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Long acting insulin

Martin M Grajower
Hypoglycemia is the major side effect of insulin therapy. The elderly are especially vulnerable to episodes of hypoglycemia, and with greater risks of complications such as falls. Two new long-acting basal insulins, glargine-300 (Gla-300) and degludec, are associated with lower incidences of hypoglycemia than previously available basal insulins. One of them, Gla-300, was studied in the elderly and has a lower incidence of hypoglycemia in patients over 65 years old. These new data should be incorporated into decision making when treating the elderly patient with insulin, whether they have type 1 or 2 diabetes...
March 2018: Endocrine Practice
O M Selivanova, S Yu Grishin, A V Glyakina, A S Sadgyan, N I Ushakova, O V Galzitskaya
We analyzed the structural properties of the peptide hormone insulin and described the mechanism of its physiological action, as well as effects of insulin in type 1 and 2 diabetes. Recently published data on the development of novel insulin preparations based on combining molecular design and genetic engineering approaches are presented. New strategies for creation of long-acting insulin analogs, the mechanisms of functioning of these analogs and their structure are discussed. Side effects of insulin preparations are described, including amyloidogenesis and possible mitogenic effect...
January 2018: Biochemistry. Biokhimii︠a︡
Tomohide Yamada, Ryuichi Kamata, Kotomi Ishinohachi, Nobuhiro Shojima, Sophia Ananiadou, Hisashi Noma, Toshimasa Yamauchi, Takashi Kadowaki
Biosimilar insulins have expanded treatment options for diabetes. We compared clinical efficacy and safety between biosimilar and originator insulins by meta-analysis. Random effects meta-analysis was performed on randomized controlled trials comparing biosimilar and originator insulins in adults with diabetes from electronic databases up to December 2017. Ten trials (4,935 patients) were assessed (2 each for LY2963016, MK-1293, Mylan's insulin glargine, and SAR342434, and 1 each for FFP-112 and Basalog). Meta-analysis revealed no differences between long-acting biosimilar and originator insulins for reduction of hemoglobin A1c at 24 weeks (0...
March 14, 2018: Diabetes, Obesity & Metabolism
Ning Wang, Yanan Zhu, Min Xie, Lintao Wang, Feiyan Jin, Yihui Li, Qingxin Yuan, Wei De
BACKGROUND/AIMS: The main pathogenic mechanism of diabetes is a decrease in the number of islet beta cells or a decline in their function. Recent studies have shown that pancreatic long noncoding RNAs (lncRNAs) have a high degree of tissue specificity and may be involved in the maintenance of islet cells function and the development of diabetes. The aim of this study was to investigate the molecular regulatory mechanism of mouse maternal expressed gene 3 (Meg3) in insulin biosynthesis in pancreatic islets...
March 6, 2018: Cellular Physiology and Biochemistry
William J Valentine, Kate Van Brunt, Kristina S Boye, Richard F Pollock
OBJECTIVE: The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany. METHODS: The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5 years, duration of diabetes of 8...
March 10, 2018: Applied Health Economics and Health Policy
Rita Kiss, Katalin Szabó, Rudolf Gesztelyi, Sándor Somodi, Péter Kovács, Zoltán Szabó, József Németh, Dániel Priksz, Andrea Kurucz, Béla Juhász, Zoltán Szilvássy
In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to long-term progression of the disease before diagnosis and treatment. Despite enormous investment into the characterization of the disease, its long-term management remains problematic, with those afflicted enduring significant degradation in quality-of-life. Current research efforts into the etiology and pathogenesis of T2DM, are focused on defining aberrations in cellular physiology that result in development of insulin resistance and strategies for increasing insulin sensitivity, along with downstream effects on T2DM pathogenesis...
March 8, 2018: International Journal of Molecular Sciences
Bahendeka Silver, Kaushik Ramaiya, Swai Babu Andrew, Otieno Fredrick, Sarita Bajaj, Sanjay Kalra, Bavuma M Charlotte, Karigire Claudine, Anthony Makhoba
A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A). Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A). Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin...
March 5, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Matthew Riopel, Jong Bae Seo, Gautam K Bandyopadhyay, Pingping Li, Joshua Wollam, Heekyung Chung, Seung-Ryoung Jung, Anne Murphy, Maria Wilson, Ron de Jong, Sanjay Patel, Deepika Balakrishna, James Bilakovics, Andrea Fanjul, Artur Plonowski, Duk-Su Koh, Christopher J Larson, Jerrold M Olefsky, Yun Sok Lee
We have previously reported that the fractalkine (FKN)/CX3CR1 system represents a novel regulatory mechanism for insulin secretion and β cell function. Here, we demonstrate that chronic administration of a long-acting form of FKN, FKN-Fc, can exert durable effects to improve glucose tolerance with increased glucose-stimulated insulin secretion and decreased β cell apoptosis in obese rodent models. Unexpectedly, chronic FKN-Fc administration also led to decreased α cell glucagon secretion. In islet cells, FKN inhibited ATP-sensitive potassium channel conductance by an ERK-dependent mechanism, which triggered β cell action potential (AP) firing and decreased α cell AP amplitude...
March 5, 2018: Journal of Clinical Investigation
Elodie Czuba, Mouhamadou Diop, Carole Mura, Anais Schaschkow, Allan Langlois, William Bietiger, Romain Neidl, Aurélien Virciglio, Nathalie Auberval, Diane Julien-David, Elisa Maillard, Yves Frere, Eric Marchioni, Michel Pinget, Séverine Sigrist
Oral administration of insulin increases patient comfort and could improve glycemic control thanks to the hepatic first passage. However, challenges remain. The current approach uses poly (D, lactic-co-glycolic) acid (PLGA) nanoparticles (NPs), an effective drug carrier system with a long acting profile. However, this system presents a bioavailability of less than 20% for insulin encapsulation. In this context, physico-chemical parameters like surface charge could play a critical role in NP uptake by the intestinal barrier...
February 28, 2018: International Journal of Pharmaceutics
Afaque H Khan, Samina Zaidi
We report five cases of treatment-resistant schizophrenia that presented with prominent negative and positive symptoms. They fulfill the criteria of diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). They showed lack of response despite receiving multiple trials of first and second generation psychotropic agents. We decided to give these patients a trial of clozapine to improve their negative and positive symptoms as well as their quality of life...
December 20, 2017: Curēus
Zhongjie Fu, Zhongxiao Wang, Chi-Hsiu Liu, Yan Gong, Bertan Cakir, Raffael Liegl, Ye Sun, Steven S Meng, Samuel B Burnim, Ivana Arellano, Elizabeth Moran, Rubi Duran, Alexander Poblete, Steve S Cho, Saswata Talukdar, James D Akula, Ann Hellström, Lois E H Smith
Retinal neuronal abnormalities occur before vascular changes in diabetic retinopathy. Accumulating experimental evidence suggests that neurons control vascular pathology in diabetic and other neovascular retinal disease. Therefore, normalizing neuronal activity in diabetes may prevent vascular pathology. We investigated whether fibroblast growth factor 21 (FGF21) prevented retinal neuronal dysfunction in insulin-deficient diabetic mice. We found that in diabetic neural retina, photoreceptor rather than inner retinal function was most affected and administration of the long-acting FGF21 analog, PF-05231023 restored the retinal neuronal functional deficits detected by electroretinography...
February 27, 2018: Diabetes
M E Trautmann, J Vora
As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon-like peptide-1 receptor agonists and insulin, which may be added on to oral glucose-lowering treatments. Among individuals receiving long-acting basal insulin as their first injectable treatment, ~40-60% are unable to achieve or maintain their target HbA1c goals...
February 25, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Yue Gao, Ke Wang, Yun Chen, Li Shen, Jianing Hou, Jianwei Xuan, Bao Liu
INTRODUCTION: To assess and compare per-day anti-diabetic medication costs for Chinese type-2 diabetes mellitus (T2DM) insulin-naïve patients between those who initiated premixed insulin analogs ("premixed group") and those who initiated long-acting insulin analogs ("long-acting group"). METHODS: Data were obtained from an electronic medical record database between 2010.01.01 and 2015.06.30 covering medical encounter records from all general hospitals in a district from Shanghai, China...
February 23, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Yuqian Liu, Hsuan-Yao Wang, Li Zhou, Yang Su, Wei-Chiang Shen
A recombinant proinsulin-transferrin fusion protein (ProINS-Tf) has been previously reported to be a novel long-lasting INS analog, acting specifically on the inhibition of hepatic glucose output. In this study, we investigated the biodistribution, activation and tissue retention of ProINS-Tf to elucidate its liver targeted anti-diabetic mechanism. The biodistribution study revealed that ProINS-Tf exhibited liver specific accumulation after a single intravenous injection, whereas transferrin (Tf) or insulin (INS) showed relatively even distribution among different organs...
February 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Péter Judák, Peter Van Eenoo, Koen Deventer
The measurement of human insulin and its synthetic analogues in biological matrices has become increasingly important not only in clinical fields but also in doping control. The use of insulin and its analogues have been included in the list of prohibited substances published by the World Anti-Doping Agency (WADA). This study describes a qualitative method for detection of insulin analogues (lispro, aspart, glulisine, glargine, degludec, detemir) in human urine. The sample preparation consists of a preconcentration step using ultrafiltration followed by an immunoaffinity extraction with an antibody precoated ELISA plate...
February 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
Eva Toft, Mikael Rydén
Do novel therapies in type 2 diabetes have protective effects on cardiovascular and renal complications? A number of new antidiabetic drug classes have been introduced on the market in the last decade. Regulatory authorities have required that their safety in type 2 diabetes populations with high cardiovascular risk must be assessed. Consequently, a large number of outcome studies have been initiated, several of which have been published in recent years. Overall, this has so far shown that long-acting insulin analogues, DPP4-inhibitors, GLP1-receptor agonists and SGLT2-inhibitors are safe...
February 20, 2018: Läkartidningen
Simon A Hinke, Anne M Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L Chiu, Steve Jarantow, Eilyn R Lacy, Yin Liang, Dana L Johnson, Jean M Whaley, Russell B Lingham, Anthony J Kihm
OBJECTIVE: Insulin resistance is a key feature of Type 2 Diabetes (T2D), and improving insulin sensitivity is important for disease management. Allosteric modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can enhance insulin sensitivity and restore glycemic control in animal models of T2D. METHODS: A novel human mAb, IRAB-A, was identified by phage screening using competition binding and surface plasmon resonance assays with the IR extracellular domain...
February 3, 2018: Molecular Metabolism
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
Sevda Gheibi, Sajad Jeddi, Mattias Carlström, Hanieh Gholami, Asghar Ghasemi
PURPOSE: Supplementation with inorganic nitrate to boost the nitrate-nitrite-nitric oxide (NO) pathway, may act as a potential therapeutic agent in diabetes. The aim of this study was to determine the effects of nitrate on carbohydrate metabolism, lipid profiles, oxidative stress, and inflammation in obese type 2 diabetic rats. METHODS: Male Wistar rats were divided into 4 groups: Control, control + nitrate, diabetes, and diabetes + nitrate. Diabetes was induced using a high-fat diet and low-dose of streptozotocin...
February 10, 2018: Nitric Oxide: Biology and Chemistry
Mark Peyrot, Timothy S Bailey, Belinda P Childs, Gérard Reach
INTRODUCTION: Type 2 diabetes mellitus (T2D) is a growing global epidemic. Due to the progressive nature of the disease, many people with T2D require insulin at some point, most commonly a long-acting (basal) insulin to assist with 24-hour control of glucose levels. OBJECTIVE: This opinion paper provides an overview of considerations for primary care providers (PCPs) in intensifying the treatment regimen when basal insulin therapy is inadequate. RESULTS: Control of mealtime hyperglycemia, in addition to fasting hyperglycemia, has been shown to be crucial in reaching A1c goals of <7...
February 12, 2018: Current Medical Research and Opinion
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