Association between hemoglobin glycation index and metabolic syndrome in Saudi adolescents: A cross-sectional study

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. The Hemoglobin Glycation Index (HGI), which quantifies the difference between observed glycated hemoglobin (HbA1c) and HbA1c predicted from fasting plasma glucose, has been proposed as a metabolic risk marker. However, evidence regarding its association with MetS remains inconsistent, particularly among adolescents. This study examined the associations between HGI and MetS, including sex-stratified patterns, among Saudi adolescents from Riyadh. This cross-sectional study included 2342 Saudi adolescents (893 boys and 1449 girls; mean age, 14.8 ± 1.7 years) recruited from secondary schools in Riyadh between September 2019 and March 2021. Anthropometric measurements, blood pressure, fasting plasma glucose, HbA1c, lipid profile, vitamin D, and selected biochemical markers were assessed. HGI was calculated as the difference between observed and predicted HbA1c, with predicted values derived from a linear regression model using fasting plasma glucose. MetS was defined using established pediatric criteria. Unadjusted binary logistic regression and correlation analyses were performed. MetS was present in 43.3% of participants and was more prevalent in boys than girls (47.1% vs 40.9%). Participants with MetS had higher body mass index, blood pressure, triglycerides, and fasting plasma glucose levels, lower high-density lipoprotein cholesterol and vitamin D levels (all P <.01). HGI was lower in participants with MetS than those without (-0.057 ± 0.60 vs -0.003 ± 0.52, P <.05), with the largest difference observed among girls. In unadjusted logistic regression analyses, higher HGI tertiles were associated with lower odds of MetS compared with the lowest tertile. Correlation analyses revealed different correlation patterns between boys and girls; however, most associations between HGI and clinical or biochemical variables were weak in magnitude. Higher HGI tertiles were inversely associated with MetS in this cross-sectional sample of Saudi adolescents, contrary to patterns commonly reported in adult populations. As these associations were unadjusted and the study was cross-sectional, they should not be interpreted as independent or causal. Longitudinal studies incorporating direct measures of insulin resistance, pubertal status, erythrocyte turnover, and inflammatory markers are needed to clarify the biological basis and directionality of the HGI-MetS association in adolescents.