Calcium-phosphate metabolism and cardiovascular risk in T1D
Stephanie Vermeulen, Mirjam E.A. Scheffer-Rath, Martine T.P. Besouw, Amarens van der Vaart, Martin H. de Borst, Annemieke M. Boot
Fibroblast growth factor 23 and calcium-phosphate metabolism in relation to cardiovascular risk factors in patients with type 1 diabetes. J Diabetes. 2024 Jun;16(6):e13500.
Cardiovascular disease (CVD) is the leading cause of mortality in people with type 1 diabetes, and traditional risk factors alone do not fully explain this burden. There is growing evidence that disturbances in mineral metabolism, particularly involving phosphate and calcium, may contribute to vascular dysfunction, even in the absence of chronic kidney disease. Fibroblast growth factor 23 (FGF23) is a key regulator of phosphate homeostasis, and elevated levels have been linked to vascular calcification, left-ventricular hypertrophy, and mortality across various populations. Little is known about FGF23 levels and their relationships with cardiovascular risk factors in people with type 1 diabetes. This study examined FGF23, calcium–phosphate metabolism and cardiovascular risk markers in adults with T1D compared with matched controls from a large population cohort.
This case–control study included 302 adults with T1D and 302 age- and sex-matched controls from the Lifelines Cohort Study (median age: 42 years; median diabetes duration: 20 years). Blood and urine samples were analysed for markers of calcium-phosphate metabolism and cardiovascular risk. Correlation and regression analyses were used to examine associations between FGF23 and cardiovascular risk factors within the T1D group.
Key findings:
- Serum phosphate, calcium, calcium-phosphate product, and alkaline phosphatase were higher in adults with T1D than in controls, although values remained within the normal range.
- In T1D, higher FGF23 levels were significantly correlated with phosphate, calcium, calcium-phosphate product, and alkaline phosphatase, but these correlations were not present in controls.
- Females with T1D had higher FGF23 levels than males, a difference not observed among controls.
- Current smokers with T1D had higher FGF23 levels than nonsmokers, whereas smoking was not associated with FGF23 in controls.
- Multivariable analysis showed that sex, phosphate, alkaline phosphatase, and parathyroid hormone together explained a modest proportion of FGF23 variation in T1D.
Although most biochemical values were within normal ranges, the pattern of associations supports the hypothesis that mineral metabolism may contribute to cardiovascular risk in T1D, independent of kidney disease, although causal mechanisms cannot be inferred due to the cross-sectional design, and that further research is needed to understand whether targeting FGF23 or phosphate metabolism could offer clinical benefit.
Concluding the authors state
"These findings may be related to the increased risk of CVDs in patients with T1D." -
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