An Analysis of the Hemoglobin Glycation Rate in the A1C-Derived Average Glucose Study Population Applying a Monte Carlo Method

Abstract

Diabetes is a huge and growing problem, and the costs to society are consistently increasing. The glycated hemoglobin A1c (HbA1c) concentration is a frequently used marker of the metabolic control. In 2008 the results of the A1c-Derived Average Glucose (ADAG) Study were reported establishing a linear relationship between HbA1c and the preceding glycemia. The aim of this study was to analyze the overall hemoglobin glycation rate constant (k) in the ADAG population applying a Monte Carlo method. We reproduced the distribution of HbA1c and plasma glucose concentrations in the ADAG population and we obtained an estimate of k equal to 1.239 ± 0.175×10− 9 L/(mmol s) assuming that red blood cells’ (RBCs) life span was equal to 120 days. The k value estimated in this study is in a good agreement with values of this parameter reported earlier. It was also demonstrated that a normal distribution of RBCs’ life span with the standard deviation of 14 days is sufficient to explain the inter-subject variability of the hemoglobin glycation rate. The obtained distribution of RBCs’ life spans is even less scattered around the mean than previously reported distributions for healthy individuals and for patients with diabetes. However, an assumption that k is the same for all the individuals implies a positive correlation of RBCs’ life span and HbA1c concentration, which was inconsistent with earlier reports. This result suggests that the hemoglobin glycation rate might increase with a deterioration of the metabolic control.KeywordsHemoglobin A1cDiabetes mellitusMathematical modelingMonte Carlo method