1002 Tabelle 4 <strong>HbA1c</strong>-Bestimmung: relevante Fragen zur Methodik. Überlegungen sind jedoch spekulativer Natur [125]. Nichtsdestotrotz ist <strong>das</strong> <strong>HbA1c</strong> in Einzelfällen nicht aussagekräftig, <strong>das</strong> heisst, es korreliert schlecht mit den tatsächlich vorhandenen Blutglukosewerten. In solchen Fällen empfehlen wir zusätzlich die Bestimmung von Fruktosamin. Fruktosaminbestimmung Das Fruktosamin ist eine Sammelbezeichnung für glykierte unspezifische Serumproteine, hauptsächlich glykiertes Albumin, welches eine Halbwertszeit von 14 bis 20 Tagen hat. Der Vorgang der Glykierung geschieht analog zum Prozess bei der <strong>HbA1c</strong>-Entstehung. Die Fruktosaminbestimmung ist als Routinelabormethode verfügbar, im Gegensatz zur spezifischen Bestimmung von glykiertem Albumin [1<strong>26</strong>]. Der Fruktosaminwert korreliert mit der mittleren Blutglukosekonzentration der vorangegangenen 2 Wochen und eignet sich deshalb zur «kurzfristigen» Beurteilung der Stoffwechsellage, beispielweise im Rahmen einer Schwangerschaft [127]. Der Normalbereich der kalorimetrischen Bestimmung mit Nitrotetrazoliumblau wird mit
Literatur Schweiz Med Wochenschr <strong>2000</strong>;130: Nr <strong>26</strong> Fortbildung 1 Holmquist WR, Schroeder WA. A new N-terminal blocking group involving a Schiff base in hemoglobin A1c. Biochemistry 1966;5:2489–2503. 2 Bookchin RM, Gallop PM. Structure of hemoglobin A1c: nature of the N-terminal beta chain blocking group. Biochem Biophys Res Commun 1968;32:86–93. 3 Huisman THJ, Dozy AM. Studies on the heterogeneity of hemoglobin. V. Binding of hemoglobin with oxidized glutathione. J Lab Clin Med 1962;60:302–19. 4 Rahbar S, Blumenfeld O, Ranney HM. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun 1969;36:838–43. 5 Trivelli LA, Ranney HM, Lai H-T. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971;248:353–7. 6 Bunn HF, Haney DN, Kamin S, Gabbay KH, Gallop PM. The biosynthesis of human hemoglobin A1c. J Clin Invest 1976;57:1652–9. 7 Koenig RJ, Peterson CM, Kilo C, Cerami A, Williamson JR. Hemoglobin A1c as an indicator of the degree of glucose intolerance in diabetes. Diabetes 1976;25:230–2. 8 Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A. Correlation of glucose regulation and hemoglobin A1c in diabetes mellitus. N Engl J Med 1976; 295:417–20. 9 Gabbay KH, Hasty K, Breslow JL, Ellison RC, Bunn HF, Gallop PM. Glycosylated hemoglobins and long-term blood glucose control in diabetes mellitus. J Clin Endocrinol Metab 1977;44:859–64. 10 Svendsen PA, Lauritzen T, Søegaard U, Nerup J. Glycosylated haemoglobin and steady-state mean blood glucose concentration in Type 1 (insulin-dependent) diabetes. Diabetologia 1982;23:403–5. 11 Jovanovic L, Peterson CM. The clinical utility of glycosylated hemoglobin. Am J Med 1981;70:331–8. 12 Goldstein DE, Little RR, Wiedmeyer HM, England JD, McKenzie EM. Glycated hemoglobin: methodologies and clinical applications. Clin Chem 1986;32(Suppl 10):B64–B70. 13 Weykamp CW, Miedema K, de Haan T, Doelman CJ. Carbamylated hemoglobin interference in glycohemoglobin assays. Clin Chem 1999;45:438–40. 14 Gonen B, Rubenstein A, Rochman H, Tanega SP, Horwitz DL. Haemoglobin A1: an indicator of the metabolic control of diabetic patients. Lancet 1977;2:734–7. 15 Kaplan LA, Cline D, Gartside P, Burstein S, Sperling M, Stein EA. Hemoglobin A1 in hemolysates from healthy and insulin-dependent diabetic children, as determined with a temperature-controlled minicolumn assay. Clin Chem 1982;28:13–8. 16 Goldstein DE. Is glycosylated hemoglobin clinically useful? N Engl J Med 1984;310:384–5. 17 Larsen ML, Horder M, Mogensen EF. Effect of long-term monitoring of glycosylated hemoglobin levels in insulindependent diabetes mellitus. N Engl J Med 1990;323: 1021–5. 18 American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 1994;17:616–23. 19 The DCCT Research Group. 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;329:977–86. 20 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. 21 Flückiger R, Berger W. Assessment of long-term glycemia: nonenzymatic protein glycosylation. Progr Clin Biochem Med 1986;3:14–9. 22 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;253:2327–32. 23 Huisman TH, Henson JB, Wilson JB. A new high-performance liquid chromatographic procedure to quantitate hemoglobin A1c and other minor hemoglobins in blood of normal, diabetic, and alcoholic individuals. J Lab Clin Med 1983;102:163–73. 24 Allen DW, Schroeder WA, Balog J. Observations on the chromatographic heterogeneity of normal and fetal human hemoglobin: a study of the effects of crystallization and chromatography on the heterogeneity and isoleucine content. JACS 1958;80:1628–34. 25 John WG, Bullock DG, MacKenzie F. Methods for the analysis of glycated haemoglobins: what is being measured? Diabet Med 1992;9:15–9. <strong>26</strong> Berger W, Flückiger R. Bestimmung der glykosylierten Hämoglobine HbA1(c) mit kommerziellen Methoden; Folgerungen aus einem Methodenvergleich. Schweiz Ärztezeitung 1984;34:1620–2. 27 Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A. Correlation of glucose regulation and hemoglobin A1c in diabetes mellitus. N Engl J Med 1976; 295:417–20. 28 Gabbay KH, Hasty K, Breslow JL, Ellison RC, Bunn HF, Gallop PM. Glycosylated hemoglobins and long-term blood glucose control in diabetes mellitus. J Clin Endocrinol Metab 1977;44:859–64. 29 James TM, Davis JE, McDonald JM, Santiago JV, Ladenson JH. Comparison of hemoglobin A1c and hemoglobin A1 in diabetic patients. Clin Biochem 1981;14:25–7. 30 Mortensen HB, Svendsen PA. Determination of haemoglobin A1c by iso-electric focusing. Effect of incubation of erythrocytes and comparison of results obtained by ionexchange chromatography. Scand J Clin Lab Invest 1981; 41:451–5. 31 Carrera T, Bonamusa L, Almirall L, Navarro JM. Should age and sex be taken into account in the determination of <strong>HbA1c</strong> reference range? Diabetes Care 1998;21:2193. 32 Nakashima K, Nishizaki O, Andoh Y. Acceleration of hemoglobin glycation with aging. Clin Chim Acta 1993; 214:111–8. 33 Hashimoto Y, Futamura A, Ikushima M. Effect of aging on <strong>HbA1c</strong> in a working male Japanese population. Diabetes Care 1995;18:1337–40. 34 Yang YC, Lu FH, Wu JS, Chang CJ. Age and sex effects on <strong>HbA1c</strong>: a study in a healthy Chinese population. Diabetes Care 1997;20:988–91. 35 Carrera T, Bonamusa L, Perich C, Juve R, Cosculluela R, Almirall L, et al. Effect of aging on <strong>HbA1c</strong> reference values determined by HPLC in an HA-8140 system [abstract]. Clin Chem 1997;43(Suppl 6):S138. 36 Stickland MH, Paton RC, Wales JK. Haemoglobin A1c concentrations in men and women with diabetes. Br Med J 1984;289:733. 37 Hindle EJ, Rostron GM, Gatt JA. Haemoglobin A1c concentrations in men and women with diabetes. Br Med J 1984;289:1001. 38 Flückiger R, et al. Nichtenzymatische Glykosylierung von Proteinen bei Diabetes mellitus. Stuttgart: Georg Thieme Verlag; 1989. 39 American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 1996;19:S8–S15. 40 Walinder O, Wibell L, Tuvemo T. Relation between hemoglobin A1 and determinations of glucose in diabetics treated with and without insulin. Diabetes Metab 1980;6:251– 5. 41 Pecoraro RE, Chen MS, Porte D Jr. Glycosylated hemoglobin and fasting plasma glucose in the assessment of outpatient glycemic control in NIDDM. Diabetes Care 1982;5:592–9. 1003