Obstructive sleep apnea in lean Vietnamese patients with type 2 diabetes: Role of FTO and TNF genetic variants.

Obstructive sleep apnea is a prevalent condition in patients with type 2 diabetes, including those with normal body weight, suggesting underlying mechanisms beyond obesity. This cross-sectional study aimed to examine the association of two genetic variants, fat mass and obesity-associated (FTO) rs9939609 and tumor necrosis factor (TNF) rs1800629, with obstructive sleep apnea in lean Vietnamese patients with type 2 diabetes. A total of 130 adults with type 2 diabetes and body mass index below 25 kg per square meter underwent clinical evaluation, sleep assessment using respiratory polygraphy, and genotyping. Obstructive sleep apnea was diagnosed in 61 participants (46.9 %). The risk allele A of the FTO variant was present in 17.2 % of the obstructive sleep apnea group, compared to only 0.7 % in the non-obstructive sleep apnea group (p < 0.001). Carriers of the A allele had a 27.8-fold increased risk of obstructive sleep apnea (95 % confidence interval: 3.6 to 214.0), independent of age, sex, body mass index, neck circumference, years of diabetes, and airway anatomy. Although the TNF variant was not significantly associated with the presence of obstructive sleep apnea (odds ratio = 2.2, 95 % confidence interval: 0.7 to 7.1, p = 0.651), it showed noticeable association with apnea-hypopnea index and oxygen desaturation metrics (p-values <0.01). Both variants were significantly associated with unfavorable upper airway characteristics, including increased Mallampati grade and neck circumference. Adding the FTO genotype to standard screening tools improved diagnostic accuracy, with the area under the curve rising from 0.92 to 0.95 and net reclassification improvement reaching 50 %. These findings support the role of metabolic and inflammatory pathways in disease risk among lean patients.