Table 2.
Studies investigating the relationship between FGF23/klotho, insulin resistance, and metabolic syndrome
| Author, Ref. | Aim | Study design | FGF23 assay | Outcome |
|---|---|---|---|---|
| Mirza et al.,73 | - To investigate relationship between FGF23 and metabolic cardiovascular risk factors in the community | -2 community-based, cross-sectional cohorts of elderly whites (n = 964 men, and n = 946 men and women, respectively) | -iFGF23 | -FGF23 was positively correlated with leptin levels -Higher FGF23 was associated with higher HOMA-IR -Elderly subjects with MetS had higher FGF23 levels than those without MetS |
| Ali et al.,74 | -To determine whether FGF23 levels are greater in obese compared with normal-weight adolescents -To determine relationship between FGF23 and IR |
-Cross-sectional study -Normotensive African American adolescents aged 13–18 years without CKD (n = 130) |
-ctFGF23 | -Plasma FGF23 was higher in obese than in normal-weight subjects -LogFGF23 was positively correlated with HOMA-IR -LogFGF23 was negatively correlated with adiponectin -LogFGF23 correlated with measures of adiposity, including BMI and waist circumference |
| Fernández-Real et al.,75 | -To evaluate relationship between FGF23 levels and metabolic parameters | -Cohort 1; Middle-aged men with BMI <40 kg/m2 (n = 133) -Cohort 2; Subjects with BMI >30 kg/m2 (n = 314) |
-iFGF23 and ctFGF23 | -In cohort 1, both iFGF23 and ctFGF23 increased linearly with IR -In cohort 2, ctFGF23 increased linearly with HOMA-IR |
| Song et al.,76 | -To investigate relationship between FGF23 and clinical characteristics in patients with coronary heart disease | -Prospective, single center, observational study - Patients with coronary heart disease treated by percutaneous coronary intervention with drug-eluting stent (n = 214) |
-FGF23 (not specified) | -FGF23 was positively correlated with fasting blood glucose and IR index |
| Wojcik et al.,88 | -To investigate correlation of serum FGF23 and glucose, insulin, and fat metabolism in obese adolescents | -Prospective study -Adolescents with simple obesity (n = 68) |
-iFGF23 | -FGF23 was negatively correlated with HOMA-IR -FGF23 was independently associated with HOMA-IR |
| Gateva et al.,89 | -To investigate relationship between calcium-phosphate metabolism markers and glucose disturbances in obese patients with prediabetes | -Cross-sectional study -Group 1; Obese patients without glycemic disturbances (n = 41) -Group 2; Obese patients with prediabetes (n = 39) |
-FGF23 (not specified) | -FGF23 was higher in obese patients with prediabetes than those with normal glucose tolerance -FGF23 levels were higher in patients with IR than their counterparts |
| Domingo et al.,77 | -To determine relationship between FGF23 and metabolic alterations | -Cross-sectional study -Group 1; HIV-1-infected patients with HIV/HALS (n = 60) -Group 2; HIV-1-infected, antiretroviral-treated patients without HALS (n = 43) -Group 3; Naive HIV-1-infected patients (n = 49) -Group 4; Healthy controls (n = 34) |
-iFGF23 and ctFGF23 | -FGF23 was positively correlated with HOMA-IR -FGF23 was increased in HIV-1- infected patients, especially in those with HALS |
| Hanks et al.,46 | -To examine associations of FGF23 and markers of inflammation, IR, and anthropometrics | -Cross-sectional study -Cohort of community-dwelling adults ≥45 years of age (n = 1040) |
-ctFGF23 | -FGF23 was positively correlated with IL-6, hsCRP, IL-10, HOMA-IR, BMI, and waist circumference in individuals without CKD, but not among individuals with CKD -FGF23 was associated with resistin irrespective of CKD status |
| Fayed et al.,82 | -To investigate association between IR and mineral metabolism in predialysis nondiabetic patients with CKD | -Cross-sectional study -Patients with CKD (n = 100) and controls (n = 20) |
-iFGF23 | -Patients with CKD had higher HOMA-IR than controls -FGF23 and serum phosphorus were the only parameters significantly correlated with HOMA-IR -FGF23 was an independent predictor of HOMA-IR |
| Nakashima et al.,90 | -To analyze relationship between resistin and FGF23 in patients with T2D who have CKD | -Cross-sectional study - Patients with T2D who have CKD (n = 422) |
-iFGF23 | -FGF23 levels were positively correlated and independently associated with resistin levels -Resistin levels were positively associated with FGF23 levels in older patients (≥64years) and in patients with a low BMI (<23.9 kg/m2) |
| Silva et al.,84 | -To evaluate the relationship between klotho and IR in patients with T2D who have CKD | -Cross-sectional study -Patients with T2D who have stage 2–3 CKD (n = 107) |
-ctFGF23 | -Klotho levels were inversely correlated with HOMA-IR and FGF23 levels, and directly correlated with vitamin D levels -FGF23 and HOMA-IR were independently associated with klotho levels |
| Garland et al.83 | -To determine relationship between IR, FGF23, and coronary artery calcification in patients with CKD | -Cross-sectional study -Predialysis patients with stage 3–5 CKD (not receiving insulin therapy) (N = 72) |
-ctFGF23 | -FGF23 was significantly correlated with HOMA-IR, waist circumference, and BMI -HOMA-IR was independently associated with increased FGF23 levels -FGF23 levels were significantly higher as number of MetS components increased |
| Kerr et al.,85 | -To determine associations between epicardial fat, and kidney related CV risk factors including obesity and IR | -Cross-sectional study -Predialysis patients with stage 3–5 CKD (n = 94) |
-ctFGF23 | -Epicardial fat deposition was higher in patients with MetS, in diabetic patients and in patients with HOMA-IR greater than the median value -LogFGF23 and HOMA-IR were correlated with epicardial fat deposition |
| Da Silva Martins et al.,86 | -To investigate association between obesity, and MetS, and CKD-BMD | -Cross-sectional study -Hemodialysis patients (n = 55) |
-ctFGF23 | -Patients with normal bone volume had higher FGF23, phosphorus and fasting insulin levels, higher BMI, and higher prevalence of MetS |
| Chen et al.,87 | -To investigate relationship between FGF23 levels and MetS in kidney transplant recipients | -Retrospective study -Patients undergoing kidney transplantation (n = 74) |
-ctFGF23 | -FGF23 levels were higher in recipients with MetS -FGF23 is an independent predictor of MetS in kidney transplant recipients |
BMI, body mass index; CKD, chronic kidney disease; CKD-BMD, chronic kidney disease-mineral and bone disorder; ctFGF23, C-terminal fibroblast growth factor 23; CV, cardiovascular; FGF23, fibroblast growth factor 23; HALS, highly active antiretroviral therapy-associated lipodystrophy syndrome; HIV-1, human immunodeficiency virus-1; HOMA-IR, homeostatic model assessment of insulin resistance; iFGF23, intact FGF23; IL, interleukin; hsCRP, high sensitivity C-reactive protein; IR, insulin resistance; MetS, metabolic syndrome; T2D, type 2 diabetes.