Midregional Fragment of Proadrenomedullin, New-Onset Albuminuria, and Cardiovascular and All-Cause Mortality in Patients With Type 2 Diabetes (ZODIAC-30)

Landman, Gijs W. D.; Dijk, Peter R. van; Drion, Iefke; Hateren, Kornelis J. J. van; Struck, Joachim; Groenier, Klaas H.; Gans, Rijk O. B.; Bilo, Henk J. G.; Bakker, Stephan J. L.; Kleefstra, Nanne

doi:10.2337/dc13-1852

Cited by 20 publications

(22 citation statements)

References 32 publications

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“…Interestingly, although several previous studies have suggested that ProADM was also associated with other adverse outcomes in addition to all-cause mortality [26, 27, 33–36, 44–46], we did not find such statistically significant association with the incidence of our secondary combined endpoint including pulmonary embolism and MACCE. Also, in contrast to another study [39], our analysis did not find an association of ProADM with new onset diabetes mellitus.…”

Section: Discussioncontrasting

confidence: 98%

Pro-Adrenomedullin predicts 10-year all-cause mortality in community-dwelling patients: a prospective cohort study

Odermatt

Meili

Hersberger

et al. 2017

BMC Cardiovasc Disord

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BackgroundSeveral studies found mid-regional pro-adrenomedullin (ProADM), the prohormone of the cardiovascular protein adrenomedullin, to be strongly associated with short-term mortality, mostly in the inpatient setting. We evaluated associations of ProADM levels with 10-year mortality in community-dwelling primary care patients with respiratory tract infections.MethodsThis is a post-hoc analysis using clinical and biomarker data of 134 primary care patients with respiratory tract infections. ProADM was measured on admission and after 7 days in batch-analysis. 10-year follow-up data was collected by GP, patient and relative tracing through phone interviews. We calculated Cox regression models and area under the receiver operating characteristics curves to assess associations of ProADM with 10-year all-cause mortality.ResultsDuring the 10-year follow-up 6% of included patients died. Median baseline ProADM blood levels (nmol/l) were significantly higher in non-survivors compared to survivors (0.5, IQR 0.4–1.3; vs. 0.2, IQR 0.1–0.5; p = 0.02) and showed a significant association with 10-year all-cause mortality in an age-adjusted cox regression model (HR: 2.5, 95%-CI: 1.0–6.1, p = 0.04). ProADM levels on day 7 showed similar results.ConclusionsThis posthoc analysis found an association of elevated ProADM blood levels and 10-year all-cause mortality in a primary care cohort with respiratory tract infections. Due to the methodological limitations including incomplete data regarding follow-up information and biomarker measurement, this study warrants validation in future larger studies.Trial registrationCurrent Controlled Trials, SRCTN73182671

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Section: Discussioncontrasting

confidence: 98%

Pro-Adrenomedullin predicts 10-year all-cause mortality in community-dwelling patients: a prospective cohort study

Odermatt

Meili

Hersberger

et al. 2017

BMC Cardiovasc Disord

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“…Higher plasma levels of ADM or of MR-proADM were observed in patients with diabetic nephropathy than in patients without nephropathy in small cross-sectional Japanese and Chinese studies (25,26). However, no independent association was observed with the incidence of new cases of albuminuria in a larger Dutch study (ZODIAC) with a median follow-up of 5.6 years (27). Association of high plasma MR-proADM with cardiovascular morbidity and mortality has also been reported in diabetic and nondiabetic subjects (21)(22)(23)(24)27).…”

Section: Discussionmentioning

confidence: 89%

“…However, no independent association was observed with the incidence of new cases of albuminuria in a larger Dutch study (ZODIAC) with a median follow-up of 5.6 years (27). Association of high plasma MR-proADM with cardiovascular morbidity and mortality has also been reported in diabetic and nondiabetic subjects (21)(22)(23)(24)27). Associations of rs2957692 and rs2957717 with plasma MRproADM have been reported in other populations (35,39).…”

Section: Discussionmentioning

confidence: 94%

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Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes

et al. 2015

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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.

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“…We evaluated the effect of liraglutide on five biomarkers that are associated with cardiovascular disease in patients with diabetes: tumour necrosis factor (TNF)‐α, a pro‐inflammatory cytokine; soluble urokinase plasminogen‐activator‐receptor (suPAR), a marker of endothelial dysfunction and inflammation; mid‐regional pro‐adrenomedullin (MR‐proADM), a marker of systemic inflammation; mid‐regional pro‐atrial natriuretic peptide (MR‐proANP), a natriuretic peptide; and copeptin, a surrogate marker of arginine vasopressin …”

Section: Introductionmentioning

confidence: 99%

Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub‐analysis of a randomized, placebo‐controlled, double‐blind, crossover trial

Scholten

Persson

Rosenlund

et al. 2017

Diabetes Obesity Metabolism

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We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: tumour necrosis factor (TNF)-α; soluble urokinase plasminogen activator receptor (suPAR); mid-regional pro-adrenomedullin (MR-proADM); mid-regional pro-atrial natriuretic peptide (MR-proANP); and copeptin, in people with type 2 diabetes with albuminuria. In a randomized, double-blind, placebo-controlled, crossover trial we enrolled people with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio [UACR] >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m . Participants received liraglutide (1.8 mg/d) and matched placebo for 12 weeks, in random order. The primary endpoint was change in albuminuria; this was a prespecified sub-study. A total of 32 participants were randomized, of whom 27 completed the study. TNF-α level was 12% (95% confidence interval [CI] 3; 20) lower after liraglutide treatment compared with placebo (P = .012); MR-proADM level was 4% (95% CI 0; 8) lower after liraglutide treatment compared with placebo (P = .038), and MR-proANP level was 13% (95% CI 4; 21) lower after liraglutide treatment compared with placebo (P = .006). In the present study, we showed anti-inflammatory effects of liraglutide treatment, reflected in reductions in levels of TNF-α and MR-proADM, while the reduction in MR-proANP levels may represent a clinically relevant benefit with regard to heart failure.

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Midregional Fragment of Proadrenomedullin, New-Onset Albuminuria, and Cardiovascular and All-Cause Mortality in Patients With Type 2 Diabetes (ZODIAC-30)

Cited by 20 publications

References 32 publications

Pro-Adrenomedullin predicts 10-year all-cause mortality in community-dwelling patients: a prospective cohort study

Pro-Adrenomedullin predicts 10-year all-cause mortality in community-dwelling patients: a prospective cohort study

Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes

Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub‐analysis of a randomized, placebo‐controlled, double‐blind, crossover trial

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