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Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss.
Pouwels, S, Sakran, N, Graham, Y, Leal, A, Pintar, T, Yang, W, Kassir, R, Singhal, R, Mahawar, K, Ramnarain, D
BMC endocrine disorders. 2022;(1):63
Abstract
Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. NAFLD is the most common chronic liver disease in the Western world. NAFLD is closely associated with metabolic disorders, including central obesity, dyslipidaemia, hypertension, hyperglycaemia and persistent abnormalities of liver function tests.In general NAFLD is a common denominer for a broad spectrum of damage to the liver, which can be due to hepatocyte injury, inflammatory processes and fibrosis. This is normally seen on liver biopsy and can range from milder forms (steatosis) to the more severe forms (non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and liver failure). In these patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH and NAFLD is mandatory. Histologic evaluation with liver biopsy remains the gold standard to diagnose NAFLD. Diagnosis of NAFLD is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. Dietary recommendations and lifestyle interventions, weight loss, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established with promising results but are difficult to maintain. Pioglitazone and vitamin E are recommended by guidelines in selected patients. This review gives an overview of NAFLD and its treatment options.
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2.
Diabetes Mellitus and COVID-19: Review Article.
Nassar, M, Daoud, A, Nso, N, Medina, L, Ghernautan, V, Bhangoo, H, Nyein, A, Mohamed, M, Alqassieh, A, Soliman, K, et al
Diabetes & metabolic syndrome. 2021;(6):102268
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Abstract
BACKGROUND AND AIMS We aim to cover most of the current evidence on the mutual effect of diabetes & COVID-19 infection on each other and the management of the COVID-19 patients with diabetes. METHODS We utilized databases to review the current evidence related to diabetes mellitus and COVID-19. RESULTS We discussed the most recent evidence of diabetes milieus and COVID-19 regarding risk factors, management, complications, and telemedicine. CONCLUSION Diabetes mellitus is associated with a significant risk of complications, extended hospital stays, and mortality in COVID-19 infected patients.
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Can We Treat Neuroinflammation in Alzheimer's Disease?
Sánchez-Sarasúa, S, Fernández-Pérez, I, Espinosa-Fernández, V, Sánchez-Pérez, AM, Ledesma, JC
International journal of molecular sciences. 2020;(22)
Abstract
Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.
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Clinical considerations in patients with diabetes during times of COVID19: An update on lifestyle factors and antihyperglycemic drugs with focus on India.
Gupta, R, Misra, A
Diabetes & metabolic syndrome. 2020;(6):1777-1781
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Abstract
BACKGROUND Diabetes is recognized as an important comorbidity in patients with COVID-19 and a large amount of literature has become available regarding this. The aim of this article is to review the literature regarding various aspects of association between diabetes and COVID-19 and to highlight clinically relevant points with focus on India. METHODS We searched Pubmed and Google Scholar databases for articles regarding diabetes and COVID-19 published between March 19, 2020 and August 30, 2020. RESULTS Diabetes and poor glycemic control are associated with increased severity and mortality in patients with COVID-19. Several clinical scenarios about hyperglycemia and COVID-19 are identified and each of these needs specific management strategies. CONCLUSION It is prudent to maintain good glycemic control in patients with diabetes in order to minimize the complications of COVID-19. There is a need for well conducted studies to asses the role of individual antihyperglycemic therapies in COVID-19 and also the behavior of new onset diabetes diagnosed either after COVID-19 infection or during this time.
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Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy.
Cintra, R, Moura, FA, Carvalho, LSF, Barreto, J, Tambascia, M, Pecoits-Filho, R, Sposito, AC
Revista da Associacao Medica Brasileira (1992). 2019;(1):70-86
Abstract
The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.
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An investigation into the therapeutic effects of statins with metformin on polycystic ovary syndrome: a meta-analysis of randomised controlled trials.
Sun, J, Yuan, Y, Cai, R, Sun, H, Zhou, Y, Wang, P, Huang, R, Xia, W, Wang, S
BMJ open. 2015;(3):e007280
Abstract
OBJECTIVES To investigate the therapeutic effects of statins with metformin on polycystic ovary syndrome (PCOS). SETTINGS Endocrinology department. PARTICIPANTS MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched until October 2014. Studies comparing statins and placebo, as well as the combination of statins and metformin and metformin alone, were included in the analysis. INTERVENTIONS Data were independently extracted by two researchers; any convergence was resolved by a third reviewer. PRIMARY AND SECONDARY OUTCOME MEASURES The following properties were extracted from the qualified trials to identify the effects of statins: clinical variables, metabolic characteristics, hormone outcomes, sign of inflammation, glucose parameters and insulin outcomes. RESULTS Data from four trials comparing statin and metformin with metformin alone were analysed. The combination of statins and metformin decreases the levels of C reactive protein (standardised mean difference (SMD) -0.91; 95% CI -1.81 to -0.02; p=0.046), triglyceride (SMD -1.37; 95% CI -2.46 to -0.28; p=0.014), total cholesterol (SMD -1.28; 95% CI -1.59 to -0.97; p=0.000) and low-density lipoprotein (LDL) cholesterol (SMD -0.74; 95% CI -1.03 to -0.44; p=0.000). However, the combined therapy fails to reduce fasting insulin (SMD -0.92; 95% CI -2.07 to 0.24; p=0.120), homeostasis model assessment of insulin resistance (SMD -1.15; 95% CI -3.36 to 1.06; p=0.309) and total testosterone (SMD -1.12; 95% CI -2.29 to 0.05; p=0.061). Analysis of the five trials comparing statin with placebo shows that statin monotherapy reduces LDL-cholesterol, triglyceride and total cholesterol. CONCLUSIONS Combined statin and metformin therapy can improve lipid and inflammation parameters, but cannot effectively improve insulin sensitivity and reduce hyperandrogenism in women with PCOS. A large-scale randomised controlled study must be conducted to ascertain the long-term effects of the therapy.
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Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods.
Moyad, MA
Asian journal of andrology. 2015;(6):874-7; discussion 876
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Abstract
Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin).
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Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes.
Scheen, AJ, Van Gaal, LF
The lancet. Diabetes & endocrinology. 2014;(11):911-22
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The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine-controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes.
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Cardiovascular therapies and associated glucose homeostasis: implications across the dysglycemia continuum.
Cooper-DeHoff, RM, Pacanowski, MA, Pepine, CJ
Journal of the American College of Cardiology. 2009;(5 Suppl):S28-34
Abstract
Certain cardiovascular drugs have adverse effects on glucose homeostasis, which may lead to important long-term implications for increased risks of adverse outcomes. Thiazide diuretics, niacin, and beta-adrenergic blockers impair glucose homeostasis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have demonstrated beneficial metabolic effects. The newer vasodilating beta-blocking agents and calcium antagonists appear to be metabolically neutral. These considerations, in addition to meticulous attention to blood pressure control and lifestyle changes, have the potential to beneficially modify glycemia and long-term risks. These considerations have particular importance in younger patients who may also have pre-diabetes or the metabolic syndrome and who are likely to require therapy over the course of decades.
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Metabolic syndrome: controversial but useful.
Stolar, M
Cleveland Clinic journal of medicine. 2007;(3):199-202, 205-8
Abstract
The metabolic syndrome--the cluster of obesity, impaired fasting glucose, elevated triglycerides, low high-density lipoprotein cholesterol, and hypertension--may not be a "real" syndrome in the strict sense. It can, however, still be a useful concept if it prompts a physician to look for and treat additional risk factors when a patient is found to have one risk factor, or if it helps persuade patients to undertake healthy lifestyle changes before they develop overt diabetes mellitus or coronary artery disease.