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

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.

Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes

“…Recently it has been reported that high extracellular phosphate increases platelet polyP content [ 32 ]. Interestingly, emerging evidence indicates that phosphate metabolism is altered in diabetes [ 33 , 34 ]. Hyperphosphatemia has been described in an animal model of diabetes [ 35 ], and diabetes is considered a major risk factor for hyperphosphatemia through kidney disease [ 36 ].…”