Update on biomarkers of glycemic control

Table 1 Characteristics of the analytical methods for hemoglobin A1c measurement

Method	Advantages	Disadvantages
Ion exchange chromatography	DCCT method, high reproducibility	Lack of specificity; interference from hemoglobinopathies and HbF
Capillary electrophoresis	High reproducibility; specificity	Time-consuming, costly
Boronate affinity chromatography	Minimal interference from hemoglobinopathies	Analyte-related unspecificity (total GHb)
Immunoassay	Specificity	Some interference from HbF

DCCT: Diabetes Control and Complications Trial; HbF: Fetal hemoglobin; GHb: Total glycated hemoglobin.

Table 2 Biological, (patho)physiological and pharmacological factors influencing hemoglobin A1c

Factor influencing HbA1c synthesis/measurement/interpretation
Age, ethnicity
Genetic factors (e.g. Glucose-6-phosphate dehydrogenase variants)
Pregnancy
Red blood cell lifespan
Haemolytic anaemia
Iron deficiency anaemia
Haemoglobin variants
Accute haemorrhage
Splenomegaly
Splenectomy
Transfusion
Chronic liver disease
End-stage renal disease
Rheumatoid arthritis
Vitamin C
Drugs (aspirin, erytropoietin, dapsone, antiretroviral agents)
Endogenous interferents (high levels of bilirubin/triglycerides)

HbA1c: Hemoglobin A1c.

Table 3 Characteristics of glycaemic biomarkers

Markers of hyperglycemia	Assessment period	Advantages	Limitations
HbA1c	2-3 mo	Fasting not necessary; low interindividual variabiliy screening tool for diabetes; association with diabetes complications; standardization	Surrogate biomarker analytical interferences; biological confounders; costs
Fructosamine	2-3 wk	Fasting not necessary; inexpensive and easily automated; good correlation with HbA1c; association with diabetes complication; marker of choice in severe chronic kidney disease	Surrogate biomarker; higher interindividual variability; unreliable in conditions with altered protein and albumin metabolism (nephrotic disease, severe liver disease), thyroid disfunction; not standardized
Glycated albumin
1,5-anhydroglucitol	1-2 wk	Fasting not necessary; glycemic excursion detection; good correlation with HbA1c; association with diabetes complications	Surrogate biomarker; unreliable in the setting of chronic kidney disease (stage 4 and 5), dialysis, pregnancy or other conditions with changes in renal threshold (sglt inhibitors); not suitable for diabetes diagnosis
Fasting glucose	8-10 h	Current glycemic status; immediate availability for daily diabetes management SMBG/CGMS	Affected by acute illness and stress; SMBG and CGMS-accuracy
Postprandial glucose	2-4 h
Indices of glycaemic variabily	24-72 h	Short-term glucose dynamics; improves glycaemic control beyond HbA1c and patient’s satisfaction/outcomes	CGMS mandatory; costs education; standardization

HbA1c: Hemoglobin A1c; SMBG: Self-monitoring of blood glucose; CGMS: Continuous glucose monitoring system.