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

Autor:	Meral R; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, USA.; Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.; Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.; Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Malandrino N; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, USA., Walter M; Clinical Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA., Neidert AH; Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA., Muniyappa R; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, USA., Oral EA; Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA., Brown RJ; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2022 Mar 24; Vol. 107 (4), pp. e1739-e1751.
DOI:	10.1210/clinem/dgab760
Abstrakt:	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-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. 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. (Published by Oxford University Press on behalf of the Endocrine Society 2021.)
Databáze:	MEDLINE
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