Exploring Medical Career Choice to Better Inform Swiss Physician Workforce Planning: Protocol for a National Cohort Study.

Background: A medical student's career choice directly influences the physician workforce shortage and the misdistribution of resources. First, individual and contextual factors related to career choice have been evaluated separately, but their interaction over time is unclear. Second, actual career choice, reasons for this choice, and the influence of national political strategies are currently unknown in Switzerland.

Transplantation of porcine adrenal spheroids for the treatment of adrenal insufficiency.

Primary adrenal insufficiency is a life-threatening disorder, which requires lifelong hormone replacement therapy. Transplantation of xenogeneic adrenal cells is a potential alternative approach for the treatment of adrenal insufficiency. For a successful outcome of this replacement therapy, transplanted cells should provide adequate hormone secretion and respond to adrenal physiological stimuli.

Mechanisms and clinical relevance of the bidirectional relationship of viral infections with metabolic diseases.

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.

Do Sugar-Sweetened Beverages Increase Fasting FGF21 Irrespective of the Type of Added Sugar? A Secondary Exploratory Analysis of a Randomized Controlled Trial.

Human fibroblast growth factor 21 (FGF21) is a multifaceted metabolic regulator considered to control sugar intake and to exert beneficial effects on glucose and lipid metabolism. Elevated serum FGF21 levels are associated with metabolic syndrome, suggesting a state of FGF21 resistance. Further, given the evidence of a hepatic ChREBP and FGF21 signaling axis, it can be assumed that SSBs containing fructose would possibly increase FGF21 concentrations.

Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death.

Pancreatic β-cells depend on the well-balanced regulation of cytosolic zinc concentrations, providing sufficient zinc ions for the processing and storage of insulin, but avoiding toxic effects. The zinc transporter ZnT8, encoded by SLC30A8,is a key player regarding islet cell zinc homeostasis, and polymorphisms in this gene are associated with altered type 2 diabetes susceptibility in man. The objective of this study was to investigate the role of ZnT8 and zinc in situations of cellular stress as hypoxia or inflammation.

COVID-19 and metabolic disease: mechanisms and clinical management.

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 developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders.

Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial.

Background & Aims: Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on lipid metabolism independently of excessive caloric intake.

Methods: A total of 94 healthy men were studied in this double-blind, randomized trial.

The Diabetes Gene JAZF1 Is Essential for the Homeostatic Control of Ribosome Biogenesis and Function in Metabolic Stress.

The ability of pancreatic β-cells to respond to increased demands for insulin during metabolic stress critically depends on proper ribosome homeostasis and function. Excessive and long-lasting stimulation of insulin secretion can elicit endoplasmic reticulum (ER) stress, unfolded protein response, and β-cell apoptosis. Here we show that the diabetes susceptibility gene JAZF1 is a key transcriptional regulator of ribosome biogenesis, global protein, and insulin translation.

Glycemic control and complications in glycogen storage disease type I: Results from the Swiss registry.

Background: Regular carbohydrate intake to avoid hypoglycemia is the mainstay of dietary treatment in glycogen storage disease type I (GSDI). The aim of this study was to evaluate the quality of dietary treatment and glycemic control in a cohort of GSDI patients, in relation to the presence of typical long-term complications.

Methods: Data of 25 patients (22 GSD subtype Ia and 3 GSDIb, median age 20y) from the Swiss hepatic glycogen storage disease registry was analyzed cross-sectionally.

Islet transplantation as safe and efficacious method to restore glycemic control and to avoid severe hypoglycemia after donor organ failure in pancreas transplantation.

The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas retransplantation. Ten patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months.

Effect of insulin glargine on recreational physical activity and TV viewing: Analysis of the randomised ORIGIN trial.

Aims: To quantify whether insulin therapy, and concomitant weight gain, affects recreational physical activity and TV viewing time using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial.

Methods: 12,537 insulin-naïve individuals with dysglycaemia were randomised to receive either basal insulin glargine or standard care and followed for a median of 6.2years.

A case-control field study on the relationships among type 2 diabetes, sleepiness and habitual caffeine intake.

Objectives: The purpose of this study was to examine the possible links between type 2 diabetes, daytime sleepiness, sleep quality and caffeine consumption.

Methods: In this case-control field study, comparing type 2 diabetic ( n=134) and non-type 2 diabetic ( n=230) participants, subjects completed detailed and validated questionnaires to assess demographic status, health, daytime sleepiness, sleep quality and timing, diurnal preference, mistimed circadian rhythms and habitual caffeine intake. All participants gave saliva under standardised conditions for CYP1A2 genotyping and quantification of caffeine concentration.

Specific and redundant roles of PKBα/AKT1 and PKBβ/AKT2 in human pancreatic islets.

Protein kinase Bα (PKBα)/AKT1 and PKBβ/AKT2 are required for normal peripheral insulin action but their role in pancreatic β cells remains enigmatic as indicated by the relatively mild islet phenotype of mice with deficiency for either one of these two isoforms. In this study we have analysed proliferation, apoptosis, β cell size and glucose-stimulated insulin secretion in human islets overexpressing either PKBα or PKBβ. Our results reveal redundant and specific functions.

Glycemia, Hypoglycemia, and Costs of Simultaneous Islet-Kidney or Islet After Kidney Transplantation Versus Intensive Insulin Therapy and Waiting List for Islet Transplantation.

Background: Long-term data of patients with type 1 diabetes mellitus (T1D) after simultaneous islet-kidney (SIK) or islet-after-kidney transplantation (IAK) are rare and have never been compared to intensified insulin therapy (IIT).

Methods: Twenty-two patients with T1D and end-stage renal failure undergoing islet transplantation were compared to 70 patients matched for age and diabetes duration treated with IIT and to 13 patients with kidney transplantation alone or simultaneous pancreas-kidney after loss of pancreas function (waiting list for IAK [WLI]). Glycemic control, severe hypoglycemia, insulin requirement, and direct medical costs were analyzed.

Glycemic Control in Simultaneous Islet-Kidney Versus Pancreas-Kidney Transplantation in Type 1 Diabetes: A Prospective 13-Year Follow-up.

Objective: In patients with type 1 diabetes and end-stage renal disease, combined transplantation of a kidney together with a pancreas or isolated pancreatic islets are options to improve glycemic control. The aim of this study was to compare their long-term outcome with regard to metabolic control and surgical complication rate, as well as function of the transplanted kidney.

Research Design And Methods: We conducted a prospective cohort study in consecutive patients receiving either a pancreas or islet transplant simultaneously with or after kidney transplantation (simultaneous pancreas-kidney [SPK]/pancreas-after-kidney [PAK] or simultaneous islet-kidney [SIK]/islet-after-kidney [IAK] transplantation).

Automated assessment of β-cell area and density per islet and patient using TMEM27 and BACE2 immunofluorescence staining in human pancreatic β-cells.

In this study we aimed to establish an unbiased automatic quantification pipeline to assess islet specific features such as β-cell area and density per islet based on immunofluorescence stainings. To determine these parameters, the in vivo protein expression levels of TMEM27 and BACE2 in pancreatic islets of 32 patients with type 2 diabetes (T2D) and in 28 non-diabetic individuals (ND) were used as input for the automated pipeline. The output of the automated pipeline was first compared to a previously developed manual area scoring system which takes into account the intensity of the staining as well as the percentage of cells which are stained within an islet.

Reduced hepatic lipid content in Pten-haplodeficient mice because of enhanced AKT2/PKBβ activation in skeletal muscle.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a major health problem and occurs frequently in the context of metabolic syndrome and type 2 diabetes mellitus. Hepatocyte-specific Pten-deficiency in mice was shown previously to result in hepatic steatosis due to hyperactivated AKT2. However, the role of peripheral insulin-sensitive tissues on PTEN- and AKT2-dependent accumulation of hepatic lipids has not been addressed.

Basal insulin glargine and microvascular outcomes in dysglycaemic individuals: results of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial.

Aims/hypothesis: As glycaemia and the incidence of microvascular diabetes complications follow a log-linear relationship, it becomes increasingly difficult to demonstrate a microvascular benefit of glucose-lowering when the HbA1c level is close to normal.

Methods: The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial randomised 12,537 people with diabetes, impaired glucose tolerance or impaired fasting glucose to receive standard glycaemic care or standard care with the addition of basal insulin glargine (A21Gly,B31Arg,B32Arg human insulin), targeting a fasting plasma glucose level ≤5.3 mmol/l.

Sugar-sweetened beverages with moderate amounts of fructose, but not sucrose, induce Fatty Acid synthesis in healthy young men: a randomized crossover study.

Context: The impact of sugar-sweetened beverages (SSB) on lipid metabolism when consumed in moderate amounts by normal weight subjects is debated.

Objective: The objective of the study was to investigate the effect of different types of sugars in SSB on fatty acid metabolism (ie, fatty acid synthesis and oxidation) in healthy young men.

Design: Thirty-four normal-weight men were studied in a randomized crossover study.

The association of basal insulin glargine and/or n-3 fatty acids with incident cancers in patients with dysglycemia.

OBJECTIVE Epidemiologic studies linking insulin glargine and glucose-lowering therapies to cancers and n-3 fatty acids to cancer prevention have not been confirmed. We aimed to assess the effect of insulin glargine and n-3 fatty acids on incident cancers within the context of the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial. RESEARCH DESIGN AND METHODS The ORIGIN trial is an international, long-term, randomized two-by-two factorial study comparing insulin glargine with standard care and n-3 fatty acids with placebo (double blind) in people with dysglycemia at high risk for cardiovascular events.

Small, dense LDL particles predict changes in intima media thickness and insulin resistance in men with type 2 diabetes and prediabetes--a prospective cohort study.

The association of small, dense low-density lipoprotein (sdLDL) particles with an increased cardiovascular risk is well established. However, its predictive value with regard to glucose metabolism and arterial disease in patients with type 2 diabetes has not been thoroughly investigated. We conducted a prospective longitudinal cohort study in patients with (pre)diabetes who were seen at baseline and after two years.