The Speed of Ingestion of a Sugary Beverage Has an Effect on the Acute Metabolic Response to Fructose.

BACKGROUND: The consumption of sweetened beverages is associated with increased risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus. OBJECTIVE: We hypothesized that the metabolic effects of fructose in sugary beverages might be modulated by the speed of ingestion in addition to the overall amount. DESIGN: Thirty healthy subjects free of any disease and medication were recruited into two groups. After overnight fasting, subjects in group 1 drank 500 mL of apple juice over an hour by drinking 125 mL every 15 min, while subjects in group 2 drank 500 mL of apple juice over 5 min. Blood samples were collected at time zero and 15, 30, 60, and 120 min after ingestion to be analyzed for serum glucose, insulin, homeostatic model assessment (HOMA-IR) score, fibroblast growth factor 21, copeptin, osmolarity, sodium, blood urea nitrogen (BUN), lactate, uric acid, and phosphate levels. RESULTS: Serum glucose, insulin, HOMA-IR, fibroblast growth factor 21, copeptin, osmolarity, sodium, BUN, and lactate levels increased following apple juice ingestion. The increases were greater in the fast-drinking group, which were more significant after 15 min and 30 min compared to baseline. The changes in uric acid were not statistically different between the groups. Phosphate levels significantly increased only in the fast-drinking group. CONCLUSION: Fast ingestion of 100% apple juice causes a significantly greater metabolic response, which may be associated with negative long-term outcomes. Our findings suggest that the rate of ingestion must be considered when evaluating the metabolic impacts of sweetened beverage consumption.

The relationship between glycemic variability and blood pressure variability in normoglycemic normotensive individuals.

BACKGROUND AND AIM: Glycemic fluctuations around a mean glucose level, referred as glycemic variability and blood pressure variability (BPV) are considered as independent risk factors for cardiovascular diseases, all-cause mortality, and cardiovascular disease-mortality. With this background in mind, we aimed to investigate the association between glycemic variability and BPV and their association in normoglycemic and normotensive individuals. MATERIALS AND METHOD: Twenty-seven normotensive normoglycemic individuals were recruited. Twenty-four hour Holter devices were utilized to measure ambulatory blood pressure (BP) while continuous glucose monitoring (CGM) devices were applied to measure glycemic variability simultaneously to the subjects. These devices were kept on for 48 h. For BP recordings, daytime, nighttime, and 24-h BP determinations, their mean and SD were calculated. From CGM measurements, mean blood glucose (MBG), SD of blood glucose, the mean amplitude of glycemic excursions (MAGE), the mean of daily differences (MODD), coefficient of variation (correction of variability for the MBG), and daytime and nighttime blood glucose were determined. RESULTS: The mean age of the subjects was 23.8 ± 2.7 years and 66% were women (18/27). In the correlation analysis between glycemic variability parameters and BPV parameters, SD of 24-h SBP was correlated with the SD of MBG (r = 0.52, P = 0.006), MAGE (r = 0.49, P = 0.009), and MODD (r = 0.46, P = 0.015). SD of daytime SBP was correlated with, MAGE (r = 0.42, P = 0.03) and MODD (r = 0.43, P = 0.02). CONCLUSION: We report correlation between glycemic variability and BPV variables in normoglycemic and normotensive healthy individuals.

Noninvasive optical coherence tomography imaging correlates with anatomic and physiologic end-organ changes in healthy normotensives with systemic blood pressure variability.

OBJECTIVE: Blood pressure variability (BPV) is considered as a novel risk factor for cardiovascular disease including left ventricular hypertrophy, vascular stiffness, and renal dysfunction. In this study, we aimed to determine the relationship between ambulatory BPV with subclinical organ damage and vascular stiffness parameters in normotensive healthy subjects. METHODS: A total of 100 healthy subjects over 18 years of age were included in this cross-sectional study. We divided the participants into two groups according to the median value of the SD of mean 24-h blood pressure (BP) (Group 1: SD of mean 24-h BP <10.15 and Group 2: SD of mean 24-h BP >10.15). BPs of these subjects were recorded over a 24-h period using ambulatory BP monitoring. Mobil-O-Graph device was used to estimate the augmentation index (AIx), pulse wave velocity (PWV), and ambulatory BP measurement. The choroidal thickness was measured by using optical coherence tomography device. RESULTS: The mean age of the patients was 25.4 ± 5.0 years. Choroidal thickness was correlated with PWV, AIx, protein excretion, and SD of systolic and diastolic BP (P < 0.05). Additionally, participants with higher BP variability have lower choroidal thickness and higher AIx. CONCLUSION: We showed that even in normotensive subjects, BPV correlates with choroid thickness. Thus, BPV can be an early prognostic parameter for pathologic vascular changes.

Elevation in serum uric acid levels predicts favourable response to erlotinib treatment in patients with metastatic non-small-cell lung cancer.

WHAT IS KNOWN AND OBJECTIVE: Erlotinib is a small molecule tyrosine kinase inhibitor which blocks the activation of epidermal growth factor receptor (EGFR), a transmembrane receptor that is upregulated in many cancer types. Inhibition of angiogenesis with consequent impairments in intratumoral microcirculation is one of the mechanisms through which EGFR inhibition halts the progression of cancer. A consequence of impaired microcirculation is intratumoral hypoxia, which results in increases in serum uric acid levels. The goal of this study was to investigate the relationship between serum uric acid levels and response to erlotinib in metastatic non-small-cell lung cancer (NSCLC). METHODS: A total of 56 patients with metastatic non-small-cell lung cancer who received erlotinib for a duration of at least 3 months were included in this retrospective cohort study. Demographic characteristics, progression status, baseline serum uric levels and 3-month serum uric acid levels were recorded and analysed. RESULTS AND DISCUSSION: Of the study population, 21 (37.5%) were female and 35 (62.5%) were male patients. No significant difference in above demographic characteristics was observed among exitus, survivor with progression and survivor without progression groups. Patients who responded favourably to erlotinib with no progression of their disease had significantly increased uric acid levels at 3-month follow-up (P = .01). Such a correlation was not observed if the patient was exitus (P = .47) or had progressed on erlotinib therapy (P = .19). WHAT IS NEW AND CONCLUSION: In conclusion, this study is the first to demonstrate significant increases in serum uric acid levels in patients with metastatic NSCLC who responded favourably to erlotinib and had no progression under erlotinib therapy. Further studies are required to confirm and characterize serum uric acid as a novel biomarker in predicting the outcome in those with metastatic NSCLC.

Can Incidental Vascular Calcifications at Mammography be Used as a Screening Biomarker for Heart and Kidney Disease?

Mammography is a screening test with extensive international application and financial infrastructure promoting accessibility and affordability. Designed specifically to detect microcalcifications, mammography is powered to detect calcifications in vessel walls. Breast arterial calcifications (BAC) are one of the most common incidental findings documented by mammography. This review considers the literature regarding BAC in relation to cardiovascular disease (CVD) and its risk factors. The aim is to assess the possibility of using BAC as an early surrogate imaging biomarker of CVD.

The effect of chronic kidney disease on lipid metabolism.

The major cause of death among chronic kidney disease patients is cardiovascular diseases. Cardiovascular and kidney disease are interrelated and increase the severity of each other. Dyslipidemia is one the major causes of cardiovascular disease among chronic kidney disease patients along with diabetes and hypertension. The relationship between dyslipidemia and chronic kidney disease is reciprocal. Dyslipidemia is known to be a risk factor for chronic kidney disease and chronic kidney disease causes major alterations on lipoprotein profile, defined as the "dyslipidemic profile" of chronic kidney disease patients. Increased triglyceride, very low density lipoprotein and oxidized low density lipoprotein as well as decreased high density lipoprotein and changes in the composition of lipoproteins contribute to the "dyslipidemic profile." Treatment strategies targeting the "dyslipidemic profile" of chronic kidney disease could contribute to prevent cardiovascular diseases. Current therapy is based on the patient kidney function and consist mainly of statins. This review focuses on the effects of chronic kidney disease on the lipoprotein profile and how this may impact novel therapeutic approaches to cardiovascular risk.

Hyperthermic intraperitonal chemotherapy is an independent risk factor for development of acute kidney injury.

PURPOSE: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) or hyperthermic intrapleural chemotherapy (HIC) has been established as the new treatment modality for selected patients with peritoneal and pleural malignancies. The purpose of the study was to compare the development of acute kidney injury (AKI) in patients who received intravenous cisplatin alone, HIPEC and underwent surgery. METHODS: This retrospective study included 104 patients who underwent different therapeutic procedures including systemic cisplatin, surgery and HIPEC or HIC using cisplatin for the treatment of peritoneal carcinomatosis from a variety of primary tumors at Koc University Hospital and American Hospital between January 2015 to December 2017. RESULTS: AKI developed in 18 (17.3%) patients. Baseline creatinine was significantly increased in 3 groups after therapies. The development of AKI was highest in patients treated with HIPEC compared to patients treated with intravenous cisplatin and patients who underwent surgery. AKI developed 31.2% in the HIPEC group (10 of 32 patients), 11.7% in the surgery group (4 of 34 patients) and 10.5% in intravenous cisplatin group (4 of 38 patients), respectively (p 0.04). CONCLUSION: HIPEC may not be so safe with regard to kidney function. Every attempt should be taken to decrease kidney damage during this procedure.

Acute effects of salt on blood pressure are mediated by serum osmolality.

It is classically thought that it is the amount of salt that is critical for driving acute blood pressure responses. However, recent studies suggest that blood pressure responses, at least acutely, may relate to changes in serum osmolality. Here, we test the hypothesis that acute blood pressure responses to salt can be altered by concomitant water loading. Ten healthy patients free of any disease and medication underwent 4 interventions each a week apart in which they took 300 mL of lentil soup with no salt (visit 1), lentil soup with 3 g salt (visit 2), or lentil soup with 3 g salt and 500 mL water (visit 3) or 750 mL water (visit 4). At each visit, hourly blood measurements and blood pressure measurements (baseline, 1st, 2nd, 3rd, and 4th hour) were performed and plasma osmolarity, sodium and copeptin levels were measured. Patients receiving the 3 g salt showed a 6 mOsm/L change in osmolality with a 2.5 mmol/L change in plasma sodium and 10 mm Hg rise in systolic blood pressure at 2 hours. When the same patients drank salty soup with water, the changes in plasma osmolarity, plasma sodium, and blood pressure were prevented. The ability to raise blood pressure acutely with salt appears dependent on changes in plasma osmolality rather than the amount of salt. Our findings suggest that concurrent intake of water must be considered when evaluating the role of salt in blood pressure.

Capillary rarefaction from the kidney point of view.

Capillary rarefaction is broadly defined as a reduction in vascular density. Capillary rarefaction in the kidneys is thought to promote hypoxia, impair hemodynamic responses and predispose to chronic kidney disease (CKD) progression and hypertension development. Various mechanisms have been suggested to play a role in the development of capillary rarefaction, including inflammation, an altered endothelial-tubular epithelial cell crosstalk, a relative deficiency in angiogenic growth factors, loss of pericytes, increased activity of Transforming growth factor -ß1 and thrombospondin-1, vitamin D deficiency, a link to lymphatic neoangiogenesis and INK4a/ARF (Cylin-dependent kinase inhibitor 2a; CDKN2A). In this review, we summarize the tools available to monitor capillary rarefaction noninvasively in the clinic, the contribution of capillary rarefaction to CKD and hypertension, the known mechanisms of capillary rarefaction, and potential future strategies to attenuate capillary rarefaction and reduce its negative impact. Therapeutic strategies to be explored in more detail include optimization of antihypertensive therapy, vitamin D receptor activators, sirtuin 1 activators, Hypoxia inducible factor prolyl hydroxylase inhibitors and stem cell therapy.

The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus.

Chronic kidney disease (CKD) has been shown to result in profound changes in the composition and functions of the gut microbial flora which by disrupting intestinal epithelial barrier and generating toxic by-products contributes to systemic inflammation and the associated complications. On the other hand, emerging evidence points to the role of the gut microbiota in the development and progression of CKD by provoking inflammation, proteinuria, hypertension, and diabetes. These observations demonstrate the causal interconnection between the gut microbial dysbiosis and CKD. The gut microbiota closely interacts with the inflammatory, renal, cardiovascular, and endocrine systems via metabolic, humoral, and neural signaling pathways, events which can lead to chronic systemic inflammation, proteinuria, hypertension, diabetes, and kidney disease. Given the established role of the gut microbiota in the development and progression of CKD and its complications, favorable modification of the composition and function of the gut microbiome represents an appealing therapeutic target for prevention and treatment of CKD. This review provides an overview of the role of the gut microbial dysbiosis in the pathogenesis of the common causes of CKD including hypertension, diabetes, and proteinuria as well as progression of CKD.

Disorders of Lipid Metabolism in Chronic Kidney Disease.

Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). One of the most important pathophysiological mechanisms for CVD in patients with CKD is the widespread and possibly accelerated formation of atherosclerotic plaques due to hyperlipidemia, uremic toxins, inflammation, oxidative stress, and endothelial dysfunction. Recent studies showed that the level of oxidized low-density lipoprotein cholesterol increases, and that high--density lipoprotein cholesterol dysfunction occurs as kidney function declines and inflammation becomes more prevalent. In this review, we aimed to discuss the effect of kidney dysfunction, oxidative stress, and inflammation on lipid -profile.

The impact of exercise on physical function, cardiovascular outcomes and quality of life in chronic kidney disease patients: a systematic review.

The prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) is increasing steadily. CKD does not only relate to morbidity and mortality but also has impact on quality of life, depression and malnutrition. Such patients often have significantly decreased physical activity. Recent evidence suggests that low physical activity is associated with morbidity, mortality, muscle atrophy, quality of life impairment, cardiovascular outcomes and depression. Based on this, it is now recommended to regularly improve the physical activity of these patients. Furthermore, studies have shown the beneficial effects of various exercise programs with respect to outcomes such as low physical activity muscle atrophy, quality of life, cardiovascular outcomes and depression. Despite these encouraging findings, the subject is still under debate, with various aspects still unknown. In this review, we tried to critically summarize the existing studies, to explore mechanisms and describe future perspectives regarding physical activity in CKD/ESRD patients.

Iron in kidney and heart failure: from theory to practice.

There is evidence that serum iron levels, regardless of the presence of anemia, directly impact outcomes in congestive heart failure (CHF) including quality of life, hospitalization rate and overall survival. Despite modern medical treatments, the prognosis of CHF remains grim. Ironically, simple iron replenishment may serve as a powerful tool in the armamentarium. This review will start from fundamental concepts of iron in oxygen delivery and analyze evidence-based outcomes in CHF iron-directed therapeutic trials. Imaging rationale that dovetails with this pathophysiology will also be detailed in a clinician-directed fashion.

Dietary and commercialized fructose: Sweet or sour?

Metabolic syndrome and diabetes are main health problems of modern life in the twenty-first century. Alarming ratios of global prevalence lead to conduct more and more researches about etiological factors and pathogenesis. Disease mechanism is elementary for advancing more efficient and practicable treatment methods. Concurrent increase in both fructose consumption with Western diet and metabolic syndrome has revealed fructose hypothesis that suggests fructose as one of etiological factor of metabolic syndrome (insulin resistance, central obesity, hypertension, etc.). Recent studies have increasingly lightened the unknowns about role of fructose on pathogenesis. This review discusses fructose hypothesis by exploring current studies and their results in wide perspective. Potential mechanisms covering low-grade inflammation or de novo lipogenesis, etc., in the development of insulin resistance and obesity are explained. Clinical trials have revealed connection of fructose-induced hyperuricemia with insulin resistance and chronic inflammatory state leading to hepatosteatosis or obesity. Further, novel hypothesizes suggesting role of fructose-induced modifications in epigenetics, gut microbiota and oxidative stress on disease pathogenesis are reviewed based on recent clinical trials. More innovative theories including fructose-induced malignancy; decreased satiety feeling, and unfavorable bone health are argued covering fructose-induced neurotransmitter changes in central nervous system, more aggressive malignancy phenotype and impaired calcium absorption.

Evaluation of serum Spondin 2 levels in the different stages of Type 2 diabetic nephropathy.

AIM: We aimed to determine whether serum SPON2 is a useful biomarker in the detection of Diabetic Nephropathy (DN) and to compare serum SPON2 levels with 24-hour urinary albumin excretion rate (UAER) in patients with DN at different stages. METHODS: The cohort included 80 adult patients with T2D and 20 healthy controls. The patients with T2D were divided into four groups according to UAER and serum creatinine (sCr) levels. Group 1 consisted of patients with normoalbuminuria (n = 20), Group 2 with microalbuminuria (n = 20), Group 3 with macroalbuminuria (n = 20) and Group 4 with albuminuria and sCr > 1.5 mg/dL (n = 20). RESULTS: There were no significant differences between the groups in terms of demographic data, C-reactive protein, HbA1c, lipids, serum uric acid levels and leukocyte counts. SPON2 levels were observed to increase linearly with increasing severity of diabetic nephropathy levels. The SPON2 levels of Group 4 were significantly higher than Group 1 and the controls, and SPON2 levels of Group 3 were significantly higher than Group 1. Blood urea nitrogen, creatinine and UAER were significantly positively correlated with SPON2; serum total protein and calcium levels were negatively correlated with SPON2 in patients with DN. CONCLUSION: We observed a linear and significant increase in SPON2 levels of patients with T2D as the stage of DN increased, but serum SPON2 level was not as effective as microalbuminuria in reflecting nephropathy. Also, serum SPON2 level was not as good as urine and tissue levels of SPON2 in detection of renal damage in DN.