Hemoglobinopati, Asetil Salisilik Asit Kullanimi Ve Üreminin İmmünoturbidimetrik Ve HPLC Hemoglobin A1c Ölçümleri Üzerine Etkileri

Yıl 2019, Cilt: 6 Sayı: 3, 142 - 147, 30.09.2019

Gülçin Şahingöz Erdal Murat Koşer Pınar Kasapoğlu Nilgün Işıksaçan

https://doi.org/10.34087/cbusbed.558634

Öz

Amaç: Tip II Diabetes
Mellitus (T2DM) en sık endokrin hastalıktır. Yüksek glikolize hemoglobin
(HbA1c) düzeylerinin kardiyovasküler hastalıklarda (KVH) risk faktörü olduğu ve
KVH'ların da diyabetik hastalarda ölüm ve sakatlığa neden olduğu bilinmektedir.
HbA1c düzeylerinin doğru ölçülmesi, hastaların tanı ve tedavi süreçlerinin
değerlendirilmesinde son derece önemli rol oynamaktadır.

 

Ülkemizde başta talasemi minör olmak üzere hemoglobin varyantları
yaygın olarak görülmektedir. Diyabetin kardiyovasküler etkileri nedeniyle de
asetilsalisilikasit (ASA) sıklıkla diyabetik hastalar tarafından
kullanılmaktadır. Diyabetik nefropati ise son dönemde hemodiyaliz gerektiren
böbrek yetmezliğine ve üremiye neden olmaktadır. Bu çalışmada
immünoturbidimetri ve yüksek performanslı sıvı kromatografi (HPLC)
yöntemlerinin 3 hasta grubunda HbA1c düzeylerini ölçmek üzere karşılaştırılması
amaçlanmıştır.

 

Gereç-Yöntem: Bu çalışmaya her biri 20
hastadan oluşan üç grup dahil edilmiştir. Bu çalışmaya 20’şer kişilik 3 hasta
grubu dahil edilmiştir. İlk grup hemoglobin elektroforezi kullanılarak
“hemoglobinopati” tanısı alan hastalardan, ikinci grup en az 6 aydır günde 100
mg veya üzerinde ASA alan hastalardan ve üçüncü grup  kronik hemodiyalize giren hastalardan
oluşmaktadır. Hastalardan alınan EDTA içeren tüplere toplanan venöz kan
örnekleri,  Premier Hb 9210 (Trinity
Biotech –USA) ve Cobas c501 (Roche –Almanya) cihazları kullanılarak analiz
edilmiştir.

 

Sonuç: Her 3 grupta immünoturbidimetri ile
HPLC yöntemi karşılaştırıldığında grupların içinde HbA1c düzeyleri arasında
anlamlı bir istatistiksel fark bulunamamıştır (p=0,462, p=0,065 p=0,062).

 

Tartışma: İmmünoturbidimetri ve HPLC,
HbA1c ölçümlerinde yaygın olarak kullanılan yöntemlerdendir.  İmmünoturbidimetrik yöntemin HbA1c
ölçümlerinde HPLC yöntemi ile arasında güçlü bir korelasyon olduğu
gösterilmiştir. HbA1c analizini etkileyebilecek 
hastalıklar ve ilaçlar göz önünde bulundurulmalıdır.

 

Anahtar Kelimeler

HbA1c, HPLC, immünoturbidimetri, hemoglobinopati, üremi

Kaynakça

• 1-American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S13-S27. doi: 10.2337/dc18-S002. Review. PubMed PMID: 29222373.
• 2-Gray SP, Jandeleit-Dahm K. The pathobiology of diabetic vascular complications--cardiovascular and kidney disease. J Mol Med (Berl). 2014 May;92(5):441-52. doi: 10.1007/s00109-014-1146-1. Epub 2014 Apr 1. Review. PubMed PMID: 24687627.
• 3- Cleland SJ. Cardiovascular risk in double diabetes mellitus--when two worlds collide. Nat Rev Endocrinol. 2012 Apr 10;8(8):476-85. doi: 10.1038/nrendo.2012.47. Review. PubMed PMID: 22488644.
• 4- Zhang PY. Cardiovascular disease in diabetes. Eur Rev Med Pharmacol Sci. 2014;18(15):2205-14. PubMed PMID: 25070828.
• 5- Aneja A, Tang WH, Bansilal S, Garcia MJ, Farkouh ME. Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med. 2008 Sep;121(9):748-57. doi: 10.1016/j.amjmed.2008.03.046. Review. PubMed PMID: 18724960.
• 6- Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N. Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med. 2004 Sep 21;141(6):413-20. PubMed PMID: 15381514.
• 7- Krishnamurti U, Steffes MW. Glycohemoglobin: a primary predictor of the development or reversal of complications of diabetes mellitus. Clin Chem. 2001;47(7):1157-65. Review. PubMed PMID: 11427445.
• 8- Miedema K. Towards worldwide standardisation of HbA1c determination. Diabetologia. 2004 Jul;47(7):1143-1148. doi: 10.1007/s00125-004-1453-0. Epub 2004 Jul 13. PubMed PMID: 15249996.
• 9- Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I et al. IFCC Working Group on HbA1c Standardization. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004 Jan;50(1):166-74. PubMed PMID: 14709644.
• 10-Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. N Engl J Med. 1971 Feb 18;284(7):353-7. PubMed PMID: 5539916.
• 11- Ma RC, Chan JC. Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States. Ann N Y Acad Sci. 2013 Apr;1281:64-91. doi: 10.1111/nyas.12098. Review. PubMed PMID: 23551121; PubMed Central PMCID: PMC3708105.
• 12- Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. Geneva: World Health Organization; 2011. PubMed PMID: 26158184.
• 13- Canatan D. Thalassemias and hemoglobinopathies in Turkey. Hemoglobin. 2014;38(5):305-7. doi: 10.3109/03630269.2014.938163. Epub 2014 Jul 17. Review. PubMed PMID: 25030194.
• 14- Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med. 2005 Mar 17;352(11):1138-45. PubMed PMID: 15784668.
• 15-Satman İ. TURDEP-II Çalışması ilk sonuçlar, 32.TEMH Kongresi, 13¬17 Ekim 2010, Antalya.kongre Kitabı, 2010:12.
• 16- Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EA et al. American Diabetes Association; American College of Cardiology Foundation; American Heart Association. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J Am Coll Cardiol. 2009 Jan 20;53(3):298-304. doi: 10.1016/j.jacc.2008.10.008. Review. PubMed PMID: 19147051.
• 17- Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103–17.
• 18- The UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1993; 352:854–65.
• 19- The UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–53.
• 20- Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, et al. Meta-Analysis: Glycosylated Hemoglobin and Cardiovascular Disease in Diabetes Mellitus. Ann Intern Med. 2004;141:421–431. doi: 10.7326/0003-4819-141-6-200409210-00007
• 21- Stettler C, Allemann S, Jüni P, Cull CA, Holman RR, Egger M et al. Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials. Am Heart J 2006;152:27–38.
• 22-American Diabetes Association. Standards of medical care in diabetes— 2010. Diabetes Care 2010;33(Suppl 1):S11– 61.
• 23- Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem. 2001 Feb;47(2):153-63. Review. Erratum in: Clin Chem 2001 Jun;47(6):1141. PubMed PMID: 11159762.
• 24- Sofronescu AG, Williams LM, Andrews DM, Zhu Y. Unexpected hemoglobin A1c results. Clin Chem. 2011 Feb;57(2):153-6. doi: 10.1373/clinchem.2010.155804. PubMed PMID: 21278358.
• 25- McDonald MJ, Shapiro R, Bleichman M, Solway J, Bunn HF. Glycosylated minor components of human adult hemoglobin. Purification, identification, and partial structural analysis. J Biol Chem. 1978 Apr 10;253(7):2327-32. PubMed PMID: 632272.
• 26- Mallia AK, Hermanson GJ, Krohn RI, Fujimoto EK, Smith PK (1981) Preparation and use of a boronic acid affinity support for separation and quantitation of glycosylated haemoglobin. Anal Lett 14:649–661.
• 27- Miedema K. Towards worldwide standardisation of HbA1c determination. Diabetologia. 2004 Jul;47(7):1143-1148. doi: 10.1007/s00125-004-1453-0. Epub 2004 Jul 13. PubMed PMID: 15249996.
• 28- Anonymous. International Hemoglobin Information Center variant list. Hemoglobin 1994;18:77–183.
• 29- Frank EL, Moulton L, Little RR, Wiedmeyer HM, Rohlfing C, Roberts WL. Effects of hemoglobin C and S traits on seven glycohemoglobin methods. Clin Chem 2000;46:864–7.
• 30-Schnedl WJ, Trinker M, Lipp RW. HbA1c determinations in patients with hemoglobinopathies. Diabetes Care 1999;22:368–9.
• 31- Reid H, Famodu AA, Photiades DP, Osamo ON. Glycosylated haemoglobin HbA1c and HbS1c in non-diabetic Nigerians. Trop Geogr Med 1992;44:131–4.
• 32- Sacks DB. Hemoglobin variants and hemoglobin A1c analysis: problem solved. Clin Chem 2003;49:1245–1247.
• 33-Chen D, Crimmins DL, Hsu FF, Lindberg FP, Scott MG. Hemoglobin Raleigh as the cause of a falsely increased hemoglobin A1c in an automated ion-exchange HPLC method. Clin Chem 1998;44: 1296–301.
• 34-Schnedl WJ, Reisinger EC, Pieberm TR, Lipp RW, Schreiber F, Hompeier P et al. Hemoglobin Sherwood Forest detected by high performance liquid chromatography for hemoglobin A1c. Hematopathology 1995;104:444–6. 18.
• 35- Genc S, Omer B, Aycan-Ustyol E, Ince N, Bal F, Gurdol F. Evaluation of turbidimetric inhibition immunoassay (TINIA) and HPLC methods for glycated haemoglobin determination. J Clin Lab Anal. 2012 Nov;26(6):481-5. doi: 10.1002/jcla.21550. PubMed PMID: 23143632.
• 36- Roberts WL, McCraw M, Cook CB. Effects of sickle cell trait and hemoglobin C on determinations of HbA1c by an immunoassay method. Diabetes Care 1998;21:983–6.
• 37-Chachou A, Randoux C, Millart H, Chanard J, Gillery P. Influence of in vivo haemoglobin carbamylation on HbA1c measurements by various methods. Clin Chem Lab Med 2000;38:321–326.
• 38- Miedema K. Electrospray mass spectroscopy for measurement of glycohemoglobin. Clin Chem 1997;43:705–7.
• 39- Weykamp CW, Penders TJ, Siebelder CW, Muskiet FA, van der Slik W. Interference of carbamylated and acetylated hemoglobins in assays of glycohemoglobin by HPLC, electrophoresis, affinity chromatography, and enzyme immunoassay. Clin Chem 1993;39: 138–42.
• 40- Halwachs-Baumann G, Katzensteiner S, Schnedl W, Pürstner P, Pieber T, Wilders-Truschnig M. Comparative evaluation of three assay systems for automated determination of hemoglobin A1c. Clin Chem. 1997 Mar;43(3):511-7. PubMed PMID: 9068596.