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Insulin Type 2 Diabetes

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https://www.readbyqxmd.com/read/28820912/impact-of-novel-palmitoylated-prolactin-releasing-peptide-analogs-on-metabolic-changes-in-mice-with-diet-induced-obesity
#1
Veronika Pražienková, Martina Holubová, Helena Pelantová, Martina Bugáňová, Zdenko Pirník, Barbora Mikulášková, Andrea Popelová, Miroslava Blechová, Martin Haluzík, Blanka Železná, Marek Kuzma, Jaroslav Kuneš, Lenka Maletínská
Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus...
2017: PloS One
https://www.readbyqxmd.com/read/28819951/metformin-a-new-old-drug
#2
Marta Patrycja Wróbel, Bogdan Marek, Dariusz Kajdaniuk, Dominika Rokicka, Aleksandra Szymborska-Kajanek, Krzysztof Strojek
For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28819835/efficacy-and-safety-of-linagliptin-in-2681-asian-patients-stratified-by-age-obesity-and-renal-function-a-pooled-analysis-of-randomized-clinical-trials
#3
Guang Ning, Tushar Bandgar, Uwe Hehnke, Jisoo Lee, Juliana C N Chan
INTRODUCTION: Asian patients with type 2 diabetes (T2D) are younger, leaner, and more likely to develop renal dysfunction than White populations. In this multiethnic analysis of data from phase 3 trials, we investigated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in Asians stratified by these subphenotypes. METHODS: Data from randomized, double-blind, placebo-controlled trials evaluating linagliptin (as monotherapy, add-on therapy to metformin ± sulfonylurea, combined with pioglitazone or added to insulin) were pooled with efficacy data from 11 randomized trials of at least 24 weeks and safety data from 15 trials of various durations...
August 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28819632/detection-of-islet-cell-immune-reactivity-with-low-glycemic-index-foods-is-this-a-concern-for-type-1-diabetes
#4
Datis Kharrazian, Martha Herbert, Aristo Vojdani
Dietary management of autoimmune diabetes includes low glycemic foods classified from the glycemic index, but it does not consider the role that immunoreactive foods may play with the immunological etiology of the disease. We measured the reactivity of either monoclonal or polyclonal affinity-purified antibodies to insulin, insulin receptor alpha, insulin receptor beta, zinc transporter 8 (ZnT8), tyrosine phosphatase-based islet antigen 2 (IA2), and glutamic acid decarboxylase (GAD) 65 and 67 against 204 dietary proteins that are commonly consumed...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28818994/efficacy-and-safety-of-diacerein-in-patients-with-inadequately-controlled-type-2-diabetes-a-randomized-controlled-trial
#5
Claudia R L Cardoso, Nathalie C Leite, Fernanda O Carlos, Andréia A Loureiro, Bianca B Viegas, Gil F Salles
OBJECTIVE: To assess, in a randomized, double-blind, and placebo-controlled trial, the efficacy and safety of diacerein, an immune modulator anti-inflammatory drug, in improving glycemic control of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-four patients with HbA1c between 7.5 and 9.5% (58-80 mmol/mol) were randomized to 48-week treatment with placebo (n = 41) or diacerein 100 mg/day (n = 43). The primary outcome was the difference in mean HbA1c changes during treatment...
August 17, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28817342/hypoglycemia-risk-related-to-double-dose-is-markedly-reduced-with-basal-insulin-peglispro-versus-insulin-glargine-in-patients-with-type-2-diabetes-mellitus-in-a-randomized-trial-imagine-8
#6
Cynthia Harris, Thomas Forst, Tim Heise, Leona Plum-Mörschel, Elaine Watkins, Qianyi Zhang, Ludi Fan, Parag Garhyan, Niels Porksen
BACKGROUND: Basal insulin peglispro (BIL) has a peripheral-to-hepatic distribution of action that resembles endogenous insulin and a prolonged duration of action with a flat pharmacokinetic/pharmacodynamic profile at steady state, characteristics that tend to reduce hypoglycemia risk compared to insulin glargine (GL). The primary objective was to demonstrate that clinically significant hypoglycemia (blood glucose ≤54 mg/dL [3.0 mmol/L] or symptoms of severe hypoglycemia) occurred less frequently within 84 h after a double dose (DD) of BIL than a DD of GL...
August 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28817248/attenuated-suppression-of-lipolysis-explains-increases-in-triglyceride-secretion-and-concentration-with-basal-insulin-peglispro-bil-relative-to-insulin-glargine-treatment-in-patients-with-type-1-diabetes
#7
Rakel Fuglsang Johansen, Esben Søndergaard, Helle Linnebjerg, Parag Garhyan, Eric Chen Quin Lam, Niels Porksen, Scott J Jacober, Søren Nielsen
AIMS: In patients with type 1 diabetes, basal insulin peglispro (BIL) lowers weight and increases plasma triglycerides (TG) and hepatic fat relative to insulin glargine (GL). To explain this, we hypothesised that BIL's attenuated peripheral effects may include increased free fatty acid flux to the liver, causing increased VLDL-TG secretion and lipid oxidation, and decreased TG adipose tissue deposition. MATERIALS AND METHODS: In this open-label, randomised, 2-period crossover study, 14 patients with type 1 diabetes received once-daily, individualised, stable BIL or GL doses for 3 weeks...
August 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28817231/effect-of-once-weekly-dulaglutide-on-hba1c-and-fasting-blood-glucose-in-patient-subpopulations-by-gender-duration-of-diabetes-and-baseline-hba1c
#8
Baptist Gallwitz, Samuel Dagogo-Jack, Vivian Thieu, Luis-Emilio Garcia-Perez, Imre Pavo, Maria Yu, Kenneth E Robertson, Nan Zhang, Francesco Giorgino
To evaluate the efficacy and safety of dulaglutide 1.5 mg and 0.75 mg in type 2 diabetes patients by subgroups of gender, duration of diabetes, and baseline HbA1c in the dulaglutide clinical development program (AWARD-1 to -6 and -8 clinical trials). MATERIALS AND METHODS: Change in HbA1c was analysed by gender, duration of diabetes (<5 years, ≥5 years and <10 years, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia, and gastrointestinal adverse events were evaluated for individual trials...
August 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28817230/recent-findings-on-fulminant-type-1-diabetes
#9
REVIEW
Lan Liu, Ling Zeng, Dan Sang, Zeyuan Lu, Jie Shen
Fulminant type 1 diabetes (fT1D) is a new subtype of type 1 diabetes proposed by Imagawa in 2000. It is a clinical syndrome characterized by a markedly rapid and almost complete destruction of pancreatic β cells. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes. The incidence of fT1D is associated with HLA DRB1*04:05DQB1*04:01, both innate and acquired immune disorders might contribute to the development of fT1D. The presence of specific innate immune responses to enterovirus infection connected with enhanced adoptive immune pathways responsible for aggressive β cell toxicity in fT1D...
August 17, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28817223/single-dose-euglycemic-clamp-studies-demonstrating-pharmacokinetic-and-pharmacodynamic-similarity-between-mk-1293-insulin-glargine-and-originator-insulin-glargine-lantus-in-type-1-diabetes-and-healthy-subjects
#10
Michael Crutchlow, John S Palcza, Kate M Mostoller, Chantal D Mahon, April M Barbour, Michael C Marcos, Yang Xu, Elaine Watkins, Linda Morrow, Marcus Hompesch
AIMS: MK-1293 is an insulin glargine that has an identical amino acid sequence to that of Lantus, the originator insulin glargine. Two euglycemic clamp studies, one in subjects with Type 1 diabetes (T1D) and one in healthy subjects, were conducted to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity between MK-1293 and Lantus commercially procured in both the European Union (EU-Lantus) and United States (US-Lantus). MATERIALS AND METHODS: Both studies were single-dose, randomized, double-blind, single-center, crossover studies with ≥7 days between dosing periods...
August 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28816922/nil-whey-protein-effect-on-glycaemic-control-after-intense-mixed-mode-training-in-t2d
#11
Kim A Gaffney, Adam Lucero, Lee Stoner, James Faulkner, Patricia Whitfield, Jeremy Krebs, David S Rowlands
While intense endurance and resistance exercise training and whey protein supplementation have both been shown to independently improve glycaemic control, no known studies have examined the effect of high-intensity mixed-mode interval training (MMIT) and whey supplementation in adults with Type-2 diabetes (T2D). PURPOSE: To determine if peri-training whey protein supplementation combined with MMIT can improve glycaemic control. METHODS: In a double-blind randomised controlled trial, 24 men (55...
August 14, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28816532/comparing-clinical-outcomes-and-costs-for-different-treatment-intensification-approaches-in-patients-with-type-2-diabetes-uncontrolled-on-basal-insulin-adding-glucagon-like-peptide-1-receptor-agonists-vs-adding-rapid-acting-insulin-or-increasing-basal-insulin
#12
Philip Levin, Tao Fan, Xue Song, Damion Nero, Brian Davis, Bong-Chul Chu
Objective-Not all patients with type 2 diabetes achieve the recommended glycated hemoglobin A1c (A1C) levels after adequate titration of basal insulin (BI). Current intensification approaches include addition of rapid-acting insulin (RAI) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA), but it is not clear which strategy results in better long-term outcomes. Methods-This retrospective analysis of health insurance claims data in the US MarketScan database compared glycemic control and healthcare resource utilization and costs 12 months after adding GLP-1 RA to BI vs adding RAI or increasing BI doses...
August 17, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28816409/genistein-represses-pepck-c-expression-in-an-insulin-independent-manner-in-hepg2-cells-and-in-alloxan-induced-diabetic-mice
#13
Barilin Dkhar, Kitboklang Khongsti, Daiahun Thabah, Donkupar Syiem, Kapaettu Satyamoorthy, Bidyadhar Das
Genistein has been reported to exert beneficial effects on type 2 diabetes mellitus (T2DM); however, the underlying molecular mechanisms involved therein have not been clearly elucidated. To address this question, the effect of the genistein on the expression of phosphoenolpyruvate carboxykinase (PEPCK), and glucose production in HepG2 cells and in alloxan-induced diabetic mice was investigated. HepG2 cells were exposed to diferrent concentration of genistein in presence or absence of modulators, and the expression of cytosolic PEPCK (PEPCK-C) and the signalling pathways was studied...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28816105/thiazolidinedione-drugs-in-the-treatment-of-type-2-diabetes-mellitus-past-present-and-future
#14
Melissa A Davidson, Donald R Mattison, Laurent Azoulay, Daniel Krewski
Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes...
August 17, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28815530/role-of-endoplasmic-reticulum-mitochondria-communication-in-type-2-diabetes
#15
Jennifer Rieusset
Although mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and disrupted lipid and calcium (Ca(2+)) homeostasis are classically associated with both insulin resistance and β-cell dysfunction in type 2 diabetes mellitus (T2DM), the interplay between these metabolic stresses is less known. Both organelles interact through contact points known as mitochondria-associated membranes (MAM), in order to exchange both lipids and Ca(2+) and regulate cellular homeostasis. Recent evidences suggest that MAM could be an important hub for hormonal and nutrient signaling in the liver and that ER-mitochondria miscommunication could participate to hepatic insulin resistance, highlighting the importance of MAM in the control of glucose homeostasis...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814963/effects-of-a-liquid-high-fat-meal-on-postprandial-lipid-metabolism-in-type-2-diabetic-patients-with-abdominal-obesity
#16
Feng Wang, Huixia Lu, Fukang Liu, Huizhen Cai, Zhixiu Song, Fei Guo, Yulan Xie, Guofang Shu, Guiju Sun
BACKGROUND: Postprandial lipemia and lipoprotein lipase (LPL) activity play crucial roles in the pathogenesis of accelerated atherosclerosis. This study aimed to evaluate the postprandial lipid metabolism after the ingestion of a liquid high-fat meal in type 2 diabetic patients with abdominal obesity, and determine if the PvuII polymorphisms of LPL influence their postprandial lipid responses. METHODS: Serum glucose, insulin, triglycerides (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were measured in fasting and postprandial state at 0...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28814962/circulating-zinc-%C3%AE-2-glycoprotein-levels-are-low-in-newly-diagnosed-patients-with-metabolic-syndrome-and-correlate-with-adiponectin
#17
Lu Lei, Kejia Li, Ling Li, Xia Fang, Tingting Zhou, Cheng Zhang, Yong Luo, Hua Liu, Xiaoqiang Li, Hongting Zheng, Lin Zhang, Gangyi Yang, Lin Gao
BACKGROUND: Zinc-α2-glycoprotein (ZAG) is a novel adipokine that reduces insulin resistance, protecting against type 2 diabetes. However, past studies have been contradictory. This cross-sectional study aims to investigate the association of circulating ZAG with metabolic syndrome (MetS) in middle-aged and older Chinese adults. METHODS: Four hundred eighty nine individuals (234 healthy controls and 255 MetS patients) were examined. All individuals were screened for MetS according to the diagnostic guidelines of the United States National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III criteria...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28814771/rna-sequencing-of-db-db-mice-liver-identifies-lncrna-h19-as-a-key-regulator-of-gluconeogenesis-and-hepatic-glucose-output
#18
Neha Goyal, Ambily Sivadas, K V Shamsudheen, Rijith Jayarajan, Ankit Verma, Sridhar Sivasubbu, Vinod Scaria, Malabika Datta
Liver plays a key role in maintaining glucose homeostasis and impaired hepatic glucose metabolism is associated with type 2 diabetes. In the present study, we used RNA sequencing to profile the transcriptome of the livers of diabetic db/db mice as compared to the normal db/+ mice and identified 218 differentially expressed genes. Amongst these, there were 3 lncRNAs that were significantly downregulated and H19 was the most altered lncRNA in the livers of db/db mice. H19 expression significantly correlated with the expression of genes of the glycolysis and gluconeogenesis pathways, which suggest that altered hepatic H19 levels can directly or indirectly modulate their expression...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814745/suppression-of-grk2-expression-reduces-endothelial-dysfunction-by-restoring-glucose-homeostasis
#19
Kumiko Taguchi, Mari Hida, Mami Hasegawa, Haruka Narimatsu, Takayuki Matsumoto, Tsuneo Kobayashi
Despite the associations between diabetic complications and vascular endothelial dysfunction, a direct therapeutic method targeting endothelial dysfunction remains poorly characterized. We have previously shown that chemical inhibition of G-protein-coupled receptor kinase 2 (GRK2) slightly enhances insulin sensitivity and reduces endothelial dysfunction in type 2 diabetic mice. In this study, we identified GRK2 as a novel therapeutic target of diabetic endothelial dysfunction and investigated the effect on diabetic endothelial dysfunction through the systemic administration of GRK2 siRNA using a hydrodynamic-based procedure, resulting in suppression of increased GRK2 protein levels in the liver...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813108/consequences-of-gestational-diabetes-to-the-brain-and-behavior-of-the-offspring
#20
Ricardo A L DE Sousa, Yasmin S Torres, Claudia P Figueiredo, Giselle F Passos, Julia R Clarke
Gestational diabetes mellitus (GD) is a form of insulin resistance triggered during the second/third trimesters of pregnancy in previously normoglycemic women. It is currently estimated that 10% of all pregnancies in the United States show this condition. For many years, the transient nature of GD has led researchers and physicians to assume that long-term consequences were absent. However, GD diagnosis leads to a six-fold increase in the risk of developing type 2 diabetes (T2D) in women and incidence of obesity and T2D is also higher among their infants...
August 14, 2017: Anais da Academia Brasileira de Ciências
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