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This review aims to describe the effect of glucolipotoxicity-induced oxidative stress and its relationship with mitochondrial dysfunction in β-cell during type 2 diabetes development.

According to the Center for Disease Control and Prevention, diabetic ketoacidosis (DKA) hospitalization rates have been steadily increasing. Due to the increasing incidence and the economic impact associated with its morbidity and treatment, effective management is key. We aimed to streamline the management of DKA in our intensive care units (ICU) by implementing a Best-Practice Advisory (BPA) that notifies providers when DKA has resolved.

A BPA was implemented on 9/15/2018. We conducted a retrospective review of patients admitted to the ICU with DKA a year before and after 9/15/2018. Adults (≥18 age) meeting DKA criteria on admission and treated with continuous insulin infusion (CII) were included. Pre-intervention group included patients admitted before BPA implementation and post-intervention group included patients admitted after. Summary and univariate analyses were performed.

A total of 282 patients were included; 162 (57%) pre-intervention and 120 (43%) post-intervention. Mean (±SD) age was 44 (±17) years. There was no significant difference in baseline characteristics such as age, sex, race, BMI, HbA1c, initial blood glucose, anion gap or bicarbonate concentration between both groups (p>0.05). Mean (±SD) total time on CII in hours was significantly lower in the post-intervention group 14.8 (±7.7) vs 17.5 (±14.3) p=0.041, 95% CI 0.11-5.3. The incidence of hypoglycemia was lower in the post-intervention group n=4 (3%) vs 17 (10%), p=0.024. There was no significant difference in hypokalemia, mortality, LOS or ICU stay between both groups (p>0.05).

The BPA introduced in our DKA management algorithm successfully reduced total time on insulin and the incidence of hypoglycemia.

The BPA introduced in our DKA management algorithm successfully reduced total time on insulin and the incidence of hypoglycemia.

Diabetes mellitus (DM) is a chronic disorder that it is caused by the absence of insulin secretion due to the inability of the pancreas to produce it (type 1 diabetes; T1DM), or due to defects of insulin signaling in the peripheral tissues, resulting in insulin resistance (type 2 diabetes; T2DM). find more Commonly, the occurrence of insulin resistance in T2DM patients reflects the high prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) manifestation in these individuals. In fact, approximately 60% T2DM patients are also diagnosed to have NAFLD, and this condition is strongly linked with insulin resistance and obesity. NAFLD is the hepatic manifestation of obesity and metabolic syndrome and includes a spectrum of pathological conditions, which range from simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), and cirrhosis and hepatocellular carcinoma. NAFLD manifestation is followed by a series of hepatic lipid deregulations and the main abnormalities are increased triglyceride levels, increased hepatic production of VLDL and a reduction of VLDL catabolism. During the progression of NAFLD, the production of ketone bodies progressively reduces while hepatic glucose synthesis and output increases. In fact, most of the fat that enters the liver can be disposed through ketogenesis, preventing the development of NAFLD and hyperglycemia.

This review will focus on the pathophysiological aspect of hepatic lipid metabolism deregulation, ketogenesis and its relevance in progression of NAFLD and T2DM.

A better understanding of the molecular mediators involved in lipid synthesis and ketogenesis can lead to new treatments for metabolic disorders in the liver, such as NAFLD.

A better understanding of the molecular mediators involved in lipid synthesis and ketogenesis can lead to new treatments for metabolic disorders in the liver, such as NAFLD.Worldwide, diabetes ranks among the ten leading causes of mortality. Prevalence of diabetes is growing rapidly in low and middle income countries. It is a progressive disease leading to serious co-morbidities, which results in increased cost of treatment and over-all health system of the country. Pathophysiological alterations in type 2 diabetes (T2D) progressed from a simple disturbance in the functioning of the pancreas to triumvirate to ominous octet to egregious eleven to dirty dozen model. Due to complex interplay of multiple hormones in T2D, there may be multifaceted approach in its management. The ‘long-term secondary complications’ in uncontrolled diabetes may affect almost every organ of the body, and finally may lead to multi-organ dysfunction. Available therapies are inconsistent in maintaining long term glycemic control and their long term use may be associated with adverse effects. There is need for newer drugs, not only for glycemic control but also for prevention or mitigation of secondary microvascular and macrovascular complications. Increased knowledge of the pathophysiology of diabetes has contributed to the development of novel treatments. Several new agents like Glucagon Like Peptide – 1 (GLP-1) agonists, Dipeptidyl Peptidase IV (DPP-4) inhibitors, amylin analogues, Sodium-Glucose transport -2 (SGLT- 2) inhibitors and dual Peroxisome proliferator-activated receptor (PPAR) agonists are available or will be available soon, thus extending the range of therapy for T2D, thereby preventing its long term complications. The article discusses the pathophysiology of diabetes along with its comorbidities, with a focus on existing and novel upcoming antidiabetic drugs which are under investigation. It also dives deep to deliberate upon the novel therapies that are in various stages of development. Adding new options with new mechanisms of action to the treatment armamentarium of diabetes may eventually help improve outcomes and reduce its economic burden.Modern lifestyle, changing eating habits and reduced physical work have been known to culminate into making diabetes a global pandemic. Hyperglycemia during the course of diabetes is an important causative factor for the development of both microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (coronary artery disease, stroke and peripheral artery disease) complications. In this article, we summarize several mechanisms accountable for the development of both microvascular and macrovascular complications of diabetes. Several metabolic and cellular events are linked to the augmentation of oxidative stress like the activation of advanced glycation endproducts (AGE) pathway, polyol pathway, protein kinase C (PKC) pathway, poly-ADP ribose polymerase (PARP) and hexosamine pathway. Oxidative stress also leads to production of reactive oxygen species (ROS) like hydroxyl radical, superoxide anion and peroxides. Enhanced levels of ROS rescind the anti-oxidant defence mechanisms associated with superoxide dismutase, glutathione and ascorbic acid.