Bariatric Surgery and Type 1 Diabetes: Unanswered Questions

In recent decades there has been an alarming increase in the prevalence of obesity in patients with type 1 diabetes leading to the development of insulin resistance and cardiometabolic complications, with mechanisms poorly clarified. While bariatric surgery has long been considered an effective treatment option for patients with type 2 diabetes, the evidence regarding its benefits on weight loss and the prevention of complications in T1DM patients is scarce, with controversial outcomes. Bariatric surgery has been associated with a significant reduction in daily insulin requirement, along with a considerable reduction in body mass index, results which were sustained in the long term. Furthermore, studies suggest that bariatric surgery in type 1 diabetes results in the improvement of comorbidities related to obesity including hypertension and dyslipidemia. However, regarding glycemic control, the reduction of mean glycosylated hemoglobin was modest or statistically insignificant in most studies. The reasons for these results are yet to be elucidated; possible explanations include preservation of beta cell mass and increased residual function post-surgery, improvement in insulin action, altered GLP-1 function, timing of surgery, and association with residual islet cell mass. A number of concerns regarding safety issues have arisen due to the reporting of peri-operative and post-operative adverse events. The most significant complications are metabolic and include diabetic ketoacidosis, severe hypoglycemia and glucose fluctuations. Further prospective clinical studies are required to provide evidence for the effect of bariatric surgery on T1DM patients. The results may offer a better knowledge for the selection of people living with diabetes who will benefit more from a metabolic surgery. © Copyright © 2020 Korakas, Kountouri, Raptis, Kokkinos and Lambadiari

The endothelial glycocalyx as a key mediator of albumin handling and the development of diabetic nephropathy

The endothelial glycocalyx is a complex mesh of proteoglycans, glycoproteins and other soluble components, which cover the vascular endothelium. It plays an important role in many physiological processes including vascular permeability, transduction of shear stress and interaction of blood cells and other molecules with the vascular wall. Its complex structure makes its precise assessment challenging, and many different visualization techniques have been used with varying results. Diabetes, one of the main disease models where disorders of the glycocalyx are present, causes degradation of the glycocalyx through a variety of molecular pathways and especially through oxidative stress due to the action of reactive oxygen species. As the glycocalyx has been primarily studied in the glomerular endo-thelium, more evidence points towards a vital role in albumin handling and, consequently, in diabetic nephropathy. Therefore, the maintenance or restoration of the integrity of the glycocalyx seems a prom-ising therapeutic target. In this review, we consider the structural and functional capacities of the endothelial glycocalyx, the available methods for its evaluation, the mechanisms through which diabetes leads to glycocalyx degradation and albuminuria, and possible treatment options targeting the glycocalyx. © 2020 Bentham Science Publishers

Stress Hyperglycemia in Children and Adolescents as a Prognostic Indicator for the Development of Type 1 Diabetes Mellitus

Hyperglycemia is a common manifestation in the course of severe disease and is the result of acute metabolic and hormonal changes associated with various factors such as trauma, stress, surgery, or infection. Numerous studies demonstrate the association of adverse clinical events with stress hyperglycemia. This article briefly describes the pathophysiological mechanisms which lead to hyperglycemia under stressful circumstances particularly in the pediatric and adolescent population. The importance of prevention of hyperglycemia, especially for children, is emphasized and the existing models for the prediction of diabetes are presented. The available studies on the association between stress hyperglycemia and progress to type 1 diabetes mellitus are presented, implying a possible role for stress hyperglycemia as part of a broader prognostic model for the prediction and prevention of overt disease in susceptible patients. © Copyright © 2021 Argyropoulos, Korakas, Gikas, Kountouri, Kostaridou-Nikolopoulou, Raptis and Lambadiari

The effect of antioxidant and anti-inflammatory capacity of diet on psoriasis and psoriatic arthritis phenotype: Nutrition as therapeutic tool?

Chronic inflammation and increased oxidative stress are contributing factors to many non-communicable diseases. A growing body of evidence indicates that dietary nutrients can activate the immune system and may lead to the overproduction of pro-inflammatory cytokines. Fatty acids as macronutrients are key players for immunomodulation, with n-3 polyunsaturated fatty acids having the most beneficial effect, while polyphenols and carotenoids seem to be the most promising antioxidants. Psoriasis is a chronic, immune-mediated inflammatory disease with multifactorial etiology. Obesity is a major risk factor for psoriasis, which leads to worse clinical outcomes. Weight loss interventions and, generally, dietary regimens such as gluten-free and Mediterranean diet or supplement use may potentially improve psoriasis’ natural course and response to therapy. However, data about more sophisticated nutritional patterns, such as ketogenic, very low-carb or specific macro-and micro-nutrient substitution, are scarce. This review aims to present the effect of strictly structured dietary nutrients, that are known to affect glucose/lipid metabolism and insulin responses, on chronic inflammation and immunity, and to discuss the utility of nutritional regimens as possible therapeutic tools for psoriasis and psoriatic arthritis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Type 1 diabetes mellitus in the SARS-CoV-2 pandemic: Oxidative stress as a major pathophysiological mechanism linked to adverse clinical outcomes

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a “cytokine storm”. Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1β, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more impor-tantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Obesity and COVID-19: Immune and metabolic derangement as a possible link to adverse clinical outcomes

Obesity and COVID-19: Immune and metabolic derangement as a possible link to adverse clinical outcomes. Am J Physiol Endocrinol Metab 319: E105-E109, 2020. First published May 27, 2020; doi: 10.1152/ajpendo.00198.2020.-Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other comorbidities. After infecting the host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a hyperinflammatory reaction through the excessive release of cytokines, a condition known as "cytokine storm,"while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNFα, IL-1, IL-6, and monocyte chemoattractant protein (MCP-1) lead to oxidative stress and defective function of innate and adaptive immunity, whereas the activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of antiinflammatory agents such as IL-1 and IL-6 blockers in similar hyperinflammatory settings, like that of rheumatoid arthritis, has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease. © 2020 the American Physiological Society

Cost-Effectiveness Analysis of an Advanced Hybrid Closed-Loop Insulin Delivery System in People with Type 1 Diabetes in Greece

Introduction: Usage of automated insulin delivery systems is increasing for the treatment of people with type 1 diabetes (T1D). This study compared long-term cost-effectiveness of the Advanced Hybrid Closed Loop MiniMed 780G (AHCL) system versus sensor augmented pump (SAP) system with predictive low glucose management (PLGM) or multiple daily injections (MDI) plus intermittently scanned continuous glucose monitoring (isCGM) in people with T1D in Greece. Methods: Analyses were performed using the IQVIA CORE Diabetes Model, with clinical input data sourced from various studies. In the AHCL versus SAP plus PLGM analysis, patients were assumed to have 7.5% baseline glycated hemoglobin (HbA1c), when comparing AHCL with MDI plus isCGM baseline HbA1c was assumed to be 7.8%. HbA1c was reduced to 7.0% following AHCL treatment initiation but remained at baseline levels in the comparator arms. Analyses were performed from a societal perspective over a lifetime time horizon. Future costs and clinical outcomes were discounted at 1.5% per annum. Results: AHCL was associated with increased quality-adjusted life expectancy of 0.284 quality-adjusted life years (QALYs) and EUR 10,173 lower mean total lifetime costs with SAP plus PLGM. Compared with MDI plus isCGM, AHCL was associated with increased quality-adjusted life expectancy of 2.708 QALYs, EUR 76,396 higher mean total lifetime costs, and an incremental cost-effectiveness ratio of EUR 29,869 per QALY. Extensive sensitivity analysis confirmed the robustness of results. Conclusions: Over patient lifetime, the MiniMed 780G system is likely to be cost saving compared with the SAP plus PLGM system and cost-effective compared with MDI plus isCGM in people with T1D in Greece. © Copyright 2022, Mary Ann Liebert, Inc., publishers 2022