Plasma phosphate and all-cause mortality in individuals with and without type 2 diabetes: the Dutch population-based lifelines cohort study

Amarens van der Vaart; Qingqing Cai; Ilja M Nolte; André P J van Beek; Gerjan Navis; Stephan J L Bakker; Peter R van Dijk; Martin H de Borst

doi:10.1186/s12933-022-01499-4

Plasma phosphate and all-cause mortality in individuals with and without type 2 diabetes: the Dutch population-based lifelines cohort study

Amarens van der Vaart^*, Qingqing Cai, Ilja M Nolte, André P J van Beek, Gerjan Navis, Stephan J L Bakker, Peter R van Dijk, Martin H de Borst

^*Bijbehorende auteur voor dit werk

Onderzoeksoutput › Academic › peer review

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INTRODUCTION: Individuals with type 2 diabetes have a substantially elevated cardiovascular risk. A higher plasma phosphate level promotes vascular calcification, which may adversely affect outcomes in individuals with type 2 diabetes. We hypothesized that the association between plasma phosphate and all-cause mortality is stronger in individuals with type 2 diabetes, compared to those without diabetes.

METHODS: We analysed the association between plasma phosphate and all-cause mortality in the Dutch population-based Lifelines cohort and in subgroups with and without type 2 diabetes, using multivariable Cox regression adjusted for potential confounders. Effect modification was tested using multiplicative interaction terms.

RESULTS: We included 57,170 individuals with 9.4 [8.8-10.4] years follow-up. Individuals within the highest phosphate tertile (range 1.00-1.83 mmol/L) were at higher risk of all-cause mortality (fully adjusted HR 1.18 [95% CI 1.02-1.36], p = 0.02), compared with the intermediate tertile (range 0.85-0.99 mmol/L). We found significant effect modification by baseline type 2 diabetes status (p-interaction = 0.003). Within the type 2 diabetes subgroup (N = 1790), individuals within the highest plasma phosphate tertile had an increased mortality risk (HR 1.73 [95% CI 1.10-2.72], p = 0.02 vs intermediate tertile). In individuals without diabetes at baseline (N = 55,380), phosphate was not associated with mortality (HR 1.12 [95% CI 0.96-1.31], p = 0.14). Results were similar after excluding individuals with eGFR < 60 mL/min/1.73 m2.

DISCUSSION: High-normal plasma phosphate levels were associated with all-cause mortality in individuals with type 2 diabetes. The association was weaker and non-significant in those without diabetes. Measurement of phosphate levels should be considered in type 2 diabetes; whether lowering phosphate levels can improve health outcomes in diabetes requires further study.

Originele taal-2	English
Artikelnummer	61
Aantal pagina's	10
Tijdschrift	Cardiovascular Diabetology
Volume	21
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1186/s12933-022-01499-4
Status	Published - 27-apr.-2022

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10.1186/s12933-022-01499-4Licentie: CC BY

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Lifelines Biobank
Bakker, S. (Creator), Dotinga, A. (Creator), Vonk, J. (Creator), Smidt, N. (Creator), Scholtens, S. (Creator), Swertz, M. (Creator), Wijmenga, C. (Creator), Wolffenbuttel, B. (Creator), Stolk, R. (Creator), van Zon, S. (Creator), Rosmalen, J. (Creator), Postma, D. S. (Creator), de Boer, R. (Creator), Navis, G. (Creator), Slaets, J. (Creator), Ormel, H. (Creator), van Dijk, F. (Creator) & Bolmer, B. (Data Manager), Lifelines, 2006
https://www.lifelines.nl/ en nog één link, https://catalogue.lifelines.nl/ (minder tonen)
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abstract = "INTRODUCTION: Individuals with type 2 diabetes have a substantially elevated cardiovascular risk. A higher plasma phosphate level promotes vascular calcification, which may adversely affect outcomes in individuals with type 2 diabetes. We hypothesized that the association between plasma phosphate and all-cause mortality is stronger in individuals with type 2 diabetes, compared to those without diabetes.METHODS: We analysed the association between plasma phosphate and all-cause mortality in the Dutch population-based Lifelines cohort and in subgroups with and without type 2 diabetes, using multivariable Cox regression adjusted for potential confounders. Effect modification was tested using multiplicative interaction terms.RESULTS: We included 57,170 individuals with 9.4 [8.8-10.4] years follow-up. Individuals within the highest phosphate tertile (range 1.00-1.83 mmol/L) were at higher risk of all-cause mortality (fully adjusted HR 1.18 [95% CI 1.02-1.36], p = 0.02), compared with the intermediate tertile (range 0.85-0.99 mmol/L). We found significant effect modification by baseline type 2 diabetes status (p-interaction = 0.003). Within the type 2 diabetes subgroup (N = 1790), individuals within the highest plasma phosphate tertile had an increased mortality risk (HR 1.73 [95% CI 1.10-2.72], p = 0.02 vs intermediate tertile). In individuals without diabetes at baseline (N = 55,380), phosphate was not associated with mortality (HR 1.12 [95% CI 0.96-1.31], p = 0.14). Results were similar after excluding individuals with eGFR < 60 mL/min/1.73 m2.DISCUSSION: High-normal plasma phosphate levels were associated with all-cause mortality in individuals with type 2 diabetes. The association was weaker and non-significant in those without diabetes. Measurement of phosphate levels should be considered in type 2 diabetes; whether lowering phosphate levels can improve health outcomes in diabetes requires further study.",

keywords = "Cohort Studies, Diabetes Mellitus, Type 2, Ethnicity, Humans, Phosphates, Vascular Calcification/complications",

author = "{van der Vaart}, Amarens and Qingqing Cai and Nolte, {Ilja M} and {van Beek}, {Andr{\'e} P J} and Gerjan Navis and Bakker, {Stephan J L} and {van Dijk}, {Peter R} and {de Borst}, {Martin H}",

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T1 - Plasma phosphate and all-cause mortality in individuals with and without type 2 diabetes

T2 - the Dutch population-based lifelines cohort study

AU - van der Vaart, Amarens

AU - Cai, Qingqing

AU - Nolte, Ilja M

AU - van Beek, André P J

AU - Navis, Gerjan

AU - Bakker, Stephan J L

AU - van Dijk, Peter R

AU - de Borst, Martin H

PY - 2022/4/27

Y1 - 2022/4/27

N2 - INTRODUCTION: Individuals with type 2 diabetes have a substantially elevated cardiovascular risk. A higher plasma phosphate level promotes vascular calcification, which may adversely affect outcomes in individuals with type 2 diabetes. We hypothesized that the association between plasma phosphate and all-cause mortality is stronger in individuals with type 2 diabetes, compared to those without diabetes.METHODS: We analysed the association between plasma phosphate and all-cause mortality in the Dutch population-based Lifelines cohort and in subgroups with and without type 2 diabetes, using multivariable Cox regression adjusted for potential confounders. Effect modification was tested using multiplicative interaction terms.RESULTS: We included 57,170 individuals with 9.4 [8.8-10.4] years follow-up. Individuals within the highest phosphate tertile (range 1.00-1.83 mmol/L) were at higher risk of all-cause mortality (fully adjusted HR 1.18 [95% CI 1.02-1.36], p = 0.02), compared with the intermediate tertile (range 0.85-0.99 mmol/L). We found significant effect modification by baseline type 2 diabetes status (p-interaction = 0.003). Within the type 2 diabetes subgroup (N = 1790), individuals within the highest plasma phosphate tertile had an increased mortality risk (HR 1.73 [95% CI 1.10-2.72], p = 0.02 vs intermediate tertile). In individuals without diabetes at baseline (N = 55,380), phosphate was not associated with mortality (HR 1.12 [95% CI 0.96-1.31], p = 0.14). Results were similar after excluding individuals with eGFR < 60 mL/min/1.73 m2.DISCUSSION: High-normal plasma phosphate levels were associated with all-cause mortality in individuals with type 2 diabetes. The association was weaker and non-significant in those without diabetes. Measurement of phosphate levels should be considered in type 2 diabetes; whether lowering phosphate levels can improve health outcomes in diabetes requires further study.

AB - INTRODUCTION: Individuals with type 2 diabetes have a substantially elevated cardiovascular risk. A higher plasma phosphate level promotes vascular calcification, which may adversely affect outcomes in individuals with type 2 diabetes. We hypothesized that the association between plasma phosphate and all-cause mortality is stronger in individuals with type 2 diabetes, compared to those without diabetes.METHODS: We analysed the association between plasma phosphate and all-cause mortality in the Dutch population-based Lifelines cohort and in subgroups with and without type 2 diabetes, using multivariable Cox regression adjusted for potential confounders. Effect modification was tested using multiplicative interaction terms.RESULTS: We included 57,170 individuals with 9.4 [8.8-10.4] years follow-up. Individuals within the highest phosphate tertile (range 1.00-1.83 mmol/L) were at higher risk of all-cause mortality (fully adjusted HR 1.18 [95% CI 1.02-1.36], p = 0.02), compared with the intermediate tertile (range 0.85-0.99 mmol/L). We found significant effect modification by baseline type 2 diabetes status (p-interaction = 0.003). Within the type 2 diabetes subgroup (N = 1790), individuals within the highest plasma phosphate tertile had an increased mortality risk (HR 1.73 [95% CI 1.10-2.72], p = 0.02 vs intermediate tertile). In individuals without diabetes at baseline (N = 55,380), phosphate was not associated with mortality (HR 1.12 [95% CI 0.96-1.31], p = 0.14). Results were similar after excluding individuals with eGFR < 60 mL/min/1.73 m2.DISCUSSION: High-normal plasma phosphate levels were associated with all-cause mortality in individuals with type 2 diabetes. The association was weaker and non-significant in those without diabetes. Measurement of phosphate levels should be considered in type 2 diabetes; whether lowering phosphate levels can improve health outcomes in diabetes requires further study.

KW - Cohort Studies

KW - Diabetes Mellitus, Type 2

KW - Ethnicity

KW - Humans

KW - Phosphates

KW - Vascular Calcification/complications

U2 - 10.1186/s12933-022-01499-4

DO - 10.1186/s12933-022-01499-4

M3 - Article

C2 - 35477475

SN - 1475-2840

VL - 21

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

IS - 1

M1 - 61

ER -

Plasma phosphate and all-cause mortality in individuals with and without type 2 diabetes: the Dutch population-based lifelines cohort study

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