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1.
Environmental risk factors of type 2 diabetes-an exposome approach.
Beulens, JWJ, Pinho, MGM, Abreu, TC, den Braver, NR, Lam, TM, Huss, A, Vlaanderen, J, Sonnenschein, T, Siddiqui, NZ, Yuan, Z, et al
Diabetologia. 2022;(2):263-274
Abstract
Type 2 diabetes is one of the major chronic diseases accounting for a substantial proportion of disease burden in Western countries. The majority of the burden of type 2 diabetes is attributed to environmental risks and modifiable risk factors such as lifestyle. The environment we live in, and changes to it, can thus contribute substantially to the prevention of type 2 diabetes at a population level. The 'exposome' represents the (measurable) totality of environmental, i.e. nongenetic, drivers of health and disease. The external exposome comprises aspects of the built environment, the social environment, the physico-chemical environment and the lifestyle/food environment. The internal exposome comprises measurements at the epigenetic, transcript, proteome, microbiome or metabolome level to study either the exposures directly, the imprints these exposures leave in the biological system, the potential of the body to combat environmental insults and/or the biology itself. In this review, we describe the evidence for environmental risk factors of type 2 diabetes, focusing on both the general external exposome and imprints of this on the internal exposome. Studies provided established associations of air pollution, residential noise and area-level socioeconomic deprivation with an increased risk of type 2 diabetes, while neighbourhood walkability and green space are consistently associated with a reduced risk of type 2 diabetes. There is little or inconsistent evidence on the contribution of the food environment, other aspects of the social environment and outdoor temperature. These environmental factors are thought to affect type 2 diabetes risk mainly through mechanisms incorporating lifestyle factors such as physical activity or diet, the microbiome, inflammation or chronic stress. To further assess causality of these associations, future studies should focus on investigating the longitudinal effects of our environment (and changes to it) in relation to type 2 diabetes risk and whether these associations are explained by these proposed mechanisms.
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2.
Chiglitazar: First Approval.
Deeks, ED
Drugs. 2022;(1):87-92
Abstract
Chiglitazar (Bilessglu®) is an orally administered, non-thiazolidinedione small-molecule agonist of α, δ and γ peroxisome proliferator-activated receptors (PPARs) being developed by Chipscreen Biosciences for the treatment of type 2 diabetes (T2D) and non-alcoholic steatohepatitis. In October 2021, chiglitazar was approved in China for use as an adjunct to diet and exercise to improve glycaemic control in adult patients with T2D. The drug is also in phase 2 clinical development in China for the treatment of non-alcoholic steatohepatitis. This article summarizes the milestones in the development of chiglitazar leading to this first approval for the treatment of T2D.
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3.
Mechanisms of action of SGLT2 inhibitors and their beneficial effects on the cardiorenal axis.
Gronda, E, Lopaschuk, GD, Arduini, A, Santoro, A, Benincasa, G, Palazzuoli, A, Gabrielli, D, Napoli, C
Canadian journal of physiology and pharmacology. 2022;(2):93-106
Abstract
Large clinical studies conducted with sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and heart failure with reduced ejection fraction have demonstrated their ability to achieve both cardiac and kidney benefits. Although there is huge evidence on SGLT2i-mediated clinical benefits both in diabetic and non-diabetic patients, the pathophysiological mechanisms underlying their efficacy are still poorly understood. Some favorable mechanisms are likely due to the prompt glycosuric action which is associated with natriuretic effects leading to hemodynamic benefits as well as a reduction in glomerular hyperfiltration and renin-angiotensin-aldosterone system activation. In addition to the renal mechanisms, SGLT2i may play a relevant role in cardiorenal axis protection by improving the cardiomyocyte metabolism, by exerting anti-fibrotic and anti-inflammatory actions, and by increasing cardioprotective adipokine expression. New studies will be needed to better understand the specific molecular mechanisms that mediate the SGLT2i favorable effects in patients suffering diabetes. Our aim is to first discuss about the molecular mechanisms underlying the cardiovascular benefits of SGLT2i in each of the main organs involved in the cardiorenal axis. Furthermore, we update on the most recent clinical trials evaluating the beneficial effects of SGLT2i in treatment of both diabetic and non-diabetic patients suffering heart failure.
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4.
Lower carbohydrate diets for adults with type 2 diabetes.
Singh, M, Hung, ES, Cullum, A, Allen, RE, Aggett, PJ, Dyson, P, Forouhi, NG, Greenwood, DC, Pryke, R, Taylor, R, et al
Diabetic medicine : a journal of the British Diabetic Association. 2022;(3):e14674
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5.
Predisposing factors for the development of diabetic ketoacidosis with lower than anticipated glucose levels in type 2 diabetes patients on SGLT2-inhibitors: a review.
Bamgboye, AO, Oni, IO, Collier, A
European journal of clinical pharmacology. 2021;(5):651-657
Abstract
PURPOSE SGLT2-inhibitors (SGLT-2i) have been linked to the risk of potential life-threatening diabetic ketoacidosis (DKA). The U.S. Food and Drug Administration and the European Medicines Agency issued warnings in 2015 and 2016 respectively on the predisposing factors to the development of DKA in individuals on an SGLT2i. New predisposing factors to DKA are still being discovered with the use of SGLT-2i. The list by FDA and EMA is yet to be updated. This article aims to provide a holistic list that includes the newer factors that have been implicated in the development of DKA. The overall aim is to guide physicians in prescribing this class of drugs for type 2 diabetes mellitus (T2D). METHOD A search was done using PUBMED, Google Scholar, and Directory of Open Access Journals with the following words: SGLT-2 Inhibitors AND Ketoacidosis were entered. We included articles from 2000 to 2020, those in English, those involving any of the approved SGLT2i medications in T2D patients, and studies that focused on DKA linked to SGLT-2i. These articles were reviewed, and relevant data extracted and compiled. RESULTS AND CONCLUSION The review has revealed that predisposing factors include (excess) alcohol consumption, female gender, starvation due to illness or fasting, withholding the use of SGLT2i for less than 48 h peri-operatively, and the existence of a variations in the expression of SGLT2 receptors. Patients should be advised on "sick day rules," and if a patient becomes unwell while on an SGLT2i, they should be advised to withhold the medication for the duration of the intercurrent illness.
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6.
Gut microbiota associations with metabolic syndrome and relevance of its study in pediatric subjects.
Carrizales-Sánchez, AK, García-Cayuela, T, Hernández-Brenes, C, Senés-Guerrero, C
Gut microbes. 2021;(1):1960135
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Abstract
Childhood obesity and T2DM have shown a recent alarming increase due to important changes in global lifestyle and dietary habits, highlighting the need for urgent and novel solutions to improve global public health. Gut microbiota has been shown to be relevant in human health and its dysbiosis has been associated with MetS, a health condition linked to the onset of relevant diseases including T2DM. Even though there have been recent improvements in the understanding of gut microbiota-host interactions, pediatric gut microbiota has been poorly studied compared to adults. This review provides an overview of MetS and its relevance in school-age children, discusses gut microbiota and its possible association with this metabolic condition including relevant emerging gut microbiome-based interventions for its prevention and treatment, and outlines future challenges and perspectives in preventing microbiota dysbiosis from the early stages of life.
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7.
SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications.
Brown, E, Heerspink, HJL, Cuthbertson, DJ, Wilding, JPH
Lancet (London, England). 2021;(10296):262-276
Abstract
SGLT2 inhibitors and GLP-1 receptor agonists are used in patients with type 2 diabetes as glucose lowering therapies, with additional benefits of weight loss and blood pressure reduction. Data from cardiovascular outcome trials have highlighted that these drugs confer protection against major cardiovascular disease in those with established atherosclerotic cardiovascular disease, reduce the risk of admission to hospital for heart failure, and reduce cardiovascular and all-cause mortality. Ongoing research using hard renal endpoints such as end stage kidney disease rather than surrogate markers might clarify the renoprotective benefits of both agents. When used for glucose lowering, SGLT2 inhibitors are most effective if the estimated glomerular filtration rate is more than 60 ml per min per 1·73m2 at initiation and should be avoided where there is a risk of diabetic ketoacidosis. GLP-1 receptor agonists are contraindicated in those with a history of medullary thyroid cancer and used with caution in patients with a history of pancreatitis of a known cause. These drugs are now second-line, or even arguably first-line, glucose lowering therapies in patients with cardiorenal disease, irrespective of glycaemic control. If an SGLT2 inhibitor or GLP-1 receptor agonist is considered suitable in patients with type 2 diabetes, treatment should be prioritised according to existing evidence: GLP-1 receptor agonists should be considered in patients at a high risk of, or with established, cardiovascular disease and SGLT2 inhibitors considered for patients with heart failure (with reduced ejection fraction) or chronic kidney disease (with or without established cardiovascular disease). There is now compelling data on the benefits of these drugs for a range of other clinical indications even without type 2 diabetes, including for GLP-1 receptor agonists in patients with obesity and overweight with weight-related comorbidities.
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Efficacy of Low-Carbohydrate Ketogenic Diet in the Treatment of Type 2 Diabetes.
Dashti, HM, Mathew, TC, Al-Zaid, NS
Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2021;(3):223-235
Abstract
Low-carbohydrate ketogenic diet (LCKD), originally used as a treatment for childhood epilepsy is currently gaining acceptance as a nutritional therapy for obesity and type 2 diabetes. In addition, this diet has a positive effect on body weight, blood glucose level, glycosylated hemoglobin, plasma lipid profile, and neurological disorders. This review focuses on the therapeutic effectiveness, negative effects, and the rationale of using LCKD for the treatment of type 2 diabetes. It is shown that LCKD contributes to the reduction in the intake of insulin and oral antidiabetic drugs in patients with type 2 diabetes. Furthermore, the data presented in this review reveal the efficacy and cost-effectiveness of LCKD in the management of type 2 diabetes.
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Use of Virtual Care for Glycemic Management in People With Types 1 and 2 Diabetes and Diabetes in Pregnancy: A Rapid Review.
Chan, CB, Popeski, N, Hassanabad, MF, Sigal, RJ, O'Connell, P, Sargious, P
Canadian journal of diabetes. 2021;(7):677-688.e2
Abstract
Our objective in this study was to answer the main research question: In patients with diabetes, does virtual care vs face-to-face care provide different clinical, patient and practitioner experience or quality outcomes? Articles (2012 to 2020) describing interventions using virtual care with the capability for 2-way, individualized interactions compared with usual care were included. Studies involving any patients with diabetes and outcomes of glycated hemoglobin (A1C), quality of care and/or patient or health-care practitioner experience were included. Systematic reviews, randomized controlled studies, quasi-experimental trials, implementation trials, observational studies and qualitative analyses were reviewed. MEDLINE and McMaster Health Evidence databases searched in June 2020 identified 59 articles. Virtual care, in particular telemonitoring, combined with a means of 2-way communications provided improvement in A1C similar or superior to usual care, with the strongest evidence for type 2 diabetes. Virtual care was generally acceptable to patients, who expressed satisfaction with their care. Health-care providers recognized benefits but raised issues of technical support, workflow and compensation.
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10.
Sodium-glucose co-transporter 2 inhibitors: game changers when handled with care?
Htet, ZM, Karim, M
Journal of the Royal Society of Medicine. 2021;(7):351-358
Abstract
Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.