Skip to main content
Erschienen in: Diabetologia 7/2012

01.07.2012 | Article

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

verfasst von: A. Abbasi, E. Corpeleijn, E. Meijer, D. Postmus, R. T. Gansevoort, R. O. B. Gans, J. Struck, H. L. Hillege, R. P. Stolk, G. Navis, S. J. L. Bakker

Erschienen in: Diabetologia | Ausgabe 7/2012

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately.

Methods

From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years.

Results

In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p interaction < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model.

Conclusions/interpretation

The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women.
Literatur
1.
Zurück zum Zitat Aoyagi T, Birumachi J, Hiroyama M et al (2007) Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. Endocrinology 148:2075–2084PubMedCrossRef Aoyagi T, Birumachi J, Hiroyama M et al (2007) Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. Endocrinology 148:2075–2084PubMedCrossRef
2.
Zurück zum Zitat Zerbe RL, Vinicor F, Robertson GL (1979) Plasma vasopressin in uncontrolled diabetes mellitus. Diabetes 28:503–508PubMedCrossRef Zerbe RL, Vinicor F, Robertson GL (1979) Plasma vasopressin in uncontrolled diabetes mellitus. Diabetes 28:503–508PubMedCrossRef
3.
Zurück zum Zitat Struck J, Morgenthaler NG, Bergmann A (2005) Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides 26:2500–2504PubMedCrossRef Struck J, Morgenthaler NG, Bergmann A (2005) Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides 26:2500–2504PubMedCrossRef
4.
Zurück zum Zitat Meijer E, Bakker SJ, Halbesma N, de Jong PE, Struck J, Gansevoort RT (2010) Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort. Kidney Int 77:29–36PubMedCrossRef Meijer E, Bakker SJ, Halbesma N, de Jong PE, Struck J, Gansevoort RT (2010) Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort. Kidney Int 77:29–36PubMedCrossRef
5.
Zurück zum Zitat 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 52:112–119PubMedCrossRef 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 52:112–119PubMedCrossRef
6.
Zurück zum Zitat Enhorning S, Wang TJ, Nilsson PM et al (2010) Plasma copeptin and the risk of diabetes mellitus. Circulation 121:2102–2108PubMedCrossRef Enhorning S, Wang TJ, Nilsson PM et al (2010) Plasma copeptin and the risk of diabetes mellitus. Circulation 121:2102–2108PubMedCrossRef
7.
Zurück zum Zitat Kirk CJ, Rodrigues LM, Hems DA (1979) The influence of vasopressin and related peptides on glycogen phosphorylase activity and phosphatidylinositol metabolism in hepatocytes. Biochem J 178:493–496PubMed Kirk CJ, Rodrigues LM, Hems DA (1979) The influence of vasopressin and related peptides on glycogen phosphorylase activity and phosphatidylinositol metabolism in hepatocytes. Biochem J 178:493–496PubMed
8.
Zurück zum Zitat Oshikawa S, Tanoue A, Koshimizu TA, Kitagawa Y, Tsujimoto G (2004) Vasopressin stimulates insulin release from islet cells through V1b receptors: a combined pharmacological/knockout approach. Mol Pharmacol 65:623–629PubMedCrossRef Oshikawa S, Tanoue A, Koshimizu TA, Kitagawa Y, Tsujimoto G (2004) Vasopressin stimulates insulin release from islet cells through V1b receptors: a combined pharmacological/knockout approach. Mol Pharmacol 65:623–629PubMedCrossRef
9.
Zurück zum Zitat Tanoue A, Ito S, Honda K et al (2004) The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J Clin Invest 113:302–309PubMed Tanoue A, Ito S, Honda K et al (2004) The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J Clin Invest 113:302–309PubMed
10.
Zurück zum Zitat Fujiwara Y, Hiroyama M, Sanbe A et al (2007) Insulin hypersensitivity in mice lacking the V1b vasopressin receptor. J Physiol 584:235–244PubMedCrossRef Fujiwara Y, Hiroyama M, Sanbe A et al (2007) Insulin hypersensitivity in mice lacking the V1b vasopressin receptor. J Physiol 584:235–244PubMedCrossRef
11.
Zurück zum Zitat Stachenfeld NS, Splenser AE, Calzone WL, Taylor MP, Keefe DL (2001) Sex differences in osmotic regulation of AVP and renal sodium handling. J Appl Physiol 91:1893–1901PubMed Stachenfeld NS, Splenser AE, Calzone WL, Taylor MP, Keefe DL (2001) Sex differences in osmotic regulation of AVP and renal sodium handling. J Appl Physiol 91:1893–1901PubMed
12.
Zurück zum Zitat Simmler LD, Hysek CM, Liechti ME (2011) Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects. J Clin Endocrinol Metab 96:2844–2850PubMedCrossRef Simmler LD, Hysek CM, Liechti ME (2011) Sex differences in the effects of MDMA (ecstasy) on plasma copeptin in healthy subjects. J Clin Endocrinol Metab 96:2844–2850PubMedCrossRef
13.
Zurück zum Zitat Brantsma AH, Bakker SJ, Hillege HL, de Zeeuw D, de Jong PE, Gansevoort RT (2005) Urinary albumin excretion and its relation with C-reactive protein and the metabolic syndrome in the prediction of type 2 diabetes. Diabetes Care 28:2525–2530PubMedCrossRef Brantsma AH, Bakker SJ, Hillege HL, de Zeeuw D, de Jong PE, Gansevoort RT (2005) Urinary albumin excretion and its relation with C-reactive protein and the metabolic syndrome in the prediction of type 2 diabetes. Diabetes Care 28:2525–2530PubMedCrossRef
14.
Zurück zum Zitat Halimi JM, Bonnet F, Lange C, Balkau B, Tichet J, Marre M (2008) Urinary albumin excretion is a risk factor for diabetes mellitus in men, independently of initial metabolic profile and development of insulin resistance. The DESIR Study. J Hypertens 26:2198–2206PubMedCrossRef Halimi JM, Bonnet F, Lange C, Balkau B, Tichet J, Marre M (2008) Urinary albumin excretion is a risk factor for diabetes mellitus in men, independently of initial metabolic profile and development of insulin resistance. The DESIR Study. J Hypertens 26:2198–2206PubMedCrossRef
15.
Zurück zum Zitat Thorand B, Lowel H, Schneider A et al (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984–1998. Arch Intern Med 163:93–99PubMedCrossRef Thorand B, Lowel H, Schneider A et al (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984–1998. Arch Intern Med 163:93–99PubMedCrossRef
16.
Zurück zum Zitat Thorand B, Baumert J, Kolb H et al (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care 30:854–860PubMedCrossRef Thorand B, Baumert J, Kolb H et al (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care 30:854–860PubMedCrossRef
17.
Zurück zum Zitat Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334PubMedCrossRef Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334PubMedCrossRef
18.
Zurück zum Zitat Lambers Heerspink HJ, Brantsma AH, de Zeeuw D, Bakker SJ, de Jong PE, Gansevoort RT (2008) Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality. Am J Epidemiol 168:897–905PubMedCrossRef Lambers Heerspink HJ, Brantsma AH, de Zeeuw D, Bakker SJ, de Jong PE, Gansevoort RT (2008) Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality. Am J Epidemiol 168:897–905PubMedCrossRef
19.
Zurück zum Zitat Monster TB, Janssen WM, de Jong PE, de Jong-van den Berg LT (2002) Pharmacy data in epidemiological studies: an easy to obtain and reliable tool. Pharmacoepidemiol Drug Saf 11:379–384PubMedCrossRef Monster TB, Janssen WM, de Jong PE, de Jong-van den Berg LT (2002) Pharmacy data in epidemiological studies: an easy to obtain and reliable tool. Pharmacoepidemiol Drug Saf 11:379–384PubMedCrossRef
20.
Zurück zum Zitat Fenske W, Stork S, Blechschmidt A, Maier SG, Morgenthaler NG, Allolio B (2009) Copeptin in the differential diagnosis of hyponatremia. J Clin Endocrinol Metab 94:123–129PubMedCrossRef Fenske W, Stork S, Blechschmidt A, Maier SG, Morgenthaler NG, Allolio B (2009) Copeptin in the differential diagnosis of hyponatremia. J Clin Endocrinol Metab 94:123–129PubMedCrossRef
21.
Zurück zum Zitat Abbasi A, Corpeleijn E, Postmus D et al (2011) Plasma procalcitonin and risk of type 2 diabetes in the general population. Diabetologia 54:2463–2465PubMedCrossRef Abbasi A, Corpeleijn E, Postmus D et al (2011) Plasma procalcitonin and risk of type 2 diabetes in the general population. Diabetologia 54:2463–2465PubMedCrossRef
22.
Zurück zum Zitat Balkau B, Lange C, Fezeu L et al (2008) Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 31:2056–2061PubMedCrossRef Balkau B, Lange C, Fezeu L et al (2008) Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 31:2056–2061PubMedCrossRef
23.
Zurück zum Zitat Pencina MJ, D'Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21PubMedCrossRef Pencina MJ, D'Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21PubMedCrossRef
24.
Zurück zum Zitat Cook NR, Ridker PM (2009) Advances in measuring the effect of individual predictors of cardiovascular risk: the role of reclassification measures. Ann Intern Med 150:795–802PubMed Cook NR, Ridker PM (2009) Advances in measuring the effect of individual predictors of cardiovascular risk: the role of reclassification measures. Ann Intern Med 150:795–802PubMed
25.
Zurück zum Zitat American Diabetes Association (2007) Standards of medical care in diabetes—2007. Diabetes Care 30 Suppl 1: S4-S41 American Diabetes Association (2007) Standards of medical care in diabetes—2007. Diabetes Care 30 Suppl 1: S4-S41
26.
Zurück zum Zitat Buijsse B, Simmons RK, Griffin SJ, Schulze MB (2011) Risk assessment tools for identifying individuals at risk of developing type 2 diabetes. Epidemiol Rev 33:46–62PubMedCrossRef Buijsse B, Simmons RK, Griffin SJ, Schulze MB (2011) Risk assessment tools for identifying individuals at risk of developing type 2 diabetes. Epidemiol Rev 33:46–62PubMedCrossRef
27.
Zurück zum Zitat Collins GS, Mallett S, Omar O, Yu LM (2011) Developing risk prediction models for type 2 diabetes: a systematic review of methodology and reporting. BMC Med 9:103PubMedCrossRef Collins GS, Mallett S, Omar O, Yu LM (2011) Developing risk prediction models for type 2 diabetes: a systematic review of methodology and reporting. BMC Med 9:103PubMedCrossRef
28.
Zurück zum Zitat McGeechan K, Macaskill P, Irwig L, Liew G, Wong TY (2008) Assessing new biomarkers and predictive models for use in clinical practice: a clinician's guide. Arch Intern Med 168:2304–2310PubMedCrossRef McGeechan K, Macaskill P, Irwig L, Liew G, Wong TY (2008) Assessing new biomarkers and predictive models for use in clinical practice: a clinician's guide. Arch Intern Med 168:2304–2310PubMedCrossRef
29.
Zurück zum Zitat 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:E1065–E1072PubMedCrossRef 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:E1065–E1072PubMedCrossRef
30.
Zurück zum Zitat Saleem U, Khaleghi M, Morgenthaler NG et al (2009) Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. J Clin Endocrinol Metab 94:2558–2564PubMedCrossRef Saleem U, Khaleghi M, Morgenthaler NG et al (2009) Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. J Clin Endocrinol Metab 94:2558–2564PubMedCrossRef
31.
Zurück zum Zitat Bhandari SS, Loke I, Davies JE, Squire IB, Struck J, Ng LL (2009) Gender and renal function influence plasma levels of copeptin in healthy individuals. Clin Sci (Lond) 116:257–263CrossRef Bhandari SS, Loke I, Davies JE, Squire IB, Struck J, Ng LL (2009) Gender and renal function influence plasma levels of copeptin in healthy individuals. Clin Sci (Lond) 116:257–263CrossRef
32.
Zurück zum Zitat Salomaa V, Havulinna A, Saarela O et al (2010) Thirty-one novel biomarkers as predictors for clinically incident diabetes. PLoS One 5:e10100PubMedCrossRef Salomaa V, Havulinna A, Saarela O et al (2010) Thirty-one novel biomarkers as predictors for clinically incident diabetes. PLoS One 5:e10100PubMedCrossRef
33.
Zurück zum Zitat Ding EL, Song Y, Malik VS, Liu S (2006) Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 295:1288–1299PubMedCrossRef Ding EL, Song Y, Malik VS, Liu S (2006) Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 295:1288–1299PubMedCrossRef
34.
Zurück zum Zitat Herder C, Karakas M, Koenig W (2011) Biomarkers for the prediction of type 2 diabetes and cardiovascular disease. Clin Pharmacol Ther 90:52–66PubMedCrossRef Herder C, Karakas M, Koenig W (2011) Biomarkers for the prediction of type 2 diabetes and cardiovascular disease. Clin Pharmacol Ther 90:52–66PubMedCrossRef
35.
Zurück zum Zitat Nakamura K, Aoyagi T, Hiroyama M et al (2009) Both V(1A) and V(1B) vasopressin receptors deficiency result in impaired glucose tolerance. Eur J Pharmacol 613:182–188PubMedCrossRef Nakamura K, Aoyagi T, Hiroyama M et al (2009) Both V(1A) and V(1B) vasopressin receptors deficiency result in impaired glucose tolerance. Eur J Pharmacol 613:182–188PubMedCrossRef
36.
Zurück zum Zitat Kajantie E, Phillips DI (2006) The effects of sex and hormonal status on the physiological response to acute psychosocial stress. Psychoneuroendocrinology 31:151–178PubMedCrossRef Kajantie E, Phillips DI (2006) The effects of sex and hormonal status on the physiological response to acute psychosocial stress. Psychoneuroendocrinology 31:151–178PubMedCrossRef
37.
Zurück zum Zitat Rhodes ME, Rubin RT (1999) Functional sex differences (‘sexual diergism’) of central nervous system cholinergic systems, vasopressin, and hypothalamic-pituitary-adrenal axis activity in mammals: a selective review. Brain Res Brain Res Rev 30:135–152PubMedCrossRef Rhodes ME, Rubin RT (1999) Functional sex differences (‘sexual diergism’) of central nervous system cholinergic systems, vasopressin, and hypothalamic-pituitary-adrenal axis activity in mammals: a selective review. Brain Res Brain Res Rev 30:135–152PubMedCrossRef
38.
Zurück zum Zitat Lancet (2011) Taking sex into account in medicine. Lancet 378:1826 Lancet (2011) Taking sex into account in medicine. Lancet 378:1826
39.
Zurück zum Zitat Oertelt-Prigione S, Parol R, Krohn S, Preissner R, Regitz-Zagrosek V (2010) Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines. BMC Med 8:70PubMed Oertelt-Prigione S, Parol R, Krohn S, Preissner R, Regitz-Zagrosek V (2010) Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines. BMC Med 8:70PubMed
Metadaten
Titel
Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study
verfasst von
A. Abbasi
E. Corpeleijn
E. Meijer
D. Postmus
R. T. Gansevoort
R. O. B. Gans
J. Struck
H. L. Hillege
R. P. Stolk
G. Navis
S. J. L. Bakker
Publikationsdatum
01.07.2012
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 7/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2545-x

Weitere Artikel der Ausgabe 7/2012

Diabetologia 7/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.