Fallstricke bei der Diabetesdiagnostik: Wird zu lax mit Laborwerten umgegangen?

Abstract

The diagnosis of diabetes is associated with pre-analytical and analytical problems. Fasting glucose (FG), oral glucose tolerance test (oGTT) and HbA_1c have advantages and shortcomings and have no equal diagnostic validity. oGTT is the most sensitive test, but its reproducibility is rather poor (CV ± 15 %). FG detects only 70 – 80 % of overt diabetes. FG is falsified by inappropriate blood sampling, intra-individual fluctuations and mistakes with the oGTT. HbA_1c despite IFCC-standardization, but with a tolerable coefficient of variation of ± 18 % in round robin tests and use of not commutable control material is not easy to interpret. HbA_1c analysis shows also interferences and is therefore of limited diagnostic value. Its threshold value of ≥ 6.5 % (≥ 48 mmol/mol Hb) is based on consensus and not on evidence. The diagnostic effort (FG and/or oGTT + HbA_1c) with serious consequences is minimal invasive, reasonable and cheap. It prevents over- and underdiagnosis.

Der Diabetes mellitus ist eine chronische Krankheit mit z. T. folgenreichen Komplikationen für den betroffenen Menschen sowie sein soziales Umfeld, die Gesundheitsökonomie und die gesamte Volkswirtschaft. Die Diagnose basiert unabhängig von der Diabetesursache auf einer zuverlässigen Labordiagnose. Diese scheint einfach zu sein, birgt aber eine Vielzahl von Fallstricken, die in der Praxis häufig ungenügend berücksichtigt werden.

Schlüsselwörter

Diabetesdiagnose - (prä-)analytische Probleme - Plasmaglukose - HbA_1c - oraler Glukosetoleranztest

Key words

diabetes diagnosis - (pre-)analytic problems - plasma glucose - HbA_1c - oral glucose tolerance test

• Literatur

• 1 Schulze M. Dife – Deutscher Diabetes-Risiko-Test (DRT). Diabetologie 2017; 12 (Suppl. 02) S264-S267
• 2 Schwarz P. FINDRISK-Test. Diabetologie 2017; 12 (Suppl. 02) S268-S270
• 3 World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO/IDF Consultation. Geneva: World Health Organization; 2006. ISBN: 978-92-4-159493-6
• 4 International Diabetes Federation. IDF clinical practice recommendations for managing type 2 diabetes in primary care (2017). Im Internet: http://www.idf.org/e-library/guidelines/128-idf-clinical-practice-recommendations-for-managing-type-2-diabetes-in-primary-care.html ; Stand: 07.11.2018
• 5 American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018. Diabetes Care 2018; 41 (Suppl. 01) S13-S27
• 6 The International Expert Committee. International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes. Diabetes Care 2009; 32: 1327-1334
• 7 Nauck M, Petermann A, Müller-Wieland D. et al. Definition, Klassifikation und Diagnostik des Diabetes Mellitus. Diabetologie 2017; 12 (Suppl. 02) S94-S100
• 8 Kerner W, Freckmann G, Müller UA. et al. Positionspapier der Kommission für Labordiagnostik in der Diabetologie der DGKL und der DDG. Diabetologie 2015; 10: 329-333
• 9 Heinemann L, Kaiser P, Freckmann G. et al. HbA1c-Messung in Deutschland: Ist die Qualität ausreichend für Verlaufskontrolle und Diagnose? Positionspapier der Kommission für Labordiagnostik in der Diabetologie der DGKL und der DDG. Diabetologie 2018; 13: 46-53
• 10 Sacks DB. A1C versus glucose testing. A comparison. Diabetes Care 2011; 34: 518-523
• 11 Kowall B, Rathmann W, Landgraf R. Is HbA1c a valid and feasible tool for the diagnosis of diabetes?. Diabetes Res Clin Pract 2011; 93: 314-316
• 12 Dagogo-Jack S. Pitfalls in the use of HbA1c as a diagnostic test: the ethnic conundrum. Nat Rev Endocrinol 2010; 6: 589-593
• 13 Bonora E, Tuomiletho J. The pros and cons of diagnosing diabetes with A1C. Diabetes Care 2011; 34 (Suppl. 02) S184-S190
• 14 Larsson-Cohn U. Differences between capillary and venous blood glucose during oral glucose tolerance tests. Scand J Clin Lab Invest 1976; 36: 805-808
• 15 Irjala K, Koskinen P, Näntö V. et al. Interpretation of oral glucose tolerance test: Capillary-venous difference in blood glucose and the effect of analytical method. Scand J Clin Lab Invest 1986; 46: 307-313
• 16 Bundesärztekammer. Neufassung der „Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen – Rili-BÄK. Dtsch Ärztebl 2014; 111: A1583-A1618
• 17 Selvin E, Crainiceanu CM, Brancati FL. et al. Short-term variability in measures of glycemia and implications for the classification of diabetes. Arch Intern Med 2007; 167: 1545-1551
• 18 Ollerton RL, Playle R, Ahmed K. et al. Day-to-day variability of fasting plasma glucose in newly diagnosed type 2 diabetic subjects. Diabetes Care 1999; 22: 394-398
• 19 The DECODE-study group on behalf of the European Diabetes Epidemiology Group. Is fasting glucose sufficient to define diabetes? Epidemiological data from 20 European studies. Diabetologia 1999; 42: 647-654
• 20 Deutsche Diabetes Gesellschaft. Stellungnahme der Kommission Labordiagnostik in der Diabetologie (KLD) zum Wert und Sinn der Minimal Difference (MD) als Beurteilungskriterium für die laboranalytische Messqualität (Juli 2017). Im Internet: http://www.deutsche-diabetes-gesellschaft.de/fileadmin/Redakteur/Stellungnahmen/2017/DDG_Stellungnahme_MD.pdf ; Stand: 07.11.2018
• 21 Köbberling J, Kerlin A, Creutzfeldt W. The reproducibility of the oral glucose tolerance test over long (5 years) and short periods (1 week). Klin Wochenschr 1980; 58: 527-530
• 22 Ko GTC, Chan JCN, Woo J. et al. The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors. Ann Clin Biochem 1998; 35: 62-67
• 23 Gordon BA, Fraser SF, Bird SR. et al. Reproducibility of multiple repeated oral glucose tolerance tests. Diabetes Res Clin Pract 2011; 94: e78-e82
• 24 Ye Y, Xie H, Zhao X. et al. The oral glucose tolerance test for the diagnosis of diabetes mellitus in patients during acute coronary syndrome hospitalization: a meta-analysis of diagnostic test accuracy. Cardiovasc Diabetol 2012; 11: 155-165
• 25 Van de Velde FP, Dierickx A, Depypere H. et al. Reproducibility and least significant differences of oral glucose tolerance test-derived parameters in a postmenopausal population without diabetes. Diabetes Metab 2017; 43: 484-487
• 26 Chai JH, Ma S, Heng D. et al. Impact of analytical and biological variations on classification of diabetes using fasting plasma glucose, oral glucose tolerance test and HbA1c. Sci Rep 2017; 7: 13721
• 27 Menke A, Rust KF, Cowie CC. Diabetes based on 2-h plasma glucose among those classified as having prediabetes based on fasting plasma glucose or A1c. Diab Vasc Dis Res 2018; 15: 46-54
• 28 Cowie CC, Rust KF, Byrd-Holt DD. et al. Prevalence of diabetes and high risk for diabetes using A1c Criteria in the U.S. population in 1988–2006. Diabetes Care 2010; 33: 562-568
• 29 van 't Riet E, Alssema M, Rijkelijkhuizen JM. et al. Relationship between A1C and glucose levels in the general dutch population. The New Hoorn Study. Diabetes Care 2010; 33: 61-66
• 30 Fajans SS, Herman WH, Oral EA. Insufficient sensitivity of hemoglobin A1C determination in diagnosis or screening of early diabetic states. Metabolism 2011; 60: 86-91
• 31 Gyberg V, De Bacquer D, Kotseva K. behalf of EUROASPIRE IV Investigators. et al. Screening for dysglycaemia in patients with coronary artery disease as reflected by fasting glucose, oral glucose tolerance test, and HbA1c: a report from EUROASPIRE IV – a survey from the European Society of Cardiology. Eur Heart J 2015; 36: 1171-1177
• 32 Shahim B, Gyberg V, De Bacquer D. et al. Undetected dysglycaemia common in primary care patients treated for hypertension and/or dyslipidaemia: on the need for a screening strategy in clinical practice. A report from EUROASPIRE IV a registry from the Euro Observational Research Programme of the European Society of Cardiology. Cardiovasc Diabetol 2018; 17: 21-32
• 33 Roth J, Müller N, Lehmann T. et al. Comparison of HbA1c measurements using 3 methods in 75 patients referred to one outpatient department. Exp Clin Endocrinol Diabetes 2018; 126: 23-26
• 34 Roth J, Müller N, Lehmann T. et al. HbA1c and age in non-diabetic subjects: An ignored association?. Exp Clin Endocrinol Diabetes 2016; 124: 637-642
• 35 Colagiuri S, Lee CM, Wong TY. for the DETECT-2 Collaboration Writing Group. et al. Glycemic thresholds for diabetes-specific retinopathy: implications for diagnostic criteria for diabetes. Diabetes Care 2011; 34: 145-150
• 36 Peter A, Fritsche A, Stefan N. et al. Diagnostic value of hemoglobin A1c for type 2 diabetes mellitus in a population at risk. Exp Clin Endocrinol Diabetes 2011; 119: 234-237
• 37 Selvin E, Steffes MW, Gregg E. et al. Performance of A1C for the classification and prediction of diabetes. Diabetes Care 2011; 34: 84-89
• 38 Kowall B, Rathmann W. HbA1c for diagnosis of type 2 diabetes. Is there an optimal cut point to assess high risk of diabetes complications, and how well does the 6.5% cutoff perform?. Diabetes Metab Syndr Obes 2013; 6: 477-491
• 39 Hoyer A, Rathmann W, Kuss O. Utility of HbA1c and fasting plasma glucose for screening of Type 2 diabetes: a meta-analysis of full ROC curves. Diabet Med 2018; 35: 317-322
• 40 Hellgren M, Hjörleifsdottir Steiner K, Bennet L. Haemoglobin A1c as a screening tool for type 2 diabetes and prediabetes in populations of Swedish and Middle-East ancestry. Prim Care Diabetes 2017; 11: 337-343