Plasma Copeptin, A Unifying Factor behind the Metabolic Syndrome

Enhörning, Sofia; Struck, Joachim; Wirfält, Elisabet; Hedblad, Bo; Morgenthaler, Nils G.; Melander, Olle

doi:10.1210/jc.2010-2981

Cited by 152 publications

(177 citation statements)

References 33 publications

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“…With regard to the differences in copeptin levels in men and women, the higher plasma copeptin level in men was consistently observed in our study and in previous studies [4,[29][30][31]. Sex is one of the major determinants of plasma levels of copeptin.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2012

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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, p00.02) and reclassification (integrated discrimination improvement [IDI] 0 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.

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Section: Discussionsupporting

confidence: 90%

“…We and others have shown before that higher plasma copeptin levels are positively associated with the metabolic syndrome, insulin resistance, the inflammatory marker hs-CRP and higher UAE in cross-sectional studies [4,29,30]. Likewise, all these conditions are known to be predictors for the risk of type 2 diabetes [13].…”

Section: Discussionmentioning

confidence: 86%

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

et al. 2012

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“…We previously showed that fasting plasma concentration of VP, measured as copeptin, strongly predicts new-onset type 2 diabetes [11], a finding later replicated in other large prospective population-based studies [12,13]. Furthermore, we showed that subjects with high copeptin concentration have an increased risk of all components of the metabolic syndrome [11,14,15] as well as cardiovascular disease and premature mortality, both in diabetics and non-diabetics [16][17][18].…”

Section: Introductionsupporting

confidence: 61%

Effects of hydration on plasma copeptin, glycemia and gluco-regulatory hormones: a water intervention in humans

et al. 2017

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Purpose High plasma copeptin, a marker of vasopressin, predicts diabetes mellitus. We tested if copeptin could be suppressed by increased water intake in healthy individuals, and if a water-induced change in copeptin was accompanied by altered concentrations of glucose, insulin or glucagon. Methods Thirty-nine healthy individuals underwent, in random order, 1 week of high water intake (3 L/day on top of habitual intake) and 1 week of normal (habitual) fluid intake (control). Fasting plasma concentrations of copeptin, glucose, insulin and glucagon were compared between the ends of both periods. Furthermore, acute copeptin kinetics were mapped for 4 h after ingestion of 1 L of water. Results After acute intake of 1 L water, copeptin was significantly reduced within 30 min, and reached maximum reduction within 90 min with on average 39% reduction (95% confidence interval (95 CI) 34-45) (p < 0.001) and remained low the entire test period (4 h). One week of increased water intake led to a 15% reduction (95 CI 5-25) (p = 0.003) of copeptin compared to control week. The greatest reduction occurred among subjects with habitually high copeptin and concentrated urine ("water-responders"). Water-responders had significant water-induced reduction of glucagon, but glucose and insulin were unaffected. Conclusions Both acute and 1 week extra water intake potently reduced copeptin concentration. In those with the greatest decline (water-responders), who are typically low drinkers with high baseline copeptin, water induced a reduction in fasting glucagon. Long-term trials assessing the effect of water on glucometabolic traits should focus on low-water drinkers with high copeptin concentration.

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“…Physical activity was defined as leisure time physical activity based on 18 items adapted from the Minnesota Leisure Time Physical Activity instrument and has been described in detail elsewhere [35]. Hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg or the use of antihypertensive medication (angiotensin-converting enzyme inhibitors, β-blockers, calcium antagonists or diuretics).…”

Section: Methodsmentioning

confidence: 99%

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease

Svensson

Kitliński

et al. 2017

Diabetologia

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Aims/hypothesis Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that any association with sleep duration would not hold for cases of incident CHD occurring before incident diabetes ('non-diabetes CHD') but would hold true for cases of incident CHD following incident diabetes ('diabetes-CHD'). Methods A total of 6966 men and 9378 women aged 45-73 years from the Malmö Diet Cancer Study, a populationbased, prospective cohort, who had answered questions on habitual sleep duration and did not have a history of prevalent diabetes or CHD were included in the analyses. Incident cases of diabetes and CHD were identified using national registers. Sex-specific Cox proportional hazards regression models were stratified by BMI and adjusted for known covariates of diabetes and CHD. Results Mean follow-up times for incident diabetes (n = 1137/ 1016 [men/women]), incident CHD (n = 1170/578), nondiabetes CHD (n = 1016/501) and diabetes-CHD (n = 154/ 77) were 14.2-15.2 years for men, and 15.8-16.5 years for women. In men, short sleep duration (< 6 h) was associated with incident diabetes (HR 1.35, 95% CI 1.01, 1.80), CHD (HR 1.41, 95% CI 1.06, 1.89) and diabetes-CHD (HR 2.34, 95% CI 1.20, 4.55). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.35, 95% CI 0.98, 1.87). Long sleep duration (≥ 9 h) was associated with incident diabetes (HR 1.37, 95% CI 1.03, 1.83), CHD (HR 1.33, 95% CI 1.01, 1.75) and diabetes-CHD (HR 2.10, 95% CI 1.11, 4.00). Long sleep duration was not associated with incident non-diabetes CHD (HR 1.33, 95% CI 0.98, 1.80). In women, short sleep duration was associated with incident diabetes (HR 1.53, 95% CI 1.16, 2.01), CHD (HR 1.46, 95% CI 1.03, 2.07) and diabetes-CHD (HR 2.88, 95% CI 1.37, 6.08).Akiko Kishi Svensson and Thomas Svensson contributed equally to this study. Electronic supplementary materialThe online version of this article (https://doi.org/10.1007/s00125-017-4464-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Plasma Copeptin, A Unifying Factor behind the Metabolic Syndrome

Abstract: Our data suggest that increased activity of the AVP system is a unifying factor in the MetS and point to a new pharmacologically modifiable system of potential importance in the treatment of MetS and prevention of cardiovascular disease.

Cited by 152 publications

References 33 publications

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

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

Effects of hydration on plasma copeptin, glycemia and gluco-regulatory hormones: a water intervention in humans

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease

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