Diagnostic potentials of HbA1c

HbA1c Range

Nondiabetes usually falls within the 4.0%–5.6% HbA1c range. The prediabetes usually has the HbA1c levels as 5.7%–6.4%, while those with 6.4% or higher HbA1c levels have diabetes.^12,28 Since diabetes is associated with several comorbidities, the recommendations for individuals with diabetes include a healthy lifestyle (diet and exercise) and maintaining the HbA1c levels below 7.0%. Diabetes-related complications are directly proportional to the levels of HbA1c – the increase in the HbA1c levels also increases the risk of such complications. Using HbA1c as a SOC test also provides some complications for the health-care providers and the patients alike. For example, in anemic (low hemoglobin) patients or those with shorter RBC lifespan (glucose-6-phosphate dehydrogenase deficiency, sickle-cell disease, etc.), the HbA1c levels may be compromised indicating a false “good” result.⁵⁸ The excessive use of vitamin C, B, and E supplements and increased levels of cholesterol, liver, and kidney diseases can also present abnormally high levels of HbA1c.^59,60 Dyslipidemia, which is an imbalance of lipids and fats circulating in the blood stream, is another debilitating disease associated with diabetes.^61,62 However, maintaining healthy glucose levels for type 2 diabetics is of paramount importance and may help in preventing micro- and macrovascular complications.⁶³ The HbA1c is also used routinely for testing gestational diabetes among pregnant women.⁶⁴ Other researchers have utilized the serum fructosamine and blood glucose for the screening of GDM.^36,37 Both these tests allow the health-care providers to establish whether the pregnant women, with associated risk facts, had developed diabetes before the pregnancy, which may have gone undiagnosed. If the HbA1c levels are not monitored closely to establish acceptable glycemic control, the higher levels of HbA1c may cause the long-axis cardiac dysfunction in the developing fetus.^65,66 There is a direct correlation between reduced HbA1c levels and reduced percentage of mortality. Maintaining healthy levels of the HbA1c significantly ameliorates the risk of cardiovascular diseases among individuals with diabetes.⁶⁷

Diagnostic Potentials of HbA1c

The ADA has recently recommended HbA1c with a cut-point ≥6.5% for diagnosing diabetes as an alternative to fasting plasma glucose (FPG ≥7.0 mmol/L)-based criteria.¹⁷ The levels of HbA1c are strongly correlated with FPG (Fig. 3).¹⁸ FPG, 2-hour post-glucose load plasma glucose, and oral glucose tolerance tests are recommended for the diagnosis of diabetes only if HbA1c testing is not possible due to unavailability of the assay, patient factors that preclude its interpretation, and during pregnancy.¹⁹ HbA1c provides a reliable measure of chronic glycemia and correlates well with the risk of long-term diabetes complications, so that it is currently considered the test of choice for monitoring and chronic management of diabetes. However, the cut-point of HbA1c from the diagnostic point of view is still controversial. Among diabetics, the blood glucose levels increase in the blood and the glucose attaches to the hemoglobin molecule in a concentration-dependent manner. The glucose-bound (glycated) hemoglobin or HbA1c provides the average glucose levels in an individual’s blood as it becomes glycated with the hemoglobin. It is important to note that the HbA1c levels are directly proportional to the blood glucose levels. A simple blood glucose test such as a fasting glucose test (FGT) is a measure of glucose concentration present in an individual’s blood at a given point of time.²⁰ The blood used for the FGT may be obtained through a needlestick of a finger or directly from the arm. A new techno logy, continuous glucose monitoring, has arrived in the market, which allows for non-prick readings.^21–23 A small chip is implanted under the skin, which provides continuous glucose monitoring readings to the sensor kept outside, and if the glucose levels are higher or lower, it sends a special signal to the sensor, thus alerting the patient and/or the health-care provider for intervention.^22,23 The FGT is an excellent test for “in the moment” glucose levels, but it does not provide detailed information about the time course trend of the glucose levels. The HbA1c test, however, is a marker of the average glucose levels spread over a two- to three-month period. Contrary to popular belief, along with the type 2 diabetes, the HbA1c is also used to diagnose, manage, and monitor the type 1 diabetes as well.²⁴ In a series of 12,785 male diabetic patients, Khan et al.¹¹ have shown that the HbA1c cut-point of 6.5% was associated with 3.78% false-negative predictions (Fig. 4), while majority of the false-negative patients had borderline FPG (7.0–8.0 mmol/L) and HbA1c (6.0%–6.5%), and therefore belonged to at-risk category on the basis of HbA1c alone criteria. These findings suggest that the status of individuals with HbA1c between 6.0% and 6.5% should be verified by combined FPG and HbA1c criteria.¹¹ Recently, Khan et al.²⁵ have provided regression equations for interconversions between the levels of FGT and HbA1c for predicting their expected values in diabetic patients.

Ref

Biomark Insights. 2016 Jul 3;11:95–104. doi: 10.4137/BMI.S38440

Significance of HbA1c Test in Diagnosis and 

Prognosis of Diabetic Patients

Shariq I Sherwani 1, Haseeb A Khan 2,✉, Aishah Ekhzaimy 3, Afshan Masood 4, Meena K Sakharkar 5tients.