Hemoglobina glicada (HbAa1c). Utilidad y limitaciones en pacientes con enfermedad renal crónica

Guillermo De'Marziani, Alicia Ester Elbert

Resumen


La diabetes tipo 2 (DM2) es uno de los grandes problemas de salud pública a nivel mundial y uno de los mayores desafíos del siglo XXI. La glucemia es un parámetro de laboratorio fácil de evaluar y ocupa un rol fundamental tanto en el diagnóstico como en el seguimiento de la DM. La determinación de proteínas glicadas, en especial la hemoglobina (HbA1c) y las proteínas séricas (fructosamina) permiten cuantificar el promedio de la misma a lo largo de semanas o meses, complementando el monitoreo glucémico. Los métodos que se implementan para lograr el control glucémico en la enfermedad renal crónica (ERC) se extrapolan de estudios con DM sin ERC, debido a la falta de evidencia de estudios randomizados de alta calidad en esta población. Se debe considerar que en ERC existen cambios metabólicos que determinan que la hemoglobina (Hb) presente comportamientos variables, motivo por el que surge la discusión de si la HbA1c constituye un marcador confiable para definir control glucémico o de utilidad en la predicción del desarrollo de complicaciones en esta subpoblación. Se presenta una revisión acerca del rol de la HbA1c en el paciente con DM sin ERC para luego mostrar las dificultades que se presentan en la subpoblación con ERC, centrándose especialmente en los pacientes en tratamiento de hemodiálisis y diálisis peritoneal.

Palabras clave


hemoglobina glicada; HbA1c; enfermedad renal crónica; diabetes; control glucémico; diálisis renal

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Referencias


Zimmet PZ, Magliano DJ, Herman WH, Shaw JE. Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol. 2014;2(1):56-64.

Zimmet PZ, Alberti KG. Epidemiology of Diabetes-Status of a Pandemic and Issues Around Metabolic Surgery. Diabetes Care. 2016;39(6):878-83.

IDF diabetes atlas. 7th ed. Brussels: International Diabetes Federation, 2015.

Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus, present and future perspectives. Nat Rev Endocrinol. 2011;8(4):228-36.

Zhang P, Zhang X, Brown J, Vistisen D, Sicree R, Shaw J, el al. Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(3):293-301.

Davidson MB. Diabetes research and diabetes care. Where do we stand? Diabetes Care. 1998;21(12):2152-60.

Sacks DB. A1C versus glucose testing: a comparison. Diabetes Care. 2011;34(2):518-23.

Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-86.

Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643-53.

Ward BW, Schiller JS, Goodman RA. Multiple chronic conditions among US adults: a 2012 update. Prev Chronic Dis. 2014;11:E62.

Alwan A, Maclean DR, Riley LM, d'Espaignet ET, Mathers CD, Stevens GA, et al. Monitoring and surveillance of chronic non-communicable diseases: progress and capacity in high-burden countries. Lancet. 2010;376(9755):1861-8.

Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Ishani A, et al. US Renal Data System 2013 Annual Data Report. Am J Kidney Dis. 2014;63(1 Suppl):A7.

National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012;60(5):850-86.

Shima K, Chujo K, Yamada M, Komatsu M, Noma Y, Mizuguchi T. Lower value of glycated haemoglobin relative to glycaemic control in diabetic patients with end-stage renal disease not on haemodialysis. Ann Clin Biochem. 2012;49(Pt 1):68-74.

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(9131):837-53.

American Diabetes Association. Glycemic Targets: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S55-S64.

Thom CS, Dickson CF, Gell DA, Weiss MJ. Hemoglobin variants: biochemical properties and clinical correlates. Cold Spring Harb Perspect Med. 2013;3(3):a011858.

Rahbar S. An abnormal hemoglobin in red cells of diabetics. Clin Chim Acta. 1968;22(2):296-8.

Dalziel M, Crispin M, Scanlan CN, Zitzmann N, Dwek RA. Emerging principles for the therapeutic exploitation of glycosylation. Science. 2014;343(6166):1235681.

Welsh KJ, Kirkman MS, Sacks DB. Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions. Diabetes Care. 2016;39(8):1299-306.

Bookchin RM, Gallop PM. Structure of hemoglobin AIc: nature of the N-terminal beta chain blocking group. Biochem Biophys Res Commun. 1968;32(1):86-93.

Shapiro R, McManus MJ, Zalut C, Bunn HF. Sites of nonenzymatic glycosylation of human hemoglobin A. J Biol Chem. 1980;255(7):3120-7.

Jeffcoate SL. Diabetes control and complications: the role of glycated haemoglobin, 25 years on. Diabet Med. 2004;21(7):657-65.

Diabetes mellitus. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1985;727:1-113.

Little RR, Wiedmeyer HM, England JD, Wilke AL, Rohlfing CL, Wians FH Jr, et al. Interlaboratory standardization of measurements of glycohemoglobins. Clin Chem. 1992;38(12):2472-8.

Goodall I. HbA1c standardisation destination, global IFCC Standardisation. How, why, where and when: a tortuous pathway from kit manufacturers, via inter-laboratory lyophilized and whole blood comparisons to designated national comparison schemes. Clin Biochem Rev. 2005;26(1):5-19.

Tominaga M, Makino H, Yoshino G, Kuwa K, Takei I, Aono Y, et al. Japanese standard reference material for JDS Lot 2 haemoglobin A1c. I: Comparison of Japan Diabetes Society-assigned values to those obtained by the Japanese and USA domestic standardization programmes and by the International Federation of Clinical Chemistry reference laboratories. Ann Clin Biochem. 2005;42(Pt 1):41-6.

Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, et al. Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med. 2002;40(1):78-89.

Weykamp C, John WG, Mosca A, Hoshino T, Little R, Jeppsson JO, et al. The IFCC Reference Measurement System for HbA1c: a 6-year progress report. Clin Chem. 2008;54(2):240-8.

Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, et al. 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;50(1):166-74.

Sacks DB; ADA/EASD/IDF Working Group of the HbA1c Assay. Global harmonization of hemoglobin A1c. Clin Chem. 2005;51(4):681-3.

Consensus Committee. Consensus statement on the worldwide standardization of the hemoglobin A1C measurement: the American Diabetes Association, European Association for the Study of Diabetes, International Federation of Clinical Chemistry and Laboratory Medicine, and the International Diabetes Federation. Diabetes Care. 2007;30(9):2399-400.

Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ, et al. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008;31(8):1473-8.

Bloomgarden ZT, Inzucchi SE, Karnieli E, Le Roith D. The proposed terminology 'A(1c)-derived average glucose' is inherently imprecise and should not be adopted. Diabetologia. 2008;51(7):1111-4.

Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-12.

Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-89.

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(2):103-17.

Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-59.

Patel A; ADVANCE Collaborative Group, MacMahon S, Chalmers J, Neal B, Woodward M, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829-40.

Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-39.

Inzucchi S, Majumdar S. Glycemic targets: what is the evidence? Med Clin North Am. 2015;99(1):47-67.

Cavalot F, Pagliarino A, Valle M, Di Martino L, Bonomo K, Massucco P, et al. Postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga Diabetes Study. Diabetes Care. 2011;34(10):2237-43.

DECODE Study Group, European Diabetes Epidemiology Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? Diabetes Care. 2003;26(3):688-96.

Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H, et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia. 1996;39(12):1577-83.

Woerle HJ, Neumann C, Zschau S, Tenner S, Irsigler A, Schirra J, et al. Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes Importance of postprandial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract. 2007;77(2):280-5.

Monnier L, Colette C, Dunseath GJ, Owens DR. The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes. Diabetes Care. 2007;30(2):263-9.

Esposito K, Giugliano D, Nappo F, Marfella R; Campanian Postprandial Hyperglycemia Study Group. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation. 2004;110(2):214-9.

Raz I, Wilson PW, Strojek K, Kowalska I, Bozikov V, Gitt AK, et al. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care. 2009;32(3):381-6.

Wei N, Zheng H, Nathan DM. Empirically establishing blood glucose targets to achieve HbA1c goals. Diabetes Care. 2014;37(4):1048-51.

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Imran SA, Rabasa-Lhoret R, Ross S. Targets for glycemic control. Can J Diabetes. 2013;37 Suppl 1:S31-4.

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-9.

Ismail-Beigi F, Moghissi E, Tiktin M, Hirsch IB, Inzucchi SE, Genuth S. Individualizing glycemic targets in type 2 diabetes mellitus: implications of recent clinical trials. Ann Intern Med. 2011;154(8):554-9.

Rohlfing C, Wiedmeyer HM, Little R, Grotz VL, Tennill A, England J, et al. Biological variation of glycohemoglobin. Clin Chem. 2002;48(7):1116-8.

Hempe JM, Gomez R, McCarter RJ Jr, Chalew SA. High and low hemoglobin glycation phenotypes in type 1 diabetes: a challenge for interpretation of glycemic control. J Diabetes Complications. 2002;16(5):313-20.

Szwergold BS, Howell SK, Beisswenger PJ. Transglycation, a potential new mechanism for deglycation of Schiff's bases. Ann N Y Acad Sci. 2005;1043:845-64.

Wisdom K, Fryzek JP, Havstad SL, Anderson RM, Dreiling MC, Tilley BC. Comparison of laboratory test frequency and test results between African-Americans and Caucasians with diabetes: opportunity for improvement. Findings from a large urban health maintenance organization. Diabetes Care. 1997;20(6):971-7.

Davidson MB, Schriger DL. Effect of age and race/ethnicity on HbA1c levels in people without known diabetes mellitus: implications for the diagnosis of diabetes. Diabetes Res Clin Pract. 2010;87(3):415-21.

Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, Coresh J, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010;362(9):800-11.

Gallagher EJ, Le Roith D, Bloomgarden Z. Review of hemoglobin A(1c) in the management of diabetes. J Diabetes. 2009;1(1):9-17.

Cohen RM, Franco RS, Khera PK, Smith EP, Lindsell CJ, Ciraolo PJ, et al. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood. 2008;112(10):4284-91.

El-Agouza I, Abu Shahla A, Sirdah M. The effect of iron deficiency anaemia on the levels of haemoglobin subtypes: possible consequences for clinical diagnosis. Clin Lab Haematol. 2002;24(5):285-9.

Ng JM, Jennings PE, Laboi P, Jayagopal V. Erythropoetin treatment significantly alters measured glycated haemoglobin (HbA1c). Diabet Med. 2008;25(2):239-40.

Karsegard J, Wicky J, Mensi N, Caulfield A, Philippe J. Spurious glycohemoglobin values associated with hydroxyurea treatment. Diabetes Care. 1997;20(7):1211-2.

Davie SJ, Gould BJ, Yudkin JS. Effect of vitamin C on glycosylation of proteins. Diabetes. 1992;41(2):167-73.

Camargo JL, Stifft J, Gross JL. The effect of aspirin and vitamins C and E on HbA1c assays. Clin Chim Acta. 2006;372(1-2):206-9.

Stevens VJ, Fantl WJ, Newman CB, Sims RV, Cerami A, Peterson CM. Acetaldehyde adducts with hemoglobin. J Clin Invest. 1981;67(2):361-9.

Garrib A, Griffiths W, Eldridge P, Hatton R, Worsley A, Crook M. Artifactually low glycated haemoglobin in a patient with severe hypertriglyceridaemia. J Clin Pathol. 2003;56(5):394-5.

Chapter 1: Definition and classification of CKD. Kidney Int Suppl (2011). 2013;3(1):19-62.

Pan Y, Jiang S, Qiu D, Shi J, Zhou M, An Y, et al. Comparing the GFR estimation equations using both creatinine and cystatin c to predict the long-term renal outcome in type 2 diabetic nephropathy patients. J Diabetes Complications. 2016;30(8):1478-87.

Bakris GL, Molitch M. Microalbuminuria as a risk predictor in diabetes: the continuing saga. Diabetes Care. 2014;37(3):867-75.

Hovind P, Tarnow L, Rossing K, Rossing P, Eising S, Larsen N, et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care. 2003;26(4):1258-64.

Thomas MC, Weekes AJ, Broadley OJ, Cooper ME, Mathew TH. The burden of chronic kidney disease in Australian patients with type 2 diabetes (the NEFRON study). Med J Aust. 2006;185(3):140-4.

Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Ishani A, et al. US Renal Data System 2013 Annual Data Report. Incidence, Prevalence, Patient Characteristics, & Treatment Modalities. Am J Kidney Dis. 2014;63(1 Suppl):e215-28.

Möllsten A, Svensson M, Waernbaum I, Berhan Y, Schön S, Nyström L, et al. Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. Diabetes. 2010;59(7):1803-8.

Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Ishani A, et al. US Renal Data System 2013 Annual Data Report. Costs of CKD. Am J Kidney Dis. 2014;63(1 Suppl):e107-18.

Nichols GA, Vupputuri S, Lau H. Medical care costs associated with progression of diabetic nephropathy. Diabetes Care. 2011;34(11):2374-8.

Williams ME, Garg R. Glycemic management in ESRD and earlier stages of CKD. Am J Kidney Dis. 2014;63(2 Suppl 2):S22-38.

Kovesdy CP, Sharma K, Kalantar-Zadeh K. Glycemic control in diabetic CKD patients: where do we stand? Am J Kidney Dis. 2008;52(4):766-77.

Mak RH. Impact of end-stage renal disease and dialysis on glycemic control. Semin Dial. 2000;13(1):4-8.

Mak RH. Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients. Kidney Int. 1992;41(4):1049-54.

Brown JN, Kemp DW, Brice KR. Class effect of erythropoietin therapy on hemoglobin A(1c) in a patient with diabetes mellitus and chronic kidney disease not undergoing hemodialysis. Pharmacotherapy. 2009;29(4):468-72.

McClellan W, Aronoff SL, Bolton WK, Hood S, Lorber DL, Tang KL, et al. The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin. 2004;20(9):1501-10.

Hsu CY, McCulloch CE, Curhan GC. Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the Third National Health and Nutrition Examination Survey. J Am Soc Nephrol. 2002;13(2):504-10.

Bosman DR, Winkler AS, Marsden JT, Macdougall IC, Watkins PJ. Anemia with erythropoietin deficiency occurs early in diabetic nephropathy. Diabetes Care. 2001;24(3):495-9.

Grossman C, Dovrish Z, Koren-Morag N, Bornstein G, Leibowitz A. Diabetes mellitus with normal renal function is associated with anaemia. Diabetes Metab Res Rev. 2014;30(4):291-6.

National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012;60(5):850-86.

Joy MS, Cefalu WT, Hogan SL, Nachman PH. Long-term glycemic control measurements in diabetic patients receiving hemodialysis. Am J Kidney Dis. 2002;39(2):297-307.

Menon V, Greene T, Pereira AA, Wang X, Beck GJ, Kusek JW, et al. Glycosylated hemoglobin and mortality in patients with nondiabetic chronic kidney disease. J Am Soc Nephrol. 2005;16(11):3411-7.

Williams ME, Lacson E Jr, Teng M, Ofsthun N, Lazarus JM. Hemodialyzed type I and type II diabetic patients in the US: Characteristics, glycemic control, and survival. Kidney Int. 2006;70(8):1503-9.

Kalantar-Zadeh K, Kopple JD, Regidor DL, Jing J, Shinaberger CS, Aronovitz J, et al. A1C and survival in maintenance hemodialysis patients. Diabetes Care. 2007;30(5):1049-55.

Williams ME, Lacson E Jr, Wang W, Lazarus JM, Hakim R. Glycemic control and extended hemodialysis survival in patients with diabetes mellitus: comparative results of traditional and time-dependent Cox model analyses. Clin J Am Soc Nephrol. 2010;5(9):1595-601.

Hoshino J, Larkina M, Karaboyas A, Bieber BA, Ubara Y, Takaichi K, et al. Unique hemoglobin A1c level distribution and its relationship with mortality in diabetic hemodialysis patients. Kidney Int. 2017;92(2):497-503.

Ramirez SP, McCullough KP, Thumma JR, Nelson RG, Morgenstern H, Gillespie BW, et al. Hemoglobin A(1c) levels and mortality in the diabetic hemodialysis population: findings from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Diabetes Care. 2012;35(12):2527-32.

Ricks J, Molnar MZ, Kovesdy CP, Shah A, Nissenson AR, Williams M, et al. Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study. Diabetes. 2012;61(3):708-15.

Beck RW, Connor CG, Mullen DM, Wesley DM, Bergenstal RM. The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading. Diabetes Care. 2017;40(8):994-9.


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