Hemoglobin Glycation Index May Enhance Diagnosis of Prediabetes, Diabetes

glucose meter
Detail of a glucose meter with a drop of blood, plus sample extraction equipment
Hemoglobin glycation index quantifies the magnitude and direction of interindividual variations in HbA1c that can be attributed to factors other than blood glucose levels.

Hemoglobin glycation index (HGI), a biomarker of variation in hemoglobin A1c (HbA1c) attributed to factors other than blood glucose concentration, can assist in predicting the diagnosis of prediabetes or diabetes, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Previous studies have shown that the use of fasting plasma glucose (FPG), 75-g oral glucose tolerance tests (OGTTs), and HbA1c can lead to markedly different results when diagnosing prediabetes and diabetes. Some literature has suggested that differences in red blood cell life span or other biological factors may affect HbA1c levels independent of the effect of plasma glucose concentration.

HGI quantifies the magnitude and direction of interindividual variation in HbA1c based on the difference between a measured and predicted HbA1c value. Because of how HGI is calculated, people with a low HGI phenotype have higher FPG than and similar HbA1c to people with a high HGI phenotype. Likewise, people with a high HGI phenotype have higher HbA1c than and similar FPG to people with a low HGI phenotype.

The researchers used data from the Vitamin D and Type 2 Diabetes (D2d; ClinicalTrials.gov Identifier: NCT01942694) study to calculate HGI, identify demographic and clinical variables associated with HGI, and determine how HGI is associated with the diagnosis of prediabetes or diabetes. For their study, researchers subtracted predicted HbA1c (calculated using the formula: 0.0164 × FPG (mg/dL) + 4.2) from the measured HbA1c of 3945 individuals to provide an HGI value that was categorized as low, moderate, or high.

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The percentages of women and blacks increased across low to high HGI subgroups (P <.001). As expected, mean FPG decreased and HbA1c increased from low to high HGI subgroups, but mean 2-hour plasma glucose during OGTT was not significantly different between the groups.

Levels of FPG in the range of prediabetes were significantly more common in individuals with low HGI compared with individuals with high HGI (83.1% vs 54.1%; P <.001). However, HbA1c levels in the prediabetes range were more common in individuals with high HGI (95.3% vs 57.0% in the low HGI subgroup; P <.001). There was no difference in the prevalence in people with 2-hour plasma glucose in the prediabetes range among HGI subgroups (P =.29).

The researchers acknowledged several study limitations, including possible interlaboratory variation. In addition, HGI has limitations as a clinical tool given that there is no single regression equation that can be used for every population.

“Our results suggest that normative values and longitudinal follow-up using HGI should be further evaluated, since HGI may serve as an additional variable when deciding which tests to use in which patients for diagnosing prediabetes and diabetes,” concluded the researchers.

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Hsia DS, Rasouli N, Pittas AG, et al. Implications of the hemoglobin glycation index on the diagnosis of prediabetes and diabetes. J Clin Endocrinol Metab. 2020;105(3):1-9