Elevated FGF-23 Linked to Insulin Resistance

QUEBEC CITY—Insulin resistance (IR) is associated with increased fibroblast growth factor-23 levels in chronic kidney disease (CKD) patients, suggesting a link between IR and renal phosphorus homeostasis, according to a cross-sectional study.

Presented at a poster session at the 3rd International Congress on Abdominal Obesity, the analysis of 72 patients with stage 3-5 CKD also showed that IR is associated with a greater severity of coronary artery calcification (CAC).

Patients with type 2 diabetes who were treated with insulin were excluded from the study. Investigators looked at fibroblast growth factor-23 (FGF-23) as a biomarker to assess disrupted renal phosphorus homeostasis. IR was assessed by the homeostasis model assessment of IR (HOMA-IR). The mean age of patients in the study was 64, the mean estimated glomerular filtration rate was 25.9 mL/min/1,73m2, the median HOMA-IR was 2.19, and the median CAC was 112 Agatston units.

“Our research question was if phosphorus homeostasis would be affected by IR in CKD patients,” explained nephrologist and principal investigator Jocelyn S. Garland, MD, FRCPC, an assistant professor in the department of medicine at Queen's University, Kingston, Ontario, Canada. As a secondary outcome, they looked at whether there was a difference in CAC.

She noted that elevated phosphorus is considered to be a cardiovascular risk factor. Studies have found that even in individuals who have phosphorus levels in the normal range, but in the higher tertile of normal, are at increased risk of cardiovascular morbidity and mortality, according to Dr. Garland.

“It is not commonly known that insulin affects a receptor in the kidney that deals with phosphorus re-absorption,” Dr. Garland said.

Dr. Garland and co-investigators divided patients into two groups, placing those with HOMA-IR values below the median in one group and those with values above the median in another group. Patients with greater HOMA-IR had significantly increased FGF-23 levels (179 vs. 109 RU/mL) and 40% higher log CAC scores (2.1 vs. 1.6). FGF-23 was also significantly and positively associated with other IR markers like abdominal waist circumference and body mass index.

“We found patients with higher levels of insulin resistance had greater FGF-23 levels, and to our knowledge that has not been described before,” Dr. Garland said.

A multi-regression statistical model showed that IR was a risk factor for elevated FGF-23, even after adjusting for factors such as parathyroid hormone, kidney function, and 1,25 dihydroxyvitamin D, all known for influencing FGF-23.         

“Insulin resistance had an independent effect on FGF-23 levels,” she said. “As insulin resistance increased, so too did the FGF-23 levels, implying that patients with higher levels of insulin resistance might be re-absorbing more phosphorus, and the effect may be higher FGF-23 levels to try and encourage the elimination [of phosphorus].”

Since IR commonly predates CKD development, an unexpected impact of IR may be excessive phosphorus retention, Dr. Garland said. “It is a very negative effect in our population,” she said.

If IR has an impact on phosphorus homeostasis, it would be a relationship that would also be applicable to the non-CKD population, Dr. Garland said.

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