplary brands, allocated the generated advice to groups with brands potentially requiring the same advice, and reviewed these allocations regarding applicability and appropriateness of the recommendations. RESULTS: For the recommendations, 411 SmPCs of 140 different active ingredients including all available galenic formulations, routes of administrations except infusions, and administration devices were screened. Finally, 515 distinct administration recommendations were included in the database. In 926 different generic groups, 29,879 allocations of brands to general advice, food advice, indications, step-by-step instructions, or combinations thereof were made. Thereby, 27,216 of the preselected allocations (91.1%) were confirmed as appropriate. In total, one third of the German drug market was labelled with information. CONCLUSIONS: Generic grouping of brands according to their active ingredient and other drug characteristics and allocation of standardized administration recommendations is feasible for a large drug market and can be integrated in a medication plan.

Inhibitory control and decision making under risk in bulimia nervosa and binge-eating disorder.

OBJECTIVE: To investigate neuropsychological mechanisms of impulsivity in patients with bulimia nervosa (BN) and binge-eating disorder (BED). METHOD: Nineteen BN patients and 31 age- and body-mass-index (BMI)-matched healthy controls (c-BN) as well as 54 overweight and obese BED patients and 43 age- and BMI-matched healthy controls (c-BED) were investigated using an inhibitory control task (stop signal task, SST) and a decision-making under risk task (game of dice task, GDT). RESULTS: Compared to c-BN, BN patients demonstrated significant greater stop signal reaction times in the SST, but no differences for the frequency of risky decisions in the GDT. BED patients did not differ from c-BED in the SST or the GDT. DISCUSSION: BN but not BED patients differed from their respective control groups concerning the "stopping" component of impulsivity. These differences in motor inhibition may contribute to the behavioral distinctions in binge-eating behavior between BN and BED.

Impact of Albumin-to-Creatinine Ratio Point-of-Care Testing on the Diagnosis and Management of Diabetic Kidney Disease.

BACKGROUND: For the diagnosis of diabetic kidney disease (DKD), quantitative albuminuria measurement using the albumin-to-creatinine ratio (ACR) is recommended according to various guidelines. It can be measured either in specialized laboratories or using ACR point-of-care testing (POCT). This observational study aims at evaluating the effect of ACR POCT utilization on the DKD diagnosis and treatment management for glycemic control and blood pressure. METHOD: Data of 717 patients with diabetes (type 1 diabetes: n = 236; type 2 diabetes: n = 463; other diabetes forms: n = 18) were assessed in three centers. The impact of ACR POCT on DKD diagnosis and treatment management for glycemic control and blood pressure was assessed using a case report form. The assessment of ACR POCT utilization purpose and relevance for physicians was documented using a questionnaire. RESULTS: Of all participants (n = 717), 39.1% had a confirmed/suspected DKD diagnosis. Hereof, 8.6% were newly diagnosed with DKD, and 9.9% were suspected with DKD based on the actual ACR POCT values. Within the group of patients with confirmed/suspected DKD (n = 280), treatment modification was performed in 46.1% of participants. A drug initiation with GLP-1 receptor agonists or SGLT2 inhibitors was performed in 11.1% or 8.9% of patients with confirmed/suspected DKD, respectively. Regarding the utilization purposes of ACR POCT, 100% of the physicians (n = 8) indicated using it to examine patients with diabetes with or without hypertension; 75% considered it very important for patients with diabetes. CONCLUSIONS: The implementation of ACR POCT may positively affect DKD diagnosis and subsequently allow better management of patients with diabetes.

Psoriasis immunometabolism: progress on metabolic biomarkers and targeted therapy.

Psoriasis is a common inflammatory disease that affects mainly the skin. However, the moderate to severe forms have been associated with several comorbidities, such as psoriatic arthritis, Crohn's disease, metabolic syndrome and cardiovascular disease. Keratinocytes and T helper cells are the dominant cell types involved in psoriasis development via a complex crosstalk between epithelial cells, peripheral immune cells and immune cells residing in the skin. Immunometabolism has emerged as a potent mechanism elucidating the aetiopathogenesis of psoriasis, offering novel specific targets to diagnose and treat psoriasis early. The present article discusses the metabolic reprogramming of activated T cells, tissue-resident memory T cells and keratinocytes in psoriatic skin, presenting associated metabolic biomarkers and therapeutic targets. In psoriatic phenotype, keratinocytes and activated T cells are glycolysis dependent and are characterized by disruptions in the TCA cycle, the amino acid metabolism and the fatty acid metabolism. Upregulation of the mammalian target of rapamycin (mTOR) results in hyperproliferation and cytokine secretion by immune cells and keratinocytes. Metabolic reprogramming through the inhibition of affected metabolic pathways and the dietary restoration of metabolic imbalances may thus present a potent therapeutic opportunity to achieve long-term management of psoriasis and improved quality of life with minimum adverse effects.

Awareness and knowledge of diabetic ketoacidosis in people with type 1 diabetes: a cross-sectional, multicenter survey.

INTRODUCTION: To evaluate awareness and knowledge of diabetic ketoacidosis (DKA), a common and potentially life-threatening complication in people living with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: A survey was developed to assess individuals' current knowledge, management, and unmet needs regarding DKA. The study was conducted in six Swiss and three German endocrine outpatient clinics specialized in the treatment of diabetes. RESULTS: A total of 333 participants completed the questionnaire (45.7% female, mean age of 47 years, average duration of T1D at 22 years). Surprisingly, 32% of individuals were not familiar with the term 'diabetic ketoacidosis'. Participants rated their own knowledge of DKA significantly lower than their physicians (p<0.0001). 46% of participants were unable to name a symptom of DKA, and 45% were unaware of its potential causes. 64% of participants did not test for ketones at all. A significant majority (67%) of individuals expressed the need for more information about DKA. CONCLUSIONS: In patients treated in specialized centers, knowledge of DKA was found to be inadequate, with a lack of understanding regarding symptoms and causes. Healthcare professionals tended to overestimate individuals' knowledge. Future efforts should focus on addressing these knowledge gaps and incorporating protective factors into the treatment of T1D.