Usefulness of glycated albumin as a biomarker for glucose control and prognostic factor in chronic kidney disease patients on dialysis (CKD-G5D)

In chronic kidney disease patients on dialysis (CKD-G5D) accurate assessment of glycemic control is vital to improve their outcome and survival. The best glycemic marker for glucose control in these patients is still debated because several clinical and pharmacological factors may affect the ability of the available biomarkers to reflect the patient's glycemic status properly. This review discusses the role of glycated albumin (GA) both as a biomarker for glucose control and as a prognostic factor in CKD-G5D; it also looks at the pros and cons of GA in comparison to the other markers and its usefulness in hemodialysis and peritoneal dialysis

AGEs, FGF-23 and Cardiovascular remodeling in Chronic Kidney Disease on Dialysis (CKD-G5D): The Protective Role of sRAGE

Introduction. High levels of advanced glycated products (AGEs) and fibroblast growth factor-23 (FGF-23) are recognized as important cardiovascular risk factors. In chronic kidney disease (CKD), FGF-23 increases as a compensatory mechanism to keep normal phosphate and AGEs accumulate due both to the increased formation and reduced elimination. Being by-products of hyperglycemia, the formation of AGEs is further increased in patients with diabetes mellitus (DM). Recently, AGEs have been shown to induce cardiac remodeling in a mouse model of renal failure by promoting FGF-23 expression. Our aim was to explore whether Chronic Kidney Disease on dialysis (CKD-G5D) with DM suffer of an increased cardiac remodeling due to the to increased AGEs formation and the further amplification of the FGF-23 response. Methods. We quantified plasma levels of glycated albumin (GA), sRAGE, the decoy receptor for AGEs, c-terminal FGF-23 (cFGF23), brain natriuretic peptide (BNP) and the inflammatory mediators C-reactive protein, tumor necrosis factor alpha and pentraxin-3 in 24 CKD-G5D patients with DM and 52 without DM. Results. The levels of sRAGE, cFGF-23, BNP and the pro-inflammatory markers evaluated were over the ranges of normality in both DM and non-DM groups. GA and sRAGE were increased in DM CKD-G5D compared to non-DM CKD-G5D patients but cFGF-23 did not differ between the two groups. Similarly, the concentrations of the pro-inflammatory molecules and BNP were almost the same in the two groups. Conclusions. The up-regulation of sRAGE could be a counteract-system against glycated products. sRAGE, by blocking glycated products, could reduce the activation of various damaging cellular mechanisms, including an increased stimulation of cFGF-23and inflammatory mediators. Indeed, since AGEs accumulation is a risk factor for development and progression of heart failure, the lack of difference also in BNP levels between the two groups reinforces the hypothesis of a protective role of sRAGE in DM CKD-G5D patients

AGEs, FGF-23 and Cardiovascular remodeling in Chronic Kidney Disease on Dialysis (CKD-G5D): The Protective Role of sRAGE

Introduction. High levels of advanced glycated products (AGEs) and fibroblast growth factor-23 (FGF-23) are recognized as important cardiovascular risk factors. In chronic kidney disease (CKD), FGF-23 increases as a compensatory mechanism to keep normal phosphate and AGEs accumulate due both to the increased formation and reduced elimination. Being by-products of hyperglycemia, the formation of AGEs is further increased in patients with diabetes mellitus (DM). Recently, AGEs have been shown to induce cardiac remodeling in a mouse model of renal failure by promoting FGF-23 expression. Our aim was to explore whether Chronic Kidney Disease on dialysis (CKD-G5D) with DM suffer of an increased cardiac remodeling due to the to increased AGEs formation and the further amplification of the FGF-23 response. Methods. We quantified plasma levels of glycated albumin (GA), sRAGE, the decoy receptor for AGEs, c-terminal FGF-23 (cFGF23), brain natriuretic peptide (BNP) and the inflammatory mediators C-reactive protein, tumor necrosis factor alpha and pentraxin-3 in 24 CKD-G5D patients with DM and 52 without DM. Results. The levels of sRAGE, cFGF-23, BNP and the pro-inflammatory markers evaluated were over the ranges of normality in both DM and non-DM groups. GA and sRAGE were increased in DM CKD-G5D compared to non-DM CKD-G5D patients but cFGF-23 did not differ between the two groups. Similarly, the concentrations of the pro-inflammatory molecules and BNP were almost the same in the two groups. Conclusions. The up-regulation of sRAGE could be a counteract-system against glycated products. sRAGE, by blocking glycated products, could reduce the activation of various damaging cellular mechanisms, including an increased stimulation of cFGF-23and inflammatory mediators. Indeed, since AGEs accumulation is a risk factor for development and progression of heart failure, the lack of difference also in BNP levels between the two groups reinforces the hypothesis of a protective role of sRAGE in DM CKD-G5D patients

Increased Levels of sRAGE in Diabetic CKD-G5D Patients : a Potential Protective Mechanism Against AGE-Related Up-Regulation of Fibroblast Growth Factor-23 and Inflammation

Advanced glycation end products (AGEs) may induce cardiac remodeling in kidney disease by promoting fibroblast growth factor 23 (FGF-23) expression. Since AGEs are increased in diabetes mellitus (DM), our first aim was to evaluate the existence of any potential association between AGEs, FGF-23, inflammation, and increased cardiovascular risk in DM patients on dialysis (CKD-G5D). Secondarily, we explored the potential role of the soluble receptor for AGEs (sRAGE) as a marker of heart failure. Levels of glycated albumin (GA), sRAGE, c-terminal FGF-23 (cFGF-23), brain natriuretic peptide (BNP), and inflammatory mediators were compared between DM and non-DM CKD-G5D patients. The levels of sRAGE, cFGF-23, BNP, and proinflammatory markers were over the ranges of normality in both DM and non-DM groups. Only GA and sRAGE levels were increased in DM compared to non-DM patients. Plasma levels of sRAGE and CRP were the only independent predictors of BNP concentration. In conclusion, in DM CKD-G5D patients, sRAGE appeared to be a marker of cardiac remodeling. Indeed, its increase could be a potential protective mechanism against the increased risk of cardiovascular complications related to AGEs and inflammation. The causal relationship between sRAGE and cardiovascular risk in these patients needs to be further confirmed by mechanistic studies

Circulating irisn is reduced in male patients with type 1 and type 2 Myotonic Dystrophies

Context: Myotonic dystrophies (DM) are dominantly inherited muscle disorders characterized by myotonia, muscle weakness, and wasting. The reasons for sarcopenia in DMs are uncleared and multiple factors are involved. Irisin, a positive hormone regulator of muscle growth and bone, may play a role. Objectives: To investigate (1) circulating irisin in a series of DM1 and DM2 male patients compared with healthy controls and (2) the relationships between irisin and anthropometric, metabolic and hormonal parameters. Design and study participants: This is a cross-sectional study. Fasting blood samples for glucometabolic, gonadic, bone markers, and irisin were collected from 28 ambulatory DM1, 10 DM2, and 23 age-matched healthy male subjects. Body composition and bone mineralization [bone mineral density (BMD)] were measured by DEXA. Echocardiographic assessment and visceral adiposity, namely, liver and epicardial fat, were investigated by ultrasound. Irisin released from cultured myotubes derived from 3 DM1, 3 DM2, and 3 healthy donors was assayed. Results: Plasma irisin levels were definitely lower in both DM1 and DM2 patients than in controls with no difference between DM1 and DM2. Irisin released from DM1 and DM2 myotubes was similar to that released from myotubes of the non-DM donors, though diabetic DM2 myotubes released more irisin than DM1 myotubes. There was no correlation between irisin and muscle strength or lean mass in both DM1 and DM2 patients. In DM1 patients, plasma irisin levels correlated negatively with oxygen consumption and positively with insulin resistance, while in DM2 patients plasma irisin levels positively correlated with fat mass at arms and legs levels. No correlation with visceral fat, left ventricular mass, and gonadal hormones could be detected. In both DM1 and DM2 patients, legs BMD parameters positively correlated with plasma irisin levels. Conclusion: Plasma irisin is reduced in both DM1 and DM2 male patients likely reflecting muscle mass reduction. Moreover, insulin resistance may contribute to modulation of plasma irisin in DM1 patients. The irisin-mediated cross talk muscle\u2013adipose tissue\u2013bone may be active also in the male myotonic dystrophies\u2019 model

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity