1.
Glucose homeostasis, nutrition and infections during critical illness.
Ingels, C, Vanhorebeek, I, Van den Berghe, G
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2018;(1):10-15
Abstract
Critical illness is a complex life-threatening disease characterized by profound endocrine and metabolic alterations and by a dysregulated immune response, together contributing to the susceptibility for nosocomial infections and sepsis. Hitherto, two metabolic strategies have been shown to reduce nosocomial infections in the critically ill, namely tight blood glucose control and early macronutrient restriction. Hyperglycaemia, as part of the endocrine-metabolic responses to stress, is present in virtually all critically ill patients and is associated with poor outcome. Maintaining normoglycaemia with intensive insulin therapy has been shown to reduce morbidity and mortality, by prevention of vital organ dysfunction and prevention of new severe infections. The favourable effects of this intervention were attributed to the avoidance of glucose toxicity and mitochondrial damage in cells of vital organs and in immune cells. Hyperglycaemia was shown to impair macrophage phagocytosis and oxidative burst capacity, which could be restored by targeting normoglycaemia. An anti-inflammatory effect of insulin may have contributed to prevention of collateral damage to host tissues. Not using parenteral nutrition during the first week in intensive care units, and so accepting a large macronutrient deficit, also resulted in fewer secondary infections, less weakness and accelerated recovery. This was at least partially explained by a suppressive effect of early parenteral nutrition on autophagic processes, which may have jeopardized crucial antimicrobial defences and cell damage removal. The beneficial impact of these two metabolic strategies has opened a new field of research that will allow us to improve the understanding of the determinants of nosocomial infections, sepsis and organ failure in the critically ill.
2.
DIABETIC KETOACIDOSIS: A COMMON DEBUT OF DIABETES AMONG AFRICAN AMERICANS WITH TYPE 2 DIABETES.
Vellanki, P, Umpierrez, GE
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2017;(8):971-978
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Abstract
OBJECTIVE More than half of African Americans (AA) with a new diagnosis of diabetic ketoacidosis have clinical and metabolic features of type 2 diabetes during follow-up. This particular presentation of diabetes has been termed as ketosis-prone type 2 diabetes (KPDM) or atypical diabetes. METHODS We review the epidemiology, diagnosis, pathophysiology, and acute and long-term management of AA with KPDM and compare these similarities to patients with type 2 diabetes. RESULTS In contrast to the long-term insulin requirement of auto-immune type 1 diabetes, patients with KPDM are able to discontinue insulin after a few months of therapy and maintain acceptable glycemic control for many years on either diet or oral agents. Patients with KPDM have significant impairment of both insulin secretion and insulin action at presentation; however, at the time of near-normoglycemia remission, insulin secretion and action improve to levels similar to hyperglycemic patients with ketosis-resistant type 2 diabetes. In the long term, however, patients with KPDM have a decline in β-cell function similar to patients with type 2 diabetes. Recent studies indicate that treatment with metformin and dipeptidyl peptidase-4 inhibitors can prolong the period of near-normoglycemia remission for several years compared to placebo therapy. CONCLUSION KPDM is a unique but common presentation of newly diagnosed African Americans with type 2 diabetes. ABBREVIATIONS A(+/-) = auto-antibody positive/negative AA = African Americans DKA = diabetic ketoacidosis FFA = free fatty acids G6PD = glucose-6-phosphate dehydrogenase GAD-65 = 65-kDA glutamic acid decarboxylase HBA1c = glycated hemoglobin A1c HHV8 = human herpes virus 8 HLA = human leukocyte antigen KPDM = ketosis-prone type 2 diabetes.
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[Drugs affecting the incretin system and renal glucose transport: do they meet the expectations of modern therapy of type 2 diabetes?].
Gumieniczek, A
Postepy higieny i medycyny doswiadczalnej (Online). 2016;:425-34
Abstract
Agents introduced into therapy of type 2 diabetes in the last few years are still the subject of numerous clinical and experimental studies. Although many studies have been completed, we still do not know all aspects of these drugs' action, especially the long-term effects of their use. Most questionable is their impact on the processes of cell proliferation, on the cardiovascular and immune systems, on lipids and uric acid metabolism. A summary of the most important observations on the use of three groups of new drugs - analogs of glucagon-like peptide 1 (GLP-1), inhibitors of dipeptidyl peptidase IV (DPPIV) and inhibitors of sodium glucose cotransporters (SGLT1 and SGLT2) - has been made, based on a review of the literature over the past five years (2010-2014). The information included in the present review concerns the structure and activity relationship, therapeutic efficacy, side effects and the observed additional therapeutic effects, which can determine new standards in therapy of diabetes and also facilitate the development of better antidiabetic drugs.
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Lessons from type 1 diabetes for understanding natural history and prevention of autoimmune disease.
Simmons, K, Michels, AW
Rheumatic diseases clinics of North America. 2014;(4):797-811
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Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disorder resulting from immune-mediated destruction of insulin-producing beta cells within the pancreatic islets. Prediction of T1D is now possible, as having 2 or more islet autoantibodies confers a 100% risk of diabetes development. With the ability to predict disease development, clinical trials to prevent diabetes onset have been completed and are currently under way. This review focuses on the natural history, prediction, and prevention trials in T1D. We review the lessons learned from these attempts at preventing a chronic autoimmune disease and apply the paradigm from T1D prevention to other autoimmune disorders.
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Primary and secondary prevention of Type 1 diabetes.
Skyler, JS
Diabetic medicine : a journal of the British Diabetic Association. 2013;(2):161-9
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Since type 1 diabetes is an immunologically mediated disease, immune intervention should alter the natural history of the disease. This article reviews prevention studies undertaken either prior to any evidence of autoimmunity (primary prevention) or after the development of islet autoantibodies (secondary prevention). Most immune intervention studies have been conducted in recent-onset type 1 diabetes (tertiary prevention), and these are not reviewed herein. The goal of primary and secondary intervention is to arrest the immune process and thus prevent or delay clinical disease. Primary prevention studies have been conducted in infants with high genetic risk. Interventions tested include several dietary manipulations, including infant formulas free of either cow's milk or of bovine insulin, infant formula supplemented with the omega-3-fatty acid docosahexaenoic acid, delayed introduction of gluten-containing foods, and vitamin D supplementation. Secondary prevention studies have been conducted in both children and adults with diabetes autoantibodies. Interventions tested include nicotinamide, insulin injections, oral insulin, nasal insulin, glutamic acid decarboxylase, and cyclosporine. Underway are secondary prevention studies with teplizumab and with abatacept.