Keeping You Informed
The importance of hemoglobin A1c testing ​in the screening, diagnosis, and monitoringof patients living with diabetes

Value of HbA1c Testing in Diabetes Management
Demonstrated by DCCT and UKPDS ​Quick Take Aways■■

William E. Winter, MD, DABCC, FACB, FACP​, Professor of Pathology, ​Immunology& Laboratory Medicine,​Pediatrics, and Molecular Genetics & Microbiology,​
University of Florida, College of Medicine■■

Prevalence of diabetes continues to increase, with many cases
going undiagnosed
Following American Diabetes Association (ADA) screening guidelines,such as starting testing at age 35, allows for early detection andtreatment to avoid worsening of complications caused by diabetes
DCCT and UKPDS set HbA1c analysis as the standard that should
be used to manage patients with diabetes
The ADA recommends HbA1c methods that are certified by the NGSP
(formerly: the National Glycohemoglobin Standardization Program)

The landmark nine-year Diabetes Control and Complications Trial (DCCT) carriedout in persons with type 1 diabetes used a high-performance liquid chromatography(HPLC) method to measure HbA1c concentrations. This study showed that the riskfor development and progression of the chronic microvascular and neuropathic
complications of type 1 diabetes was closely related to the degree of glycemic
control.2 Thus, the DCCT results have been used to establish specific diabetes
treatment goals using HbA1c as an index of a patient’s average plasma glucose.
The United Kingdom Prospective Diabetes Study (UKPDS) used HbA1c values
to show that lowering plasma glucose levels also reduced the incidence ofcomplications in individuals with type 2 diabetes.3
The results of the DCCT and UKPDS demonstrated the importance of HbA1c testingin managing patients living with diabetes. The DCCT and UKPDS also illustrated how
HbA1c tests can predict a patient’s risk for complications. The greater a patient’s
HbA1c value, the higher their risk of complication.4

Diabetes Prevalence
The prevalence of diabetes continues to increase. The International DiabetesFederation (IDF) estimates that 10% of the world’s population presently is affectedby diabetes. By 2045, nearly 800 million adults will be living with diabetes.1 Because
type 2 diabetes may not have symptoms in its early stages, type 2 diabetes may
go undiagnosed for several years. Currently 1 in approximately every 2 people withdiabetes is not diagnosed.1

Correlation between HbA1c level andrisk for diabetic complications

Diabetes Complications​
As diabetes progresses, it causes long-term damage to various organs, including
the eyes, kidneys, nerves, heart, liver, and blood vessels. Screening for diabetes isimportant for early detection to allow for prompt treatment to slow the progressionof the disease and its complications. Improved glucose control reduces the risk ofcomplications in persons with type 1 diabetes or type 2 diabetes.2-4

HbA1c Testing
Hemoglobin A1c tests measure the patient’s average plasma glucose over thepast ~90 days. A HbA1c value taken every 2–3 months serves as an indicator ofglucose control over those months, providing an objective view of the patient’scontrol between checkups. HbA1c is more advantageous than other methods ofglycemia (glucose) assessment because the patient does not need to fast orconsume a glucose challenge drink before testing.
In an individual with no abnormalities of glucose metabolism, HbA1c values arenormally less than 5.7% (39 mmol/mol); in a patient with diabetes, this concentration
may double or even triple depending upon the degree of hyperglycemia. With
early detection of diabetes, proper therapy, and the normalization of plasma glucose
levels in patients with diabetes, HbA1c values can often gradually approachnormal concentrations.
The ADA recommends that methods used to measure HbA1c should bestandardized to the Diabetes Control and Complications Trial (DCCT) assay
and certified by the NGSP. NGSP-reported results are now standardized bycomparison to the reference method as described by the International
Federation of Clinical Chemistry (IFCC).5

Visit bio-rad.com/forhealthcareproviders for more information.

Using HbA1c to Screen for Diabetes​
The World Health Organization, the International Expert Committee, and the ADA
recommend the use of HbA1c to screen for and diagnose diabetes.6-8 Under defined
circumstances, certain groups of children and adults (and all adults aged 35 and older)should be screened for type 2 diabetes.8

Diagnosing​ DiabetesMonitoring Patients Living with Diabetes​

REFERENCES

There are different ways to diagnose diabetes, including the measurement of HbA1c
concentrations.8 In symptomatic subjects (e.g., persons who report polyuria, polydipsia and/or unexplained weight loss) or in the setting of a diabetic crisis (e.g., diabetic ketoacidosisor hyperglycemic hyperosmolar state), a single finding of hyperglycemia is sufficient todiagnose diabetes. To diagnose diabetes in asymptomatic subjects, hyperglycemia should
be observed twice on a single day (assessed using two different measures such as anelevated fasting plasma glucose and an elevated HbA1c). Alternatively, in asymptomaticsubjects, diabetes can be diagnosed by observing hyperglycemia on two separate days.
The diagnosis of diabetes in pregnancy continues to evolve and a thorough discussion ofthis topic is available in the latest ADA guidelines.8

The ADA guidelines state that the therapeutic goal in caring for patients with diabetes
should be the normalization of blood glucose levels when considered in the context of
the risk of hypoglycemia, life expectancy, and the balance of the benefits versus the riskof improved control. Numerous investigations have shown a strong correlation between
HbA1c levels and glycemic control as assessed by traditional glucose assays.16-18

1. IDF Diabetes Atlas, 10th edn (2021). International Diabetes Federation, Brussels, Belgium.
Available at: https://www.diabetesatlas.org. https://www.diabetesatlas.org

3. U.K. Prospective Diabetes Study (UKPDS) Group (1998). Intensive blood-glucose control withsulphonylureas or insulin compared with conventional treatment and risk of complications inpatients with type 2 diabetes (UKPDS 33). Lancet 352, 837-53.
4. DCCT Research Group (1996). The Absence of a Glycemic Threshold for the Developmentof Long-Term Complications: The Perspective of Diabetes Control and Complications Trial.
Diabetes Care 5, 1289-98.

ADA Criteria for Screening Diabetes​

ADA Hyperglycemia Criteria8
Defining Criteria

Prediabetes

Hyperglycemia

Fasting Plasma Glucose

100–125 mg/dL≥126 mg/dL

5.6–6.9 mmol/L≥7.0 mmol/L

140–199 mg/dL≥200 mg/dL

7.8–11.0 mmol/L

2h Plasma Glucose during 75g OGTTHbA1cRandom plasma glucose – patient with classicScreening for diabetes should beconsidered in the following circumstances:8■

Patients 35 years of age or older​≥11.1 mmol/L■

Patients with HIV​

5.7%–6.4%

≥6.5%

■

39–47 mmol/mol≥48 mmol/mol

Not applicable

symptoms of hyperglycemia≥200 mg/dL≥11.1 mmol/L

When using a HbA1c testing method, it is important to keep in mind that certain factors(e.g., hemoglobinopathies or alterations in the lifespan of red blood cells, etc.) may falsely
increase or decrease HbA1c results.9-13 Therefore, it could be considered good medical
practice for physicians to evaluate the HbA1c result alongside a complete blood count,patient history, and other tests that may help identify potential biases. To ensure thataccurate HbA1c results are obtained for all patients, it is important to know if a patient has
a hemoglobin variant and how that variant can affect his or her HbA1c.19

At a GlanceHbA1c

Adult with diabetes
meeting glycemic goals<7% (<53 mmol/mol)■ A lower HbA1c goal may be acceptable if significant
hypoglycemia or other adverse consequences oftreatment can be avoided■ A less stringent goal such as <8% (<64 mmol/mol)
may be appropriate when life expectancy is limitedor the harms of treatment exceed the benefits

HbA1c Testing
Per Year2x■■≥7% (≥53 mmol/mol)Children with diabetes
meeting glycemic goals<7% (<53 mmol/mol)■ A lower goal such as <6.5% (<48 mmol/mol) may be
acceptable in various circumstances■ A less stringent goal such as <7.5% (<58 mmol/mol) or <8% (<64 mmol/mol) may be acceptable invarious circumstances

2xPrediabetes has been
diagnosed

5.7–6.4% (39–47 mmol/mol)

1xPatients with normal
HbA1c values*<5.7% (<39 mmol/mol)

4x■*See hyperglycemia table

A-354 © 2022 Bio-Rad Laboratories, Inc. DG22-1109 2022/12■

Every 3 years

Physical inactivity●

Relatives with diabetes●High-risk ethnicity●

History of cardiovascular disease
HDL cholesterol <35 mg/dL (<0.90 mmol/L) and/or
a triglyceride level >250 mg/dL (>2.82 mmol/L)●Hypertension (≥140/90 mmHg or on therapy)●

Women with polycystic ovary syndrome●Conditions associated with insulin resistance

Screening Follow-Up Frequency8​■

Adult with diabetes notmeeting glycemic goals
and/or therapy has recently
changedAdults who are overweight (BMI >25 kg/m ) and have one
or more of the following risk factors:●

5. NGSP (2010). IFCC Standardization of HbA1c. http://www.ngsp.org/ifccngsp.asp,
accessed November 17, 2022.
6. Geneva: World Health Organization (2011). Use of Glycated Haemoglobin (HbA1c) in theDiagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation.
7.

2●8,14,15Condition

2. DCCT Research Group (1993). The Effect of Intensive Treatment of Diabetes on theDevelopment and Progression of Long-Term Complications in Insulin-Dependent Mellitus.
New England Journal of Medicine 329, 977-86.

If results are normal, testing should be repeated at a minimumof 3-year intervals with consideration for more frequent testing
depending on initial results and risk status
Patients with prediabetes should be retested yearly
Women diagnosed with gestational diabetes mellitus shouldhave lifelong testing at least every 3 years
Patients meeting treatment goals and with stable glycemiccontrol should be monitored with an HbA1c test at least
2 times a year
Patients whose therapy has changed or who are notmeeting glycemic goals, should be monitored with anHbA1c test performed quarterlyInternational Expert Committee (2009). International Expert Committee Report on the Roleof the A1C Assay in the Diagnosis of Diabetes. Diabetes Care 32, 1327-1334.

8. American Diabetes Association Professional Practice Committee (2023). Classificationand Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2023. Diabetes Care46 (Suppl 1), S19-S40.
9. Wang Y et al. (2007). Misleading glycated hemoglobin results in a patient with hemoglobin
SC disease. Clin Chem 53, 1394-5.
10. McCready F and Cundy T (2009). Effects of splenectomy for hereditary spherocytosis on
glycated haemoglobin in a woman with Type 2 diabetes. Diabet Med 26, 570-1.
11. Pallais JC et al. (2011). Case records of the Massachusetts General Hospital: Case 7-2011:a 52-year-old man with upper respiratory symptoms and low oxygen saturation levels.
N Engl J Med 364, 957-66.
12. Rhea JM et al. (2013). Unintended reporting of misleading Hb A(1c) values when using assays
incapable of detecting hemoglobin variants. Arch Pathol Lab Med 137, 1788-91.
13. Rhea JM and Molinaro R (2014). Pathology consultation on HbA(1c) methods andinterferences. Am J Clin Pathol 141, 5-16.
14. American Diabetes Association Professional Practice Committee (2023). 6. Glycemic Targets:Standards of Medical Care in Diabetes-2023. Diabetes Care 46 (Suppl 1), S97-S110.
15. Redondo MJ et al. (2021). The Evolution of Hemoglobin A1c Targets for Youth with Type 1
Diabetes: Rationale and Supporting Evidence. Diabetes Care 44, 301-312.
16. Gonen BA et al. (1977). Hemoglobin A1: An Indicator of the Metabolic Control of DiabeticPatients. Lancet 2, 734-7.
17. Koenig RJ et al. (1976). Hemoglobin A1c as an indicator of the Degree of Glucose Intolerancein Diabetes. Diabetes 25, 230-2.
18. Koenig RJ et al. (1976). Correlation of Glucose Regulation and Hemoglobin A1c in Diabetes
Mellitus. New England Journal of Medicine 295, 417-20.
19. Little RR et al. (2015). Effects of 49 Different Rare Hb Variants on HbA1c Measurement inEight Methods. Journal of Diabetes Science and Technology 9, 849-856.

Visit bio-rad.com/forhealthcareproviders for more information.

See also At a Glance in the Diagnosing section.

For educational purposes only and not intended to provide medical advice and diagnosis.
Bio-Rad is a trademark of Bio-Rad Laboratories, Inc.