Lipodystrophy Severity Score to Assess Disease Burden in Lipodystrophy

Abstract Context Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities. Objective Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact. Design An 8-domain LDS was developed by eight disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at two different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in two cohorts of patients with lipodystrophy treated with metreleptin. Results LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by one or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility, and high reliability by intraclass correlation coefficients (>0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R=0.79-0.99, P<0.001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P<0.001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P=0.04). Conclusions The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.