In the Journals

FGF23 affects mortality, CV risk in type 2 diabetes with mildly impaired kidney function

There is an association between higher levels of fibroblast growth factor 23, or FGF23, and greater cardiovascular and mortality risks for adults with type 2 diabetes and normal or mildly impaired kidney function, according to findings published in Diabetes Care.

“So far, most studies had focused on the role of FGF23 in patients with reduced kidney function,” Martin H. de Borst, MD, PhD, a consultant nephrologist, adjunct professor of medicine at the University of Groningen and University Medical Center in the Netherlands, and Stanley M.H. Yeung, of the division of nephrology in the department of internal medicine at the University of Groningen and University Medical Center Groningen in the Netherlands, told Healio. “Now, we have shown that FGF23 levels are also linked with adverse outcomes in patients with type 2 diabetes and normal — or mildly impaired — kidney function. This hormone may therefore be relevant to a larger group of individuals than previously thought.”

De Borst, Yeung and colleagues assessed FGF23 levels in 310 adults with type 2 diabetes and an eGFR of 60 mL/min/1.73 m2 or more (mean age, 61.5 years; 42.1% women) from the Diabetes and Lifestyle Cohort Twente (DIALECT) study. In addition, the researchers used hospital surveillance data to evaluate all-cause mortality and major adverse CV events across a median of 5.8 years of follow-up.

Compared with 110 participants with an eGFR of less than 60 mL/min/1.73 m2 from the original DIALECT cohort, those included in de Borst and colleagues’ analysis had lower FGF23 levels (84.2 relative units/mL vs. 146.5 relative units/mL; P < .001).

Kidneys 2019 Adobe 
There is an association between higher levels of fibroblast growth factor 23, or FGF23, and greater cardiovascular and mortality risks for adults with type 2 diabetes and normal or mildly impaired kidney function.
Source: Adobe Stock

The researchers reported 28 deaths and 47 major adverse CV events among participants. In fully adjusted models, the researchers found all-cause mortality risk was 2.74 times greater (HR = 2.74; 95% CI, 1.72-4.36) and major adverse CV event risk was 1.56 times greater (HR = 1.56; 95% CI, 1.01-2.4) with each doubling of FGF23. Additionally, in fully adjusted models, the researchers found all-cause mortality risk was 3.33 times greater (HR = 3.33; 95% CI, 1.65-6.73) with each doubling of FGF23 for those with an eGFR of at least 90 mL/min/1.73 m2, although major adverse CV event risk was not changed by a statistically significant margin.

The researchers compared these results with those from a similar analysis among participants in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, which included 348 adults with type 2 diabetes and an eGFR of at least 60 mL/min/1.73 m2. All-cause mortality risk was 1.41 times greater (HR = 1.41; 95% CI, 1.06-1.89) and major adverse CV event risk was 1.46 times greater (HR = 1.46; 95% CI, 1.06-2) with each doubling of FGF23 in fully adjusted models in this cohort.

“Our study suggests that type 2 diabetes in itself may deregulate FGF23; this is in line with previous studies supporting bone and mineral abnormalities in [patients with diabetes]. Hopefully, our study will contribute to more research on the impact of diabetes on FGF23 and the role of FGF23 in relation to clinical outcomes in patients with type 2 diabetes,” the researchers said. “We do not anticipate that our study has direct impact on clinical practice, as it is still unclear if FGF23 could be used as a biomarker to assess the severity of disease progression or it could be used as a target to lower the levels in order to decrease the detrimental effects of FGF23 and to lower the risk of adverse outcomes.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.

There is an association between higher levels of fibroblast growth factor 23, or FGF23, and greater cardiovascular and mortality risks for adults with type 2 diabetes and normal or mildly impaired kidney function, according to findings published in Diabetes Care.

“So far, most studies had focused on the role of FGF23 in patients with reduced kidney function,” Martin H. de Borst, MD, PhD, a consultant nephrologist, adjunct professor of medicine at the University of Groningen and University Medical Center in the Netherlands, and Stanley M.H. Yeung, of the division of nephrology in the department of internal medicine at the University of Groningen and University Medical Center Groningen in the Netherlands, told Healio. “Now, we have shown that FGF23 levels are also linked with adverse outcomes in patients with type 2 diabetes and normal — or mildly impaired — kidney function. This hormone may therefore be relevant to a larger group of individuals than previously thought.”

De Borst, Yeung and colleagues assessed FGF23 levels in 310 adults with type 2 diabetes and an eGFR of 60 mL/min/1.73 m2 or more (mean age, 61.5 years; 42.1% women) from the Diabetes and Lifestyle Cohort Twente (DIALECT) study. In addition, the researchers used hospital surveillance data to evaluate all-cause mortality and major adverse CV events across a median of 5.8 years of follow-up.

Compared with 110 participants with an eGFR of less than 60 mL/min/1.73 m2 from the original DIALECT cohort, those included in de Borst and colleagues’ analysis had lower FGF23 levels (84.2 relative units/mL vs. 146.5 relative units/mL; P < .001).

Kidneys 2019 Adobe 
There is an association between higher levels of fibroblast growth factor 23, or FGF23, and greater cardiovascular and mortality risks for adults with type 2 diabetes and normal or mildly impaired kidney function.
Source: Adobe Stock

The researchers reported 28 deaths and 47 major adverse CV events among participants. In fully adjusted models, the researchers found all-cause mortality risk was 2.74 times greater (HR = 2.74; 95% CI, 1.72-4.36) and major adverse CV event risk was 1.56 times greater (HR = 1.56; 95% CI, 1.01-2.4) with each doubling of FGF23. Additionally, in fully adjusted models, the researchers found all-cause mortality risk was 3.33 times greater (HR = 3.33; 95% CI, 1.65-6.73) with each doubling of FGF23 for those with an eGFR of at least 90 mL/min/1.73 m2, although major adverse CV event risk was not changed by a statistically significant margin.

The researchers compared these results with those from a similar analysis among participants in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, which included 348 adults with type 2 diabetes and an eGFR of at least 60 mL/min/1.73 m2. All-cause mortality risk was 1.41 times greater (HR = 1.41; 95% CI, 1.06-1.89) and major adverse CV event risk was 1.46 times greater (HR = 1.46; 95% CI, 1.06-2) with each doubling of FGF23 in fully adjusted models in this cohort.

“Our study suggests that type 2 diabetes in itself may deregulate FGF23; this is in line with previous studies supporting bone and mineral abnormalities in [patients with diabetes]. Hopefully, our study will contribute to more research on the impact of diabetes on FGF23 and the role of FGF23 in relation to clinical outcomes in patients with type 2 diabetes,” the researchers said. “We do not anticipate that our study has direct impact on clinical practice, as it is still unclear if FGF23 could be used as a biomarker to assess the severity of disease progression or it could be used as a target to lower the levels in order to decrease the detrimental effects of FGF23 and to lower the risk of adverse outcomes.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.