Accuracy of Flash Glucose Monitoring in Patients with Diabetes Mellitus on Hemodialysis and Its Relationship with Hydration Status.

BACKGROUND: The use of flash-glucose monitoring system FreeStyle Libre (FSL) has demonstrated benefits in metabolic control and quality of life in different populations with diabetes mellitus (DM), being funded in many countries. Due to this, DM subjects on hemodialysis (HD) are using FSL despite the accuracy in this population being unclear. The aims of the present study are to assess the accuracy of FSL in DM subjects on HD, its relationship to hydration status, and patient satisfaction. MATERIAL AND METHODS: A prospective study in 16 patients with DM in a chronic HD program was conducted. Interstitial glucose values from FSL during a 14-day period were compared to capillary glucose measurements obtained at the same time. Hydration status was measured via bioimpedance spectroscopy. Satisfaction with FSL was obtained from an ad hoc satisfaction questionnaire. RESULTS: A total of 766 paired interstitial and capillary glucose levels were analyzed. A correlation coefficient of 0.936 was determined and a mean absolute relative difference (MARD) value of 23%, increasing to 29% during HD. MARD was not related to hydration status. Interstitial glucose values were lower during HD (100.1 ± 17 mg/dL) than within the 12 hours after (125.1 ± 39 mg/dL; P = .012) and the days without HD (134.2 ± 32 mg/dL; P = .001). Subjects showed high satisfaction with FSL. CONCLUSION: The accuracy of FSL in DM patients on HD is lower than in other populations, especially during HD sessions and is not related with the hydration status. Despite this, the degree of patient satisfaction with FSL is very high.

Phytosterols and Omega 3 Supplementation Exert Novel Regulatory Effects on Metabolic and Inflammatory Pathways: A Proteomic Study.

Cardiovascular disease (CVD) remains one of the major causes of death and disability worldwide. In addition to drug treatment, nutritional interventions or supplementations are becoming a health strategy for CVD prevention. Phytosterols (PhyS) are natural components that have been shown to reduce cholesterol levels; while poly-unsaturated fatty acids (PUFA), mainly omega-3 (ω3) fatty acids, have shown to reduce triglyceride levels. Here we aimed to investigate whether the proteins in the main lipoproteins (low density lipoproteins (LDL) and high density lipoproteins (HDL)) as well as proteins in the lipid free plasma fraction (LPDP) were regulated by the intake of PhyS-milk or ω3-milk, in overweight healthy volunteers by a proteomic based systems biology approach. The study was a longitudinal crossover trial, including thirty-two healthy volunteers with body mass index (BMI) 25-35 kg/m² (Clinical Trial: ISRCTN78753338). Basal samples before any intervention and after 4 weeks of intake of PhyS or ω3-milk were analyzed. Proteomic profiling by two dimensional electrophoresis (2-DE) followed by mass spectrometry-(MALDI/TOF), ELISA, Western blot, conventional biochemical analysis, and in-silico bioinformatics were performed. The intake of PhyS-milk did not induce changes in the lipid associated plasma protein fraction, whereas ω3-milk significantly increased apolipoprotein (Apo)- E LDL content (p = 0.043) and induced a coordinated increase in several HDL-associated proteins, Apo A-I, lecitin cholesterol acyltransferase (LCAT), paraoxonase-1 (PON-1), Apo D, and Apo L1 (p < 0.05 for all). Interestingly, PhyS-milk intake induced a reduction in inflammatory molecules not seen after ω3-milk intake. Serum amyloid P component (SAP) was reduced in the LPDP protein fraction (p = 0.001) of subjects taking PhyS-milk and C-C motif chemokine 2 (CCL2)expression detected by reverse transcription polymerase chain reaction (RT-PCR) analysis in white blood cells was significantly reduced (p = 0.013). No changes were observed in the lipid-free plasma proteome with ω3-milk. Our study provides novel results and highlights that the PhyS-milk induces attenuation of the pro-inflammatory pathways, whereas ω3-milk induces improvement in lipid metabolic pathways.

Differential associations between glomerular filtration rate and duration of obesity depending on the presence or absence of left ventricular diastolic dysfunction.

BACKGROUND: A robust and consistent association between increasing body mass index (BMI) and chronic kidney disease (CKD) has been reported in several observational studies. Obesity remains the main preventable risk factor for CKD because it largely mediates diabetes and hypertension, the 2 most common etiologies for end-stage kidney disease (ESKD). Obesity is associated weakly with early stages of kidney disease but strongly with kidney progression to ESKD, even after adjustment for hypertension and diabetes. AIM: To assess the relationship between estimated glomerular filtration rate (eGFR) and trans-thoracic echocardiography left ventricular function parameters in a cohort of patients with obesity. MATERIALS & METHODS: Cross-sectional study involving 324 obese (BMI=44.0±2.2Kg/m(2)) apparently healthy asymptomatic patients with an eGFR >60ml/min/1.73m(2). Each patient underwent transthoracic echocardiography and a blood testing. The eGFR was addressed by the CKD-EPI formula. RESULTS: All patients had a normal systolic function whereas 24.5% disclosed diastolic dysfunction (DD). Hypertension and type 2 diabetes mellitus prevalence were 34.5% and 4.5% (respectively). All patients disclosed an eGFR >60ml/min while none of them disclosed hyperfiltration (eGFR >120ml/min). eGFR correlated inversely with BMI and the duration of obesity and positively with diastolic function parameters (P<0.001 for all, respectively). Patients with diastolic dysfunction displayed lower eGFR (P<0.0005) and longer duration of obesity (P<0.0005). CONCLUSIONS: Obesity and its duration are likely to impose hemodynamic changes affecting simultaneously both heart (diastolic dysfunction) and kidney (decreased glomerular filtration rate). Larger prospective studies are warranted.

Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk.

The benefits of dietary phytosterols (PhySs) and long-chain n-3 PUFA (ω3) have been linked to their effects as cholesterol- and triglyceride (TGL)-lowering agents. However, it remains unknown whether these compounds have further metabolic effects on LDL lipid composition. Here, we studied the effects of PhyS- or ω3-supplemented low-fat milk (milk) on the LDL-lipidome. Overweight and moderately hypercholesterolemic subjects (n = 32) were enrolled in a two-arm longitudinal crossover study. Milk (250 ml/day), enriched with either 1.57 g PhyS or 375 mg ω3 (EPA + DHA), was given to the participants during two sequential 28 day intervention periods. Compared with baseline, PhyS-milk induced a higher reduction in the LDL cholesterol (LDLc) level than ω3-milk. LDL resistance to oxidation was significantly increased after intervention with PhyS-milk. Changes in TGL and VLDL cholesterol were only evident after ω3-milk intake. Lipidomic analysis revealed a differential effect of the PhyS- and ω3-milk interventions on the LDL lipid metabolite pattern. Content in LDL-glycerophospholipids was reduced after PhyS-milk intake, with major changes in phosphatidylcholine (PC) and phosphatidylserine subclasses, whereas ω3-milk induced significant changes in the long-chain polyunsaturated cholesteryl esters and in the ratio PC36:5/lysoPC16:0, associated to a reduced inflammatory activity. In conclusion, daily intake of milk products containing PhyS or ω3 supplements induce changes in the LDL-lipidome that indicate reduced inflammatory and atherogenic effects, beyond their LDLc- and TGL-lowering effects.

Hypovitaminosis D in type 2 diabetes: relation with features of the metabolic syndrome and glycemic control.

AIM: To assess the association of hypovitaminosis D with clinical and biochemical characteristics of type 2 diabetic patients and to determine the effect of glycemic control optimization on 25-hydroxyvitamin D (25(OH)D) concentrations. METHODS: Cross-sectional study of 63 patients with type 2 diabetes (mean age 60 ± 9.8 years, 69.8% men). Twenty of the 63 patients were also studied before and after glycemic control optimization. RESULTS: Mean 25(OH)D concentrations were 63.64 ± 25.51 nmol/L and 74.6% of patients had hypovitaminosis D. Compared with patients with vitamin D sufficiency, patients with hypovitaminosis D had higher prevalence of overweight or obesity (72.3% versus 37.5%; p = 0.012) and higher VLDL cholesterol (VLDL-c) (0.71 (0.24-3.59) versus 0.45 (0.13-1.6) mmol/L; p = 0.011) and C-reactive protein (3.28 (0.36-17.69) versus 1.87 (0.18-17.47) mg/L; p = 0.033) concentrations. The composition of HDL particles also differed in both groups, with higher relative content of triglycerides and lower of cholesterol in patients with hypovitaminosis D. After adjustment for age, seasonality and BMI, differences remained significant for VLDL-c and triglyceride content of HDL. No differences were found regarding other diabetes characteristics. Improvement of glycemic control (HbA1c 9.4 (7.6-14.8) versus 7.3 (6.2-8.7)%; p = 0.000) was accompanied by a decrease in 25(OH)D concentrations (72.7 ± 33.3 to 59.0 ± 21.0 nmol/L; p = 0.035). Correlation analysis revealed that changes in 25(OH)D concentrations were negatively associated to changes in HbA1c (r - 0.482; p = 0.032). CONCLUSION: Hypovitaminosis D is associated with features of the metabolic syndrome in type 2 diabetes and improvement of glycemic control decreases 25(OH)D concentrations.

Serum alanine aminotransferase predicts interventricular septum thickness and left ventricular mass in patients with nonalcoholic fatty liver disease.

BACKGROUND: Alanine aminotransferase (ALT) is a marker of nonalcoholic fatty liver disease (NAFLD) and predicts type 2 diabetes mellitus (DM2) as well as coronary events independently of traditional risk factors and the features of the metabolic syndrome. The extent to which interventricular septum thickness (IVS) and left ventricular mass (LVM) are associated with ALT levels in cohorts of individuals with body weights ranging from overweight to morbid obesity and NAFLD remains still unknown. MATERIALS AND METHODS: This was a cross-sectional pilot study involving 151 young White participants with liver ultrasound-proven NAFLD. Standard echocardiograms were used to define LVM, IVS, and left ventricle diastolic function [mitral inflow velocity pattern (E/A ratio) and mitral annulus velocity by tissue Doppler imaging (Em/Am ratio)]. Participants were classified according to ALT quartiles: p25, p50, p75, and p100. RESULTS: The study included 36 men and 115 women with an age of 38.4 ± 0.7 years and BMI of 43.9 ± 0.6 kg/m2. p100 participants disclosed significantly higher homeostasis model assessment (P=0.003), DM2 (P=0.002), and hypertension (P=0.01) prevalence, whereas LVM, IVS, E/A, and Em/Am ratios were significantly higher in this group when compared with their p25 peers (P<0.01). IVS's and LVM's variance were significantly predicted by the statistical models including ALT independently of BMI, hypertension, and DM2. CONCLUSION: ALT levels predict both IVS and LVM in NAFLD individuals irrespective of their BMI, DM2, hypertension, age, and sex. ALT levels behave as a surrogate marker of left ventricular hypertrophy in overweight and/or obese NAFLD patients. Hence, it seems worth obtaining cardiac ultrasounds in NAFLD patients with elevated ALT levels.

Vitamin D concentrations in familial combined hyperlipidemia: effects of lipid lowering treatment.

BACKGROUND: Vitamin D deficiency has been linked to several cardiovascular risk factors but information regarding vitamin D concentrations in familial combined hyperlipidemia (FCHL) is lacking. Our objective was to examine vitamin D concentrations in patients with FCHL and to study the effects of lipid-lowering therapy. METHODS: We conducted a cross sectional study on 59 patients with FCHL and 48 healthy controls. We analyzed 25-hydroxyvitamin D (25(OH)D) concentrations and their association with lipid parameters, anthropometric measures, C-reactive protein and homeostasis model assessment (HOMA) index. Twenty-three patients with FCHL were also included in a longitudinal study conducted to analyze 25-hydroxyvitamin D concentrations before and after treatment for dyslipidemia. RESULTS: After adjustment for body mass index and seasonality, patients with FCHL had lower vitamin D concentrations than controls. Adjusted means (standard error of the mean (S.E.M)) for 25(OH)D according to the presence or absence of FCHL were 62.8 (3.6) nmol/L for patients with FCHL and 74.8 (4.1) nmol/L for controls (p = 0.021). In FCHL, hypovitaminosis D was associated with features of atherogenic dyslipidemia. After lipid-lowering therapy, vitamin D concentrations increased (51.0 ± 31.3 to 58.9 ± 24.6 nmol/L (P = 0.022)). However, changes in 25(OH)D concentrations did not correlate with changes in other parameters. CONCLUSIONS: Our findings suggest that FCHL is associated with decreased vitamin D concentrations and that treatment for dyslipidemia improves vitamin D status through an unknown mechanism. Further studies are needed to replicate these data in larger populations and to elucidate the mechanisms involved in this association.

The association of hypovitaminosis d with the metabolic syndrome is independent of the degree of obesity.

Background. It remains uncertain whether the metabolic syndrome (MS) or insulin resistance contribute to the association between vitamin D deficiency and obesity. Methods. We conducted a cross-sectional survey of 343 subjects who were overweight or obese. We analyzed anthropometric data and the presence or absence of MS. Additionally, we determined 25-hydroxyvitamin D (25OHD) and insulin concentrations, and the HOMA index was calculated. Chi-square test,Mann-Whitney U test, Student's t-tests,and logistic regression analysis were used. Results. The mean age of the patients was 42 ± 11 years, and 65.9% were women. The mean BMI was 34.7 ± 8.3 kg/m(2) and 25(OH)D levels were 53.7 ± 29.8 nmol/L. Forty-six patients (13.4%) had MS. Vitamin D status was associated with the degree of obesity, especially with a BMI > 40 kg/m(2). Patients with MS had lower levels of 25(OH)D than patients without (43.3 ± 29.0 versus 55.3 ± 29.6 mmol/L, resp.), and the odds ratio for hypovitaminosis D was 2.7 (confidence interval (CI), 1.14-6.4) (P = .023) for patients with MS versus patients without MS, irrespective of the degree of obesity. Conclusions. Our data confirm the association between vitamin D and MS and suggest that this association is independent of the degree of obesity.

Hypovitaminosis D and morbid obesity.

There is scarce and flawed data regarding vitamin D status in morbidly obese patients. More often than not, vitamin D deficits have been linked with bariatric surgery, not considering that the deficit may well precede surgery. Moreover, several pathophysiologic mechanism might explain, in part, vitamin D deficits. Conversely, the association between vitamin D deficits and secondary hyperparathyroidism in morbidly obese patients has been reported before and after bariatric surgery. Taking into account the elevated prevalence of vitamin D deficits in morbidly obese patients, its associated comorbidity, and the efficacy and low cost of its treatment to restore normal serum values of 25-OH-vitamin D, it seems advisable to recommend routine monitoring of serum calcium, phosphorus, and 25-OH-vitamin D levels in morbidly obese patients and to implement calcium and vitamin D supplementation whenever necessary.

Effects of bariatric surgery on vitamin D status and secondary hyperparathyroidism: a prospective study.

BACKGROUND: Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. Scattered data are available regarding the effects of bariatric surgery on vitamin D status. We studied calcium metabolism and vitamin D status before and after bariatric surgery. METHODS: In this prospective study, 64 patients (M5/F59) fulfilled the inclusion criteria (i.e. 2 calcidiol serum determinations in the winter season) among 457 morbidly obese individuals who underwent Roux-en-Y gastric bypass (RYGBP) a mean of 36 months previously. Laboratory data (serum calcium, phosphorus, creatinine, alkaline phosphatase, albumin, calcidiol, albumin and iPTH) were determined before and after RYGBP. Pre- and postoperative calcidiol levels were categorized as being normal (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L). Pre- and postoperative mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus. RESULTS: RYGBP produced a significant weight loss coupled with a simultaneous increase in calcidiol (+28%, P<0.0005) and decrements in total alkaline phosphatase (-53%, P<0.0005) and iPTH (-74%, P=0.001). Corrected serum calcium, phosphorus, and creatinine levels were indistinguishable before and after RYGBP. Additionally, 37.5% of the patients maintained their calcidiol category, while 42.2 % improved it and 20.3% lost one category. CONCLUSIONS: RYGBP does not completely correct pre-existing vitamin D deficient states with secondary hyperparathyroidism. Low calcidiol bioavailability and or insufficient sunlight exposure do probably persist after bariatric surgery. While randomized controlled studies are warranted, it seems advisable to support vitamin D supplementation as well as increasing sunlight exposure in the morbidly obese population.

Unchanged hypovitaminosis D and secondary hyperparathyroidism in morbid obesity after bariatric surgery.

BACKGROUND: Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. We assessed whether bariatric surgery alters the 25-hydroxyvitamin D (calcidiol) and intact parathyroid hormone (iPTH) levels in patients presenting with morbid obesity. METHODS: A cross-sectional survey was conducted on 144 patients of whom 80 had not undergone bariatric surgery, while 64 had bariatric surgery at a mean of 36 months previously. Calcidiol levels were defined as being normal (>50 nmol/L), insufficient (2550 nmol/L) and deficient (<25 nmol/L). Mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus. RESULTS: 80% of the patients presented low vitamin D levels and mild secondary hyperparathyroidism. Previous surgery or the presence of diabetes did not influence calcidiol levels. Corrected serum calcium, phosphorus, alkaline phosphatase, iPTH and Calcidiol were similar between subjects with and without surgery. CONCLUSIONS: Vitamin D deficient states with secondary hyperparathyroidism in the morbidly obese precede and are not significantly affected by bariatric surgery. Hypovitaminosis D with secondary hyperparathyroidism due to low calcidiol bio-availability should be added to the crowded list of sequelae of morbid obesity. While further studies are warranted, it seems advisable to support vitamin D supplementation in the morbidly obese population.