The relationship between BMI and glycated albumin to glycated hemoglobin (GA/A1c) ratio according to glucose tolerance status

Glycated albumin to glycated hemoglobin (GA/A1c) ratio is known to be inversely related with body mass index (BMI) and insulin secretory capacity. However, the reasons for this association remain unknown. We aimed to investigate whether BMI directly or indirectly influences GA/A1c by exerting effects on insulin secretion or resistance and to confirm whether these associations differ according to glucose tolerance status. We analyzed a total of 807 subjects [242 drug-naïve type 2 diabetes (T2D), 378 prediabetes, and 187 normal glucose tolerance (NGT)]. To assess the direct and indirect effects of BMI on GA/A1c ratio, structural equation modeling (SEM) was performed. GA/A1c ratio was set as a dependent variable, BMI was used as the independent variable, and homeostasis model assessment-pancreatic beta-cell function (HOMA-b), homeostasis model assessment-insulin resistance (HOMA-IR), glucose level were used as mediator variables. The estimates of a direct effect of BMI on GA/A1c to be the strongest in NGT and weakest in T2D (20.375 in NGT, 20.244 in prediabetes, and 20.189 in T2D). Conversely, the indirect effect of BMI on GA/A1c exerted through HOMA-b and HOMA-IR was not statistically significant in NGT group, but significant in prediabetes and T2D groups (0.089 in prediabetes, 20.003 in T2D). It was found that HOMA-b or HOMA-IR indirectly influences GA/A1c in T2D and prediabetes group through affecting fasting and postprandial glucose level. The relationship between GA/A1c and BMI is due to the direct effect of BMI on GA/A1c in NGT group, while in T2D and prediabetes groups, this association is mostly a result of BMI influencing blood glucose through insulin resistance or secretion.