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Journal of Endocrinological Investigation

, Volume 41, Issue 7, pp 799–808 | Cite as

Copeptin and insulin resistance: effect modification by age and 11 β-HSD2 activity in a population-based study

  • S. CanivellEmail author
  • M. Mohaupt
  • D. Ackermann
  • M. Pruijm
  • I. Guessous
  • G. Ehret
  • G. Escher
  • A. Pechère-Bertschi
  • B. Vogt
  • O. Devuyst
  • M. Burnier
  • P.-Y. Martin
  • B. Ponte
  • M. Bochud
Original Article

Abstract

Purpose

Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11β-hydroxysteroid-dehydrogenase-type 2 (11β-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11β-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population.

Methods

This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18–90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11β-HSD2 activity were presented as appropriate.

Results

Plasma copeptin was higher in men [median 5.2, IQR (3.7–7.8) pmol/L] than in women [median 3.0, IQR (2.2–4.3) pmol/L], P < 0.0001. HOMA-IR was positively associated with copeptin after full adjustment if 11β-HSD2 activity was high [β (95% CI) = 0.32 (0.17–0.46), P < 0.001] or if age was high [β (95% CI) = 0.34 (0.20–0.48), P < 0.001], but not if either 11β-HSD2 activity or age was low. There was a positive association of type 2 diabetes with copeptin [OR (95% CI) = 2.07 (1.10–3.89), P = 0.024), but not for MetS (OR (95% CI) = 1.12 (0.74–1.69), P = 0.605), after full adjustment.

Conclusions

Our data suggest that age and apparent 11β-HSD2 activity modulate the association of copeptin with insulin resistance at the population level but not MeTS or diabetes. Further research is needed to corroborate these results and to understand the mechanisms underlying these findings.

Keywords

Copeptin Insulin resistance Interaction 11-β hydroxysteroid dehydrogenase type 2 enzyme Aging 

Notes

Acknowledgements

We thank the study nurses Marie-Odile Levy, Guler Gök-Sogüt, Ulla Schüpbach, and Dominique Siminski for their involvement and help with recruitment. We also thank Sandrine Estoppey and JulienWeber for their help in logistic and database management. We thank the study nurses involved in the study and the recruitment: Marie-Odile Levy, GulerGök Sogüt, Ulla Spüchbach, Dominique Siminski.

Compliance with ethical standards

Conflict of interest

There is no conflict of interested in this present work.

Ethical approval

This research involves human participants and all participants have signed a written consent.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

40618_2017_807_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 kb)
40618_2017_807_MOESM2_ESM.docx (107 kb)
Supplementary material 2 (DOCX 106 kb)

References

  1. 1.
    Asferg CL, Andersen UB, Linneberg A, Goetze JP, Jeppesen JL (2014) Copeptin, a surrogate marker for arginine vasopressin secretion, is associated with higher glucose and insulin concentrations but not higher blood pressure in obese men. Diabet Med J Br Diabet Assoc 31(6):728–732.  https://doi.org/10.1111/dme.12411 CrossRefGoogle Scholar
  2. 2.
    Enhorning S, Bankir L, Bouby N, Struck J, Hedblad B, Persson M, Morgenthaler NG, Nilsson PM, Melander O (2013) Copeptin, a marker of vasopressin, in abdominal obesity, diabetes and microalbuminuria: the prospective Malmo Diet and Cancer Study cardiovascular cohort. Int J Obes 37(4):598–603.  https://doi.org/10.1038/ijo.2012.88 CrossRefGoogle Scholar
  3. 3.
    Enhorning S, Struck J, Wirfalt E, Hedblad B, Morgenthaler NG, Melander O (2011) Plasma copeptin, a unifying factor behind the metabolic syndrome. J Clin Endocrinol Metab 96(7):E1065–E1072.  https://doi.org/10.1210/jc.2010-2981 CrossRefPubMedGoogle Scholar
  4. 4.
    Enhorning S, Wang TJ, Nilsson PM, Almgren P, Hedblad B, Berglund G, Struck J, Morgenthaler NG, Bergmann A, Lindholm E, Groop L, Lyssenko V, Orho-Melander M, Newton-Cheh C, Melander O (2010) Plasma copeptin and the risk of diabetes mellitus. Circulation 121(19):2102–2108.  https://doi.org/10.1161/circulationaha.109.909663 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Saleem U, Khaleghi M, Morgenthaler NG, Bergmann A, Struck J, Mosley TH Jr, Kullo IJ (2009) Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. J Clin Endocrinol Metab 94(7):2558–2564.  https://doi.org/10.1210/jc.2008-2278 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Struck J, Morgenthaler NG, Bergmann A (2005) Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides 26(12):2500–2504.  https://doi.org/10.1016/j.peptides.2005.04.019 CrossRefPubMedGoogle Scholar
  7. 7.
    Morgenthaler NG, Struck J, Alonso C, Bergmann A (2006) Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 52(1):112–119.  https://doi.org/10.1373/clinchem.2005.060038 CrossRefPubMedGoogle Scholar
  8. 8.
    Roussel R, Fezeu L, Marre M, Velho G, Fumeron F, Jungers P, Lantieri O, Balkau B, Bouby N, Bankir L, Bichet DG (2014) Comparison between copeptin and vasopressin in a population from the community and in people with chronic kidney disease. J Clin Endocrinol Metab 99(12):4656–4663.  https://doi.org/10.1210/jc.2014-2295 CrossRefPubMedGoogle Scholar
  9. 9.
    Roussel R, El Boustany R, Bouby N, Potier L, Fumeron F, Mohammedi K, Balkau B, Tichet J, Bankir L, Marre M, Velho G (2016) Plasma copeptin, AVP gene variants, and incidence of Type 2 diabetes in a cohort from the community. J Clin Endocrinol Metab 101(6):2432–2439.  https://doi.org/10.1210/jc.2016-1113 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Rothermel J, Kulle A, Holterhus PM, Toschke C, Lass N, Reinehr T (2016) Copeptin in obese children and adolescents: relationships to body mass index, cortisol and gender. Clin Endocrinol (Oxf).  https://doi.org/10.1111/cen.13235 CrossRefGoogle Scholar
  11. 11.
    Rubis B, Krozowski Z, Trzeciak WH (2006) Arginine vasopressin stimulates 11beta-hydroxysteroid dehydrogenase type 2 expression in the mineralocorticosteroid target cells. Mol Cell Endocrinol 256(1–2):17–22.  https://doi.org/10.1016/j.mce.2006.04.032 CrossRefPubMedGoogle Scholar
  12. 12.
    Crowley RK, Hughes B, Gray J, McCarthy T, Hughes S, Shackleton CH, Crabtree N, Nightingale P, Stewart PM, Tomlinson JW (2014) Longitudinal changes in glucocorticoid metabolism are associated with later development of adverse metabolic phenotype. Eur j endocrinol Eur Fed Endoc Soc 171(4):433–442.  https://doi.org/10.1530/eje-14-0256 CrossRefGoogle Scholar
  13. 13.
    Di Dalmazi G, Pagotto U, Pasquali R, Vicennati V (2012) Glucocorticoids and type 2 diabetes: from physiology to pathology. J Nutr Metab 2012:525093.  https://doi.org/10.1155/2012/525093 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Pereira CD, Azevedo I, Monteiro R, Martins MJ (2012) 11beta-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus. Diabetes Obes Metab 14(10):869–881.  https://doi.org/10.1111/j.1463-1326.2012.01582.x CrossRefPubMedGoogle Scholar
  15. 15.
    Funder JW, Pearce PT, Smith R, Smith AI (1988) Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242(4878):583–585CrossRefPubMedGoogle Scholar
  16. 16.
    Pivonello R, De Leo M, Vitale P, Cozzolino A, Simeoli C, De Martino MC, Lombardi G, Colao A (2010) Pathophysiology of diabetes mellitus in Cushing’s syndrome. Neuroendocrinology 92(Suppl 1):77–81.  https://doi.org/10.1159/000314319 CrossRefPubMedGoogle Scholar
  17. 17.
    Newell-Price J, Bertagna X, Grossman AB, Nieman LK (2006) Cushing’s syndrome. Lancet 367(9522):1605–1617.  https://doi.org/10.1016/s0140-6736(06)68699-6 CrossRefPubMedGoogle Scholar
  18. 18.
    Hollis G, Huber R (2011) 11beta-Hydroxysteroid dehydrogenase type 1 inhibition in type 2 diabetes mellitus. Diabetes Obes Metab 13(1):1–6.  https://doi.org/10.1111/j.1463-1326.2010.01305.x CrossRefPubMedGoogle Scholar
  19. 19.
    Stewart PM, Tomlinson JW (2009) Selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 for patients with metabolic syndrome: is the target liver, fat, or both? Diabetes 58(1):14–15CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Stomby A, Andrew R, Walker BR, Olsson T (2014) Tissue-specific dysregulation of cortisol regeneration by 11betaHSD1 in obesity: has it promised too much? Diabetologia 57(6):1100–1110.  https://doi.org/10.1007/s00125-014-3228-6 CrossRefPubMedGoogle Scholar
  21. 21.
    Mussig K, Remer T, Haupt A, Gallwitz B, Fritsche A, Haring HU, Maser-Gluth C (2008) 11beta-hydroxysteroid dehydrogenase 2 activity is elevated in severe obesity and negatively associated with insulin sensitivity. Obesity (Silver Spring) 16(6):1256–1260.  https://doi.org/10.1038/oby.2008.218 CrossRefGoogle Scholar
  22. 22.
    Milagro FI, Campion J, Martinez JA (2007) 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity. J Steroid Biochem Mol Biol 104(1–2):81–84.  https://doi.org/10.1016/j.jsbmb.2006.10.006 CrossRefPubMedGoogle Scholar
  23. 23.
    Ponte B, Pruijm M, Ackermann D, Vuistiner P, Guessous I, Ehret G, Alwan H, Youhanna S, Paccaud F, Mohaupt M, Pechere-Bertschi A, Vogt B, Burnier M, Martin PY, Devuyst O, Bochud M (2014) Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study. J Am So Nephrol 26(6):1415–1425.  https://doi.org/10.1681/asn.2014030260 CrossRefGoogle Scholar
  24. 24.
    Ponte B, Pruijm M, Ackermann D, Vuistiner P, Eisenberger U, Guessous I, Rousson V, Mohaupt MG, Alwan H, Ehret G, Pechere-Bertschi A, Paccaud F, Staessen JA, Vogt B, Burnier M, Martin PY, Bochud M (2014) Reference values and factors associated with renal resistive index in a family-based population study. Hypertension 63(1):136–142.  https://doi.org/10.1161/hypertensionaha.113.02321 CrossRefPubMedGoogle Scholar
  25. 25.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419CrossRefPubMedGoogle Scholar
  26. 26.
    Third Report of the National Cholesterol Education Program (NCEP) (2002) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 106(25):3143–3421CrossRefGoogle Scholar
  27. 27.
    Shackleton CH (1993) Mass spectrometry in the diagnosis of steroid-related disorders and in hypertension research. J Steroid Biochem Mol Biol 45(1–3):127–140CrossRefPubMedGoogle Scholar
  28. 28.
    Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH (1999) Cortisol metabolism in human obesity: impaired cortisone ≥ cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab 84(3):1022–1027.  https://doi.org/10.1210/jcem.84.3.5538 PubMedCrossRefGoogle Scholar
  29. 29.
    Tamma G, Goswami N, Reichmuth J, De Santo NG, Valenti G (2014) Aquaporins, vasopressin and aging: current perspectives. Endocrinology 156:777–778.  https://doi.org/10.1210/en.2014-1812 CrossRefPubMedGoogle Scholar
  30. 30.
    Melander O (2016) Vasopressin, from regulator to disease predictor for diabetes and cardiometabolic risk. Ann Nutr Metab 68(Suppl 2):24–28.  https://doi.org/10.1159/000446201 CrossRefPubMedGoogle Scholar
  31. 31.
    Chapman K, Holmes M, Seckl J (2013) 11beta-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev 93(3):1139–1206.  https://doi.org/10.1152/physrev.00020.2012 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  • S. Canivell
    • 1
    Email author
  • M. Mohaupt
    • 2
  • D. Ackermann
    • 2
  • M. Pruijm
    • 3
  • I. Guessous
    • 4
    • 5
  • G. Ehret
    • 6
  • G. Escher
    • 2
  • A. Pechère-Bertschi
    • 7
  • B. Vogt
    • 2
  • O. Devuyst
    • 8
  • M. Burnier
    • 9
    • 10
  • P.-Y. Martin
    • 11
  • B. Ponte
    • 11
  • M. Bochud
    • 1
  1. 1.Institute of Social and Preventive MedicineLausanne University HospitalLausanneSwitzerland
  2. 2.University Clinic for Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University HospitalUniversity of BernBernSwitzerland
  3. 3.Service of Nephrology and HypertensionUniversity Hospital of Lausanne (CHUV)LausanneSwitzerland
  4. 4.Department of Community Medicine, Primary Care and Emergency MedicineUniversity Hospital of GenevaGenevaSwitzerland
  5. 5.Institute of Social and Preventive MedicineUniversity Hospital of LausanneLausanneSwitzerland
  6. 6.Cardiology Service, Department of Specialties of Internal MedicineUniversity Hospital of GenevaGenevaSwitzerland
  7. 7.Unit of Hypertension, Departments of Specialties of Medicine and Community Medicine and Primary Care and Emergency MedicineGeneva University HospitalsGenevaSwitzerland
  8. 8.Institute of PhysiologyUniversity of ZurichZurichSwitzerland
  9. 9.Nephrology ServiceUniversity Hospital of LausanneLausanneSwitzerland
  10. 10.Department of Clinical ResearchUniversity of BernBernSwitzerland
  11. 11.Nephrology Service, Department of Specialties of Internal MedicineUniversity Hospital of GenevaGenevaSwitzerland

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