Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy.
J Clin Endocrinol Metab
; 107(4): e1739-e1751, 2022 03 24.
Article
em En
| MEDLINE
| ID: mdl-34677608
ABSTRACT
CONTEXT Leptin replacement with metreleptin improves glycemia and hypertriglyceridemia in severely hypoleptinemic patients with generalized lipodystrophy (GLD), but its effects are variable in partially leptin-deficient patients with partial lipodystrophy (PLD). OBJECTIVE:
Compare 3 leptin assays (Study I); identify diagnostic performance of leptin assays to detect responders to metreleptin for each assay (Study II).DESIGN:
Study I cross-sectional analysis of average bias between leptin assays. Study II retrospective analysis of diagnostic accuracy of potential leptin cut points to detect clinical responders to metreleptin.SETTING:
National Institutes of Health; University of Michigan. PARTICIPANTS ANDINTERVENTIONS:
Study I Metreleptin-naïve patients with lipodystrophy (GLD, n = 33, PLD, n = 67) and healthy volunteers (n = 239). Study II GLD (n = 66) and PLD (n = 84) patients treated with metreleptin for 12 months. OUTCOMEMEASURES:
Leptin concentrations by Millipore radioimmunoassay (RIA), Millipore enzyme-linked immunosorbent assay (MELISA), and R&D Systems enzyme-linked immunosorbent assay (RDELISA). Response to metreleptin therapy was defined as either reduction ≥1.0% in A1c or ≥30% in serum triglycerides.RESULTS:
RDELISA measured 3.0 ± 9.5 ng/mL higher than RIA; MELISA measured 11.0 ± 17.8 and 14.0 ±19.2 less than RIA and RDELISA, respectively. Leptin by RIA, MELISA, and RDELISA modestly predicted metreleptin response in GLD + PLD [receiver operating characteristic (ROC) area under the curve (AUC) 0.74, 0.69, and 0.71, respectively; P < 0.01 for all] with lower predictive power in PLD (ROC AUC 0.63, 0.61 and 0.65, respectively; P > 0.05 for all). The only reproducible cut point identified on sensitivity analyses was RIA leptin 7.2 ng/mL (sensitivity 56%; specificity 78%).CONCLUSIONS:
Three common leptin assays are not interchangeable, and a reliable cut point to select responders to metreleptin was not identified.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leptina
/
Lipodistrofia
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos