High hemoglobin glycation index is associated with increased risk of diabetes: A population-based cohort study in China

Abstract

Purpose: The hemoglobin glycation index (HGI) quantifies the mismatch between glycated hemoglobin A1c and average glycemia among individuals. Currently, it is unknown the potential role of HGI in exhaustively evaluating the progression of glucose metabolism/the risk of developing diabetes mellitus. Therefore, this study aimed to investigate the association between HGI and the risk of incident diabetes.

Methods: A total of 7,345 participants aged at least 40 years and without diabetes were divided into three groups according to the tertile of their baseline HGI level and followed for a median of 3.24 years to track new-onset diabetes. Using multivariate Cox regression analyses, we explored the association between the HGI, both categorized and continuous, and incident diabetes.

Results: During follow-up, 742 subjects (263 males and 479 females) developed diabetes mellitus. Higher HGI was associated with an increased risk of diabetes, even when adjusted for confounding factors, and every standard deviation increase in HGI was associated with a significant risk increase of 30.6% for diabetes (hazard ratio 1.306, 95% confidence interval 1.232-1.384).

Conclusions: Participants with a higher HGI were at a higher risk of future diabetes, irrespective of their glycemic conditions. Consequently, HGI may be employed to identify individuals at high risk for diabetes.

Keywords: biological variation; diabetes mellitus; glycated hemoglobin A1c; hemoglobin glycation index; risk factor.

Figure 1

Study flowchart of participants. FPG, fasting plasma glucose; 2hPG, 2-h plasma glucose; HbA1c, hemoglobin A1c; HGI, hemoglobin glycation index; OGTT, oral glucose tolerance test.

Figure 2

Scattergram of HbA1c versus FPG. There is a clear linear relation between HbA1c and FPG [HbA1c (%) = 3.335 + 0.025 FPG (mg/dL), P <0.001, R^{2 =} 0.528]. HbA1c: hemoglobin A1c; FPG: fasting plasma glucose.

Figure 3

Incidence of diabetes for HGI categories by baseline glucometabolic status ^# Glucometabolic status is assessed using oral glucose tolerance test results (including fasting plasma glucose and 2-h plasma glucose). *compared with low HGI group, P <0.05 HGI: hemoglobin glycation index.

Figure 4

Forest plot of HRs for incident diabetes per SD difference in HGI and HbA1c. Circles represent HGI, and squares represent HbA1c in different Cox regression models. Model 1 was adjusted for age and sex. Model 2 was adjusted for the variables in model 1 plus body mass index, systolic blood pressure, diastolic blood pressure, hypertension, antihypertensive medication, total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Model 3 was adjusted for all variables in model 2 plus the baseline fasting plasma glucose and 2-h plasma glucose at the OGTT. CI, confidence interval; HbA1c, hemoglobin A1c; HGI, hemoglobin glycation index; HR, hazard ratios; OGTT, oral glucose tolerance test.