Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy

MERAL R., Malandrino N., Walter M., Neidert A. H., Muniyappa R., Oral E. A., ...Daha Fazla

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, cilt.107, sa.4, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 107 Sayı: 4
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1210/clinem/dgab760
  • Dergi Adı: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, Chemical Abstracts Core, CINAHL, EMBASE, Food Science & Technology Abstracts, Gender Studies Database, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: lipodystrophy, leptin, metreleptin, RIA, ELISA, assay, cut point, LONG-TERM EFFICACY, REPLACEMENT THERAPY, GENERALIZED LIPODYSTROPHY, OBESITY, WEIGHT, HUMANS, GENDER, SAFETY
  • İstanbul Üniversitesi Adresli: Evet

Özet

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 and Interventions Study I: Metreleptin-naive 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. Outcome Measures 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.