Liraglutide for the treatment of type 2 diabetes genetic,january 1st netflix,diets to reverse diabetes 66 - Plans Download


American Gastroenterological Association Medical Position Statement: Nonalcoholic Fatty Liver Disease.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, has several non- glycemic properties, but its effect on carotid intima-media thickness (IMT), a recognized marker of subclinical atherosclerosis, is still unknown. A prospective study of 8A months duration in 64 patients with type-2 diabetes and no prior history of coronary artery disease evaluated whether adding liraglutide to metformin affects carotid IMT, measured by color doppler ultrasound. Liraglutide decreases carotid IMT after 8A months treatment independently of its effect on plasma glucose and lipids concentrations.
IntroductionLiraglutide is a long-acting human glucagon-like peptide-1 (GLP-1) analog suitable for once-daily administration in patients with type-2 diabetes (T2DM). DiscussionThis pilot study shows, for the first time, that liraglutide has desirable effect on carotid IMT in patients with T2DM after 8 months of therapy. National Institute for Clinical Excellence (2000) Guidance on rosiglitazone for type 2 diabetes mellitus. Is a once-daily human analogue injection approved for the treatment of type 2 diabetes in adults. Lowers blood sugar levels by stimulating the release of insulin from beta cells and reducing the release of glucagon from alpha cells when blood sugar levels are high and by slowing gastric emptying. Also, reduces body weight and body fat mass in people with type 2 diabetes through mechanisms involving reduced hunger and lowered energy intake. Has been directly compared, in terms of safety and efficacy, against commonly-used diabetes treatments like glimepiride, rosiglitazone, glargine, exenatide and sitagliptin in phase 3a and b clinical trials. Metformin or a sulphonylurea in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin or sulphonylurea. Metformin and a sulphonylurea or metformin and a thiazolidinedione in patients with insufficient glycaemic control despite dual therapy.
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A drug used by people with type 2 diabetes to regulate blood sugar led to pancreatic beta cell burnout in mice exposed to high doses over a period of six months. Liraglutide is one of a relatively new family of drugs that work by mimicking the effects of a hormone, called glucagon-like peptide-1 (GLP-1), naturally secreted by the intestine after eating to help stabilize blood sugar levels.
Midhat Abdulreda and Per-Olof Berggren of the of University of Miami Miller School of Medicine Diabetes Research Institute used humanized micea€”mice with human pancreatic islets transplanted in the back of the eyea€”as a testing ground for incretin mimetics.
Whether a similar pancreatic beta cell burnout could take place in patients is unknown, and due to the expense and invasiveness of the procedures needed to find out, it may not be something that is easy to learn. A recent study published in the journal PNAS shows that young capillary vessels rejuvenate aged pancreatic islets. Starting from human skin cells, researchers at the University of Iowa have created human insulin-producing cells that respond to glucose and correct blood-sugar levels in diabetic mice. Researchers at the University of Massachusetts Medical School have discovered a new pathway that triggers regeneration of beta cells in the pancreas, a key development that may aid in the development of diabetes treatments.
Cells that express neurogenin 3 (NGN3) may one day be harnessed to create a plentiful supply of insulin-producing beta cells for the treatment of diabetes, a study led by researchers at the University of South Florida suggests. Microtubulesa€”cellular "highways" that deliver cargo to the cell membrane for secretiona€”have a surprising role in pancreatic beta cells.
A group of 10 women with type 2 DM and obesity, with T2DM duration 6 months - 2 years, drug naive or getting 1000-2500 gr metformin for at least 6 months with ultrasound markers of fatty liver and elevated ALT without hepatic insufficiency.
Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence.
Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. The role of visceral adipose tissue in the pathogenesis of non-alcoholic fatty liver disease. Elevation of markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in non-alcoholic fatty liver disease. Rosiglitasone for nonalcoholic steatohepatitis: one year results of randomized placebo controlled Fatty Liver Improvement with Rosiglitasone (FLIRT) Trial. High Prevalence of Advanced NAFLD in Type 2 Diabetic Patients with Normal Liver Enzymes and Effect of Liraglutide on NAFLD: metaanalysis of the LEAD Program, 70th ADA Scientific Sessions Abstract Book, Poster number 1552, 2010.


Clinical studies have demonstrated glucose-reducing effects, improvements in pancreatic beta cell function and a low risk of hypoglycaemic events with this agent [1]. This effect seems to be achieved by mechanisms independent of induced changes in plasma glucose and lipid concentrations. Food and Drug Administration (FDA) approved the new drug application for Victoza®, the first once-daily human glucagon-like injection for the treatment of type 2 diabetes. GLP-1 is a natural hormone in the body that plays a critical role in maintaining a healthy level of sugar in the blood.
Using a humanized mouse model, they show that, following the initial improvement in human pancreatic function, prolonged daily liraglutide treatment for over 200 days is associated with compromised insulin release and dysregulated glucose homeostasis, indicating islet cell metabolic exhaustion. The study, published February 11 in Cell Metabolism, adds to the continuing conversation about the long-term effects of liraglutide and similar drugs on the pancreas.
Based on studies in rodents, these drugsa€”also called incretin mimeticsa€”may also improve insulin release and prevent the loss of insulin-producing beta cells, meaning they could potentially help slow down the progression of type 2 diabetes. Mice with diabetes were subjected to liraglutide treatment for over 200 days, and effects on human beta cells were evaluated. Using the humanized mouse model, the researchers next plan to investigate the effect of incretin mimetics with various anti-diabetic drug combinations on human pancreatic cells from healthy donors and people with type 2 diabetes. Weight, BMI, HbA1C, ALT, AST, hepatic elasticity were measured before liraglutide 1.2 mg daily and 6 month after treatment. Liraglutide has also shown favorable effects on inflammatory markers, such as C-reactive protein (CRP), tumour necrosis factor-I± (TNF-I±) and plasminogen activator inhibitor type-1 (PAI-1) [2, 3]. The project design included a medical examination, biochemical analyses and the eco-color-doppler examination of carotid arteries.
Total cholesterol, triglycerides and HDL-cholesterol were measured by standard enzymatic-colorimetric methods [6a€“8], while LDL-cholesterol was calculated using the Friedewald formula.Color doppler ultrasound of carotid arteriesB-mode real-time ultrasound was performed at baseline and after 4 and 8A months of therapy to evaluate the arterial wall thickness in the carotid arteries. This is somewhat consistent to a very recent study, where GLP-1 analogue therapy reduced several inflammatory markers, independently of the glycaemic or body weight effects induced by the GLP-1 analogue [10].
Victoza is indicated as an addition to diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus. However, more research is needed to assess the potential safety of continuing treatment with these drugs. With all of this promise, reports of side effects made researchers look at the safety of their long-term use.
This revealed an unexpected effect in that the human pancreatic cells eventually stopped releasing insulin, raising concerns about beta cell function after extended exposure to the drug.
Further, liraglutide seems to also have an impact on diabetic dyslipidemia, reducing total cholesterol, triglycerides and low density lipoproteins (LDL)-cholesterol levels, with a concomitant increase in high density lipoproteins (HDL)-cholesterol [3, 4].These favorable effects of liraglutide on multiple metabolic pathways may have beneficial effects on atherosclerosis and possibly reduce risk for cardiovascular disease. The procedures adopted were in agreement with the Helsinki Declaration of 1975 as revised in 1983, and were approved by the Ethics Council of the University of Palermo. Yet, no significant correlation was found between changes in carotid IMT and changes in all the evaluated parameters (data not shown).We have further performed multivariate analysis, in order to assess potential independent associations between decreased carotid IMT and clinical and laboratory variables evaluated at baseline.
Pioglitazone therapy also slowed progression of carotid atherosclerosis in subjects with prediabetes, independently of changes in cardio-metabolic risk factors [11].Although not yet directly demonstrated, it is possible that liraglutide has beneficial effects on the process of atherosclerotic plaque formation. In 7 women ALT level normalization was seen, in 3 women - ALT level reduction by 43, 37, 40% respectively.
However, prospective studies to elucidate the clinical impact of liraglutide on cardiovascular outcomes in patients with T2DM, such as the international LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) study, are still ongoing [5]. The ultrasound examination was performed in a standardized manner with fixed angles of insonation.As previously reported [9], patients were examined in the supine position, and each carotid wall or segment was examined to identify the thickest intimal-medial site. Such baseline parameters included gender, age, smoking habit, past history of cardiovascular diseases, duration of diabetes, as well as plasma HbA1c, LDL-cholesterol, HDL-cholesterol and triglycerides. Pre-clinical data have shown that liraglutide is able to reduce infarct size in mice with experimental myocardial infarction [12], while exenatide, a synthetic GLP-1 receptor agonist, reduced intimal hyperplasia in insulin resistant rats [13]. The other authors have no relevant conflict of interest to disclose.Authorsa€™ contributionsMR wrote the manuscript and researched data. Life expectancy in the 370, 000 people with type 1 diabetes mellitus (T1DM) in the UK remains lower than those without diabetes. We performed a pilot study to explore, for the first time, the effects of liraglutide on carotid intima-media thickness (IMT), a recognized marker of subclinical atherosclerosis, thus providing a preliminary view on the potential impact of this therapeutic intervention on cardiovascular risk of patients with T2DM.
At admission they underwent a medical examination and were excluded from the study if they had clinical evidence of liver dysfunction or renal failure. Each scan of the common carotid artery began just above the clavicle, and the transducer was moved to the carotid bifurcation and along the internal carotid artery.


Further, in patients with type-2 diabetes, the stimulation of GLP-1 secretion seems to have a significant impact on cardiovascular risk [14]. Find out all about Diabetes UK: what we do, our position on diabetes issues, and how we are governed. The delivery of care is variable, with a substantial north-south divide in England for major lower limb amputations1.
5%) or less1: this is lower than the clinical guideline on type 1 diabetes published in 2014, which recommended an HbA1c target of less than 7. Yet, in a recent study a 6-month GLP-1 receptor agnist treatment did not modulate vascular function, despite significant improvements in body composition and glycaemic control [15].Regarding other liraglutide effects found in the present study, body weight significantly reduced after 4A months of therapy but we found no further change after 8A months of treatment.
WHO in 2006: definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. GLP-1 receptor agonists in type 2 diabetes – NICE guidelines versus clinical practice.
Fifty-three percent of the subjects were current smokers and 64% had hypertension diagnosed by the following: systolic or diastolic blood pressure, respectively, a‰?140 or a‰?90A mmHg or previous pharmacological therapy with antihypertensive drugs. At each of these sites we determined the IMT, defined as the distance between the echogenic line representing the intimal blood interface and the outer echogenic line representing the adventitial junction. Finally, when the effect of liraglutide on carotid IMT was adjusted for the use of lipid-lowering drugs, the effect of liraglutide remained significant (data not shown).
In another study [16], liraglutide induced significant and persistent weight loss up to 6A months of follow-up in obese Japanese patients with type 2 diabetes. Cost-utility analysis of liraglutide compared with sulphonylurea or sitaglitpin, all as add-on to metformin monotherapy in type 2 diabetes mellitus.
Forty-five patients were already taking anti-hypertensive or lipid-lowering drugs, and such medications were maintained at the same doses until the end of the study.
In the present study liraglutide treatment was also able to significantly reduce plasma total- and LDL-cholesterol concentrations; further, LDL-cholesterol was the only variable showing an independent associations with decreased carotid IMT at multivariate analysis.
In details, 21 subjects were taking beta-blockers, 15 angiotensin-converting enzyme inhibitors, 12 calcium entry blockers and 20 diuretics. Univariate analysis was performed using paired t-test, while correlation analysis was performed using the Spearman rank correlation method. ANOVA was used to test changes in all evaluated parameters from baseline to 4A months and to 8A months of treatment. Indeed, using different methodologies, it has been shown that GLP-1 improves endothelial function in patients with type-2 diabetes or the metabolic syndrome; such methodologies included strain-gauged plethysmography and flow-mediated dilation [19a€“21]. The guarantor for this work is MR Preliminary data on this study were reported at the 2012 Annual Conference of the American Diabetes Association. Further, in pre-clinical studies, liraglutide improved endothelial function and inhibited the progression of vascular disease via the effects on plaque stability and endothelial function [22, 23].Previous studies have investigated the effects of anti-diabetic agents on carotid IMT.
For instance, the CHICAGO (Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone) trial [24] was a randomized, double-blind, multicenter study, which evaluated the effect of pioglitazone vs glimepiride on changes in carotid IMT in patients with type-2 diabetes. By contrast, in a very recent study [25], vildagliptin was able to reduce carotid IMT by about 0.10A mm after only 3A months of therapy in 90 patients with type-2 diabetes. The very recent data on the cardiovascular outcome with the use of saxagliptin and alogliptin highlight the need of more studies for incretin-based therapies [26, 27], including the GLP-1 analogues. It is hoped that the ongoing international LEADER study will provide useful answers in this regard [5].A limitation of the present study is the lack of the placebo (control) arm. Although we did not investigate the effect of metformin alone on carotid IMT, previous studies have shown that metformin therapy has mild or null effects on carotid IMT [28a€“30]. It is therefore unlikely that metformin was responsible for the strong and significant decrease in carotid IMT that we have found after 4 and 8A months of therapy.
Also, it needs to be highighted that in the present study we administered liraglutide as add-on therapy in patients who were already receiving metformin therapy. To our knowledge, the present study is the first one to examine the effects of liraglutide on carotid IMT.



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