Diyabet ve Diyabete Bağlı Fizyolojik ve Farmakokinetik Değişiklikler

Yıl 2017, Sayı: 2, 105 - 123, 01.06.2017

Tuğba Gülsün Selma Şahin

Öz

Ölüme neden olan hastalıklar arasında ilk beş sırada yer alan diyabet; karbonhidrat, yağ ve protein metabolizmasında bozukluk ile karakterize olan kronik kompleks metabolik bir hastalıktır. Diyabet Tip 1, Tip 2, diyabetin diğer spesifik türleri ve gestasyonel diyabet olarak sınıflandırılmaktadır. Diyabette, insülin salınımının azalması ve karbonhidrat, yağ ve protein metabolizmasında bozukluklar sonucunda akut veya kronik komplikasyonlar görülmektedir. Ayrıca diyabette ilaç metabolize eden enzimlerin ve ilaçların taşınmasından sorumlu olan absorptif ve eksorptif taşıyıcıların düzeylerinde diyabete bağlı değişiklikler olması nedeniyle ilaçların hem farmakokinetik hem de farmakodinamik özelliklerinde değişiklikler olabilmektedir. Diyabet tedavisinde kullanılan oral antidiyabetikler; pankreastan insülin salımını artıranlar, insülin duyarlılığını artıranlar ve glikoz emilimini azaltanlar olarak üç sınıfta toplanmaktadır. Dünya nüfusunun artması, yaşlanma, kentleşme, obezite sıklığı ve fiziksel hareketsizlik gibi nedenlerden dolayı diyabette gözlenen artış nedeniyle diyabet tüm dünyada öncelikli araştırma alanlarına girmiştir. Bu derlemede diyabetin sınıflandırılması, prevelansı, komplikasyonları, tedavisi, deneysel diyabet geliştirilmesi ve diyabette enzim ve taşıyıcı seviyelerindeki değişiklikler üzerinde odaklanılmıştır.

Anahtar Kelimeler

Diyabet, oral terapi, komplikasyonlar, prevelans, enzim ve taşıyıcı proteinler

Diabetes and Diabetes Associated Physiologic and Pharmacokinetic Changes

Öz

Diabetes which is among the top five diseases causing death, is a chronic complex metabolic disease characterized by impaired carbohydrate, fat and protein metabolism. Diabetes is classified as Type 1, Type 2, other specific types of diabetes and gestational diabetes. Acute or chronic complications are seen in diabetes as a result of decreased insulin release and disorders in carbohydrate, fat and protein metabolism. In addition, both pharmacokinetic and pharmacodynamic properties of drugs may alter due to changes in the levels of drug metabolizing enzymes and absorptive and efflux transporters responsible for drug transport. Oral antidiabetics used in the treatment of diabetes are collected in three groups; increasing insulin secretion from pancreas, increasing insulin sensitivity, and decreasing glucose absorption. Diabetes has entered into priority research areas all over the world due to the observed increase in diabetes such reasons as increase in world population, aging, urbanization, obesity frequency and physical inactivity. In this review, it was focused on the definition, classification, prevalence, complications, treatment of diabetes and development of experimental diabetes, and changes in the enzymes and transporters levels.

Anahtar Kelimeler

Diabetes, oral therapy, complications, prevalence, enzymes and transporters

Kaynakça

• Landersdorfer CB, Jusko WJ: Pharmacokinetic/pharmacodynamic modelling in diabetes mellitus. Clinical Pharmacokinetics 2008, 47(7): 417-448.
• Bastaki A: Diabetes mellitus and its treatment. International Journal of Diabetes and Metabolism 2005, 13(3):111.
• Mealey BL, Ocampo GL: Diabetes mellitus and periodontal disease. Periodontology 2000 2007, 44:127-153.
• Türkiye Halk Sağlığı Kurumu, 2015 April 10. Available from: http://diyabet.gov.tr/index. php?lang=tr&page=32.
• Society for Endocrinology BES 2014., 2015 September 5. Available from: http://www.endocrine- abstracts.org/ea/0034/SFEBES2014AbstractBook.pdf.
• Rosenfeld L: Insulin: discovery and controversy. Clinical Chemistry 2002, 48(12): 2270-2288.
• Wild S, Roglic G, Green A, Sicree R, King H: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27(5): 1047-1053.
• Seclen SN, Rosas ME, Arias AJ, Huayta E, Medina CA: Prevalence of diabetes and impaired fasting glucose in Peru: report from PERUDIAB, a national urban population-based longitudinal study. BMJ Open Diabetes Research & Care 2015, 3(1):1-7.
• IDF Diabetes Atlas, 2015 June 14. Available from: http://www.idf.org/diabetesatlas/update-2014.
• Navas-Acien A, Silbergeld EK, Streeter RA, Clark JM, Burke TA, Guallar E: Arsenic exposure and type 2 diabetes: a systematic review of the experimental and epidemiological evidence. Environmental Health Perspectives 2006, 114(5): 641-648.
• Donovan D: Principles of Diabetes Mellitus. Dordrecht: London: Kluwer Academic Publishers Boston, USA, 2002.
• Kelestimur F, Cetin M, Paşaoğlu H, Coksevim B, Cetinkaya F, Unlühizarci K, Unal S, Köker AH: The prevalence and identification of risk factors for type 2 diabetes mellitus and impaired glucose tolerance in Kayseri, Central Anatolia, Turkey. Acta Diabetologica 1999, 36(1-2):85-91.
• Guariguataa L, Whitingb DR, Hambletonc I, Beagleya J, Linnenkampa U, Shawd JE: Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Research and Clinical Practice 2014, 103(2):137-149.
• Fawcett D: A Text Book of Histology. Chapman&Hall, New York, USA, 1994.
• Moore KL, Persaud TVN, Torchia MG: The Developing Human: Clinically Oriented Embryology. Elsevier Saunders, Philidelphia, USA, 1993.
• Ross MH, Kaye GI, Pawlina W: Histology: A Text and Atlas: With Cell and Molecular Biology. Wolters Kluwer Health, Philidelphia, USA, 2011.
• Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA: Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. 1922. Canadian Medical Association Journal 1991, 145(10): 1281-1286.
• MacDonald PE, Rorsman P: Oscillations, intercellular coupling, and insulin secretion in pancreatic beta cells. PLoS Biology 2006, 4(2):e49.
• Guyton AC, Hall JE: Textbook of Medical Physiology. Pennsylvania: Elsevier Saunders, Philadelphia: USA, 2006.
• Krook A: A balancing act of optimising insulin dose and insulin sensitivity in type 1 diabetes. Journal of Endocrinology 2011, 211(1):1-2.
• American Diabetes Association: Standards of medical care in diabetes-2007. Diabetes Care 2007, 30(suppl 1):S4-S41.
• Barag SH: Insulin therapy for management of type 2 diabetes mellitus: strategies for initiation and long-term patient adherence. The Journal of American Osteopathic Association 2011, 111(7 Suppl 5): S13-19.
• US Department and Health and Human Services: Diabetes., 2015 May 2. Available from: http:// www.niddk.nih.gov/about-niddk/researchareas/diabetes/Pages/diabetes.aspx.
• Diabetes: Differences Between Type 1 and 2 - Topic Overview, 2016 September 1. Available from: http://www.webmd.com/diabetes/tc/diabetes-differences-between-type-1-and-2-topic-overview.
• Type 1 Diabetes vs. Type 2 Diabetes, 2016 September 10. Available from: http://www.diffen.com/ difference/Type_1_Diabetes_vs_Type_2_Diabetes; .
• Fowler MJ: Microvascular and macrovascular complications of diabetes. Clinical Diabetes 2008, 26(2):77-82.
• American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care 2004, 27 (Suppl 1):S5-S10.
• Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH, Hotamisligil GS: Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004, 306(5695):457-461.
• American Diabetes Association: Standards of medical care for patients with diabetes mellitus. Diabetes Care 2013, 26(Suppl 1):S33-S50.
• Karakurt F: Gestasyonel diabetes mellitus tanı ve tedavisi. Yeni Tıp Dergisi 2009, 26 (3):134-138.
• Setji TL, Brown AJ, Feinglos MN: Gestational diabetes mellitus. Clinical Diabetes 2005, 23(1):17-24.
• Buchanan TA, Xiang AH: Gestational diabetes mellitus. Journal of Clinical Investigation 2005, 115(3):485-491.
• Singh SK, Rastogi A: Gestational diabetes mellitus. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 2008, 2(3):227-234.
• American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care 2011, 34 (Suppl 1): S62-69.
• Bastaki W, Mothaffer F, Varro J, Al-Ghanim M, Malak L, Ayyash E, Asfar S: Primary hepatic carcinoid tumor. Medical Principles and Practice 2005, 14(4): 288-291.
• Goldstein D: Diabetes Mellitus: pathophysiology, etiologies, complications, management, and laboratory evaluation. Clinical Chemistry 2003, 49(2):347-347.
• Skyler JS: Diabetes mellitus: pathogenesis and treatment strategies. Journal of Medicinal Chemistry 2004, 47(17):4113-4117.
• Clark CM, Lee DA: Prevention and treatment of the complications of diabetes mellitus. The New England Journal of Medicine 1995, 332(18):1210-1217.
• American Diabetes Association: Complications., 2016 November 15. Available from: http://www. diabetes.org/living-with-diabetes/complications/.
• Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Kirkman MS, Lernmark A, Metzger BE, Nathan DM: Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care 2011, 34(6): e61-99.
• American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care 2007, 30 (Suppl 1):S42-47.
• US Department of Health and Human Services: Diagnosis of Diabetes and Prediabetes, 2015 July 7. Available from: http://diabetes.niddk.nih.gov/dm/pubs/diagnosis/.
• Alkharfy KM: Influence of overt diabetes mellitus on cyclosporine pharmacokinetics in a canine model. Experimental Diabetes Research 2009, 2009:1-6.
• Daily EB, Aquilante CL: Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies. Pharmacogenomics 2009, 10(9):1489-1510.
• Kim KA, Park JY: Inhibitory effect of glyburide on human cytochrome P450 soforms in human liver microsomes. Drug Metabolism and Disposition 2003, 31(9):1090-1092.
• Zhou M, Xia L, Wang J: Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metabolism and Disposition 2007, 35(10):1956-1962.
• Kalliokoski A, Neuvonen M, Neuvonen PJ, Niemi M: The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range. British Journal of Clinical Pharmacology 2008, 66(6): 818-825.
• Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM: Clinical pharmacokinetics of metformin. Clinical Pharmacokinetics 2011, 50(2):81-98.
• Nakamoto T, Oda Y, Imaoka S, Funae Y, Fujimori M: Effect of phenobarbital on the pharmacokinetics of lidocaine, monoethylglycinexylidide and 3-hydroxylidocaine in the rat: correlation with P450 isoform levels. Drug Metabolism and Disposition 1997, 25(3):296-300.
• Yang KH, Choi YH, Lee U, Lee JH, Lee MG: Effects of cytochrome P450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats: involvement of CYP2C11, 2E1, 3A1 and 3A2 in furosemide metabolism. Journal of Pharmacy and Pharmacology 2009, 61(1):47-54.
• Lee JH, Lee MG: Telithromycin pharmacokinetics in rat model of diabetes mellitus induced by alloxan or streptozotocin. Pharmaceutical Research 2008, 25(8):1915-1924.
• Cheng Q, Aleksunes LM, Manautou JE, Cherrington NJ, Scheffer GL, Yamasaki H, Slitt AL: Drug-metabolizing enzyme and transporter expression in a mouse model of diabetes and obesity. Molecular Pharmaceutics 2008, 5(1):77-91.
• Gangopadhyay KK, Ryder RE: Nontraumatic rhabdomyolysis: an unusual complication of diabetic hyperosmolar nonketotic (HONK) state. Journal of the Royal Society of Medicine 2006, 99(4):200.
• Varughese GI, Scarpello JHB: Non-traumatic rhabdomyolysis: the emerging role of CYP 3A4 in diabetes mellitus. Journal of the Royal Society of Medicine 2006, 99(8): 385-386.
• Horton F, Wright J, Smith L, Hinton PJ, Robertson MD: Increased intestinal permeability to oral chromium (51 Cr) -EDTA in human Type 2 diabetes. Diabetic Medicine 2014, 31(5):559-563.
• Garcia-Lafuente A, Antolin M, Guarner F, Crespo E, Malagelada J: Modulation of colonic barrier function by the composition of the commensal flora in the rat. Gut 2001, 48(4):503-507.
• Cani PD, Osto M, Geurts L, Everard A: Involvement of gut microbiota in the development of low- grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 2012, 3(4):279-288.
• Gulsun T: İlaçların Absorpsiyonu ve Permeabilitesi Üzerine Diyabetin Etkisinin İncelenmesi. Hacettepe University, PhD. Thesis (Supervisor: Sahin S. 2016).
• Zhu L: Gastric mucosal blood flow and blood viscosity in patients with diabetes. Zhonghua Yi Xue Za Zhi 1993, 73(8): 476-8, 511.
• Vidon N, Chaussade S, Noel M, Franchisseur C, Huchet B, Bernier JJ: Metformin in the digestive tract. Diabetes Research and Clinical Practice 1988, 4(3):223-229.
• Jones KL, Russo A, Stevens JE, Wishart JM, Berry MK, Horowitz M: Predictors of delayed gastric emptying in diabetes. Diabetes Care 2001, 24(7):1264-1269.
• Rafsanjani FN, Adeli S, Ardakani ZV, Ardakani JV, Ardakani JV, Ghotbi P: Effects of diabetes mellitus on gastric motility in rats. Pakistan Journal of Physiology 2009, 5(1):20-24.
• Della-Coletta A, Eller M: The bioavailability of tolazamide in diabetic patients and healthy subjects. Pharmacological Research 1988, 5:174.
• Adithan C, Danda D, Shashindran CH, Bapna JS, Swaminathan RP, Chandrasekar S: Differential effect of type I and type II diabetes mellitus on antipyrine elimination. Methods Finding in Experimental Clinical Pharmacology 1989, 11(12):755-758.
• O'Connell ME, Awni WM, Goodman M, Cass O, Melikian AP, Wright GJ, Matzke GR: Bioavailability and disposition of metoclopramide after single- and multiple-dose administration in diabetic patients with gastroparesis. Journal of Clinical Pharmacology 1987, 27(8):610-614.
• Lerner PI, Weinstein L: Abnormalities of absorption of benzylpenicillin G and sulfoxazole in patients with diabetes mellitus. The American Journal of the Medical Sciences 1964, 248:37-51.
• Yee GC, Evans WE: Reappraisal of guidelines for pharmacokinetic monitoring of aminoglycosides. Pharmacotherapy 1981, 1(1):55-75.
• Havas S, Donner T: Tight control of type 1 diabetes: recommendations for patients. American Family Physician 2006, 74(6): 971-978.
• Chakrabarti R, Rajagopalan R: Diabetes and insulin resistance associated disorders: Disease and the therapy. Current Sciences 2002, 83(12):1533-1538.
• Krentz AJ, Ferner RE, Bailey CJ: Comparative tolerability profiles of oral antidiabetic agents. Drug Safety 1994, 11(4):223-241.
• Çorakçı A: Tip II Diabetes Mellitus’da İlaç Seçimi., 2011 June 15. Available from: http://www. gata.edu.tr/dahilibilimler/ichastaliklari/files/kitaplar/130.pdf.
• Eray E: Tip 2 Diyabet Tedavisi., 2015 April 21. Available from: http://ichastaliklaridergisi.org/ managete/fu_folder/2005-02/html/2005-12-2-066-071.htm.
• Hazman Ö: Sitagliptin: Tip 2 Diyabet Tedavisi için Yeni Oral Antidiyabetik Ajan. Aku Journal of Science 2011, 11(2011):1-13.
• Joel Z, Per-Henrik G: Strategies for Diabetes Management: Using Newer Oral Combination Therapies Early in the Disease. Diabetes Therapy 2016, 7: 621-639.
• Islam MS, Loots du T: Experimental rodent models of type 2 diabetes: a review. Methods and Findings in Experimental and Clinical Pharmacology 2009, 31(4):249-261.
• İrer SV, Alper G: Deneysel diyabet modelleri. Türk Klinik Biyokimya Dergisi 2004, 2(3):127- 136.
• Nagafuchi S, Toniolo A: Viral diabetes: Virus diabetogenicity and host susceptibility. Immunoendocrinology 2015, 2:1-13.
• Szkudelski T: The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research 2001, 50(6):537-546.
• Bolzan AD, Bianchi MS: Genotoxicity of streptozotocin. Mutation Research 2002, 512(2-3):121-134.
• Srinivasan K, Ramarao P: Animal models in type 2 diabetes research: an overview. Indian Journal of Medical Research 2007, 125(3):451-472.
• Abeeleh MA, Ismail ZB, Alzaben KR, Abu-Halaweh SA, Al-Essa MK, Abuabeeleh J, Alsmady MM: Induction of diabetes mellitus in rats using intraperitoneal streptozotocin: a comparison between 2 strains of rats. European Journal of Scientific Research 2009, 32(3):398.
• Sokeng S, Rokeya B, Mostafa M, Nahar N, Mosihuzzaman M, Ali L, Kamtchouing P: Antihyperglycemic effect of bridelia ndellensis ethanol extract and fractions in streptozotocin induced diabetic rats. African Journal of Traditional Complementary and Alternative Medicines 2005, 2(2):94-102.
• Degirmenci I, Kalender S, Ustuner MC, Basaran A: The effects of acarbose and Rumex patientia on liver ultrastructure in streptozotocin-induced diabetic (type II) rats. Drugs under Experimental and Clinical Research 2002, 28(6):229-234.
• Shirwaikar A, Rajendran K, Dinesh Kumar C, Bodla R: Antidiabetic activity of aqueous leaf extract of Annona squamosa in streptozotocin-nicotinamide type 2 diabetic rats. Journal of Ethnopharmacology, 2004, 91(1):171-175.
• Tahara A, Matsuyama-Yokono A, Nakano R, Someya Y, Shibasaki M: Effects of antidiabetic drugs on glucose tolerance in streptozotocin-nicotinamide-induced mildly diabetic and streptozotocin- induced severely diabetic mice. Hormone and Metabolic Research 2008, 40(12):880-886.
• Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, Novelli M, Ribes G: Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998, 47(2):224-229.