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Cardio-renal-metabolic disease in primary care setting.
Ibrahim, M, Ba-Essa, EM, Baker, J, Cahn, A, Ceriello, A, Cosentino, F, Davies, MJ, Eckel, RH, Van Gaal, L, Gaede, P, et al
Diabetes/metabolism research and reviews. 2024;(3):e3755
Abstract
In the primary care setting providers have more tools available than ever before to impact positively obesity, diabetes, and their complications, such as renal and cardiac diseases. It is important to recognise what is available for treatment taking into account diabetes heterogeneity. For those who develop type 2 diabetes (T2DM), effective treatments are available that for the first time have shown a benefit in reducing mortality and macrovascular complications, in addition to the well-established benefits of glucose control in reducing microvascular complications. Some of the newer medications for treating hyperglycaemia have also a positive impact in reducing heart failure (HF). Technological advances have also contributed to improving the quality of care in patients with diabetes. The use of technology, such as continuous glucose monitoring systems (CGM), has improved significantly glucose and glycated haemoglobin A1c (HbA1c) values, while limiting the frequency of hypoglycaemia. Other technological support derives from the use of predictive algorithms that need to be refined to help predict those subjects who are at great risk of developing the disease and/or its complications, or who may require care by other specialists. In this review we also provide recommendations for the optimal use of the new medications; sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like peptide-receptor agonists 1 (GLP1RA) in the primary care setting considering the relevance of these drugs for the management of T2DM also in its early stage.
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Lipid-lowering in diabetes: An update.
Chait, A, Eckel, RH, Vrablik, M, Zambon, A
Atherosclerosis. 2023;:117313
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is accelerated in people with diabetes. Dyslipidemia, hyperglycemia, oxidative stress, and inflammation play a role via a variety of mechanisms operative in the artery wall. In addition, some unique features predispose people with type 1 diabetes to accelerated atherosclerosis. Various organizations have created guidelines that provide advice regarding screening, risk assessment, and roadmaps for treatment to prevent ASCVD in diabetes. Management of dyslipidemia, especially with statins, has proven to be of immense benefit in the prevention of clinical CVD. However, since many patients fail to attain the low levels of low-density lipoproteins (LDL) recommended in these guidelines, supplemental therapy, such as the addition of ezetimibe, bempedoic acid or PCSK9 inhibitors, is often required to reach LDL goals. As a result, the upfront use of combination therapies, particularly a statin plus ezetimibe, is a rational initial approach. The addition to statins of drugs that specifically lower triglyceride levels has not proven beneficial, although the addition of icosapent-ethyl has been shown to be of value, likely by mechanisms independent of triglyceride lowering. Newer treatments in development, including apoC-III and ANGPTL3 inhibitors, seem promising in further reducing apoB-containing lipoproteins.
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.
Tobias, DK, Merino, J, Ahmad, A, Aiken, C, Benham, JL, Bodhini, D, Clark, AL, Colclough, K, Corcoy, R, Cromer, SJ, et al
Nature medicine. 2023;(10):2438-2457
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Abstract
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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ADA/EASD Precision Medicine in Diabetes Initiative: An International Perspective and Future Vision for Precision Medicine in Diabetes.
Nolan, JJ, Kahkoska, AR, Semnani-Azad, Z, Hivert, MF, Ji, L, Mohan, V, Eckel, RH, Philipson, LH, Rich, SS, Gruber, C, et al
Diabetes care. 2022;(2):261-266
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Reconsidering the role of glycaemic control in cardiovascular disease risk in type 2 diabetes: A 21st century assessment.
Aroda, VR, Eckel, RH
Diabetes, obesity & metabolism. 2022;(12):2297-2308
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Abstract
It is well known that the multiple factors contributing to the pathogenesis of type 2 diabetes (T2D) confer an increased risk of developing cardiovascular disease (CVD). Although the relationship between hyperglycaemia and increased microvascular risk is well established, the relative contribution of hyperglycaemia to macrovascular events has been strongly debated, particularly owing to the failure of attempts to reduce CVD risk through normalizing glycaemia with traditional therapies in high-risk populations. The debate has been further fuelled by the relatively recent discovery of the cardioprotective properties of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Further, as guidelines now recommend individualizing glycaemic targets, highlighting the importance of achieving glycated haemoglobin (HbA1c) goals safely, the previously observed negative influences of intensive therapy on CVD risk might not present if trials were repeated using current-day treatments and individualized HbA1c goals. Emerging longitudinal data illuminate the overall effect of excess glucose, the impacts of magnitude and duration of hyperglycaemia on disease progression and risk of CVD complications, and the importance of glycaemic control at or early after diagnosis of T2D for prevention of complications. Herein, we review the role of glucose as a modifiable cardiovascular (CV) risk factor, the role of microvascular disease in predicting macrovascular risk, and the deleterious impact of therapeutic inertia on CVD risk. We reconcile new and old data to offer a current perspective, highlighting the importance of effective, early treatment in reducing latent CV risk, and the timely use of appropriate therapy individualized to each patient's needs.
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Mechanistic Insights from REDUCE-IT STRENGTHen the Case Against Triglyceride Lowering as a Strategy for Cardiovascular Disease Risk Reduction.
Mason, RP, Eckel, RH
The American journal of medicine. 2021;(9):1085-1090
Abstract
Elevated triglyceride (TG) levels have been linked to residual atherosclerotic cardiovascular risk in patients with controlled low-density lipoprotein cholesterol. However, outcome trials testing TG-lowering agents have failed to demonstrate cardiovascular risk reduction in statin-treated subjects. One such example is the recent STRENGTH trial, which tested mixed omega fatty acids (n3-FAs, 4 g/d) in high-risk patients with elevated TGs. Similar to trials using fibrates and niacin, the STRENGTH trial failed despite effective TG lowering. Results from these studies have contributed to skepticism about the use of TG-lowering therapy for cardiovascular risk. However, new mechanistic insights are provided by the REDUCE-IT trial that used icosapent ethyl (IPE), a purified formulation of the n3-FA eicosapentaenoic acid. In high-risk patients, IPE reduced a composite of cardiovascular events (25%, P < .001) in a manner not predicted by TG lowering. Benefits with IPE appear linked to broad pleiotropic actions associated with on-treatment eicosapentaenoic acid levels. These studies indicate that although TGs are a potential biomarker of cardiovascular risk, there is no evidence that TG lowering itself is an effective strategy for reducing such risk.
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COVID-19 and metabolic disease: mechanisms and clinical management.
Steenblock, C, Schwarz, PEH, Ludwig, B, Linkermann, A, Zimmet, P, Kulebyakin, K, Tkachuk, VA, Markov, AG, Lehnert, H, de Angelis, MH, et al
The lancet. Diabetes & endocrinology. 2021;(11):786-798
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Abstract
Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.
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Effects of ad libitum food intake, insufficient sleep and weekend recovery sleep on energy balance.
Depner, CM, Melanson, EL, Eckel, RH, Higgins, JA, Bergman, BC, Perreault, L, Knauer, OA, Birks, BR, Wright, KP
Sleep. 2021;(11)
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Abstract
STUDY OBJECTIVES Insufficient sleep is believed to promote positive energy balance (EB) and weight gain. Increasing weekend sleep duration to "recover" from weekday sleep loss is common, yet little is known regarding how weekend recovery sleep influences EB. We conducted a randomized controlled trial to assess how: (1) 2 days and 8 days of insufficient sleep and (2) ad libitum weekend recovery sleep impact EB (energy intake [EI] - energy expenditure [EE]). METHODS Following ten baseline days with 9 h per night sleep opportunities, participants completed one of three 10-day experimental protocols with ad libitum EI: control (9 h sleep opportunities; n = 8; 23 ± 5 years [mean ± SD]); sleep restriction (SR; 5 h sleep opportunities; n = 14; 25 ± 5 years); sleep restriction with weekend recovery sleep (SR + WR; 5 days insufficient sleep, 2 days ad libitum weekend recovery sleep, 3 days recurrent insufficient sleep; n = 14; 27 ± 4 years). RESULTS Twenty-four hour EB increased (p < 0.001; main effect) by an average of 797.7 ± 96.7 (±SEM) kcal during the 10-day experimental protocol versus baseline with no significant differences between groups. Percent change from baseline in 24 h-EE was higher (p < 0.05) on day 2 of insufficient sleep (SR and SR + WR groups; 10 ± 1%) versus adequate sleep (control group; 4 ± 3%). CONCLUSIONS In this between-group study, the effects of adequate sleep and insufficient sleep, with or without or weekend recovery sleep, on 24 h-EB were similar. Examining EB and body weight changes using within-subject cross-over designs and "free-living" conditions outside the laboratory (e.g. sleep extension) are needed to advance our understanding of the links between insufficient sleep, weekend recovery sleep and weight-gain.
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Lipid management for cardiovascular risk reduction in type 1 diabetes.
Tell, S, Nadeau, KJ, Eckel, RH
Current opinion in endocrinology, diabetes, and obesity. 2020;(4):207-214
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Abstract
PURPOSE OF REVIEW To review the recent evidence for lipid management in type 1 diabetes (T1D) for cardiovascular risk reduction. RECENT FINDINGS Individuals with T1D are at increased risk for cardiovascular morbidity and mortality, with atherosclerosis beginning as early as adolescence. Elevated low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein (a) are associated with increased cardiovascular risk in T1D. Although high-density lipoprotein cholesterol (HDL-C) in T1D is often normal or higher than in nondiabetic controls, HDL in T1D has structural alterations, which make it proatherogenic rather than cardioprotective. Similarly, although LDL-C is not particularly elevated in T1D, LDL still contributes to cardiovascular risk. Studies in individuals with diabetes have primarily included T2D participants, with a much smaller number of T1D participants; such studies have shown that lipid-lowering therapies, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL-C levels and cardiovascular events in both those with and without diabetes. Individuals with T1D have increased cholesterol absorption, suggesting that ezetimibe may be particularly effective in T1D. Results of the REDUCE-IT trial show cardiovascular risk reduction from high-dose omega-3 fatty acid (Icosapent Ethyl) therapy in patients with diabetes (primarily type 2 diabetes), independent of triglyceride lowering, but similar data in T1D are currently lacking. SUMMARY Individuals with T1D are at high risk of cardiovascular disease, necessitating close lipid monitoring and management from adolescence through adulthood.
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Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery.
Rubino, F, Cohen, RV, Mingrone, G, le Roux, CW, Mechanick, JI, Arterburn, DE, Vidal, J, Alberti, G, Amiel, SA, Batterham, RL, et al
The lancet. Diabetes & endocrinology. 2020;8(7):640-648
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Plain language summary
Bariatric surgery has been proven for weight loss in people with severe obesity. However, during the covid-19 pandemic, surgery has been postponed for many individuals. Under normal conditions, patients who are awaiting bariatric surgery are prioritised based on weight, however this does not necessarily reflect severity of their condition. This review paper aimed to develop new criteria in order to help prioritise individuals who are awaiting bariatric surgery. The authors began by reviewing the reasons for delaying bariatric surgery and the need for beds, the risks of covid-19 transmission during the procedure and the severe covid-19 complications that individuals with obesity can experience were discussed. A recommendation was made that all patients having bariatric surgery be tested for Covid-19. Solutions were proposed for those awaiting surgery such as diets, exercise, optimal blood sugar control and the potential use of weight loss medications. Prioritisation of surgery should focus on clinical need; it should be accessible and minimise harm from delays. Individuals with obesity and type 2 diabetes should be prioritised based on those who have an increased risk of death, determined by whether the individual; has poor blood sugar control despite maximal use of medications to control it, uses insulin, has previous heart disease, has liver disease or if they have other risk factors. It was concluded that weight alone is inadequate to prioritise candidates for bariatric surgery. Disease severity should be at the centre of decisions, especially when access to surgery is reduced, as is during the Covid -19 pandemic. This paper could be used by healthcare professionals to understand how to prioritise their obese and type 2 diabetic patients who are awaiting bariatric surgery.
Abstract
The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.