Markers Of Glucose Metabolism Research Articles

Postprandial Metabolic Responses to High-fat Feeding in Healthy Adults Following Ingestion of Oolong Tea–Derived Polymerized Polyphenols: A Randomized, Double-blinded, Placebo-controlled Crossover Study

BackgroundPolymerized polyphenols (PP) found in oolong tea can inhibit pancreatic lipase activity in vitro, and pilot work indicates that this may reduce postprandial lipemia. Since tea contains caffeine and catechins, the interactions between these ingredients and PP warrant investigation. ObjectivesTo assess whether PP ingested alone or with caffeine and catechins lowers postprandial lipemia. MethodsFifty healthy adults [mean (SD) age: 26 (7) y; BMI (in kg/m2): 24.0 (2.7); female: n = 16] completed 4 oral lipid tolerance tests in a placebo-controlled randomized, crossover design. Participants ingested 40 g of fat with either 1) placebo, 2) 100 mg PP, 3) 150 mg PP, or 4) 100 mg PP plus 50 mg caffeine and 63 mg catechins (PP + CC). Blood was sampled for 3 h postprandially to assess concentrations of serum and plasma triacylglycerol and plasma markers of lipid (NEFA; glycerol; LDL and HDL cholesterol; and ApoA-I, A-II, B, C-II, C-III, and E) and glucose metabolism (glucose, insulin, and C-peptide). ResultsSerum and plasma triacylglycerol concentrations and lipid metabolism variables generally increased following any test drink ingestion (main effect of time, p < 0.001). Nevertheless, for the lipid metabolism responses, there were no statistically significant condition–time interactions and no statistically significant differences in incremental or total area under the curve between conditions, apart from HDL cholesterol (p = 0.021). Ingesting 100 mg PP + CC lowered peak plasma glucose, insulin, and C-peptide concentrations compared with all other conditions 30 min postingestion (p < 0.001), with persistent alterations in glucose concentrations observed for 90 min compared with placebo and 100 mg PP conditions. ConclusionsPP ingested at doses ≤150 mg does not clearly alter early-phase postprandial triacylglycerol concentrations in healthy adults, irrespective of the presence or absence of caffeine and catechins. Nevertheless, caffeine and catechins added to PP lowered postprandial glucose and insulin concentrations.This trial was registered in ClinicalTrials.gov as NCT03324191 (https://clinicaltrials.gov/ct2/show/NCT03324191).

Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway.

Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway.

The characteristics of elevated blood pressure in abdominal obesity correspond to primary hypertension: a cross-sectional study

BackgroundObesity-related hypertension and the associated metabolic abnormalities are considered as a distinct hypertensive phenotype. Here we examined how abdominal fat content, as judged by waist:height ratio, influenced blood pressure and hemodynamic profile in normotensive subjects and never-treated hypertensive patients.MethodsThe 541 participants (20–72 years) underwent physical examination and laboratory analyses and were divided into age and sex-adjusted quartiles of waist:height ratio. Supine hemodynamics were recorded using whole-body impedance cardiography, combined with analyses of radial tonometric pulse wave form and heart rate variability.ResultsMean waist:height ratios in the quartiles were 0.46, 0.51, 0.55 and 0.62. Radial and aortic blood pressure, systemic vascular resistance, pulse wave velocity, markers of glucose and lipid metabolism, leptin levels and C-reactive protein were higher in quartile 4 when compared with quartiles 1 and 2 (p < 0.05 for all). Cardiac index was lower in quartile 4 versus quartile 1, while no differences were seen in heart rate variability, augmentation index, plasma renin activity, and aldosterone concentration between the quartiles. Linear regression analyses showed independent associations of abdominal obesity with higher aortic systolic and diastolic blood pressure, systemic vascular resistance, and pulse wave velocity (p < 0.05 for waist:height ratio in all regression models).ConclusionHigher waist:height ratio was associated with elevated blood pressure, systemic vascular resistance, and arterial stiffness, but not with alterations in cardiac sympathovagal modulation or activation of the circulating renin-angiotensin-aldosterone system. Although obesity-related elevation of blood pressure has distinct phenotypic features, these results suggest that its main characteristics correspond those of primary hypertension.Trial registrationClinicalTrails.gov NCT01742702 (date of registration 5th December 2012).

Association between serum S100A11 levels and glucose metabolism in diabetic process

BackgroundDiabetes mellitus (DM) is a prevalent non-communicable metabolic disease, and S100A11 is a newly identified gene closely related to metabolism. The association of S100A11 with diabetes is unclear. This study aimed to assess the relationship between S100A11 and markers of glucose metabolism in patients with different glucose tolerance and gender.MethodsThis study included 97 participants. Baseline data were obtained, and the serum levels of S100A11 and metabolic markers (glycated hemoglobin [HbA1c], insulin release test, and oral glucose tolerance test) were measured. Linear and nonlinear correlations between serum S100A11 levels and HOMA-IR, HOMA of β, HbA1c, insulin sensitivity index (ISI), corrected insulin response (CIR), and oral disposition index (DIo) were analyzed. The expression of S100A11 was also detected in mice.ResultsSerum S100A11 levels increased in patients with impaired glucose tolerance (IGT) of both genders. S100A11 mRNA and protein expression increased in obese mice. There were nonlinear correlations between S10011 levels and CIR, FPI, HOMA-IR, whole-body ISI in the IGT group. S100A11 was nonlinearly correlated with HOMA-IR, hepatic ISI, FPG, FPI, and HbA1c in the DM group. In the male group, S100A11 was linearly correlated with HOMA-IR and nonlinearly correlated with DIo (derived from hepatic ISI) and HbA1c. In the female population, S100A11 was nonlinearly correlated with CIR.ConclusionsSerum S100A11 levels were highly expressed in patients with IGT and in the liver of obese mice. In addition, there were linear and nonlinear correlations between S100A11 and markers of glucose metabolism, demonstrating that S100A11 has a role in diabetes.Trial registration ChiCTR1900026990

Screening for PTSD and TBI in Veterans using Routine Clinical Laboratory Blood Tests

Post-traumatic stress disorder (PTSD) is a mental disorder diagnosed by clinical interviews, self-report measures and neuropsychological testing. Traumatic brain injury (TBI) can have neuropsychiatric symptoms similar to PTSD. Diagnosing PTSD and TBI is challenging and more so for providers lacking specialized training facing time pressures in primary care and other general medical settings. Diagnosis relies heavily on patient self-report and patients frequently under-report or over-report their symptoms due to stigma or seeking compensation. We aimed to create objective diagnostic screening tests utilizing Clinical Laboratory Improvement Amendments (CLIA) blood tests available in most clinical settings. CLIA blood test results were ascertained in 475 male veterans with and without PTSD and TBI following warzone exposure in Iraq or Afghanistan. Using random forest (RF) methods, four classification models were derived to predict PTSD and TBI status. CLIA features were selected utilizing a stepwise forward variable selection RF procedure. The AUC, accuracy, sensitivity, and specificity were 0.730, 0.706, 0.659, and 0.715, respectively for differentiating PTSD and healthy controls (HC), 0.704, 0.677, 0.671, and 0.681 for TBI vs. HC, 0.739, 0.742, 0.635, and 0.766 for PTSD comorbid with TBI vs HC, and 0.726, 0.723, 0.636, and 0.747 for PTSD vs. TBI. Comorbid alcohol abuse, major depressive disorder, and BMI are not confounders in these RF models. Markers of glucose metabolism and inflammation are among the most significant CLIA features in our models. Routine CLIA blood tests have the potential for discriminating PTSD and TBI cases from healthy controls and from each other. These findings hold promise for the development of accessible and low-cost biomarker tests as screening measures for PTSD and TBI in primary care and specialty settings.

Alfuzosin ameliorates diabetes by boosting PGK1 activity in diabetic mice

AimsDiabetes mellitus (DM) has become a global problem, causing a huge economic burden. The purpose of this study is to find a new potential method and mechanism for the treatment of DM. Main methodsThe oxidation, glycation and insulin resistance cell models were built to screen the potential anti-diabetic chemicals. Then the DM mice were induced by the combination of high-fat diet (HFD) and intraperitoneal injection of streptozotocin (50 mg/kg) for five days. The alfuzosin (1.2 mg/kg) was administered by intraperitoneal injection once daily for sequential 12 weeks. Fasting blood glucose, blood lipid, oxidative stress and key markers of glucose metabolism were detected. PGK1/AKT/GLUT4 pathway related proteins were analyzed by Western blot. Key findingsAlfuzosin ameliorated oxidative stress, glycative stress and insulin resistance in HepG2 cells. Further, in a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, alfuzosin reduced fasting blood glucose, improved insulin sensitivity. Mechanically, alfuzosin activated PGK1 directly to stimulate the protein kinase B (AKT) signaling pathway, thus facilitating glucose uptake as well as improving insulin resistance. SignificanceThe present finding has shed a new light on the treatment of DM and provides validation for PGK1 as a therapeutic target for DM.

The association between plasma zinc concentrations and markers of glucose metabolism in adults in Cameroon.

An abnormal Zn status has been suggested to play a role in the pathogenesis of type 2 diabetes. However, epidemiological studies of the relationship between plasma Zn concentrations and diabetes are sparse and inconclusive. We aimed to investigate the association between plasma Zn concentrations and glycaemic markers (fasting glucose, 2-h glucose and homeostatic model assessment of insulin resistance) in rural and urban Cameroon. We studied 596 healthy adults (63·3 % women) aged 25-55 years in a population-based cross-sectional study. The mean plasma Zn concentration was 13·7 ± 2·7 µmol/L overall, with higher levels in men (14·4 ± 2·9 µmol/l) than in women (13·2 ± 2·6 µmol/l), P-value < 0·0001. There was an inverse relationship between tertiles of plasma Zn and 2-h glucose concentrations (P-value for linear trend = 0·002). The difference in 2-h glucose between those in the highest tertile of plasma Zn compared to the lowest was -0·63 (95 % CI - 1·02, -0·23) mmol/l. This remained significant after adjusting for age, sex, smoking status, alcohol intake, education level, area of residence, adiposity and objectively measured physical activity -0·43(-0·82, -0·04). Similar inverse associations were observed between plasma Zn concentrations and fasting glucose and homeostatic model assessment of insulin resistance when adjusted for socio-demographic and health-related behavioural characteristics. The current findings of an inverse association between plasma Zn concentrations and several markers of glucose homeostasis, together with growing evidence from intervention studies, suggest a role for Zn in glucose metabolism. If supported by further evidence, strategies to improve Zn status in populations may provide a cheap public health prevention approach for diabetes.

Liver-expressed antimicrobial peptide 2 is associated with improved pancreatic insulin secretion in adults with overweight and obesity.

To examine association of liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous ghrelin antagonist with anorexiant effects, to key cardiometabolic risk factors in people with overweight and obesity. In this cross-sectional study, we sought to identify associations between LEAP2 levels and cardiometabolic risk factors, including body composition (dual X-ray absorptiometry), insulin and glucose metabolism (oral and intravenous glucose tolerance tests and hyperinsulinaemic-euglycaemic clamps), plasma lipids and inflammation markers (ELISA and multiplex assays). In 65 participants with overweight or obesity (63.1% male, mean age 31.3 ± 8.5 years), LEAP2 levels were associated with total body fat, but not with body mass index or waist-hip ratio in both univariable and age- and sex-adjusted models (P < 0.05). Higher LEAP2 level was also positively associated with higher insulin secretion in univariable (P=0.047) and multivariable models adjusted for age, sex and body fat (P=0.03), but not with fasting glucose levels (P ≥ 0.05). Higher LEAP2 levels were associated insulin resistance (P=0.07) after adjustment for age and sex, but the association disappeared after an additional adjustment for body fat (P=0.2). There was an inverse association between LEAP2 levels and nuclear factor kappa-B (NFκB) activity in the peripheral blood mononuclear cells in age-, sex- and body fat-adjusted models (P=0.04). There were no associations with cardiovascular risk factors (lipids, blood pressure) or other inflammation markers. These results provide important insights into the association between LEAP2 and cardiometabolic health in a high-risk population of individuals with overweight and obesity. This is a first report of an association between LEAP2 and insulin secretion, insulin sensitivity and NFκB activity. LEAP2 may represent an important potential therapeutic target to promote insulin secretion in people with type 2 diabetes and obesity.

Several Metabolite Families Display Inflexibility during Glucose Challenge in Patients with Type 2 Diabetes: An Untargeted Metabolomics Study.

Metabolic inflexibility is a hallmark of insulin resistance and can be extensively explored with high-throughput metabolomics techniques. However, the dynamic regulation of the metabolome during an oral glucose tolerance test (OGTT) in subjects with type 2 diabetes (T2D) is largely unknown. We aimed to identify alterations in metabolite responses to OGTT in subjects with T2D using untargeted metabolomics of both plasma and subcutaneous adipose tissue (SAT) samples. Twenty subjects with T2D and twenty healthy controls matched for sex, age, and body mass index (BMI) were profiled with untargeted metabolomics both in plasma (755 metabolites) and in the SAT (588) during an OGTT. We assessed metabolite concentration changes 90 min after the glucose load, and those responses were compared between patients with T2D and controls. Post-hoc analyses were performed to explore the associations between glucose-induced metabolite responses and markers of obesity and glucose metabolism, sex, and age. During the OGTT, T2D subjects had an impaired reduction in plasma levels of several metabolite families, including acylcarnitines, amino acids, acyl ethanolamines, and fatty acid derivates (p &lt; 0.05), compared to controls. Additionally, patients with T2D had a greater increase in plasma glucose and fructose levels during the OGTT compared to controls (p &lt; 0.05). The plasma concentration change of most metabolites after the glucose load was mainly associated with indices of hyperglycemia rather than insulin resistance, insulin secretion, or BMI. In multiple linear regression analyses, hyperglycemia indices (glucose area under the curve (AUC) during OGTT and glycosylated hemoglobin (HbA1c)) were the strongest predictors of plasma metabolite changes during the OGTT. No differences were found in the adipose tissue metabolome in response to the glucose challenge between T2D and controls. Using a metabolomics approach, we show that T2D patients display attenuated responses in several circulating metabolite families during an OGTT. Besides the well-known increase in monosaccharides, the glucose-induced lowering of amino acids, acylcarnitines, and fatty acid derivatives was attenuated in T2D subjects compared to controls. These data support the hypothesis of inflexibility in several metabolic pathways, which may contribute to dysregulated substrate partitioning and turnover in T2D. These findings are not directly associated with changes in adipose tissue metabolism; therefore, other tissues, such as muscle and liver, are probably of greater importance.

Sociodemographic, Anthropometric, Body Composition, Nutritional, and Biochemical Factors Influenced by Age in a Postmenopausal Population: A Cross-Sectional Study.

Postmenopausal aging has become relevant for understanding health during the transition life stages-the aging process being involved in several disturbances of the human condition. The present study aimed to investigate the relationship between postmenopausal aging and sociodemographic, anthropometric, body composition, nutritional, and biochemical (i.e., protein and lipid profiles, phosphorous-calcium metabolism, and antioxidant status) factors in postmenopausal women. This cross-sectional study enrolled 78 healthy postmenopausal women (44-76 years). The anthropometrical data showed no differences by age. Biochemical parameters, especially those involved in the protein and phosphorous-calcium metabolism, were influenced by age in our cohort of postmenopausal women. In contrast, no associations were found when considering lipid and antioxidant parameters. Height, fiber intake, blood glucose, protein profile and phosphorous-calcium metabolism markers seem to be the most affected nutritional-related factors by age in our cohort of healthy postmenopausal women. Primary prevention strategies focused on parameters at risk of disruption with postmenopausal aging are necessary to ensure the quality of life in older ages.

Dairy product consumption and type 2 diabetes in an Argentinian population: is there an association?

Introduction: dairy products have long been recommended as part of a healthy eating plan, but there is a controversial opinion about whether or not they should be included in the diet of people with type 2 diabetes (T2D). Objective: the aim of this study was to know if there is an association between the intake of total dairy and dairy subgroups and the chance of having T2D, and the status of markers of glucose metabolism. Methods: three hundred and forty-two adult subjects participated in the study. A validated food-frequency questionnaire was applied to establish the dairy intake. Clinical-pathological and anthropometric variables (height, weight, waist circumference and serum concentrations of blood glucose, glycated hemoglobin [HbA1c], high sensitive C-reactive protein [hs-CRP], tumor necrosis factor alpha [TNFα], interleukin [IL] 6 and IL-10) were measured. Consumption tertiles were calculated for each dairy subgroup. Correlation coefficients, multiple linear regression models and logistic regression models were used to assess the relation between dairy product consumption and markers of glucose metabolism. Results: a negative correlation was observed between the consumption of fermented dairy products and IL-10 (r = -0.27, p = 0.0206). Fermented dairy products were inversely associated with blood glucose, and HbA1c. Total dairy intake was positively associated with a lower chance of having diabetes in tertiles 2 and 3 of consumption, in relation to the reference tertile, adjusted for age, smoking habit, and alcohol intake, body mass index (BMI) and dietary variables. Conclusions: with this study, we broaden our understanding of the role of dairy intake in diabetes risk. However, more long-term studies are needed to confirm the associations and explore different confounding factors.

Serum calprotectin levels as markers of inflammation, insulin resistance and hyperandrogenism in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common, complex endocrine, and metabolic disorder. Inflammation has been thought to play an important role in PCOS pathogenesis in recent years, and various inflammatory markers have been investigated; however, no definite conclusion has been reached. As a multifunctional regulatory protein in different inflammatory processes, calprotectin may play a role in the etiology of PCOS. Therefore, based on this hypothesis, we aimed to determine serum calprotectin concentrations in women with PCOS and to compare them with healthy controls. This cross-sectional study was conducted at a tertiary referral center during the study period. Forty-three women (n = 43) with PCOS and 47 women (n = 47) in the control group were enrolled in this cross-sectional study. Serum calprotectin concentrations were measured using enzyme-linked immunosorbent assay and compared with markers of glucose and lipid metabolism. Clinical characteristics and hormonal parameters were evaluated in both groups. Levels of serum calprotectin were measured as 347 ± 28.8 and 188 ± 15.3 ng/mL in the PCOS and healthy control groups, respectively (P = .009). The mean homeostatic model assessment for insulin resistance[1] index and total testosterone levels were significantly higher in the PCOS group than in the control group (both P < .001). Spearman's correlation test demonstrated linear correlations between calprotectin and C-reactive protein, waist circumference, insulin resistance index, and total testosterone levels in the PCOS group (all P < .05). Serum calprotectin levels were higher in women with PCOS. This biomarker may be an indirect sign of insulin resistance, hyperandrogenism, or chronic inflammation in women with PCOS.

Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study

BackgroundThe prevalence of type 2 diabetes has dramatically increased in the past years. Increasing evidence supports that blood DNA methylation, the best studied epigenetic mark, is related to diabetes risk. Few prospective studies, however, are available. We studied the association of blood DNA methylation with diabetes in the Strong Heart Study. We used limma, Iterative Sure Independence Screening and Cox regression to study the association of blood DNA methylation with fasting glucose, HOMA-IR and incident type 2 diabetes among 1312 American Indians from the Strong Heart Study. DNA methylation was measured using Illumina’s MethylationEPIC beadchip. We also assessed the biological relevance of our findings using bioinformatics analyses.ResultsAmong the 358 differentially methylated positions (DMPs) that were cross-sectionally associated either with fasting glucose or HOMA-IR, 49 were prospectively associated with incident type 2 diabetes, although no DMPs remained significant after multiple comparisons correction. Multiple of the top DMPs were annotated to genes with relevant functions for diabetes including SREBF1, associated with obesity, type 2 diabetes and insulin sensitivity; ABCG1, involved in cholesterol and phospholipids transport; and HDAC1, of the HDAC family. (HDAC inhibitors have been proposed as an emerging treatment for diabetes and its complications.)ConclusionsOur results suggest that differences in peripheral blood DNA methylation are related to cross-sectional markers of glucose metabolism and insulin activity. While some of these DMPs were modestly associated with prospective incident type 2 diabetes, they did not survive multiple testing. Common DMPs with diabetes epigenome-wide association studies from other populations suggest a partially common epigenomic signature of glucose and insulin activity.

Effect of yoga intervention on skeletal muscle linked glucose homeostasis in pre-diabetic individuals: Study protocol for a randomized controlled trial

BackgroundThe pre-diabetic stage is important in terms of identification and timely management due to its reversible nature. Along with other factors, insulin resistance in skeletal muscle is often considered as primary defect before development of overt hyperglycemia and Diabetes Mellitus (DM). Physical exercises are beneficial in prevention of DM by improving skeletal muscle mediated glucose metabolism. Evidence suggests that Yoga interventions appear to be equal and/or superior to exercise in most outcome measures. As the Yogic postures are relatable to exercises, they are considered to improve skeletal muscle function and reverse the pre-diabetic stage. MethodsThis open-labelled, randomized clinical study is planned to evaluate effect of Yoga interventions on muscle mass, strength, endurance and flexibility which are direct/indirect indicators of fat deposition in skeletal muscles. Association between changes in muscle quality/ functionality and glycemic control will also be explored. With ethics committee permission, 120 pre-diabetic individuals of either sex between age group of 35–49 years with BMI range of 25–35 kg/m2 and family history of Type 2 Diabetes Mellitus (T2DM) will be recruited after obtaining written informed consent. They will be randomly allocated to either Yoga or exercise group by computer generated randomized method in a 1:1 ratio. One group will receive defined Yoga interventions, while other group will receive fixed program of physical exercises. Prior to initiating this 12-week study, both groups will undergo a training session for 4 weeks under supervision of a trained instructor. The outcome measures will be parameters related to muscle quality/functionality and glucose metabolism markers. DiscussionOur study aims to explore practicality of Yoga in pre-diabetic stage on skeletal muscle related glycemic control, which is novel. Additionally, the study will generate awareness about pre-diabetes and provide people with active coping skills for reversing it.

Mid- and long-term changes in satiety-related hormones, lipid and glucose metabolism, and inflammation after a Mediterranean diet intervention with the goal of losing weight: A randomized, clinical trial.

Obesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one. To compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome. A randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55-75 and 60-75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometric and classical cardiovascular risk factors were also determined. A multivariate statistical model was employed to compare the two groups. Linear mixed-effect models were performed to compare changes in risk factors and biomarkers between intervention groups and over time. Compared to participants in the control group, those in intervention one showed greater improvements in weight, waist circumference, insulin (P < 0.001), glucose metabolism-related compounds (P < 0.05), triglyceride-related lipid profile (P < 0.05), leptin, blood pressure, and pro-inflammatory markers such as PAI-1 (P < 0.001) at mid-and/or long-term. High-sensitivity C-reactive protein, resistin, and vifastin also decreased in both groups. A weight loss intervention employing a hypocaloric MedDiet and physical activity promotion has beneficial effects on adiposity, glucose metabolism, lipid profile, leptin, and pro-inflammatory markers, such as PAI-1 in both mid-and long-term.

Retinal Microvascular Dysfunction Occurs Early and Similarly in Mild Alzheimer's Disease and Primary-Open Angle Glaucoma Patients.

Purpose: To assess the similarities and differences in retinal microvascular function between mild Alzheimer’s disease (AD) patients, early-stage primary open angle glaucoma (POAG) patients and healthy controls. Methods: Retinal vessel reactivity to flickering light was assessed in 10 AD, 19 POAG and 20 healthy age matched control patients by means of dynamic retinal vessel analysis (DVA, IMEDOS, GmbH, Jena, Germany) according to an established protocol. All patients additionally underwent BP measurements and blood analysis for glucose and lipid metabolism markers. Results: AD and POAG patients demonstrated comparable alterations in retinal artery reactivity, in the form of an increased arterial reaction time (RT) to flicker light on the final flicker cycle (p = 0.009), which was not replicated by healthy controls (p > 0.05). Furthermore, the sequential changes in RT on progressing from flicker one to flicker three were found to differ between healthy controls and the two disease groups (p = 0.001). Conclusion: AD and POAG patients demonstrate comparable signs of vascular dysfunction in their retinal arteries at the early stages of their disease process. This provides support for the concept of a common underlying vascular aetiology in these two neurodegenerative diseases.

Self-reported dietary omega-3 polyunsaturated fatty acids are associated with adipose tissue markers and glucose metabolism in apparently healthy subjects

Background Plasminogen activator inhibitor 1 (PAI-1) and resistin are associated with dysfunctional adipose tissue (AT)-related metabolic complications. The role of dietary eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids in this relationship is unknown. Aim To investigate the association of EPA and DHA with PAI-1 and resistin, as well as the role of this association on the glucose metabolism of apparently healthy subjects. Subjects and methods Thirty-six healthy individuals were included. Validated food frequency questionnaires were used to analyse dietary habits. Inflammatory and glucose metabolism markers were quantified. Subcutaneous AT samples were obtained, and adipocyte number, area, and macrophage content were assessed. Results In 36 subjects aged 56 ± 8 years and with a body mass index of 26 ± 4 kg/m2, logEPA, and logDHA showed significant association with logresistin and a marginal association with PAI-1. Adipocyte number, area, and lognumber of macrophages per adipocyte significantly correlated with PAI-1 but not with logresistin. Although logEPA and logDHA were independently associated with loginsulin, loginsulin resistance, and C-Peptide, the addition of logresistin, but not of PAI-1, into the multivariable model, abolished the associations. Conclusions EPA and DHA could modulate glucose metabolism across AT functional states. Our data indicate that this association is independent of other metabolic risk factors.

Dietary Salvia hispanica L. Seed Counteracted Kidney Failure in Experimental Metabolic Syndrome

Metabolic Syndrome (MS) has become a major health hazard in the current world by triggering cardiovascular and renal pathologies. Chia seed is a rich source of bioactive food components (n-3 fatty acids, antioxidants and fiber, among others) with several benefits on cardiovascular health. Therefore, we hypothesized that the intake of chia seed could counteract kidney failure of MS by protecting against lipid accretion, oxidative stress and fibrosis in this tissue. An experimental model of MS was induced by feeding male Wistar rats for 3 months with a sucrose-rich diet (SRD) containing corn oil as a source of fat. During the next 3 months, half of the animals continued with SRD. The other half received the SRD in which corn oil was replaced by Salvia hispanica L. seeds (chia) (SRD+C). The control group received a reference diet (RD). In experimental MS, dietary administration of chia seed significantly decreased albumin and glucose urine levels (p&lt;0.05). Chia reverted fibrosis (SiriusRed-collagen staining), morphological anomalies and the altered markers (PEPCK and FBPase) of renal glucose metabolism (p&lt;0.05). These effects were accompanied by a decrease in the accumulation of triglycerides and oxidative stress biomarkers (ROS and lipid peroxides) in kidney (p&lt;0.05). The mechanisms included down-regulation of key enzymes of fatty acid biosynthesis (ACC, FAS and G6PDH) and up-regulation of antioxidant defenses (GSH, GR and GPx activities). Dietary chia seed counteracted renal failure in an experimental model of MS, indicating that it could be an exceptional food for the clinical management of this disorder.

Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis

Aims/hypothesisThe clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect.MethodsAll participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions.ResultsA total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD.Conclusions/interpretationAt least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.Graphical abstract

Effects of angiotensin receptor-neprilysin inhibitors (ARNIs) on the glucose and fat metabolism biomarkers leptin and fructosamin

Abstract Background Heart Failure with reduced ejection fraction (HFrEF) has a life time risk about 20% among adults aged 40 years or older and a 5-year mortality rate about 60% [1,2]. However novel therapies have shown to improve this outcome. One novel agent are angiotensin receptor-neprilysin inhibitors (ARNIs) that increase the BNP levels via inhibiting neprilsyin [3]. This has beneficial effects on heart failure by reducing preload, inflammation and fibrosis. Neprilysin also interacts with leptin and is known to correlate with the incidence and progression of heart failure if chronically elevated [4]. Furthermore beneficial affects of ARNI therapy on glucose metabolism were reported in a post-hoc analysis of the PARADIGM-HF trial [5]. In this study we aim to investigate the effect of ARNI therapy on the fat metabolism markers leptin and on the glucose metabolism marker fructosamin. Methods In total, we included 74 patients with HFrEF with ischemic (N=37) and non-ischemic (n=37) origin in the present study. The mean NYHA class was II–III, the mean BMI 28 (SD 6.3). Patients had well established heart failure therapy before starting ARNI therapy with sacubitril/valsartan. 88% of patients were on ACE-inhibitors, 86% on beta blockers and 68% on mineralocorticoid receptor antagonists. Serum samples were obtained and analyzed for leptin, fructosamin and pBNP before and 3–6 month after ARNI therapy. The clinical parameters LVEF and NYHA class were assessed before and 3–6 month after ARNI therapy. Results Baseline leptin level was 15.0 (SD 17.2), baseline fructosamin level was 370.1 (SD 167.7) and baseline pBNP level was 1494.9 (SD 1281.4). Under therapy a significant improvement of ejection fraction from 29,8% to 37,5% (7,7 SD 8,5 P≤0.001), an improvement of NYHA stadium from 2.46 (SD 0.62) to 1.96 (SD 0.63, p=0.005) and a significant decrease of pBNP (562.1 SD 1256.4, p=0.018) was found. Along with that, a significant increase in leptin levels (3.6 SD 8.85, p=0.012) and a significant increase in fructosamine levels (93.5 SD 160.6, p=0.013) was shown. Conclusion Under therapy with ARNI we showed a sufficient therapy response with improvement of ejection fraction and decrease of pBNP in line with literature. Surprisingly metabolism biomarkers did significantly worsen under the first three to six month after new ARNI therapy. To distinguish between a side effect of ARNI therapy or consequence of heart failure itself further investigations are needed. Funding Acknowledgement Type of funding sources: None.