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1.
Insulin resistance in bariatric surgery.
Stenberg, E, Thorell, A
Current opinion in clinical nutrition and metabolic care. 2020;(4):255-261
Abstract
PURPOSE OF REVIEW To give an updated review on the underlying mechanisms and clinical effects of improved glucose control after bariatric surgery. RECENT FINDINGS The basic principles of the mechanism for the metabolic effects of bariatric surgery can be categorized into calorie restriction, deviation of nutrients, and reduced amounts of adipose tissue. Recent findings suggest the importance of early changes following deviation of nutrients to more distal parts of the small bowel resulting in altered release of gastrointestinal hormones, altered gut microbiota, and weight-reduction. In the long-term, loss of adipose tissue results in reduced inflammation and improved insulin sensitivity. From a clinical perspective these changes are associated with remission of diabetes in patients with morbid obesity and type 2 diabetes, prevention of diabetes in patients with insulin resistance without overt type 2 diabetes and prevention of both microvascular and macrovascular complications for all patients with morbid obesity. SUMMARY At present, bariatric surgery remains the most effective treatment option to improve glucose control and long-term complications associated with hyperglycemia in patients with obesity.Although the mechanisms behind these metabolic effects remain only partially understood, further knowledge on these complex mechanisms may help identifying durable treatment options for morbid obesity and important metabolic comorbidities.
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2.
Insulin Resistance in Obese Children: What Can Metabolomics and Adipokine Modelling Contribute?
Rupérez, FJ, Martos-Moreno, GÁ, Chamoso-Sánchez, D, Barbas, C, Argente, J
Nutrients. 2020;(11)
Abstract
The evolution of obesity and its resulting comorbidities differs depending upon the age of the subject. The dramatic rise in childhood obesity has resulted in specific needs in defining obesity-associated entities with this disease. Indeed, even the definition of obesity differs for pediatric patients from that employed in adults. Regardless of age, one of the earliest metabolic complications observed in obesity involves perturbations in glucose metabolism that can eventually lead to type 2 diabetes. In children, the incidence of type 2 diabetes is infrequent compared to that observed in adults, even with the same degree of obesity. In contrast, insulin resistance is reported to be frequently observed in children and adolescents with obesity. As this condition can be prerequisite to further metabolic complications, identification of biological markers as predictive risk factors would be of tremendous clinical utility. Analysis of obesity-induced modifications of the adipokine profile has been one classic approach in the identification of biomarkers. Recent studies emphasize the utility of metabolomics in the analysis of metabolic characteristics in children with obesity with or without insulin resistance. These studies have been performed with targeted or untargeted approaches, employing different methodologies. This review summarizes some of the advances in this field while emphasizing the importance of the different techniques employed.
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3.
Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance.
Kojta, I, Chacińska, M, Błachnio-Zabielska, A
Nutrients. 2020;(5)
Abstract
Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. The exact mechanism by which adipose tissue induces insulin resistance is still unclear. It has been demonstrated that obesity is associated with the adipocyte dysfunction, macrophage infiltration, and low-grade inflammation, which probably contributes to the induction of insulin resistance. Adipose tissue synthesizes and secretes numerous bioactive molecules, namely adipokines and cytokines, which affect the metabolism of both lipids and glucose. Disorders in the synthesis of adipokines and cytokines that occur in obesity lead to changes in lipid and carbohydrates metabolism and, as a consequence, may lead to insulin resistance and type 2 diabetes. Obesity is also associated with the accumulation of lipids. A special group of lipids that are able to regulate the activity of intracellular enzymes are biologically active lipids: long-chain acyl-CoAs, ceramides, and diacylglycerols. According to the latest data, the accumulation of these lipids in adipocytes is probably related to the development of insulin resistance. Recent studies indicate that the accumulation of biologically active lipids in adipose tissue may regulate the synthesis/secretion of adipokines and proinflammatory cytokines. Although studies have revealed that inflammation caused by excessive fat accumulation and abnormalities in lipid metabolism can contribute to the development of obesity-related insulin resistance, further research is needed to determine the exact mechanism by which obesity-related insulin resistance is induced.
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4.
Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes.
Wu, Y, Zhou, A, Tang, L, Lei, Y, Tang, B, Zhang, L
Journal of diabetes research. 2020;:6138438
Abstract
Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and unclear pathogenesis, is a serious menace to human health. Bile acids are the end products of cholesterol catabolism and play an important role in maintaining cholesterol homeostasis. Furthermore, increasing studies suggest that bile acids may regulate glucose tolerance, insulin sensitivity, and energy metabolism, suggesting that bile acids may represent a potential therapeutic target for T2DM. This study summarizes the metabolism of bile acids and, more importantly, changes in their concentrations, constitution, and receptors in diabetes. Furthermore, we provide an overview of the mechanisms underlying the role of bile acids in glucose and lipid metabolism, as well as the occurrence and development of T2DM. Bile acid-targeted therapy may represent a valid approach for T2DM treatment.
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5.
Prehabilitation: metabolic considerations.
Chabot, K, Gillis, C, Carli, F
Current opinion in clinical nutrition and metabolic care. 2020;(4):271-276
Abstract
PURPOSE OF REVIEW The major components of ERAS attenuate the inflammatory response and modulate metabolism in direction of sparing body protein and preserving function. However, these perioperative interventions might have limited effectiveness on postoperative outcomes if preoperative risk factors are not addressed and optimized. RECENT FINDINGS The preoperative metabolic perturbations characterized by insulin resistance and sarcopenia might predispose patients to a higher degree of postoperative catabolism. High-risk populations for such metabolic disturbances include elderly and frail patients, and patients with metabolic syndrome. Research on the effect of prehabilitation on perioperative metabolism is limited, but recent findings suggest that interventions designed to improve insulin sensitivity prior to surgery might represent a promising therapeutic target to minimize surgical complications. SUMMARY The present paper will discuss the metabolic implications of modulating preoperative risk factors with elements of multimodal prehabilitation, such as exercise training and nutrition.
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6.
Visceral Fat: Culprit or Canary?
Jensen, MD
Endocrinology and metabolism clinics of North America. 2020;(2):229-237
Abstract
Although visceral fat is strongly correlated with the metabolic complications of obesity, the existing data indicate it is not the cause of these complications. Excess release of free fatty acids (FFA) from adipose tissue lipolysis can account for a sizable portion of the metabolic complications of obesity. In humans, upper-body subcutaneous adipose tissue accounts for most systemic FFA, whereas visceral fat contributes a modest portion of the excess amount to which the liver is exposed. This pattern is maintained in upper-body/visceral obesity, except that greater amounts of visceral fat expose the liver to more FFA from visceral adipose tissue lipolysis.
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7.
Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids.
Ye, Z, Wang, S, Zhang, C, Zhao, Y
Frontiers in endocrinology. 2020;:617
Abstract
As important metabolic substrates, branched-chain amino acids (BCAAs) and fatty acids (FAs) participate in many significant physiological processes, such as mitochondrial biogenesis, energy metabolism, and inflammation, along with intermediate metabolites generated in their catabolism. The increased levels of BCAAs and fatty acids can lead to mitochondrial dysfunction by altering mitochondrial biogenesis and adenosine triphosphate (ATP) production and interfering with glycolysis, fatty acid oxidation, the tricarboxylic acid cycle (TCA) cycle, and oxidative phosphorylation. BCAAs can directly activate the mammalian target of rapamycin (mTOR) signaling pathway to induce insulin resistance, or function together with fatty acids. In addition, elevated levels of BCAAs and fatty acids can activate the canonical nuclear factor-κB (NF-κB) signaling pathway and inflammasome and regulate mitochondrial dysfunction and metabolic disorders through upregulated inflammatory signals. This review provides a comprehensive summary of the mechanisms through which BCAAs and fatty acids modulate energy metabolism, insulin sensitivity, and inflammation synergistically.
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8.
Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments.
Wang, M, Tan, Y, Shi, Y, Wang, X, Liao, Z, Wei, P
Frontiers in endocrinology. 2020;:568
Abstract
Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging, and general obesity. The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes. Nevertheless, there are two major reasons to cause diabetes: impaired insulin secretion and impaired insulin action. Furthermore, the individual diagnosis of obesity and sarcopenia should be combined to adequately define sarcopenic obesity. Also, the diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms. Healthy diet and physical activity are beneficial to both sarcopenic obesity and diabetes, but there are only recommended drugs for diabetes. This review consolidates and discusses the latest research in pathogenesis, diagnosis, and treatments of diabetes and sarcopenic obesity.
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9.
Targeting the Zinc Transporter ZIP7 in the Treatment of Insulin Resistance and Type 2 Diabetes.
Adulcikas, J, Sonda, S, Norouzi, S, Sohal, SS, Myers, S
Nutrients. 2019;(2)
Abstract
Type 2 diabetes mellitus (T2DM) is a disease associated with dysfunctional metabolic processes that lead to abnormally high levels of blood glucose. Preceding the development of T2DM is insulin resistance (IR), a disorder associated with suppressed or delayed responses to insulin. The effects of this response are predominately mediated through aberrant cell signalling processes and compromised glucose uptake into peripheral tissue including adipose, liver and skeletal muscle. Moreover, a major factor considered to be the cause of IR is endoplasmic reticulum (ER) stress. This subcellular organelle plays a pivotal role in protein folding and processes that increase ER stress, leads to maladaptive responses that result in cell death. Recently, zinc and the proteins that transport this metal ion have been implicated in the ER stress response. Specifically, the ER-specific zinc transporter ZIP7, coined the "gate-keeper" of zinc release from the ER into the cytosol, was shown to be essential for maintaining ER homeostasis in intestinal epithelium and myeloid leukaemia cells. Moreover, ZIP7 controls essential cell signalling pathways similar to insulin and activates glucose uptake in skeletal muscle. Accordingly, ZIP7 may be essential for the control of ER localized zinc and mechanisms that disrupt this process may lead to ER-stress and contribute to IR. Accordingly, understanding the mechanisms of ZIP7 action in the context of IR may provide opportunities to develop novel therapeutic options to target this transporter in the treatment of IR and subsequent T2DM.
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10.
Type 2 Diabetes Mellitus, Insulin Resistance, and Vitamin D.
Sacerdote, A, Dave, P, Lokshin, V, Bahtiyar, G
Current diabetes reports. 2019;(10):101
Abstract
PURPOSE OF REVIEW There is a growing, largely inconsistent, literature on the role of vitamin D in association with type 2 diabetes, insulin resistance/insulin secretion, glycemic indices, and complications of type 2 diabetes. Pathophysiologic, bystander, preventive, and treatment roles of vitamin D have all been proposed. In this focused review, we attempt to organize and clarify our current information in this area. RECENT FINDINGS Clinical study interpretation is difficult because of variability in dosage, dosage form, study duration, and populations studied, as well as recently reported normal human polymorphisms in vitamin D synthesis and catabolism, vitamin D-binding protein, and vitamin D receptors in addition to a host of potential epigenetic confounders. Low vitamin D status appears to be associated with type 2 diabetes and most other insulin resistance disorders reported to date. The extraskeletal benefits of supplementation/repletion in these disorders in our species, with a few highlighted exceptions, remain to be established. This focused review attempts to summarize our current knowledge in this burgeoning area through a review of key meta-analyses, observational studies, randomized control trials, and Mendelian randomization studies and will hopefully serve as a guide to indicate future research directions and current best practice.