Interaction of sex and diabetes on the association between hemoglobin glycation index, hemoglobin A1c and serum uric acid

Abstract

Background Hemoglobin glycation index (HGI), which is calculated by blood glucose and hemoglobin A1c(HbA1c), reflects the individual discrepancy in HbA1c. This study aimed to investigate the association between HGI/HbA1c and serum uric acid(SUA) stratified by sex and diabetes. Methods The study recruited 33772 participants who underwent physical examinations between April 2016 and August 2021 in Beijing Chao-Yang Hospital. A random subsample of 3000 subjects was utilized to calculate the formula of HGI and data of the remaining 30772 participants were used for analysis. HGI and HbA1c were categorized according to quartiles (Q1, Q2, Q3, Q4), using Q1 as the reference. We used multiple linear regression and restricted cubic splines for data analysis. Results 30772 participants with a mean age of 44.4 years old were included in the analysis, 48.6% (N = 14944) of which were female and 7.7% (N = 2363) with diabetes. Associations of HGI, HbA1c and SUA were modified by sex and diabetes. The relationship between SUA levels and HGI was positive in women without diabetes, with one unit increase in HGI associating with an 11.3 μmol/L increase in SUA (P < 0.001) after adjusting for other confounders. On average, each one-unit increase in HbA1c was associated with a 14.3 μmol/L decrease in SUA in women with diabetes, a 14.9 μmol/L decrease in SUA in men with diabetes, and a 16.5 μmol/L increase in SUA in women without diabetes (all P < 0.001). The SUA levels in men without diabetes showed a bell-shaped relation with HbA1c, increasing as the HbA1c rose to around 5.7% and then falling with a further increase of HbA1c (P < 0.001). Conclusions SUA levels were inversely correlated with HbA1c in diabetic patients, also in men with prediabetes (HbA1c ≥ 5.7%), but positively correlated with HbA1c and HGI in women without diabetes. Glycemic control may help to reduce the risk of hyperuricemia in non-diabetes women.

Relationship between baseline and changed serum uric acid and the incidence of type 2 diabetes mellitus: a national cohort study

“…The accumulating evidence clarifies that as a protective hormone, estrogen declines as women go through menopause, leading to a higher level of SUA, impairing endothelial function and causing insulin resistance. The protective function of estrogen gradually disappears, resulting in the eventual onset of diabetes ( 25 , 64 ). Another study indicated that SUA might induce the β cell dysfunction only in females, suggesting a close association between the higher SUA level and T2DM ( 58 ).…”

Association between Glycosylated Hemoglobin and Serum Uric Acid: A US NHANES 2011–2020

“…A retrospective study in China found that SUA was positively correlated with hyperinsulinemia and insulin resistance in prediabetic patients [ 4 ]. However, a study of the Chinese population found that HbA1c was negatively correlated with SUA in diabetic patients, but HbA1c was positively correlated with hemoglobin glycosylation index in women without diabetes [ 5 ]. Studies have also shown an inverted U-shaped relationship between HbA1c and SUA in both sexes and men's inflection point reaches earlier than women's [ 6 ].…”