title: Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes.
abstract: Production of adrenomedullin (ADM), a vasodilator peptide, increases in response to ischemia and hypoxia in the vascular wall and the kidney. This may be an adaptive response providing protection against organ damage. We investigated the hypothesis that ADM has a nephroprotective effect in two prospective cohorts of patients with type 2 diabetes recruited in France. The highest tertile of plasma MR-proADM (a surrogate for ADM) concentration at baseline was associated with the risk of renal outcomes (doubling of plasma creatinine concentration and/or progression to end-stage renal disease) during follow-up in both cohorts. Four SNPs in the ADM gene region were associated with plasma MR-proADM concentration at baseline and with eGFR during follow-up in both cohorts. The alleles associated with lower eGFR were also associated with lower plasma MR-proADM level. In conclusion, plasma MR-proADM concentration was associated with renal outcome in patients with type 2 diabetes. Our data suggest that the ADM gene modulates the genetic susceptibility to nephropathy progression. Results are consistent with the hypothesis of a reactive rise of ADM in diabetic nephropathy, blunted in risk alleles carriers, and with a nephroprotective effect of ADM. A possible therapeutic effect of ADM receptor agonists in diabetic renal disease would be worth investigating.
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France gilberto.velho@inserm.fr.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.affiliation: INSERM, Centre d'Investigation Clinique (CIC) 1402, Poitiers, France UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ragot
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Assistance Publique - Hôpitaux de Paris, Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, DHU FIRE, Paris, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mohammedi
authors.affiliation: Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Gand
authors.affiliation: INSERM, Centre d'Investigation Clinique (CIC) 1402, Poitiers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Fraty
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fumeron
authors.affiliation: INSERM, Centre d'Investigation Clinique (CIC) 1402, Poitiers, France UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France INSERM, Research Unit 1082, Poitiers, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Saulnier
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Naima
authors.initials: N
authors.lastname: Bellili-Munoz
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Bouby
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Assistance Publique - Hôpitaux de Paris, Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, DHU FIRE, Paris, France UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Potier
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Alhenc-Gelas
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Assistance Publique - Hôpitaux de Paris, Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, DHU FIRE, Paris, France UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.affiliation: INSERM, Centre d'Investigation Clinique (CIC) 1402, Poitiers, France UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France INSERM, Research Unit 1082, Poitiers, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.affiliation: INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France Assistance Publique - Hôpitaux de Paris, Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, DHU FIRE, Paris, France UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
mesh_terms: D053607:Adrenomedullin / Q000097:blood* / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000209:etiology / Q000235:genetics
chemical_list: C507862:ADM protein, human; D010446:Peptide Fragments; D011498:Protein Precursors; C574167:mid-regional pro-adrenomedullin, human; D053607:Adrenomedullin; D003404:Creatinine