HbA1c

Determination of blood glucose concentration (blood glucose; BG; glucose) alone only allows assessment of the diabetic’s current metabolic status at the time of blood sampling. However, because blood glucose levels are dependent on circadian (daily) rhythms and can also fluctuate widely due to diet or other factors, other laboratory parameters are needed for longer-term assessment. The long-term glycemic parameter HbA1c is particularly suitable for assessing glycemia (increased blood glucose levels) over the past days or weeks. The HbA1c is, so to speak, the “blood glucose memory“. It allows the physician to assess the metabolic situation over the last 4-6 weeks. Glucose and other monosaccharides (simple sugars) react in a concentration-dependent manner with the free amino groups of the proteins they can reach (protein). This reaction is called glycation. In particular, glycated hemoglobins – glycated red blood pigment – are suitable as long-term parameters of blood glucose concentration. The extent of glycation depends not only on the lifetime of hemoglobins – which is relatively stable at 100-120 days – but also on the duration and the level of blood glucose. That is, the higher the blood glucose level, the higher the percentage of HbA1c in total hemoglobin.

The procedure

Material needed

• EDTA whole blood or capillary blood

Preparation of the patient

• Not required

Disruptive factors

• “False” high levels of HbA1c due to:
  • Anemia (iron deficiency anemia) [low MCV and MCH values as a sign of iron deficiency].
  • Infectious and tumor anemia
  • Terminal renal failure ([creatinine > 5 mg/dl]: carbamylated HbA).
  • Hemoglobinopathies (HbH, HbF, Wayne type, etc.).
  • Splenectomy and aplastic anemia.
  • Organ transplantation
  • Medications (high doses of acetylsalicylic acid (ASA); immunosuppressants, protease inhibitors).
• “False” low levels of HbA1c due to:
  • Nutritional (high alcohol / fat consumption).
  • Folic acid deficiency (pregnancy)
  • Competitive sports
  • High altitudes (sensitivity of HbA1c decreases with increasing altitude).
  • Higher erythrocyte turnover.
  • Chronic renal failure with shortened erythrocyte survival.
  • Hemoglobinopathies (HbS, HbC, HbD)
  • Hemolytic anemia
  • Liver cirrhosis with shortened erythrocyte survival.
  • Blood loss
  • After blood transfusions
  • Medications (erythropoietin, iron supplementation).

In addition, there are two other major factors that have been insufficiently considered in the interpretation of HbA1c values:

• Lower diagnostic value in different populations (e.g., elderly, different ethnic groups).
• Overdiagnosis in people with genetic hyperglycemia.

Normal values

Normal values for adults

Physiological range	5 to 6
Good diabetes control	6 to 8
Diabetes setting should be improved	> 8 %
The German Diabetes Society (DDG) e.V. recommends a target HbA1c value of 6.5 to 7.5 percent in its guidelines.

Method of determination used: HPLC, high-performance liquid chromatography. Old HbA1c values in percent (NGSP) correspond to HbA1c values in mmol/mol as follows:

Alt		New
6,0 %	corresponds to	42 mmol/mol
6,5 %	corresponds to	48 mmol/mol
7,0 %	corresponds to	53 mmol/mol
7,5 %	corresponds to	58 mmol/mol

The reference range for healthy individuals is 20 to 42 HbA1c [mmol/mol].

Indications

• Long-term monitoring of carbohydrate metabolism in type 1 diabetes mellitus + type 2 diabetes mellitus.

HbA1c should be monitored at the following intervals:

• Type 1 diabetes
  • Circa 3-4 times per year with conventional therapy
  • Every 1 to 2 months with intensive therapy
• Type 2 diabetes – 2 times per year in stable patients.
• Gestational diabetes mellitus (GDM) – every 1 to 2 months.

Interpretation

Interpretation of increased values

• If the HbA1c is elevated by one percent, the blood glucose level in the preceding months was on average 30 mg/dl above the normal range!
• Diabetes setting should be improved if the HbA1c > 8%.

Interpretation of lowered values

• Not relevant to the disease

Further notes

• Diagnostics
  • HbA1c less than 5.7%: Diabetes mellitus excluded
  • HbA1c of 5.7- 6.7%: Measurement of glucose (DDG) [patients who have an HbA1c ≥ 5.6% on random testing are most likely to develop diabetes]
  • HbA1c greater than 6.5%: Diabetes mellitus [Both the German Diabetes Society and the American Diabetes Association consider glycated hemoglobin to be a relevant diagnostic marker, provided that it has been determined according to an internationally standardized procedure]
• Therapy
  • Individualized HbA1c target corridor of 6.5-7.5% (48-58 mmol/mol).
  • A HbA1c target value close to 6.5%, only if this can be achieved by lifestyle changes and/or metformin! (DEGAM)
• Hospitalization: patients at a median age of 57 years (13,522 participants) with elevated serum HbA1c levels, had more frequent hospitalizations over the subsequent 20 years:
  • HbA1c <5.7%: 3.7% ten or more inpatient admissions.
  • Patients with known diabetes and good glycemic control (HbA1c < 7.0%): 13.5%.
  • Poor control: 18.2%
• Mortality/sterility rates (cardiovascular and cancer mortality) of diabetic patients in relation to HbA1c levels.
  • < 6,5 %: +30 %
  • 6,5-6,9 %: +60 %
  • 7,0-7,9 %: +60 %
  • 8,0-8,9 %: +120 % (+170 %)
  • > 9,0 %: +160% (+220 %)