Fibroblast growth factor 23 is associated with the development of gestational diabetes mellitus.

BACKGROUND: Besides its established impact on bone and mineral metabolism, it was suggested that fibroblast growth factor 23 (FGF23) might play an important role in the pathogenesis of type 2 diabetes. The impact of FGF23 on gestational diabetes mellitus (GDM), however, is not well understood. iFGF23 ELISAs measure the intact FGF23 molecule, whereas cFGF23 assays measure intact FGF23 as well as degradation products of FGF23. OBJECTIVES: The aim of this study is to compare the association of maternal and foetal cFGF23 and iFGF23 with GDM in a German birth cohort. METHODS: cFGF23 and iFGF23 were analysed in 826 random mother/child pairs from the Berlin Birth Cohort. RESULTS: Mothers who developed GDM had higher concentrations of iFGF-23 compared to mothers who did not suffer from GDM (19.73 vs. 13.23 pg/mL, p < 0.0001), but not higher concentrations of cFGF-23. Multivariant regression analyses showed that gestational diabetes is associated with iFGF23 independently of confounding factors such as age, BMI, ethnic background, family history of diabetes, smoking during pregnancy, and recurrent pregnancy loss. This, however, was only seen when using an iFGF23 ELISA measuring just the full length FGF23 and not in addition FGF23 fragments. No differences in both iFGF23 and cFGF23 concentrations between the GDM and non-GDM groups were detected in cord blood samples of the offspring. CONCLUSIONS: This study of a representative German birth cohort showed that maternal but not foetal iFGF23 is independently associated with GDM.

Free vitamin D is independently associated with systolic blood pressure in diabetic patients with impaired kidney function.

Vitamin D contributes to blood pressure (BP) regulation. We compared the association of BP in diabetic patients with either total vitamin D - the standard way of analyzing the vitamin D status - or free vitamin D, because only free vitamin D passes the cell membrane and interacts with the nuclear vitamin D receptor (VDR). An analytical cross-sectional study was conducted with 178 diabetic patients with impaired kidney function. Free and total vitamin D concentrations were measured in all patients. Multiple linear regression analysis considering patient age, sex, body mass index, height, smoking and drinking situation, the use of antihypertensive drugs, cholecalciferol treatment, C-reactive protein and estimated glomerular filtration rate as confounding factors were conducted to compare the association of free and total vitamin D with systolic and diastolic blood pressure (SBP and DBP). Multiple linear regression analysis revealed that neither SBP nor DBP was correlated with total vitamin D (SBP, 95% CI -0.405 ~ 0.159, p = 0.390; DBP, 95% CI -0.131 ~ 0.142, p = 0.933) (Table 2). However, the concentration of free vitamin D was independently associated with SBP (95% CI -2.691 ~ -0.210; p = 0.022) (Table 3), but not with DBP (95% CI -0.934 ~ 0.285; p = 0.293). In conclusion, free - but not total - vitamin D serum concentrations in patients with diabetes and impaired kidney function are inversely correlated with SBP. This study suggests that free vitamin D measurements might be more clinically relevant - as compared to measurements of total vitamin D - to adjust vitamin D therapy in diabetic patients with impaired kidney function.

Prevalence and risk factors for hyperhomocysteinemia: a population-based cross-sectional study from Hunan, China.

OBJECTIVES: Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aimed to investigate the prevalence and risk factors for hyperhomocysteinemia, especially modifiable lifestyle factors, such as smoking behaviour and dietary factors. DESIGN: Population-based cross-sectional study. SETTING: Hunan Province, China PARTICIPANTS: A total of 4012 participants completed the study, between July 2013 and March 2014. The median age is 55 (interquartile range: 45-63) years, with 1644 males (41%) and 2368 females (59%). MAIN OUTCOME MEASURES: Homocysteine level were measured by the microplate enzyme immunoassay method. Hyperthomocysteinemia was defined as ≥15 µmol/L. Questionnaire was used to investigate potential risk factors of hyperhomocysteinemia. Crude odd ratio (OR) or adjusted OR with 95% CI were determined by using univariable or multivariable logistic regression models. RESULTS: The prevalence of hyperhomocysteinemia is 35.4% (45.4% vs 28.5% for men, women, respectively). One-year increase in age is significantly associated with 2% higher risk of hyperhomocysteinemia (OR=1.02, 95% CI: 1.01 to 1.03). One unit increase of BMI is associated with 5% higher risk of hyperhomocysteinemia (OR=1.05, 95% CI: 1.03 to 1.07). Compared with the non-smoker, smoking participants have a 24% higher risk of hyperhomocysteinemia (OR=1.24, 95% CI: 1.006 to 1.53), while the risk for those quitting smoking are not significantly different (OR=1.14, 95% CI: 0.85 to 1.54). compared with those consuming fruit and vegetable at least once every day, those consuming less than once every day had a significantly higher risk of hyperhomocysteinemia (OR=1.29, 95% CI:1.11 to 1.50). In addition, we found there were significant sex interaction with education level or alcohol drinking on the risk of hyperhomocysteinemia (pinteraction <0.05). CONCLUSIONS: Higher BMI and older age are potential risk factors for hyperhomocysteinemia. Current smoking but not quitting smoking is associated with higher risk of hyperhomocysteinemia. Fruit and vegetable consumption may have protective effect against hyperhomocysteinemia. Alcohol consumption or education level might interact to influence the risk of hyperhomocysteinemia.

Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium.

BACKGROUND: The use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11-12% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate. The number of in-hospital examinations using iodine-based contrast media has been significantly increasing over the last decade. In order to protect patients from possible complications of such examinations, new biomarkers are needed that are able to predict a risk of contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily of renal cellular origin. Therefore, we assessed if urinary cGMP concentration may predict major adverse renal events (MARE) after contrast media exposure during coronary angiography. METHODS: Urine samples were prospectively collected from non-randomized consecutive patients with either diabetes or preexisting impaired kidney function receiving intra-arterial contrast medium (CM) for emergent or elective coronary angiography at the Charité Campus Mitte, University Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours after CM exposure. Patients were followed up over 90 days for occurrence of death, initiation of dialysis, doubling of plasma creatinine concentration or MARE. RESULTS: In total, 289 consecutive patients were included into the study. Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean±SD was predictive for the need of dialysis (no dialysis: 89.77±92.85 µM/mM, n = 277; need for dialysis: 140.3±82.90 µM/mM, n = 12, p = 0.008), death (no death during follow-up: 90.60±92.50 µM/mM, n = 280; death during follow-up: 169.88±81.52 µM/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE: 86.02±93.17 µM/mM, n = 271; MARE: 146.64±74.68 µM/mM, n = 18, p<0.001) during the follow-up of 90 days after contrast media application. cGMP/creatinine ratio stayed significantly increased at values exceeding 120 µM/mM in patients who developed MARE, required dialysis or died. CONCLUSIONS: Urinary cGMP/creatinine ratio ≥ 120 µM/mM before CM exposure is a promising biomarker for the need of dialysis and all-cause mortality 90 days after CM exposure in patients with preexisting renal impairment or diabetes.

Why should we measure free 25(OH) vitamin D?

Vitamin D, either in its D2 or D3 form, is essential for normal human development during intrauterine life, kidney function and bone health. Vitamin D deficiency has also been linked to cancer development and some autoimmune diseases. Given this huge impact of vitamin D on human health, it is important for daily clinical practice and clinical research to have reliable tools to judge on the vitamin D status. The major circulating form of vitamin D is 25-hydroxyvitamin D (25(OH)D), although it is not the most active metabolite, the concentrations of total 25-hydroxyvitamin D in the serum are currently routinely used in clinical practice to assess vitamin D status. In the circulation, vitamin D - like other steroid hormones - is bound tightly to a special carrier - vitamin D-binding protein (DBP). Smaller amounts are bound to blood proteins - albumin and lipoproteins. Only very tiny amounts of the total vitamin D are free and potentially biologically active. Currently used vitamin D assays do not distinguish between the three forms of vitamin D - DBP-bound vitamin D, albumin-bound vitamin D and free, biologically active vitamin D. Diseases or conditions that affect the synthesis of DBP or albumin thus have a huge impact on the amount of circulating total vitamin D. DBP and albumin are synthesized in the liver, hence all patients with an impairment of liver function have alterations in their total vitamin D blood concentrations, while free vitamin D levels remain mostly constant. Sex steroids, in particular estrogens, stimulate the synthesis of DBP. This explains why total vitamin D concentrations are higher during pregnancy as compared to non-pregnant women, while the concentrations of free vitamin D remain similar in both groups of women. The vitamin D-DBP as well as vitamin D-albumin complexes are filtered through the glomeruli and re-uptaken by megalin in the proximal tubule. Therefore, all acute and chronic kidney diseases that are characterized by a tubular damage, are associated with a loss of vitamin D-DBP complexes in the urine. Finally, the gene encoding DBP protein is highly polymorphic in different human racial groups. In the current review, we will discuss how liver function, estrogens, kidney function and the genetic background might influence total circulating vitamin D levels and will discuss what vitamin D metabolite is more appropriate to measure under these conditions: free vitamin D or total vitamin D.

Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography.

BACKGROUND: Vitamin-D-binding protein (VDBP) is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH) vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage. METHOD: We included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death). RESULTS: Increased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 ± 299.61 ng/ml, n = 303; need for dialysis: 613.07 ± 700.45 ng/ml, n = 11, Mean ± SD, p<0.001), death (no death during follow-up: 121.41 ± 324.45 ng/ml, n = 306; death during follow-up: 522.01 ± 521.86 ng/ml, n = 8; Mean ± SD, p<0.003) and MARE (no MARE: 112.08 ± 302.00 ng/ml, n = 298; MARE: 506.16 ± 624.61 ng/ml, n = 16, Mean ± SD, p<0.001) during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule-1 (KIM-1) and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes. CONCLUSIONS: Urinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.