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Olga Montvida, Jonathan Shaw, Lawrence Blonde, Sanjoy K Paul
AIMS: To inform patients and their carers about the probability of reducing HbA1c to clinically desirable levels and sustainability of such control over 2 years with major second-line anti-diabetic therapies under individual risk scenario, with and without third-line intensification. MATERIALS AND METHODS: From US Centricity Electronic Medical Records, 163,081 patients with type 2 diabetes aged 18-80 years, who initiated metformin; intensified with DPP-4 inhibitor (DPP-4i), GLP-1 receptor agonist (GLP-1RA), sulfonylurea, insulin, or thiazolidinedione; and continued second-line ≥ 6 month, were selected...
March 14, 2018: Diabetes, Obesity & Metabolism
S K Singh
No abstract text is available yet for this article.
January 2018: Indian Journal of Endocrinology and Metabolism
Sanjay Kalra, Silver Bahendeka, Rakesh Sahay, Sujoy Ghosh, Fariduddin Md, Abbas Orabi, Kaushik Ramaiya, Sameer Al Shammari, Dina Shrestha, Khalid Shaikh, Sachitha Abhayaratna, Pradeep K Shrestha, Aravinthan Mahalingam, Mazen Askheta, Aly Ahmed A Rahim, Fatimah Eliana, Hari K Shrestha, Sandeep Chaudhary, Nancy Ngugi, Jean Claude Mbanya, Than Than Aye, Tint Swe Latt, Zhanay A Akanov, Abbas Raza Syed, Nikhil Tandon, A G Unnikrishnan, S V Madhu, Ali Jawa, Subhankar Chowdhury, Sarita Bajaj, Ashok Kumar Das
For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles...
January 2018: Indian Journal of Endocrinology and Metabolism
Se Hee Min, Jeong-Hwa Yoon, Sun Joon Moon, Seokyung Hahn, Young Min Cho
Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline...
March 13, 2018: Scientific Reports
Yeon Young Cho, Sung-Il Cho
AIMS: We explored the risks associated with metformin plus sulfonylurea (MET+SU) or MET plus a dipeptidyl peptidase-4 inhibitor (MET+DPP4i) for hypoglycemia, cardiovascular disease (CVD) events and all-cause mortality in type 2 diabetes (T2D) patients with comorbidities. METHODS: This retrospective cohort study is based on the South Korean National Health Insurance Service-National Sample Cohort, enrolling T2D patients with one or more diabetes-related comorbidities who switched from monotherapy to MET+SU or MET+DPP4i between July 1, 2008 and December 31, 2013...
March 9, 2018: Metabolism: Clinical and Experimental
Scott J Pilla, James R Dotimas, Nisa M Maruthur, Jeanne M Clark, Hsin-Chieh Yeh
AIMS: When patients with type 2 diabetes initiate insulin, metformin should be continued while continuation of other antihyperglycemics has unclear benefit. We aimed to identify practice patterns in antihyperglycemic therapy during the insulin transition, and determine factors associated with metformin continuation. METHODS: We performed a retrospective analysis of the Look AHEAD (Action for Health in Diabetes) trial which randomized overweight/obese adults under ambulatory care for type 2 diabetes to an intensive lifestyle intervention or diabetes support and education...
March 7, 2018: Diabetes Research and Clinical Practice
Laure Garcin, Dulanjalee Kariyawasam, Kanetee Busiah, Anne-Laure Fauret-Amsellem, Fleur Le Bourgeois, Laurence Vaivre-Douret, Hélène Cavé, Michel Polak, Jacques Beltrand
Chromosome 6 abnormalities such as paternal uniparental isodisomy, paternal 6q24 duplication, and maternal DMR (differentially methylated region) hypomethylation are a common cause of transient neonatal diabetes mellitus (TNDM). Oral sulfonylurea (SU) is used off-label to treat permanent neonatal diabetes mellitus owing to potassium channel mutation but has not been evaluated in TNDM. Our objective was to evaluate the efficacy and safety of SU therapy in chromosome 6-related TNDM. Description of 3 case reports and literature review was the subject of the study...
March 4, 2018: Pediatric Diabetes
Yu Chen, Lin Chen, Hong Zhang, Shibo Huang, Yuqing Xiong, Chunhua Xia
Sulfonylureas (SUs) such as glibenclamide, gliclazide, glimepiride, glipizide and gliquidone are one of the first oral medicines available for the treatment of type 2 diabetes, and are widely used for the treatment of hyperglycaemia. The hepatic transporters, organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), play an important role in the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. Drug-drug interactions mediated by OATP1B1/1B3 may result in the hepatic transporting change for drug substrates...
March 2, 2018: Basic & Clinical Pharmacology & Toxicology
Mitsuyoshi Namba, Toshio Iwakura, Rimei Nishimura, Kohei Akazawa, Munehide Matsuhisa, Yoshihito Atsumi, Jo Satoh, Toshimasa Yamauchi
Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey...
March 2, 2018: Journal of Diabetes Investigation
Wen-Xiu Xin, Luo Fang, Qi-Lu Fang, Xiao-Wei Zheng, Hai-Ying Ding, Ping Huang
BACKGROUND: To assess the association between hypoglycemic agents and prognosis of lung cancer patients with diabetes. METHODS: A comprehensive literature search was performed in PubMed, Web of Science, Embase, and Cochrane Library until May 2017. The search yielded 2593 unique citations, of which 18 articles met inclusion criteria. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by a fixed-effects or random-effects model. RESULTS: The pooled HRs favoring metformin users were 0...
March 2018: Medicine (Baltimore)
Torben Stermann, Franziska Menzel, Carmen Weidlich, Kay Jeruschke, Jürgen Weiß, Delsi Altenhofen, Tim Benninghoff, Anna Pujol, Fatima Bosch, Ingo Rustenbeck, D Margriet Ouwens, G Hege Thoresen, Christian de Wendt, Sandra Lebek, Tanja Schallschmidt, Martin Kragl, Eckhard Lammert, Alexandra Chadt, Hadi Al-Hasani
The RabGTPase-activating protein TBC1D1 has been shown to be a key regulator of glucose and lipid metabolism in skeletal muscle. Its function in pancreatic islets, however, is not yet fully understood. Here, we aimed to clarify the specific impact of TBC1D1 on insulin secretion and substrate utilization in pancreatic islets. We analyzed the dynamics of glucose-stimulated insulin secretion (GSIS) and lipid metabolism in isolated islets from Tbc1d1-deficient mice (D1KO). To further investigate the underlying cellular mechanisms, we conducted pharmacological studies in these islets...
February 22, 2018: Endocrinology
N M Phani, M Vohra, P Adhikari, S K Nagri, U Shashikiran, S C D'Souza, P R R Kalluri, K Satyamoorthy, P S Rai
BACKGROUND: Several SNPs were identified through GWAS for their association with type 2 diabetes which has implications to pancreatic β-cell physiology. OBJECTIVE: We aimed to study the role of risk alleles of TCF7L2, KCNJ11, CDKN2A, CDKAL1, IGF2BP2, SLC30A8 and KCNQ1 along with pharmacokinetic variants in response to sulfonylureas. METHOD: We performed a prospective study on 209 newly diagnosed subjects; treatment naive T2D subjects were recruited...
February 22, 2018: Current Molecular Medicine
Carolina I Ghanem, Jose E Manautou
Liver transporters play an important role in the pharmacokinetics and disposition of pharmaceuticals, environmental contaminants, and endogenous compounds. Among them, the family of ATP-Binding Cassette (ABC) transporters is the most important due to its role in the transport of endo- and xenobiotics. The ABCC sub-family is the largest one, consisting of 13 members that include the cystic fibrosis conductance regulator (CFTR/ABCC7); the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) and the multidrug resistance-associated proteins (MRPs)...
February 21, 2018: Current Medicinal Chemistry
Zhimin Huang, Juan Liu, Kaka Ng, Xuesi Wan, Lijuan Xu, Xiaoying He, Zhihong Liao, Yanbing Li
AIMS: Glimepiride is a sulfonylurea known to have unique insulin mimetic and sensitizing effect. We aimed to study the efficacy of glimepiride in a patient with type A insulin resistance syndrome. METHODS: A 15-year-old female with type A insulin resistance syndrome was treated with glimpiride for 6 months. Self-monitoring of blood glucose was recorded, OGTTs on glucose and insulin were measured during the treatment. Hyperinsulinemic euglycemic clamp was used to evaluate whole body insulin sensitivity before and after the treatment...
February 22, 2018: Journal of Diabetes Investigation
Milton Packer
Current guidelines for diabetes recommend that physicians attain a glycated hemoglobin (HbA1c) ≤ 7.0%, but this target may not be applicable to those with heart failure. Fourteen studies of patients with chronic heart failure that examined the relationship between the level of glycated hemoglobin and the risk of death specified whether the HbA1c was influenced by treatment with antidiabetic medications. In patients with heart failure not receiving glucose-lowering drugs, mortality was not increased if the HbA1c was <7...
February 22, 2018: Diabetes, Obesity & Metabolism
Yang Zhou, Cheng Hu, Xinjie Zhao, Ping Luo, Jingyi Lu, Qing Li, Miao Chen, Dandan Yan, Xin Lu, Hongwei Kong, Weiping Jia, Guowang Xu
Sulfonylureas are one of the commonly used drugs in type 2 diabetes mellitus (T2DM) but with considerable incidence of monotherapy failure. However, the mechanism of patients' drug response is unclear, and suitability evaluation biomarkers are in urgent need for precision medicine. In this study, a pseudotargeted gas chromatography-mass spectrometry method was employed to investigate the serum metabolic profiling of 66 significant responders and 24 nonsignificant responders at baseline and 16 weeks after gliclazide modified-release (MR) monotherapy...
February 28, 2018: Journal of Proteome Research
Simon J Fisher, Xingyue Huang, Manjiri Pawaskar, Edward A Witt, Swapnil Rajpathak, R Ravi Shankar, Silvio E Inzucchi
PURPOSE: The aim of the current study is to assess the patient and physician experience and knowledge of hypoglycemia in the management of type 2 diabetes (T2DM). METHODS: T2DM patients (N = 1002) completed questionnaires on hypoglycemia experience, familiarity, and fear. Their responses were compared across various antihyperglycemic treatment regimens; specifically, (1) insulin only or insulin combined with sulfonylurea [SU] and/or metformin, (2) SU only with/without metformin, and (3) neither insulin nor SU...
February 19, 2018: Endocrine
Piotr Bednarczyk, Anna Kicinska, Michal Laskowski, Bogusz Kulawiak, Rafal Kampa, Agnieszka Walewska, Milena Krajewska, Wieslawa Jarmuszkiewicz, Adam Szewczyk
Mitochondrial ATP-regulated potassium channels are present in the inner membrane of the mitochondria of various cells. In the present study, we show for the first time mitochondrial ATP-regulated potassium channels in human dermal fibroblast cells. Using the patch-clamp technique on the inner mitochondrial membrane of fibroblasts, we detected a potassium channel with a mean conductance equal to 100 pS in symmetric 150 mM KCl. The activity of this channel was inhibited by a complex of ATP/Mg2+ and activated by potassium channel openers such as diazoxide or BMS 191095...
February 16, 2018: Biochimica et Biophysica Acta
Lisa R Letourneau, Siri Atma W Greeley
The majority of patients diagnosed with diabetes less than 6 months of age, and many cases diagnosed between 6 and 12 months of age, have a gene mutation that causes permanent or transient hyperglycemia. Recent research advances have allowed for the discovery of new causes of congenital diabetes, including genes involved in pancreatic development (GATA4, NKX2-2, MNX1) and monogenic causes of autoimmune dysregulation (STAT3, LRBA). Ongoing follow-up of patients with KCNJ11 and ABCC8 mutations has supported the safety and efficacy of sulfonylureas, as well as the use of insulin pumps and continuous glucose monitors in infants with insulin-requiring forms of monogenic diabetes...
February 14, 2018: Current Opinion in Genetics & Development
Laura T Dickens, Rochelle N Naylor
PURPOSE OF REVIEW: Monogenic diabetes accounts for 1-2% of all diabetes cases, but is frequently misdiagnosed as type 1, type 2, or gestational diabetes. Accurate genetic diagnosis directs management, such as no pharmacologic treatment for GCK-MODY, low-dose sulfonylureas for HNF1A-MODY and HNF4A-MODY, and high-dose sulfonylureas for KATP channel-related diabetes. While diabetes treatment is defined for the most common causes of monogenic diabetes, pregnancy poses a challenge to management...
February 15, 2018: Current Diabetes Reports
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