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Background. Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely medi...
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Background. Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely mediated by the gut incretin hormones. This potentiation is termed the incretin effect and is reduced in type 2 diabetes. The impact of psoriasis on gastrointestinal factors involved in glucose metabolism has not previously been examined.
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Currently the prevalence of obesity and diabetes is increasing throughout the world. The unsatisfactory long-term results observed in the treatment of both are due to their complex pathophysiologies and the difficulties related to...
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Currently the prevalence of obesity and diabetes is increasing throughout the world. The unsatisfactory long-term results observed in the treatment of both are due to their complex pathophysiologies and the difficulties related to maintaining lifestyle changes. From the knowledge of the incretin effect and its alteration in patients with type 2 diabetes mellitus, GLP-1 receptor agonists arise, molecules with high structural homology with native GLP-1. Scientific evidence supports its use for the long-term treatment of diabetes, especially in the presence of associated cardiovascular and/or renal failure. In 2009, the use of liraglutide for patients with diabetes was approved in Europe, and in 2014 it was signed for the first time in the United States to treat obesity, since it was observed that the use of these drugs causes significant weight loss.
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Aims: People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β-cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intrave...
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Aims: People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β-cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses. Methods: Four hour 50-g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35-41) kg/m 2]; (ii) Eight obese subjects with NGT [BMI: 33 (35-38) kg/m 2]; (iii) Eight lean patients with T2DM [BMI: 24 (22-25) kg/m 2]; and (iv) Eight lean healthy subjects [BMI: 23 (20-25) kg/m 2]. Results: The incretin effect was significantly (p < 0.05) reduced in patients with T2DM {obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p < 0.05). Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects. Conclusions: Our findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin-resistant state have NGT.
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BackgroundFew studies have focused on postprandial incretin responses to different carbohydrate meals. Therefore, we designed a study to compare the different effects of two carbohydrates (75g oral glucose, a monosaccharide and 10...
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BackgroundFew studies have focused on postprandial incretin responses to different carbohydrate meals. Therefore, we designed a study to compare the different effects of two carbohydrates (75g oral glucose, a monosaccharide and 100g standard noodle, a polysaccharide, with 75g carbohydrates equivalently) on postprandial glucose, insulin and incretin responses in different glucose tolerance groups.
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Incretins, which are insulinotropic gastrointestinal hormones, are produced mainly in K and L cells of the small intestine under the influence of nutritional stimuli. The best known incretins are glucagon-like peptide-1 (GLP-1) an...
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Incretins, which are insulinotropic gastrointestinal hormones, are produced mainly in K and L cells of the small intestine under the influence of nutritional stimuli. The best known incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones perform several functions: they stimulate insulin secretion in the pancreatic beta cells; they inhibit glucagon release from the alpha cells of the pancreas (GIP not in humans); they slow down gastric emptying and may directly suppress appetite; and, moreover, they indirectly increase peripheral glucose tolerance/insulin sensitivity. The insulinotropic and glucagonostatic effects of GLP-1 are glucose dependent. The incretins also have numerous other properties which are still being discovered and introduced in different branches of medicine. The patents mentioned in this work concern the use of incretins in diabetology, cardiology, gastroenterology and nuclear medicine. The pleiotropic effects of incretins offer therapeutic possibilities in numerous fields of medicine.
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Background: Type 2 Diabetes Mellitus is a long term metabolic disorder that is characterized by high blood sugar, insulin resistance, and lack of insulin. Based on the understanding of the pathogenesis of T2DM, several distinct ph...
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Background: Type 2 Diabetes Mellitus is a long term metabolic disorder that is characterized by high blood sugar, insulin resistance, and lack of insulin. Based on the understanding of the pathogenesis of T2DM, several distinct pharmacological therapies have been developed but many of them are producing significant adverse drug reactions. Objectives: The present study helps to understand the progression of hepatic degeneration in diabetes mellitus upon treatment with vildalgliptin and insulin. This study is aimed to evaluate the toxicity of combined therapy of vildagliptin and insulin in alloxan induced diabetic rats. Methods: Adult male albino Wistar rats were distributed among 5 groups, and induced diabetes with alloxan. The alterations in glucose metabolizing enzyme activities were determined spectrophotometrically in the liver homogenate and confirmed by histological study. The hematological count has been carried out in all experimental groups to understand the toxicity of combinatorial therapy. Results: The histopathological studies showed pathological changes in the cellular architecture and microcytic hepatic nuclei. The level of haemoglobin, red blood cells and platelet count has been lowered drastically when compared to the monotherapy showing that the combinatorial therapy makes the animal anaemic. The level of lymphocytes has been considerably reduced in the combinatorial therapy showing the loss of immunity. The glucose metabolizing enzymes have been significantly altered showing the glucose metabolism is severely affected in combinatorial therapy showing it was not properly metabolized. Conclusion: The above studies have clearly proves that vildagliptin and insulin drug therapy shows toxicity on metabolic organs and blood cells. So our studies will be really helpful for developing new drugs which are devoid of adverse effects.
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Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a mainstay of treatment options for type 2 diabetes. They contribute to lowering blood glucose levels, generally have a favorable tolerability profile, and ca...
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Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a mainstay of treatment options for type 2 diabetes. They contribute to lowering blood glucose levels, generally have a favorable tolerability profile, and can be used alone or in combination with other antidiabetic agents. Based on the duration of their effects, GLP-1 RAs can be divided into two classes: short-acting and long-acting. Differences exist between these sub-classes, and between each drug, in terms of pharmacokinetic and pharmacodynamic profiles. Therefore, prescribers cannot necessarily assume GLP-1 RA 'class effects', especially in terms of tolerability.
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Aims Glucagon‐like peptide‐1 (GLP‐1) receptor agonists are appealing as glucose‐lowering therapy for individuals with type 2 diabetes mellitus (T2DM) as they also reduce body weight and are associated with low rates of hypogly...
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Aims Glucagon‐like peptide‐1 (GLP‐1) receptor agonists are appealing as glucose‐lowering therapy for individuals with type 2 diabetes mellitus (T2DM) as they also reduce body weight and are associated with low rates of hypoglycaemia. This analysis assessed the long‐term cost‐effectiveness of semaglutide 0.5 and 1 mg vs dulaglutide 1.5 mg (two once‐weekly GLP‐1 receptor agonists) from a UK healthcare payer perspective, based on the head‐to‐head SUSTAIN 7 trial, to inform healthcare decision making. Materials and Methods Long‐term outcomes were projected using the IQVIA CORE Diabetes Model (version 9.0). Baseline cohort characteristics, changes in physiological parameters and adverse event rates were derived from the 40‐week SUSTAIN 7 trial. Costs to a healthcare payer were assessed, and these captured pharmacy costs and costs of complications. Utilities were taken from published sources. Results Once‐weekly semaglutide 0.5 and 1 mg were associated with improvements in quality‐adjusted life expectancy of 0.04 and 0.10 quality‐adjusted life years, respectively, compared with dulaglutide 1.5 mg. Clinical benefits were achieved at reduced costs, with lifetime cost savings of GBP 35 with once‐weekly semaglutide 0.5 mg and GBP 106 with the once‐weekly semaglutide 1 mg, resulting from fewer diabetes‐related complications due to better glycaemic control. Therefore, both doses of once‐weekly semaglutide were considered dominant vs dulaglutide 1.5 mg (improving outcomes and reducing costs). Conclusions Compared with treatment with dulaglutide, once‐weekly semaglutide represents a cost‐effective option for treating individuals in the UK with T2DM who are not achieving glycaemic control with metformin, projected to both improve clinical outcomes and reduce costs.
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New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose prediabetes and type 2 diabetes have changed the constitution of the two populations. We aimed to investigate the pathophysiological characteristics o...
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New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose prediabetes and type 2 diabetes have changed the constitution of the two populations. We aimed to investigate the pathophysiological characteristics of individuals with HbA1c-defined prediabetes and type 2 diabetes, respectively. Ten subjects with HbA1c-defined prediabetes, i.e. HbA1c from 5.7 to 6.4 % (39-46 mmol/mol), eight newly diagnosed patients with HbA1c-defined type 2 diabetes [HbA1c ≥6.5 % (≥48 mmol/mol)], and ten controls with HbA1c lower than 5.7 % (<39 mmol/mol), were studied. Blood was sampled over 4 h on two separate days after a 75 g-oral glucose tolerance test and an isoglycaemic intravenous glucose infusion, respectively. Blood was analysed for glucose, insulin, C-peptide, glucagon, and incretin hormones. Insulinogenic index, disposition index, glucagon suppression, and incretin effect were evaluated. Subjects with HbA1c-defined prediabetes showed significantly lower insulinogenic index (P = 0.02), disposition index (P = 0.001), and glucagon suppression compared with controls; and similar (P = NS) insulinogenic index and glucagon suppression and higher disposition index (P = 0.02) compared to HbA1c-diagnosed type 2 diabetic patients. The patients with type 2 diabetes showed lower insulinogenic index (P = 0.0003), disposition index (P < 0.0001), and glucagon suppression compared with the controls. The incretin effect was significantly (P < 0.05) reduced in patients with HbA1c-defined type 2 diabetes compared to subjects with HbA1c-defined prediabetes and controls. Plasma levels of incretin hormones were similar across the three groups. HbA1c associated negatively with insulinogenic index, disposition index, and incretin effect. Our findings show clear alpha- and beta-cell dysfunction in HbA1c-defined type 2 diabetes compatible with the previously described pathophysiology of plasma glucose-defined type 2 diabetes. Furthermore, in HbA1c-defined prediabetes, we show defective insulin response in combination with inappropriate suppression of glucagon, which may constitute new targets for pharmacological interventions.
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