Stefan Stefan Richard Bornstein

• Universitätsklinikum Carl Gustav Carus Dresden

Corticosteroids regulate vital processes, including stress responses, systemic metabolism, and blood pressure. Here, we show that corticosteroid synthesis is related to the polyunsaturated fatty acid (PUFA) content of mitochondrial phospholipids in adrenocortical cells. Inhibition of the rate-limiting enzyme of PUFA synthesis, fatty acid desaturase...

Background: Pheochromocytomas and paragangliomas have up to a 20% rate of metastatic disease that cannot be reliably predicted. This study prospectively assessed whether the dopamine metabolite, methoxytyramine, might predict metastatic disease, whether predictions might be improved using machine learning models that incorporate other features, an...

Viruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of death. Another public health concern is the increase of non-communicable metabolic diseases in the last four decades. In this Review, we revisit the scientific evidence supporting the...

The Diabetes Prevention Program Outcomes Study demonstrated that even temporary resolution of prediabetes (remission) to normal glucose regulation (NGR) prevents development of T2D and vascular complications. However, cellular mechanisms are unknown. We have previously shown in the Prediabetes Lifestyle Intervention Study, a German Center for Diabe...

Heterogeneity in type 2 diabetes (T2D) can be represented by a tree-like structure using reverse graph-embedded dimensionality reduction. We aimed to validate this approach and study if intensified phenotyping stratifies complications. Participants (n=927) of the German Diabetes Study (GDS) with recent-onset T2D were mapped onto a two-dimensional t...

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA has remained unanswered. Consequently, it is still unclear if DDAH2 may be a potential target for ADMA-l...

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants fr...

Iridoviridae, such as the lymphocystis disease virus-1 (LCDV-1) and other viruses, encode viral insulin-like peptides (VILPs) which are capable of triggering insulin receptors (IRs) and insulin-like growth factor receptors. The homology of VILPs includes highly conserved disulfide bridges. However, the binding affinities to IRs were reported to be...

In the aftermath of the COVID-19 pandemic, we are witnessing an unprecedented wave of post-infectious complications. Most prominently, millions of patients with Long-Covid complain about chronic fatigue and severe post-exertional malaise. Therapeutic apheresis has been suggested as an efficient treatment option for alleviating and mitigating sympto...

Fragestellung Bei Neudiagnose eines Diabetes mellitus Typ 2 (T2D) ist der Beginn einer Insulintherapie abhängig von der ärztlichen Beurteilung. Dies führt zu nicht selten zu hyper-/hypoglykämer Dekompensation. Daher untersuchten wir einen möglichen Zusatznutzen der C-Peptid-Glukose-Ratio (CGR) zur Prädiktion einer Insulintherapie und des glykämisch...

Obesity is associated with a higher risk of severe COVID-19 and increased mortality. In the current study, we have investigated the expression of ACE2, NRP1, and HMGB1, known to facilitate SARS-CoV-2 cell entry, in adipose tissue from non-COVID-19 control patients with normal weight, overweight and obesity. All factors were expressed, but no signif...

Elevated serum concentrations of glucocorticoids (GCs) result in excessive lipid accumulation in white adipose tissue (WAT) as well as dysfunction of thermogenic brown adipose tissue (BAT) - ultimately leading to the development of obesity and metabolic disease. Here, we hypothesized that activation of the sympathetic nervous system either via cold...

Background: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. Methods: We did a multicentre, open-label, randomised tria...

Context: Pheochromocytomas/paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface thera...

Aims: Weaimed to compare theconcentrations of GLP-1, glucagon and GIP (established regulators of glucose homeostasis) and glicentin (emerging new metabolic marker)during an OGTT in patients with normal glucose tolerance (NGT), prediabetes and diabetes at onset, and one-year before, when all had prediabetes. Methods: GLP-1, glucagon, GIP and glic...

Simple Summary The vault complex, consisting of a major vault protein (MVP), two minor vault proteins (VPARP and TEP1), and small untranslated vault RNA molecules, is considered the largest intracellular ribonucleoprotein particle. Although in recent years vaults were believed to be involved in multidrug resistance (MDR), the exact function of this...

Precision therapeutics is emerging as a new medical concept that focuses on the unique characteristics of an individual in order to develop personalized prevention or treatment strategies. In this article, we summarize important aspects of precision therapeutics in type 2 diabetes mellitus. First, we discuss precision prevention and how lifestyle i...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) can infect multiple tissues, including endocrine organs, such as the pancreas, adrenal, thyroid, and adipose tissue. The main receptor for SARS-CoV-2, ACE2, is ubiquitously expressed in the cells of the endocrine organs and accordingly, the...

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European...

Background Mounting evidence shows association between COVID-19 and new diagnoses of diabetes. It is unclear, however, if COVID-19 increases detection of pre-existing diabetes or if it can induce new-onset of the disease. Methods We established a global online registry of COVID-19-related diabetes (CoviDIAB) using a web-enabled data capture system...

The objective of this work was to investigate whether impaired insulin secretion can be restored by lifestyle intervention in specific subphenotypes of prediabetes. One thousand forty-five participants from the Prediabetes Lifestyle Intervention Study (PLIS) were assigned to 6 recently established prediabetes clusters. Insulin secretion was assesse...

A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and non-alcoholic steato-hepatitis. Here we identified two heat-shock proteins, Heat-Shock-Protein70 and Glucose-Regulated Protein78, which are increased in the jejunum of rats on a high-fat diet. We demonstrated a causal link between these proteins and hepatic and whole-bod...

Background: Atherosclerosis is considered a chronic inflammation of arterial vessels with the involvement of several immune cells causing severe cardiovascular diseases. Lipoprotein apheresis (LA) improves cardiovascular conditions of patients with severely disturbed lipid metabolism. In this context, little is known about the impact of LA on vari...

Comorbid diabetes with depression is a challenging and often under-recognized clinical problem. During the current COVID-19 pandemic, a communicable disease is thriving on the increasing incidences of these non-communicable diseases. These three different health problems are bidirectionally connected forming a vicious cycle. Firstly, depressed indi...

Glucocorticoids (GC) are an integral part of anti-inflammatory therapy. However, their therapeutic effectiveness is limited by their deleterious adverse effects such as the development of obesity, diabetes, and cardiometabolic disease. GC-induced obesity arises from excessive fat accumulation in white adipose tissue (WAT) as well as suppressed ther...

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPG...

Pheochromocytomas (PCCs) are rare but potentially lethal tumors that arise from the adrenal medulla. The clinical suspicion and diagnosis of PCC can be challenging due to the non-specific nature of signs and symptoms. In many patients, infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could lead to long-term symptoms inclu...

A continual increase in cases of Long Covid constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggests that up to 20% of people with confirmed with SARS-CoV-2 suffer from clinically relevant symptoms of Long Covid several weeks to mo...

Over the past century, since the discovery of insulin, the therapeutic offer for diabetes has grown exponentially, in particular for type 2 diabetes. However, the drugs in the diabetes pipeline are even more promising because of their impressive anti-hyperglycemic effects coupled with a remarkable weight loss. An ideal medication for type 2 diabete...

Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bi...

This study aimed at investigating the nature of SARS-CoV-2-specific immunity in patients with mild COVID-19 and sought to identify parameters most relevant for the generation of neutralizing antibody responses in convalescent COVID-19 patients. In the majority of the examined patients a cellular as well as humoral immune response directed to SARS-C...

The coronavirus disease 2019 (COVID-19) pandemic is currently one of the major health concerns worldwide accounting for many deaths and posing a great social and economic burden. Early activation of adrenal hormone secretion is pivotal to surviving systemic microbial infections. In addition, clinical studies demonstrated that glucocorticoids might...

The COVID-19 Pandemic has led to a world health crisis with major socioeconomic consequences that have deeply affected our daily lives. Until the end of May 2022, more than 500 million people have been infected by COVID-19 and more than 6 million have died from the disease. Unprecedented efforts in research, illustrated by the more than 250 000 pub...

COVID-19 may influence human fertility and sexuality in several ways. Different cell types in gonads show a constitutive expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), which provide potential entry pathways for SARS-CoV-2. In addition to the biological effects of a COVID-19 infection on t...

Objective Clinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis. Design This multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoho...

Diabetes mellitus is one of the most frequent diseases in the general population. Electrical stimulation is a treatment modality based on the transmission of electrical pulses into the body that has been widely used for improving wound healing and for managing acute and chronic pain. Here, we discuss recent advancements in electroceuticals and hapt...

Major advancements are expected in medicine and healthcare in the 21st century- “Digital Age”, mainly due to the application of data technologies and artificial intelligence into healthcare. In this perspective article we share a short story depicting the future Cushings’ Disease patient and the postulated diagnostic and management approaches. In t...

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at...

Progressive dysfunction and failure of insulin-releasing β-cells is a hallmark of type 2 diabetes (T2D). To study mechanisms of β-cell loss in T2D, we performed islet single-cell RNA-sequencing of two obese mouse strains differing in their diabetes susceptibility. On a control diet, we identified six β-cell clusters with similar abundance in both s...

Adrenocortical carcinoma (ACC) is a rare, heterogenous and highly malignant disease. Management of ACC is dependent on disease stage with complete surgical resection as the only potentially curative option. However, advanced, un-resectable, metastatic stages and also recurrences often require systemic treatments, which are unfortunately nowadays st...

In the aftermath of the corona pandemic, long-COVID or post-acute COVID-19 syndrome still represents a great challenge, and this topic will continue to represent a significant health problem in the coming years. At present, the impact of long-COVID on our health system cannot be fully assessed but according to current studies, up to 40% of people w...

When the corona pandemic commenced more than two years ago, it was quickly recognized that people with metabolic diseases show an augmented risk of severe COVID-19 and an increased mortality compared to people without these comorbidities. Furthermore, an infection with SARS-CoV-2 has been shown to lead to an aggravation of metabolic diseases and in...

Obesity is an increasing health problem all over the world. In combination with the current COVID-19 pandemic, this has turned into a massive challenge as individuals with overweight and obesity at all ages show a significant increase in their risk of getting severe COVID-19. Around 20% of all patients that were hospitalized for COVID-19 suffered f...

Elevated plasma concentrations of asymmetric dimethylarginine (ADMA) are associated with an increased risk of mortality and adverse cardiovascular outcomes. ADMA can be metabolized by dimethylarginine dimethylaminohydrolases (DDAHs) and by alanine-glyoxylate aminotransferase 2 (AGXT2). Deletion of DDAH1 in mice leads to elevation of ADMA in plasma...

Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bil...

Aim: To investigate the prevalence of biopsy-proven non-alcoholic steatohepatitis (NASH) in a cohort of patients with morbid obesity and with or without type 2 diabetes (T2D) and to find non-invasive predictors of NASH severity. Methods: We evaluated a cohort of 412 subjects (age 19-67 years, body mass index-BMI: 44.98 kg/m2), who underwent fine...

The Covid-19 pandemic has provided new and strong evidence for poor outcomes of viral infection in patients with poor metabolic health. Insulin resistance is at the root of many metabolic conditions and a key driver of their progression as it promotes ineffectual inflammation whilst impairing immune functions. In a vicious circle, insulin resistanc...

It is increasingly clear that pancreatic islet replacement is needed to provide a comprehensive treatment for the growing numbers of patients with type 1 diabetes mellitus. Advances from the past year suggest that this goal might now be within reach.

The symptoms of long COVID and chronic adrenal insufficiency have striking similarities. Therefore, we aim to raise awareness of assessing adrenal function in patients with long COVID.

Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship betwee...

Adrenocortical carcinoma is a heterogeneous and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. In this study, we have assessed for the preclinical gold standard NCI-H295 in direct comparison with the more recently established MUC-1 and a here newly reported ACC cell line (TVBF-7) the mutational status of impor...

Alterations of the hypothalamus pituitary-axis on one hand and heightened rates of somatic diseases and mortality on the other hand are consistently found for PTSD and MDD patients. A possible link between these factors might be the immune system, in particular pro- and anti-inflammatory cytokines. A ‘low-grade inflammation’ in PTSD and MDD patient...

Erkrankungen der Nebennierenrinde erfordern im Rahmen der Severe-acute-respiratory-syndrome-coronavirus-2(SARS-CoV-2)-Pandemie eine besondere Aufmerksamkeit. Zum einen können SARS-CoV-2-Infektionen sich auch extrapulmonal manifestieren und endokrine Störungen – insbesondere im Bereich der Nebennierenrinde – verursachen. Zum anderen sind Patienten m...

The cytosolic protein rubicon (RUBCN) has been implicated in the removal of necrotic debris and autoimmunity. However, the role of RUBCN in models of acute kidney injury (AKI), a condition that typically involves necrotic kidney tubules, was not investigated. Here, we demonstrate that RUBCN-deficient mice are hypersensitive to renal damage induced...

This editorial refers to ‘Bariatric surgery and cardiovascular disease: a systematic review and meta-analysis', by S. L. van Veldhuisen et al., https://doi.org/10.1093/eurheartj/ehac071.

Background Pancreas surgery remains technically challenging and is associated with considerable morbidity and mortality. Identification of predictive risk factors for complications have led to a stratified surgical approach and postoperative management. The option of simultaneous islet autotransplantation (sIAT) allows for significant attenuation o...

Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. I...

Continuous activation of hypoxia pathways in pheochromocytomas and paragangliomas (PPGLs) is associated with higher disease aggressiveness, for which effective treatment strategies are still missing. Most of the commonly used in vitro models lack characteristics of these pseudohypoxic tumors, including elevated expression of hypoxia-inducible facto...

Dexamethasone is widely used as an immunosuppressive therapy and recently as COVID-19 treatment. Here, we demonstrate that dexamethasone sensitizes to ferroptosis, a form of iron-catalyzed necrosis, previously suggested to contribute to diseases such as acute kidney injury, myocardial infarction, and stroke, all of which are triggered by glutathion...

Introduction: Body-mass index is a major determinant of left-ventricular-mass (LVM). Bariatric-metabolic surgery (BMS) reduces cardiovascular mortality. Its mechanism of action, however, often encompasses a weight-dependent effect. In this translational study, we aimed at investigating the mechanisms by which BMS leads to LVM reduction and functio...

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins medi...

ZUSAMMENFASSUNG Als Hausärzte und Diabetologen werden wir in den nächsten Jahren mit den Langzeitfolgen der Pandemie zu tun haben. Neben der Viruserkrankung selbst haben die Maßnahmen zur Pandemiebekämpfung bisher noch nicht absehbare Kollateralschäden verursacht. Berichte und Studien aus allen Ländern, in denen es zu Lockdowns, Ausgangssperren, Ho...

ZUSAMMENFASSUNG Ein Großteil der Menschen, die an einer SARS-CoV-2-Infektion versterben, sind Diabetiker. Ein noch größerer Anteil der COVID-19-Verstorbenen nach einem Impfdurchbruch sind Diabetiker. Es scheint so zu sein, dass die Co-Inzidenz von Diabetes sowie metabolischem Syndrom und der COVID-19-Erkrankung ein entscheidender Trigger für Morbid...

ZUSAMMENFASSUNG Über 10 % der deutschen Bevölkerung leiden an metabolischen Krankheiten wie Diabetes, Adipositas, oder nicht alkoholischer Steatohepatitis. Betroffene sind während der COVID-19-Pandemie einem besonderen Risiko ausgesetzt, gibt es doch zahlreiche Hinweise auf eine bidirektionale Beziehung zwischen diesen Krankheiten und COVID-19. Ein...

ZUSAMMENFASSUNG Es wurde lange diskutiert, ob COVID-19 zu neu auftretendem Diabetes führen kann. Jedoch jetzt, fast 2 Jahre nach Beginn der Pandemie, haben mehrere Studien berichtet, dass neu auftretender Diabetes mit COVID-19 in Verbindung gebracht wird. Stoffwechselerkrankungen sind mit einem erhöhten Risiko für schweres COVID-19 verbunden und um...

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at...

Major advancements are expected in medicine and healthcare in the 21st century- "Digital Age", mainly due to the application of data technologies and artificial intelligence into healthcare. In this perspective article we share a short story depicting the future Cushings' Disease patient and the postulated diagnostic and management approaches. In t...

Zusammenfassung Erkrankungen der Nebennierenrinde erfordern im Rahmen der Severe-acute-respiratory-syndrome-coronavirus-2(SARS-CoV-2)-Pandemie eine besondere Aufmerksamkeit. Zum einen können SARS-CoV-2-Infektionen sich auch extrapulmonal manifestieren und endokrine Störungen – insbesondere im Bereich der Nebennierenrinde – verursachen. Zum anderen...

Background: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-an...

Background The presence or future development of metastatic pheochromocytomas or paragangliomas (mPPGLs) can be difficult to diagnose or predict at initial presentation. Since production of catecholamines from mPPGLs is different from non-metastatic tumors (non-mPPGLs), this study aimed to clarify whether presenting catecholamine-related signs and...

Aims/hypothesis Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in in...

The adrenal gland consists of two tissues, cortex and medulla, united under one capsule. Adrenal stem/progenitor cells play a key role in development and homeostasis. Here, we describe a protocol for generating primary cultures of adrenal cells from mice. We describe techniques for separating the cortex and medulla, generating spheroid cultures con...

Hypokalemia plays a central role for case finding, course, treatment decision, and prognosis of patients with primary aldosteronism. However, to date there is a lack of high-level evidence about the incidence of primary aldosteronism in hypokalemic patients. The IPAHK+study is an epidemiological, cross-sectional, monocentric study to provide eviden...

In May 2020, a pregnant woman in her 37th pregnancy week was diagnosed with COVID-19 in St. Petersburg in Russia. All treatments failed and the patient died after 11 days due to acute respiratory distress syndrome. A stillborn child was removed by caesarian section. Pathological investigations showed that the child died due to antenatal asphyxia wi...

Context Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need. Objective This work aimed to establish the utility of plasma steroid profiling combined with m...

Hypertriglyceridaemia represents one of the most prevalent lipid abnormalities, however it is often eclipsed by focus on LDL cholesterol and is frequently overlooked by clinicians, despite it being an important cardiovascular risk factor. For most patients, hypertriglyceridaemia arises from a combination of environmental factors and multiple geneti...

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developin...

The impact of dietary sodium reduction on mouse models of type 2 diabetes is not well understood. Therefore, we analyzed the effect of a low-salt diet on obesity and parameters of type 2 diabetes in db/db mice. Five-week-old male db/db and lean db/m mice were fed a normal salt (0.19% Na+, NS) or a low-salt diet (<0.03% Na+, LS) for 5 weeks. Body an...

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developin...