Obstructive sleep apnoea severity and insulin resistance in children with Prader-Willi Syndrome: the SPISE index as a candidate metabolic marker.

We compared two surrogate markers of insulin sensitivity - the single-point insulin sensitivity estimator (SPISE) and HOMA-IR - and evaluated their associations with OSA severity in children with genetically confirmed PWS and a symptomatic non-syndromic referral group (NSR) with available polysomnography (PSG) and fasting biochemical data. In this single-centre retrospective cross-sectional study, OSA severity was indexed by the obstructive apnoea-hypopnoea index (oAHI), central AHI (cAHI) and oxygen desaturation index (ODI), and caregiver-reported symptoms by the PSQ-SRBD scale. Multivariable models were fitted within the PWS group. Of 458 PSG studies screened, 31 children with PWS and 47 NSR met the inclusion criteria. cAHI was higher in PWS (p < 0.001), and PSQ-SRBD scores were slightly lower, despite a similar oAHI distribution. Within the PWS group, oAHI correlated inversely with SPISE (ρ =  - 0.378, p = 0.036). In multivariable models adjusted for age, sex, BMI-SDS, and growth hormone therapy, higher oAHI was associated with lower SPISE (B =  - 0.154, p = 0.015), whereas the association with ln(HOMA-IR) was borderline (B = 0.081, p = 0.0497). ODI correlated with SPISE (ρ =  - 0.427, p = 0.017) but not with HOMA-IR (ρ = 0.319, p = 0.081). Phase-stratified analyses showed oAHI-SPISE correlations in phases 2 and 3 and an oAHI-HOMA-IR correlation in phase 3.

conclusionIn children with PWS, OSA severity was associated with markers of impaired insulin sensitivity. The associations of SPISE with oAHI and ODI support its further investigation as a candidate metabolic correlate of OSA severity. These findings are hypothesis-generating and require validation in larger independent cohorts. WHAT IS KNOWN: • OSA is highly prevalent in PWS. OSA severity is associated with insulin resistance in adults and in non-syndromic children with obesity, but this relationship and the insulin-independent SPISE index have not been evaluated in PWS. WHAT IS NEW: • OSA severity was associated with impaired insulin sensitivity markers in children with PWS. • SPISE, derived from lipids and BMI without fasting insulin, was associated with oAHI and ODI in PWS; it merits further investigation as a candidate metabolic correlate of OSA severity.