Baseline leptin and longitudinal LDL-C changes in relation to sleep-disordered breathing: The Toon Health Study

Existing evidence regarding the effect of leptin on low-density lipoprotein cholesterol (LDL-C) is inconsistent. One possible explanation for this inconsistency is sleep-disordered breathing (SDB), a common condition associated with both leptin and dyslipidemia.

This study aimed to clarify the role of leptin in the regulation of LDL-C in humans and to examine whether SDB modifies this association.

We analyzed data from the Toon Health Study. Among those who completed baseline examinations, leptin and LDL-C measurements were available for 1113 participants. Follow-up examinations were conducted 5 years later. SDB was assessed using overnight pulse oximetry. Longitudinal changes in LDL-C were evaluated using linear mixed-effects models. Serum leptin levels were analyzed in sex-specific quartiles; for stratified analyses, high leptin was defined as above the sex-specific 75th percentile.

Over the 5-year follow-up period, upper-quartile baseline leptin levels were associated with a pronounced decline in LDL-C compared with the lowest quartile. Comparison of the high and low leptin groups revealed that this association was evident only among participants without SDB (n = 149 and 570, respectively). When a stricter cutoff of oxygen desaturation index (<2) was applied, the association remained significant (n = 79 and 347, respectively). Moreover, the 3-way interaction term (leptin × time × SDB status) reached statistical significance.

Higher baseline leptin levels were associated with a statistically significant decline in LDL-C over 5 years, particularly among individuals without SDB. These results suggest that SDB modifies the longitudinal association between leptin and LDL-C.