HbA 1c

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HbA 1c is the part of the red blood pigment hemoglobin in the red blood cells ( erythrocytes ) to which glucose (blood sugar) is bound. This blood sugar-dependent binding of glucose to hemoglobin A1 ( glycation ) takes place without enzymes ( Amadori rearrangement ).

The hemoglobin content of the blood can be measured and is given in grams of hemoglobin per deciliter of blood (g / dl) or in millimoles of hemoglobin per liter of blood (mmol / l; 1 mole of hemoglobin weighs 64458 g). The proportion of HbA 1c in the hemoglobin content of the blood, the so-called HbA1c value, corresponds - colloquially - to long-term blood sugar , i.e. H. the blood sugar level of the last 8-12 weeks (the mean life span of the erythrocytes).

units

The HbA 1c value is given as a percentage of the total hemoglobin, or based on 1 mol of hemoglobin in millimoles of HbA1c per mol (mmol / mol ). However, there are various glycation products, as it is a non-specific reaction. In order to standardize the measurement worldwide, a working group of the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) defined HbA 1c as the stable product of a coupling of glucose to the N -terminal valine of the beta chain of hemoglobin A1.

An indication in percent (%) is still common. The international unit (SI unit) introduced as recommended by the IFCC is mmol / mol hemoglobin. According to a guideline of the German Medical Association of April 1, 2008, the HbA 1c value should now also be given in this unit. This value can also be referred to as HbA 1c M to better distinguish it from the percentage . The conversion formula is:

HbA 1c [mmol / mol Hb] = (HbA 1c [%] - 2.15) x 10.929

HbA 1c [%] = (HbA 1c [mmol / mol Hb] / 10.929) + 2.15

Sampling (preanalytics)

The glycosylated hemoglobin HbA 1c is determined from whole blood, which mostly contains EDTA as an anticoagulant. Requirements for the storage and treatment of the sample material depend on the analysis system used. Usually the sample can be kept for one to two weeks at 4 ° C or can be stored for several months at −20 ° C.

Laboratory diagnostics

Various methods are available today for measuring the HbA1c value, including: a. the high pressure liquid chromatography (HPLC), the Thiobarbituratmethode, the affinity chromatography , the enzyme immunoassay and immunoturbidimetric. Each method has its own advantages and disadvantages.

Standard range and interpretation

According to the guidelines of the German Diabetes Society (DDG) from 2017, the normal range is below 5.7% or 39 mmol / mol of total hemoglobin.

Diabetes mellitus

The DDG has been recommending HbA1c for diagnosing diabetes mellitus since 2010. It explains this by an improvement in measurement accuracy, which has been achieved through international standardization, and the diagnostic values ​​are based on epidemiological studies carried out in recent years. As a result, diabetes mellitus is excluded at a value below 5.7%, whereas manifest diabetes mellitus is above 6.5%. In the case of results between 5.7% and 6.4%, however, an oral glucose tolerance test (OGTT) should be carried out for a confirmed diagnosis. Likewise, the HbA1c value is only suitable for diagnosing the metabolic disorder if patient-specific influencing variables are not to be expected that could lead to a falsification of the result.

In iron deficiency anemia, for example, the HbA1c value is measured incorrectly , since in this case the breakdown of the erythrocytes is slowed down.

On the other hand, false low values ​​can occur in hemolytic anemia, liver cirrhosis, chronic kidney failure and increased new synthesis of erythrocytes. The values ​​can be falsified even after severe blood loss or a blood transfusion. The HPLC method can give incorrect values ​​in the case of genetic disorders of the hemoglobin (e.g. sickle cell anemia, thalassemia).

In the meantime, the American Diabetes Association (ADA) also recommends HbA1c and the above values ​​for diagnosing or excluding diabetes mellitus.

In individual cases, the determination can still show strong method-dependent differences despite NGSP standardization. It is therefore recommended to always monitor a patient using the same method.

The HbA 1c is measured every three months in patients with diabetes mellitus. The aim of the therapy is that the HbA 1c value remains below 7 to 8% in order to delay or avoid possible long-term consequences of this disease.

Conversion table

Various formulas were used to convert the HbA 1c value measured in the laboratory into the underlying 3-month blood sugar mean value:

  • Mean blood sugar [mg / dl] = (HbA 1c [%] · 33.3) - 86
  • Mean blood sugar (plasma) [mg / dl] = (HbA 1c [%] x 35.6) - 77.3

Due to a relatively secure database, Nathan et al. developed a relatively precise conversion formula:

  • Mean blood sugar [mg / dl] = (HbA 1c [%] x 28.7) - 46.7

The following table shows the conversion of the HbA 1c value into the average blood sugar value according to Nathan et al. The figures in the table should only serve as rough guidelines, as short-term high values ​​(e.g. after eating) sometimes do not form stable bonds (thus raising the average, but not the HbA 1c value).

HbA 1c (in%) HbA 1c (in mmol / mol) mean blood sugar in mg / dl mean blood sugar in mmol / l
4.0 20th 68 3.8
5.0 31 97 5.4
6.0 42 126 7.0
6.5 47 140 7.8
7.0 53 154 8.6
7.5 58 169 9.4
8.0 64 183 10.2
8.5 69 197 11.0
9.0 75 212 11.8
9.5 80 226 12.6
10.0 86 240 13.4
10.5 91 255 14.1
11.0 97 269 14.9
11.5 102 283 15.7
12.0 108 298 16.5

Recently, the HbA1c value can also be extrapolated or estimated (estimated A1C) from continuous glucose monitoring (CGM); In some cases, however, considerable deviations from the HbA1c value measured in the laboratory are possible.

Increases and decreases in HbA1c due to changes in blood sugar levels

Information about the increase in the HbA1c value when the blood sugar level rises can hardly be found in the specialist literature; a communication shows that the maximum HbA1c increase rate is approx. 3% in 120 days, i.e. H. about 0.025 percentage points per day, in people with diabetes. The HbA1c increase follows the current blood sugar increase with a delay. The maximum HbA1c decrease rate was investigated in people with diabetes mellitus, in whom the treatment resulted in an abrupt and permanent blood sugar lowering up to normalization. With them, an increased HbA1c value is reduced by a maximum of approx. 0.1 percentage points per day. The decrease / normalization of the HbA1c value follows the current blood sugar decrease with a delay. With a slight permanent decrease in the blood sugar level, the HbA1c value decreases more slowly and to a lesser extent.

Strong, abrupt and permanent lowering of blood sugar levels that have been excessively high for a long time (with HbA1c lowering by more than 0.7% points per month) can acutely worsen an existing diabetic retinopathy in people with diabetes (so-called "early worsening of diabetic retinopathy") , as well as a painful diabetic neuropathy . In some of these cases, increasing blood sugar levels (and therefore HbA1c levels) can reverse the deterioration. Injecting a VEGF inhibitor (e.g. bevacizumab ) into the eye can also bring about an improvement.

Effects of the HbA1c value on diabetes therapy

Without HbA1c determination, diabetes therapy used to be medically controlled only on the basis of punctual glucose determinations in the blood (blood sugar) and urine. With knowledge of the respective HbA1c values ​​of their patients, doctors were able to improve their therapy instructions (and patients their adherence to therapy) to such an extent that excessive HbA1c values ​​fell by an average of 0.6 percentage points per year and were ultimately medically acceptable in over half of the patients examined Area.

Web links

Individual evidence

  1. ↑ cf. Glycosylation
  2. ↑ Hans Reinauer, Werner A. Scherbaum. Diabetes mellitus: New reference standard for HbA 1c . Dtsch Arztebl 106 (17), 2009, pp. A-805 / B-686 / C-670
  3. ↑ R. Landgraf and M. Haslbeck: Laboruntersuchungen . In: Hellmut Mehnert, Eberhard Standl, Klaus-Henning Usadel, Hans-Ulrich Häring (eds.): Diabetology in clinic and practice . 5th edition. Georg Thieme, Stuttgart 2003 (91-95 pages).
  4. ↑ Practical recommendations. Website of the German Diabetes Society.
  5. ^ Diagnosis. American Diabetes Association website.
  6. ↑ Executive Summary: Standards of Medical Care in Diabetes - 2010 . In: Diabetes Care . tape 33 , Supplement_1, December 2009, p. S4-S10 , doi : 10.2337 / dc10-S004 ( diabetesjournals.org [accessed July 11, 2011]).
  7. ^ Curt L. Rohlfing et al .: Defining the Relationship Between Plasma Glucose and HbA1c. Diabetes Care, February 2002, vol. 25, no. 2, 275-278. PMID 11815495 , doi: 10.2337 / diacare.25.2.275 .
  8. ↑ DM Nathan, J. Kuenen, R.Borg, H.Zheng, D.Schoenfeld, RJ Heine; Ac-derived Average Glucose Study Group: Translating the HbA1c assay into estimated average glucose values. In: Diabetes Care. 2008, pp. 1473-1478 , accessed January 17, 2020 .
  9. ↑ Richard M. Bergenstal, Roy W.Beck, Kelly L. Close, George Grunberger, David B. Sacks, Aaron Kowalski, Adam S. Brown, Lutz Heinemann, Grazia Aleppo, Donna B. Ryan, Tonya D. Riddlesworth and William T. Cefalu .: Glucose Management Indicator (GMI): A New Term for Estimating A1C From Continuous Glucose Monitoring . In: Diabetes Care . tape 41 , 2018, doi : 10.2337 / dc18-1581 (2275-2280 p.).
  10. ↑ a b E. Chantelau, R. Meyer-Schwickerath. Reversion of 'early worsening' of diabetic retinopathy by deliberate restoration of poor metabolic control. Ophthalmologica 217, 2003, pp. 373-377.
  11. ↑ E. Chantelau. Decay of hemoglobin A1c upon return to normoglycaemia.Letter. Diabetologia 35, 1992, p. 191.
  12. ↑ ME Rech. Observations on the decay of glycated hemoglobin HbA1c in diabetic patients. Experimental and Clinical Endocrinology and Diabetes. 104, 1996, pp. 102-105.
  13. ↑ E. Chantelau. Retinopathy worsening after an improvement in blood sugar - a diabetic paradox is unraveled. Journal presentation. Diabetes & Metabolism 8, 1999, pp. 177-181.
  14. ↑ Heike Elisabeth Schwarze. When is it to be feared that diabetic retinopathy will worsen when blood sugar is lowered? Literature review and presentation of own cases. Dissertation. Medical Faculty of Heinrich Heine University Düsseldorf 2002. German National Library http://d-nb.info/966170083
  15. ^ CH Gibbons, R. Freeman. Treatment-induced neuropathy of diabetes: iatrogenic complication of diabetes. Brain 138, 2015, pp. 43-52.
  16. ↑ Kathrin Doppler, Claudia Sommer. Treatment-induced diabetic neuropathy: rapid glucose lowering as a trigger. Deutsches Ärzteblatt 112, 2015, pp. 33–34.
  17. ^ William E. Jackson, Garrett S. Mitchell. Diabetic macular edema and early worsening - a cruel paradox (Scientific Poster Presentation). Annual Pediatric Poster Session, The Children's Hospital, Denver, Colorado, January 23, 2004.
  18. ↑ Shueh Wen Lim, Peter van Wijngaarden, Colin A. Harper, Salmaan H. Al-Qureshi: Early teaching of diabetic retinopathy due to intensive glycemic control. In: Clinical & Experimental Ophthalmology. 2019, pp. 265-273 , accessed January 17, 2020 .
  19. ↑ ML Larsen, M Horder, EF Mogensen: Effect of long-term glycosylated hemoglobin levels in insulin-dependent diabetes. (PDF) In: New England Journal of Medicine 323. 1990, pp. 1021-1025 , accessed February 12, 2020 .
  20. ^ CL Arfken, LE Schmidt, NH White, JV Santiago. Temporal trends in glycemic control of insulin treated patients with diabetes mellitus (DM). Abstract 460. Diabetes 1992; 41 / Suppl. 1: 129 A