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Diabetes pharmacogenetics

Tanja Dujic, Kaixin Zhou, Sook Wah Yee, Nienke van Leeuwen, Catherine E de Keyser, Martin Javorský, Srijib Goswami, Linda Zaharenko, Mette Marie H Christensen, Mattijs Out, Roger Tavendale, Michiaki Kubo, Monique M Hedderson, Amber A van der Heijden, Lucia Klimčáková, Valdis Pirags, Adriaan Kooy, Kim Brøsen, Janis Klovins, Sabina Semiz, Ivan Tkáč, Bruno H Stricker, Colin N A Palmer, Leen M 't Hart, Kathleen M Giacomini, Ewan R Pearson
Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporters genes, with inconsistent results. To clarify the significance of these variants in glycaemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (OCT1, OCT2, MATE1, MATE2-K and OCTN1) were analysed in up to 7,968 individuals...
November 10, 2016: Clinical Pharmacology and Therapeutics
Cornelius Kürten, Mladen Tzvetkov, Volker Ellenrieder, Harald Schwörer
History and clinical findings | We report about a 79 year old non-diabetic patient who was admitted to the emergency room with severe hypoglycemia (blood glucose level: 36 mg / dl and Glasgow Coma Scale Score: 3). After the infusion of G40 % her blood glucose level stabilised. The patient reported to have taken 50 mg of Tramadol during the night to treat her headache. Investigations and diagnosis | No other differential diagnosis for hypoglycemia (i.e. diabetes, insulinoma, severe liver or kidney disease) could be established...
September 2016: Deutsche Medizinische Wochenschrift
Kamini Vasudev, Yun-Hee Choi, Ross Norman, Richard B Kim, Ute I Schwarz
OBJECTIVE: Atypical antipychotics are linked to a higher incidence of metabolic side effects, including weight gain, dyslipidemia, and diabetes. In this study, we examined the prevalence and potential genetic predictors of metabolic side effects in 60 adult patients on clozapine. METHOD: Genetic variants of relevance to clozapine metabolism, clearance, and response were assessed through targeted genotyping of cytochrome P450 enzymes CYP1A2 and CYP2C19, the efflux transporter ABCB1, the serotonin receptor (HTR2C), leptin (LEP), and leptin receptor (LEPR)...
September 28, 2016: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
Alfi Yasmina, Anthonius de Boer, Vera H M Deneer, Patrick C Souverein, Olaf H Klungel
AIMS: The aims of the present study were to assess antiplatelet drug use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet nonpersistence. METHODS: The present study was conducted in 4690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with a first MI between 1986 and 2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System...
September 23, 2016: British Journal of Clinical Pharmacology
Shalini Singh, Kauser Usman, Monisha Banerjee
Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control...
August 10, 2016: World Journal of Diabetes
Lane B Benes, Nikhil S Bassi, Michael H Davidson
The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management have placed greater emphasis on high-intensity statin dosing for those with known cardiovascular disease or diabetes mellitus. Differences in risk of hepatotoxicity, new onset diabetes and rhabdomyolysis specifically between the high-intensity statins and the most common moderate-intensity statin, simvastatin, were not found to a significant degree in this review. Rather, baseline characteristics and drug-drug interactions (DDIs) appear to be more important regarding the risk of these adverse effects...
September 2016: Progress in Cardiovascular Diseases
Belén Pastor-Villaescusa, Javier Caballero-Villarraso, M Dolores Cañete, Raúl Hoyos, José Maldonado, Gloria Bueno, Rosaura Leis, Ángel Gil, Ramón Cañete, Concepción M Aguilera
BACKGROUND: Overweight and obesity are considered to be serious public health problems. In pediatric populations, insulin resistance, dyslipidemia, and hypertension associated with obesity occur with increased frequencies. Metformin is an oral anti-hyperglycemic agent that has been demonstrated to be efficacious in the treatment of diabetic and non-diabetic obese adults. A considerable amount of pharmacogenetic research has demonstrated that genetic variation is one of the major factors affecting metformin response...
2016: Trials
André J Scheen
Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic, pathophysiological and clinical point of view. Thus, the response to any antidiabetic medication may considerably vary between individuals. Numerous glucose-lowering agents, with different mechanisms of action, have been developed, a diversified armamentarium that offers the possibility of a patient-centred therapeutic approach...
July 2016: Diabetes Research and Clinical Practice
Adem Y Dawed, Louise Donnelly, Roger Tavendale, Fiona Carr, Graham Leese, Colin N A Palmer, Ewan R Pearson, Kaixin Zhou
OBJECTIVE: Thiazolidinediones (TZDs) are putatively transported into the liver by OATP1B1 (encoded by SLCO1B1) and metabolized by CYP450 2C8 enzyme (encoded by CYP2C8). While CYP2C8*3 has been shown to alter TZD pharmacokinetics, it has not been shown to alter efficacy. RESEARCH DESIGN AND METHODS: We genotyped 833 Scottish patients with type 2 diabetes treated with pioglitazone or rosiglitazone and jointly investigated association of variants in these two genes with therapeutic outcome...
November 2016: Diabetes Care
Ivan Tkáč
Pharmacogenetics is the study of how genes (individual genotypes) affect a persons response to drugs. At present, recommendations made about the treatment of some monogenic forms of diabetes are based on genetic diagnostics. The first studies in the field of pharmacogenetics of oral antidiabetics have now been published which have identified associations of individual genetic variants with response to treatment. The response to sulfonylurea derivatives was significantly associated with the variants KCNJ11/ABCC8, TCF7L2 and CYP2C9...
March 2016: Vnitr̆ní Lékar̆ství
Ivan Tkáč, Ivana Gotthardová
Incretin effect enhancers are drugs used in the treatment of Type 2 diabetes and include GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (gliptins). Variants in several genes were shown to be involved in the physiology of incretin secretion. Only two gene variants have evidence also from pharmacogenetic studies. TCF7L2 rs7903146 C>T and CTRB1/2 rs7202877 T>G minor allele carriers were both associated with a smaller reduction in HbA1c after gliptin treatment when compared with major allele carriers...
May 2016: Pharmacogenomics
Harald Staiger, Elke Schaeffeler, Matthias Schwab, Hans-Ulrich Häring
Many clinical treatment studies have reported remarkable interindividual variability in the response to pharmaceutical drugs, and uncovered the existence of inadequate treatment response, non-response, and even adverse drug reactions. Pharmacogenetics addresses the impact of genetic variants on treatment outcome including side-effects. In recent years, it has also entered the field of clinical diabetes research. In modern type 2 diabetes therapy, metformin is established as first-line drug. The latest pharmaceutical developments, including incretin mimetics, dipeptidyl peptidase 4 inhibitors (gliptins), and sodium/glucose cotransporter 2 inhibitors (gliflozins), are currently experiencing a marked increase in clinical use, while the prescriptions of α-glucosidase inhibitors, sulfonylureas, meglitinides (glinides), and thiazolidinediones (glitazones) are declining, predominantly because of reported side-effects...
October 2015: Review of Diabetic Studies: RDS
Adem Yesuf Dawed, Kaixin Zhou, Ewan Robert Pearson
Type 2 diabetes is one of the leading causes of morbidity and mortality, consuming a significant proportion of public health spending. Oral hypoglycemic agents (OHAs) are the frontline treatment approaches after lifestyle changes. However, huge interindividual variation in response to OHAs results in unnecessary treatment failure. In addition to nongenetic factors, genetic factors are thought to contribute to much of such variability, highlighting the importance of the potential of pharmacogenetics to improve therapeutic outcome...
2016: Pharmacogenomics and Personalized Medicine
Kaixin Zhou, Helle Krogh Pedersen, Adem Y Dawed, Ewan R Pearson
Genomic studies have greatly advanced our understanding of the multifactorial aetiology of type 2 diabetes mellitus (T2DM) as well as the multiple subtypes of monogenic diabetes mellitus. In this Review, we discuss the existing pharmacogenetic evidence in both monogenic diabetes mellitus and T2DM. We highlight mechanistic insights from the study of adverse effects and the efficacy of antidiabetic drugs. The identification of extreme sulfonylurea sensitivity in patients with diabetes mellitus owing to heterozygous mutations in HNF1A represents a clear example of how pharmacogenetics can direct patient care...
June 2016: Nature Reviews. Endocrinology
Aniruddha Agarwal, Sally A Ingham, Keegan A Harkins, Diana V Do, Quan Dong Nguyen
Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR...
February 2016: Pharmacogenomics
E R Pearson
Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C-peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non-response to glucagon-like peptide-1 receptor agonists, and thiazolidinediones are more effective in insulin-resistant patients...
June 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Chiranjib Chakraborty, Minna J Hsu, Govindasamy Agoramoorthy
The type 2 diabetes or T2D mellitus has turn into an epidemic throughout the globe in recent years. Various forms of treatment modalities have been available for patients with T2D with some major classes of approved drugs that include Sulfonylureas, Meglitinides, Biguanides, Thiazolidinedione, Alpha-glucosidase inhibitors, GLP-1 analogs, DPP-4 Inhibitors, and SGLT2 inhibitors. This review focuses on the drug metabolizing enzymes (DME), gene polymorphisms, and inter-individual variability in therapeutics including adverse reaction effects involving Phase-I DME and Phase-II in general...
2015: Current Drug Metabolism
Mojgan Allahdini, Behnam Kamalidehghan, Leila Akbari, Parisa Azadfar, Ali Rahmani, Fatemeh Ahmadipour, Goh Yong Meng, Abbas Masserrat, Massoud Houshmand
BACKGROUND: Pharmacogenetics is the study of genetic polymorphisms affecting responses to drug therapy. The common rs7903146 (C>T) polymorphism of the TCF7L2 gene has recently been associated with type 2 diabetes (T2D). In this study, prevalence of the rs7903146 (C>T) polymorphism in the TCF7L2 gene for prediction of T2D risk was examined in an Iranian population of different ethnicities. METHODS: The prevalence of rs7903146 (C>T) and the predicted phenotypes, including extensive metabolizers, intermediate metabolizers, and poor metabolizers were investigated in blood samples of 300 unrelated healthy individuals in an Iranian population, including Fars, Turk, Lure, and Kurd, using polymerase chain reaction restriction fragment length polymorphism and direct genomic DNA sequencing...
2015: Drug Design, Development and Therapy
Peter A Goulden, Jaime Vengoechea, Kent McKelvey
Personalized medicine in diabetes is a topic which has gained significant momentum in recent years (Raz et al. 2013). A rapid rise in the number and combinations of diabetes therapies coupled with an unprecedented rise in diabetes prevalence rates has necessitated diabetes guidelines which emphasize the need for personalized patient-centered care (ADA 2014). There are many questions regarding the role genetics may be able to play in guiding therapy. Recent pharmacogenetic research has revealed polymorphisms that may impact patient response to metformin (Dong et al 2011) and glucagon-like-polypeptide-1 therapies (Smushkin et al...
September 2015: Journal of the Arkansas Medical Society
Melanie F Myers, Sara L Fernandes, Lora Arduser, Jennifer L Hopper, Laura M Koehly
PURPOSE: The purpose of this study was to describe type 2 diabetes (T2DM) communication and risk reduction recommendations from the perspective of family members at risk for T2DM based on family history. METHODS: Semistructured qualitative interviews were conducted with 33 individuals with a first-degree relative with T2DM. Participants were recruited from the community and a previous pharmacogenetics study. Deductive and inductive codes were applied to the transcripts...
December 2015: Diabetes Educator
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