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https://www.readbyqxmd.com/read/28088843/evaluating-surrogate-marker-information-using-censored-data
#1
Layla Parast, Tianxi Cai, Lu Tian
Given the long follow-up periods that are often required for treatment or intervention studies, the potential to use surrogate markers to decrease the required follow-up time is a very attractive goal. However, previous studies have shown that using inadequate markers or making inappropriate assumptions about the relationship between the primary outcome and surrogate marker can lead to inaccurate conclusions regarding the treatment effect. Currently available methods for identifying and validating surrogate markers tend to rely on restrictive model assumptions and/or focus on uncensored outcomes...
January 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#2
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#3
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088237/association-between-diabetes-mellitus-and-multi-drug-resistant-tuberculosis-a-protocol-for-a-systematic-review-and-meta-analysis
#4
Balewgizie Sileshi Tegegne, Tesfa Dejenie Habtewold, Melkamu Merid Mengesha, Johannes G M Burgerhof
INTRODUCTION: Multi-drug-resistant tuberculosis (MDR-TB) has emerged as a challenge to global tuberculosis (TB) control and remains a major public health concern in many countries. Diabetes mellitus (DM) is an increasingly recognized comorbidity that can both accelerate TB disease and complicate its treatment. The aim of this study is to summarize available evidence on the association of DM and MDR-TB among TB patients and to provide a pooled estimate of risks. METHODS: All studies published in English before October 2016 will be searched using comprehensive search strings through PubMed, EMBASE, Web of Science, and WHO Global Health Library databases which have reported the association of DM and MDR-TB in adults with TB (age > =15)...
January 14, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28088126/severe-hypoalbuminemia-and-steatohepatitis-leading-to-death-in-a-young-vegetarian-female-8-months-after-mini-gastric-bypass-a-case-report
#5
Mohammad Kermansaravi, Mohammad Reza Abdolhosseini, Ali Kabir, Abdolreza Pazouki
BACKGROUND: Hypoalbuminemia is an important complication after Mini Gastric Bypass (MGB) and is more frequent in vegetarians, diabetic nephropathy, and alcoholic and liver disease patients. The patients must be followed in regular intervals and serum albumin must be checked in every visit after MGB. Hypoalbuminemia must be prevented by good protein regimes. CASE SUMMARY: A 29 years old female was admitted 8 month after Laparoscopic Mini Gastric Bypass with malaise, dyspnea, icter, nausea, vomiting, diarrhea and edema of extremities from 2 weeks before admission...
December 11, 2016: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28088113/modulatory-effect-of-vanillic-acid-on-antioxidant-status-in-high-fat-diet-induced-changes-in-diabetic-hypertensive-rats
#6
Kolanji Vinothiya, Natarajan Ashokkumar
The worldwide incidence of diabetes has increased dramatically along with widespread lifestyle and dietary changes. Diets high in fat are strongly associated with the development of obesity and can induce insulin resistance in humans and animals. It is clear that obesity constitutes a risk factor for contributing to the development of type 2 diabetes. In the present study, we investigated the therapeutic potential action of vanillic acid on diabetes associated complications using a rat model. Rats were made diabetic hypertensive by high fat diet (HFD) for 20 weeks and were treated with vanillic acid (50mg/kg bw) for last 8 weeks...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088030/efficacy-and-safety-of-linagliptin-metformin-single-pill-combination-as-initial-therapy-in-drug-na%C3%A3-ve-asian-patients-with-type-2-diabetes
#7
Yiming Mu, Changyu Pan, Bei Fan, Uwe Hehnke, Xiuzhen Zhang, Xuejun Zhang, Xiaoyue Wang, Jingdong Liu, Ying Zhang, Jianling Du, Jianhua Ma, Yan Gong
AIM: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control. METHODS: Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2...
December 5, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28088029/an-updated-meta-analysis-of-cohort-studies-diabetes-and-risk-of-alzheimer-s-disease
#8
REVIEW
Jieyu Zhang, Chunxiang Chen, Shuizhen Hua, Hairong Liao, Meixiang Wang, Yan Xiong, Fei Cao
BACKGROUND: In recently, several large longitudinal population-based studies have shown that the rate of cognitive decline is accelerated in elderly people with diabetes mellitus. But the relation between diabetes and AD is still an area of controversy. The objective of this review was to update the evidence for or against diabetes as a risk factor of AD. METHODS: We searched the literature from their inception to May 2016 without restriction of language. We included all longitudinal population-based studies examining the association between diabetes and risk of AD...
November 9, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28087575/treating-inflammation-and-infection-in-the-21st-century-new-hints-from-decoding-resolution-mediators-and-mechanisms
#9
REVIEW
Charles N Serhan
Practitioners of ancient societies from the time of Hippocrates and earlier recognized and treated the signs of inflammation, heat, redness, swelling, and pain with agents that block or inhibit proinflammatory chemical mediators. More selective drugs are available today, but this therapeutic concept has not changed. Because the acute inflammatory response is host protective to contain foreign invaders, much of today's pharmacopeia can cause serious unwanted side effects, such as immune suppression. Uncontrolled inflammation is now considered pathophysiologic and is associated with many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity, and asthma, as well as classic inflammatory diseases (e...
January 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28087508/international-variation-in-outcomes-among-people-with-cardiovascular-disease-or-cardiovascular-risk-factors-and-impaired-glucose-tolerance-insights-from-the-navigator-trial
#10
Marilia Harumi Higuchi Dos Santos, Abhinav Sharma, Jie-Lena Sun, Karen Pieper, John J V McMurray, Rury R Holman, Renato D Lopes
BACKGROUND: Regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. Our objective was to evaluate regional variation in risk of new-onset diabetes mellitus, cardiovascular outcomes, and treatment effects in participants from the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial. METHODS AND RESULTS: NAVIGATOR randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5-year follow-up...
January 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28087385/berberine-exerts-renoprotective-effects-by-regulating-the-ages-rage-signaling-pathway-in-mesangial-cells-during-diabetic-nephropathy
#11
Yuan-Ye Qiu, Li-Qin Tang, Wei Wei
In this study, we explored the effect of berberine treatment on the AGEs-RAGE pathway in a rat model of diabetic nephropathy, and we investigated the mechanism by which key factors caused kidney injury and the effects of berberine. In vivo, berberine improved fasting blood glucose, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney. Western blotting and immunohistochemistry revealed significant increases in the levels of AGEs, RAGE, P-PKC-β and TGF-β1 in injured kidneys, and these levels were markedly decreased by treatment with berberine...
January 10, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28087318/etiologies-of-community-onset-urinary-tract%C3%A2-infections-requiring-hospitalization-and%C3%A2-antimicrobial-susceptibilities-of%C3%A2-causative-microorganisms
#12
Chih-Chien Chiu, Tzu-Chao Lin, Rui-Xin Wu, Ya-Sung Yang, Po-Jen Hsiao, Yi Lee, Jung-Chung Lin, Feng-Yee Chang
BACKGROUND: Community-onset urinary tract infections (CoUTIs) are the most common bacterial infections, and a decline in antibiotic susceptibility causes many clinical challenges. Adequate empiric antibiotic treatment can decrease unnecessary hospital stays and complications, while reducing the antimicrobial resistance progression. METHODS: From October 2014 to April 2015, we retrospectively enrolled patients who were at least 18 years old and required hospitalization for CoUTIs...
December 18, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28087255/unknown-face-of-known-drugs-what-else-can-we-expect-from-angiotensin-converting-enzyme-inhibitors
#13
REVIEW
Anna Wzgarda, Robert Kleszcz, Monika Prokop, Katarzyna Regulska, Milosz Regulski, Jaroslaw Paluszczak, Beata J Stanisz
The renin-angiotensin system (RAS) is one of important systems among homeostatic mechanisms that controls the function of cardiovascular, renal and adrenal systems. As RAS has a very complex nature, it has been also found as related to the control of cell migration and apoptosis. Angiotensin-converting enzyme inhibitors (ACEI) are drugs most commonly used in the modulation of RAS activity. ACEI have been extensively described as effective in the treatment of hypertension among adults, but also as drugs delaying progression in diabetic nephropathy and reducing mortality in left ventricular dysfunction and congestive heart failure...
January 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28087246/adipocytokines-and-anthropometric-measures-in-type-2-diabetics
#14
Shubhangi M Harke, Suresh P Khadke, Abhijit A Ghadge, Ashwini S Manglekar, Shashank S Shah, Arundhati G Diwan, Aniket A Kuvalekar
AIM: Type 2 diabetes mellitus has assumed pandemic proportions worldwide. Aggressive management of hyperglycemia in diabetics is a primary goal of treatment. We have previously reported favorable effects of oral hypoglycemic agents on adipocytokines. Aim of the present study was to investigate the relationship of adipocytokines with anthropometric measures and biochemical parameters in type 2 diabetics. METHODS: Clinically diagnosed type 2 diabetics and age, gender matched healthy volunteers were recruited for study...
December 30, 2016: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28087233/anti-diabetic-effects-of-inonotus-obliquus-polysaccharides-chromium-iii-complex-in-type-2-diabetic-mice-and-its-sub-acute-toxicity-evaluation-in-normal-mice
#15
Cong Wang, Zhongqin Chen, Yuxiang Pan, Xudong Gao, Haixia Chen
Polysaccharides are important bioactive ingredients from Inonotus obliquus. This study aimed to synthesize and characterize a novel I. obliquus polysaccharides-chromium (III) complex (UIOPC) and investigate the anti-diabetic effects in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) mice and sub-acute toxicity in normal mice. The molecular weight of UIOPC was about 11.5 × 10 (4) Da with the chromium content was 13.01% and the chromium was linked with polysaccharides through coordination bond...
January 10, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28087208/-child-langerhans-cell-histiocytosis
#16
Jean Donadieu, Sébastien Héritier
DEFINITION: Langerhans cell histiocytosis (LCH) is defined by the association of a clinical and radiological involvement and a biopsy of a pathological tissue. Extension: it can affect any organ or system of the body but most commonly the bone (80% of cases), the skin (33%) and the pituitary (25%). Other organs are concerned such as liver, spleen, hematopoietic system and the lungs (15% each), lymph nodes (5-10%) and central nervous system (CNS) excluding the pituitary (2-4%). Natural history: the natural history of the disease is very heterogeneous, ranging from auto-regressive lesions to a disease affecting multiple organs with fatal consequences, while some lesions may be responsible for permanent sequels...
January 10, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28086952/glucagon-like-peptide-1-analogues-an-efficient-therapeutic-option-for-the-severe-insulin-resistance-of-lipodystrophic-syndromes-two-case-reports
#17
Joana Oliveira, Eva Lau, Davide Carvalho, Paula Freitas
BACKGROUND: Lipodystrophic syndromes are uncommon medical conditions which are normally associated with metabolic disorders, such as diabetes mellitus, dyslipidemia, and fatty liver disease. These complications are generally difficult to treat, particularly diabetes, due to severe insulin resistance. We present two case reports of successful treatment of diabetes with glucagon-like peptide-1 analogues in patients with clinical features of lipodystrophic syndromes. CASE PRESENTATION: Two white women aged 49 and 60 years manifested marked central body fat deposition with severe lipoatrophy of their limbs and buttocks and pronounced acanthosis nigricans...
January 13, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28086951/sodium-glucose-transporter-2-sglt2-inhibition-with-empagliflozin-improves-cardiac-diastolic-function-in-a-female-rodent-model-of-diabetes
#18
Javad Habibi, Annayya R Aroor, James R Sowers, Guanghong Jia, Melvin R Hayden, Mona Garro, Brady Barron, Eric Mayoux, R Scott Rector, Adam Whaley-Connell, Vincent G DeMarco
Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28086882/differential-effects-of-glucagon-like-peptide-1-receptor-agonists-on-heart-rate
#19
REVIEW
Martin Lorenz, Francesca Lawson, David Owens, Denis Raccah, Christine Roy-Duval, Anne Lehmann, Riccardo Perfetti, Lawrence Blonde
While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms)...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28086872/dapagliflozin-decreases-small-dense-low-density-lipoprotein-cholesterol-and-increases-high-density-lipoprotein-2-cholesterol-in-patients-with-type-2-diabetes-comparison-with-sitagliptin
#20
Toshiyuki Hayashi, Tomoyasu Fukui, Noriko Nakanishi, Saki Yamamoto, Masako Tomoyasu, Anna Osamura, Makoto Ohara, Takeshi Yamamoto, Yasuki Ito, Tsutomu Hirano
BACKGROUND: The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies. METHODS: This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment...
January 13, 2017: Cardiovascular Diabetology
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