Iptive results of continuous variables are expressed as mean and SD for Gaussian variables. Parameters that did not fulfill normal distribution were logarithmically transformed to improve symmetry for subsequent analyses. The relation between variables was analyzed by simple correlation (Pearson’s test). Multiple linear regression analyses were performed 25033180 in a stepwise manner to predict circulating FGF-23 concentration. Levels of statistical significance were set at P,0.05.FGF-23 and Insulin ResistanceTable 1. Anthropometrical and biochemical characteristics of the study subjects in Cohort 1.Table 2. Anthropometrical, clinical and biochemical characteristics of the study subjects in Cohort 2.n Age (years) BMI (kg/m2) Waist perimeter (cm) Systolic blood pressure(mmHg) Diastolic blood pressure (mmHg) Cholesterol (mg/dl) LDL-cholesterol (mg/dl) HDL-cholesterol (mg/dl) Log fasting triglycerides (mg/dl) Fasting glucose (mg/dl) Post-load glucose OGTT (mg/dl) Post-load insulin OGTT (mU/L) Log Insulin sensitivity (1024*min21*mU/L) Log serum ferritin (ng/ml) Creatinine (mg/dl) PTH (pg/ml) Vitamin D (ng/ml) Serum phosphate (mg/dl) iFGF-23 (pg/ml) Ct FGF23 (pg/ml)133 men 51.8611.6 27.663.5 92.669.8 127.7614.8 80.569.6 213.9638.01 138.08635.2 53.1612.2 1.9760.24 97.5611.2 135.1645.7 70.4663.7 0.460.2 2.0960.35 1.0160.1 44614.4 21.866.5 3.9360.69 28.867.8 51620.7 n Age (years) BMI (kg/m2) Waist perimeter (cm) Fat mass (kg) Systolic blood pressure(mmHg) Diastolic blood pressure (mmHg) Right ICAIMT (mm) Left ICAIMT (mm) Radium T-score Lumbar T-score Cholesterol (mg/dl) LDL-cholesterol (mg/dl) HDL-cholesterol (mg/dl) Log fasting triglycerides (mg/dl) Fasting glucose (mg/dl) Fasting insulin (mU/L) Post-load glucose OGTT (mg/dl) Post-load insulin OGTT (mU/L) HOMAMen 262 42.267.4 34.169.5 107.8621.8 38.9620.5 136618.5 78.1611.1 0.5860.12 0.6260.12 0.7 (21?.7)Women 52 40.868.6 33.3610.6 96.1621.2 40.3618.7 127.8617 71610.1 0.5360.15 0.5460.`p 0.4 0.7 0.02 0.7 0.05 0.006 0.2 0.0.35 (20.3?.5) 0.3 0.02 0.6 0.5 ,0.0001 0.07 0.5 0.3 0.6 0.20.8 (21.2?.42) 0.35 (21?.7) 192.4630.6 121.4626.6 45.8613.2 2.0260.2 92.1611.2 7.6 (1.8?2.2) 120.4634.9 52.5643.9 1.91 (0.14?.76) 2.360.3 0.8260.14 48.3614.8 3.260.3 18.368.39 32.769.3 54.4621.8 197638.7 116.3633.9 61.6619.3 1.9360.19 89.8616.6 4.9 (2?.9) 116.1642.9 44.1.07 (0.41?.08) 0.2 1.5760.4 0.6660.11 47.9620 3.3660.4 20.3611.7 35.1616.2 72.04634.1 ,0.0001 ,0.0001 0.9 0.16 0.4 0.4 0.BMI, Body mass index; CRP, C reactive protein, iFGF-23, fibroblast growthfactor-23, CtFGF-23, C-terminal FGF-23 OGTT, oral glucose tolerance test; PTH, parathyroid hormone. doi:10.1371/journal.pone.0058961.tLog serum ferritin (ng/ml) Creatinine (mg/dl) PTH (pg/ml) Serum phosphate (mg/dl)ResultsAnthropometrical and biochemical characteristics of subjects included in cohort 1 and 2 are shown in Table 1 and 2, respectively. We first explored the possible association of serum FGF-23 concentrations with obesity. In all subjects 16574785 as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI and increased with obesity Lecirelin status (Figure 1). In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations decreased linearly with insulin sensitivity (Figure 2 and Table 3). While iFGF-23 was associated with serum creatinine, CtFGF-23 was linked to serum ferritin concentration (r = 20.20, p = 0.02, Table 3). Multiple linear regression models were Indolactam V site constructed to predict circulating intact or C-terminal FGF-23 levels, with.Iptive results of continuous variables are expressed as mean and SD for Gaussian variables. Parameters that did not fulfill normal distribution were logarithmically transformed to improve symmetry for subsequent analyses. The relation between variables was analyzed by simple correlation (Pearson’s test). Multiple linear regression analyses were performed 25033180 in a stepwise manner to predict circulating FGF-23 concentration. Levels of statistical significance were set at P,0.05.FGF-23 and Insulin ResistanceTable 1. Anthropometrical and biochemical characteristics of the study subjects in Cohort 1.Table 2. Anthropometrical, clinical and biochemical characteristics of the study subjects in Cohort 2.n Age (years) BMI (kg/m2) Waist perimeter (cm) Systolic blood pressure(mmHg) Diastolic blood pressure (mmHg) Cholesterol (mg/dl) LDL-cholesterol (mg/dl) HDL-cholesterol (mg/dl) Log fasting triglycerides (mg/dl) Fasting glucose (mg/dl) Post-load glucose OGTT (mg/dl) Post-load insulin OGTT (mU/L) Log Insulin sensitivity (1024*min21*mU/L) Log serum ferritin (ng/ml) Creatinine (mg/dl) PTH (pg/ml) Vitamin D (ng/ml) Serum phosphate (mg/dl) iFGF-23 (pg/ml) Ct FGF23 (pg/ml)133 men 51.8611.6 27.663.5 92.669.8 127.7614.8 80.569.6 213.9638.01 138.08635.2 53.1612.2 1.9760.24 97.5611.2 135.1645.7 70.4663.7 0.460.2 2.0960.35 1.0160.1 44614.4 21.866.5 3.9360.69 28.867.8 51620.7 n Age (years) BMI (kg/m2) Waist perimeter (cm) Fat mass (kg) Systolic blood pressure(mmHg) Diastolic blood pressure (mmHg) Right ICAIMT (mm) Left ICAIMT (mm) Radium T-score Lumbar T-score Cholesterol (mg/dl) LDL-cholesterol (mg/dl) HDL-cholesterol (mg/dl) Log fasting triglycerides (mg/dl) Fasting glucose (mg/dl) Fasting insulin (mU/L) Post-load glucose OGTT (mg/dl) Post-load insulin OGTT (mU/L) HOMAMen 262 42.267.4 34.169.5 107.8621.8 38.9620.5 136618.5 78.1611.1 0.5860.12 0.6260.12 0.7 (21?.7)Women 52 40.868.6 33.3610.6 96.1621.2 40.3618.7 127.8617 71610.1 0.5360.15 0.5460.`p 0.4 0.7 0.02 0.7 0.05 0.006 0.2 0.0.35 (20.3?.5) 0.3 0.02 0.6 0.5 ,0.0001 0.07 0.5 0.3 0.6 0.20.8 (21.2?.42) 0.35 (21?.7) 192.4630.6 121.4626.6 45.8613.2 2.0260.2 92.1611.2 7.6 (1.8?2.2) 120.4634.9 52.5643.9 1.91 (0.14?.76) 2.360.3 0.8260.14 48.3614.8 3.260.3 18.368.39 32.769.3 54.4621.8 197638.7 116.3633.9 61.6619.3 1.9360.19 89.8616.6 4.9 (2?.9) 116.1642.9 44.1.07 (0.41?.08) 0.2 1.5760.4 0.6660.11 47.9620 3.3660.4 20.3611.7 35.1616.2 72.04634.1 ,0.0001 ,0.0001 0.9 0.16 0.4 0.4 0.BMI, Body mass index; CRP, C reactive protein, iFGF-23, fibroblast growthfactor-23, CtFGF-23, C-terminal FGF-23 OGTT, oral glucose tolerance test; PTH, parathyroid hormone. doi:10.1371/journal.pone.0058961.tLog serum ferritin (ng/ml) Creatinine (mg/dl) PTH (pg/ml) Serum phosphate (mg/dl)ResultsAnthropometrical and biochemical characteristics of subjects included in cohort 1 and 2 are shown in Table 1 and 2, respectively. We first explored the possible association of serum FGF-23 concentrations with obesity. In all subjects 16574785 as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI and increased with obesity status (Figure 1). In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations decreased linearly with insulin sensitivity (Figure 2 and Table 3). While iFGF-23 was associated with serum creatinine, CtFGF-23 was linked to serum ferritin concentration (r = 20.20, p = 0.02, Table 3). Multiple linear regression models were constructed to predict circulating intact or C-terminal FGF-23 levels, with.