Standardizing the haemoglobin glycation index.

Aims: A high haemoglobin glycation index (HGI) is associated with greater risk for hypoglycaemia and chronic vascular disease. Standardizing how the HGI is calculated would normalize results between research studies and hospital laboratories and facilitate the clinical use of HGI for assessing risk.

Methods: The HGI is the difference between an observed HbA1c and a predicted HbA1c obtained by inserting fasting plasma glucose (FPG) into a regression equation describing the linear relationship between FPG and HbA1c in a reference population. We used data from the 2005-2016 U.S. National Health and Nutrition Examination Survey (NHANES) to identify a reference population of 18,675 diabetes treatment-naïve adults without self-reported diabetes. The reference population regression equation (predicted HbA1c = 0.024 FPG + 3.1) was then used to calculate the HGI and divide participants into low (<-0.150), moderate (-0.150 to <0.150) and high (≥0.150) HGI subgroups. Diabetes status was classified by OGTTs.

Results: As previously reported in multiple studies, a high HGI was associated with black race independent of diabetes status, and with older age, higher BMI and higher CRP in normal and prediabetic but not diabetic participants. The mean HGI was 0.6% higher in self-reported diabetic adults. The HGI was not associated with plasma insulin, HOMA-IR or 2 h OGTT in participants classified as normal, prediabetic or diabetic.

Conclusions: The regression equation derived from this demographically diverse diabetes treatment-naïve adult NHANES reference population is suitable for standardizing how the HGI is calculated for both clinical use and in research to mechanistically explain population variation in the HGI and why a high HGI is associated with greater risk for chronic vascular disease.