title: One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes.
abstract: Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency. Patients, with a mean [± standard error of the mean (s.e.m.)] age of 39.2 (±4) years, presented with familial partial lipodystrophy (n = 11, 10 women) or congenital generalized lipodystrophy (n = 5, four women). Their mean (± s.e.m.) BMI (23.9 ± 0.7 kg/m(2) ), glycated haemoglobin levels (8.5 ± 0.4%) and serum triglycerides levels (4.6 ± 0.9 mmol/l) significantly decreased within 1 month of metreleptin therapy, then remained stable. Insulin sensitivity (from hyperglycaemic or euglycaemic-hyperinsulinaemic clamps, n = 4 and n = 12, respectively), insulin secretion during graded glucose infusion (n = 12), and acute insulin response to i.v. glucose adjusted to insulin sensitivity (disposition index, n = 12), significantly increased after 1 year of metreleptin therapy. The increase in disposition index was related to a decrease in percentage of total and trunk body fat. Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies.
authors.affiliation: Sorbonne Universités, UPMC, Univ Paris 06, Paris, France.|Centre de Recherche Saint-Antoine, INSERM, UMR_S938, Paris, France.|ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Vatier
authors.affiliation: Service de Diabétologie et Endocrinologie, AP-HP, Groupe Hospitalier Lariboisière-Saint-Louis, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Fetita
authors.affiliation: Service de Biochimie, AP-HP, Hôpital Saint-Louis, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Boudou
authors.affiliation: Service de Diabétologie et Endocrinologie, AP-HP, Groupe Hospitalier Lariboisière-Saint-Louis, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Tchankou
authors.affiliation: Département de Pharmacie, AP-HP, Hôpital Saint-Louis, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Deville
authors.affiliation: Service de Diabétologie et Endocrinologie, AP-HP, Groupe Hospitalier Lariboisière-Saint-Louis, Paris, France.|Centre de Recherche des Cordeliers, INSERM, UMR_S1138, Paris, France.
authors.forename: Jp
authors.initials: J
authors.lastname: Riveline
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.affiliation: Service de Pédiatrie, Centre Hospitalier de Meaux, Meaux, France.
authors.forename: L
authors.initials: L
authors.lastname: Mathivon
authors.affiliation: Service d'Endocrinologie, Diabétologie, Nutrition, AP-HP, Hôpital Bichat, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Travert
authors.affiliation: Service de Pédiatrie, CHRU Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Morin
authors.affiliation: Service d'Endocrinologie et Métabolismes, Centre Hospitalier, Argenteuil, France.
authors.forename: J
authors.initials: J
authors.lastname: Cahen
authors.affiliation: Sorbonne Universités, UPMC, Univ Paris 06, Paris, France.|Centre de Recherche Saint-Antoine, INSERM, UMR_S938, Paris, France.|ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.|Laboratoire Commun de Biologie et Génétique Moléculaires, AP-HP, Hôpital Saint-Antoine, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Lascols
authors.affiliation: ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.|Service de Diabétologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Andreelli
authors.affiliation: Service d'Endocrinologie, Centre Hospitalier Universitaire Côte-de-Nacre, Caen, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Reznik
authors.affiliation: Service d'Endocrinologie, Centre Hospitalier Régional d'Orléans, Orléans, France.
authors.forename: E
authors.initials: E
authors.lastname: Mongeois
authors.affiliation: Département de Pharmacie, AP-HP, Hôpital Saint-Louis, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Madelaine
authors.affiliation: Service d'Endocrinologie et Métabolisme, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
authors.forename: Mc
authors.initials: M
authors.lastname: Vantyghem
authors.affiliation: Service de Diabétologie et Endocrinologie, AP-HP, Groupe Hospitalier Lariboisière-Saint-Louis, Paris, France.|Centre de Recherche des Cordeliers, INSERM, UMR_S1138, Paris, France.|University Paris-Diderot Paris-7, Paris, France.
authors.forename: Jf
authors.initials: J
authors.lastname: Gautier
authors.affiliation: Sorbonne Universités, UPMC, Univ Paris 06, Paris, France.|Centre de Recherche Saint-Antoine, INSERM, UMR_S938, Paris, France.|ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.|Laboratoire Commun de Biologie et Génétique Moléculaires, AP-HP, Hôpital Saint-Antoine, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Vigouroux
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D034904:Lamin Type A / Q000235:genetics; D020738:Leptin / Q000031:analogs & derivatives* / Q000172:deficiency / Q000627:therapeutic use; D008060:Lipodystrophy / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D013577:Syndrome; D014280:Triglycerides / Q000378:metabolism
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D034904:Lamin Type A; D020738:Leptin; D014280:Triglycerides; C494847:LMNA protein, human; C415771:metreleptin
keywords: glucose metabolism; insulin resistance; insulin secretion; leptin; lipodystrophy; observational study