HGI measures how far a person’s HbA1c lies above or below average compared to other people with similar blood glucose concentrations. Multiple studies confirm that high HGI is associated with greater risk for iatrogenic hypoglycemia in diabetes patients and chronic vascular disease in diabetic and nondiabetic populations. However, significant differences in how blood glucose is assessed and in the demographic composition of different study populations have resulted in marked interstudy differences in the slopes and intercepts of regression equations used to calculate HGI. The purpose of the present study was to develop a standard linear regression equation that could be widely used to calculate HGI in diverse human populations. To accomplish this, we used data from the demographically diverse 1999-2016 National Health and Nutrition Examination Survey (NHANES) to identify 18,675 participants age ≥20 y without self-reported diabetes. The regression equation developed from this treatment naïve adult reference population was HbA1c = 0.024 FPG + 3.1. HGI was calculated for reference population participants who were then subdivided into 1) low, moderate, and high subgroups, and 2) normal, prediabetic and diabetic subgroups based on OGTT results. Novel observations include lack of association between HGI and hemoglobin concentration, plasma insulin or HOMA-IR. Consistent with previous reports, high HGI was associated with 1) black race regardless of diabetes status, 2) older age and higher BMI in nondiabetic but not diabetic participants, and 3) no difference in 2 h OGTT results in normal, prediabetic or treatment naïve diabetic participants. Standardizing how HGI is calculated across studies will facilitate clinical and basic research to better understand 1) why some people have lower or higher than average HbA1c levels independent of blood glucose concentration, 2) why high HGI is associated with greater risk for chronic vascular disease in diabetic and nondiabetic people, and 3) what can be done to reduce risk in high HGI people.


D.S. Hsia: None. S. Yang: None. S. Liu: None. J.M. Hempe: None.


National Institute of General Medical Sciences (U54GM104940)

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