Markers Of Glucose Metabolism Research Articles

Oral Supplementation of Sodium Butyrate Attenuates the Progression of Non-Alcoholic Steatohepatitis.

Sodium butyrate (SoB) supplementation has been suggested to attenuate the development of non-alcoholic fatty liver disease (NAFLD). Here, we determined the therapeutic potential of SoB on NAFLD progression and molecular mechanism involved. Eight-week old C57BL/6J mice were pair-fed a fat-, fructose- and cholesterol-rich diet (FFC) or control diet (C). After 8 weeks, some mice received 0.6g SoB/kg bw in their respective diets (C+SoB; FFC+SoB) or were maintained on C or FFC for the next 5 weeks of feeding. Liver damage, markers of glucose metabolism, inflammation, intestinal barrier function and melatonin metabolism were determined. FFC-fed mice progressed from simple steatosis to early non-alcoholic steatohepatitis, along with significantly higher TNFα and IL-6 protein levels in the liver and impaired glucose tolerance. In FFC+SoB-fed mice, disease was limited to steatosis associated with protection against the induction of Tlr4 mRNA and iNOS protein levels in livers. SoB supplementation had no effect on FFC-induced loss of tight junction proteins in the small intestine but was associated with protection against alterations in melatonin synthesis and receptor expression in the small intestine and livers of FFC-fed animals. Our results suggest that the oral supplementation of SoB may attenuate the progression of simple steatosis to steatohepatitis.

The Antioxidant and Antihyperglycemic Activities of Bottlebrush Plant (Callistemon lanceolatus) Stem Extracts.

Background: Diabetes mellitus, a metabolic disease, is a major health concern today throughout the world. Callistemon lanceolatus (Myrtaceae), commonly known as bottlebrush, has been used by Indian tribal communities for the treatment of many diseases. The purpose of this study was to explore antioxidant and antihyperglycemic potential of methanolic and aqueous extracts of the stem of C. lanceolatus in vitro and in vivo. Methods: Phytoconstituents of C. lanceolatus stem were extracted in methanol and water sequentially followed by phytochemical analysis. The in vitro antioxidant potential of aqueous and methanolic extracts was assessed by metal ion chelating, free radical scavenging, and reducing power assays. The in vivo antihyperglycemic activity of the oral methanolic extract was studied in alloxan-induced diabetic rats. Bodyweight and blood glucose were monitored regularly. After the treatment period, serum was examined for total cholesterol, triglycerides, high-density lipoprotein (HDL), bilirubin, creatinine, urea, glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatase (ALP). Results: Methanolic extract exhibited superior antioxidant activity to aqueous extract. A marked increase in levels of serum markers, viz., glucose, triglycerides, total cholesterol, bilirubin, urea, creatinine, SGOT, SGPT, and ALP along with a reduction in HDL was observed in diabetic rats. Methanol extract treatment for 28 days accounted for a decrease in blood glucose and other metabolic markers accompanied by an improvement in body weight and HDL level in hyperglycemic rats. Conclusions: The present study suggests that C. lanceolatus methanolic stem extract possesses antioxidant and antihyperglycemic activities and has potential as a therapeutic agent in diabetes.

Exploring abnormal glucose metabolism in pregnancy among Australian Chinese migrants

ObjectiveGestational diabetes mellitus (GDM) is a metabolic disorder of pregnancy that is increasingly prevalent among Chinese women. Few studies have examined whether the migration status of Chinese women contributes to...

Supplementation with Korean Red Ginseng Improves Current Perception Threshold in Korean Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. Methods This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. Results Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. Conclusion Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.

Oral butyrate does not affect innate immunity and islet autoimmunity in individuals with longstanding type 1 diabetes: a randomised controlled trial.

The pathophysiology of type 1 diabetes has been linked to altered gut microbiota and more specifically to a shortage of intestinal production of the short-chain fatty acid (SCFA) butyrate, which may play key roles in maintaining intestinal epithelial integrity and in human and gut microbial metabolism. Butyrate supplementation can protect against autoimmune diabetes in mouse models. We thus set out to study the effect of oral butyrate vs placebo on glucose regulation and immune variables in human participants with longstanding type 1 diabetes. We administered a daily oral dose of 4g sodium butyrate or placebo for 1month to 30 individuals with longstanding type 1 diabetes, without comorbidity or medication use, in a randomised (1:1), controlled, double-blind crossover trial, with a washout period of 1month in between. Participants were randomly allocated to the 'oral sodium butyrate capsules first' or 'oral placebo capsules first' study arm in blocks of five. The clinical investigator received blinded medication from the clinical trial pharmacy. All participants, people doing measurements or examinations, or people assessing the outcomes were blinded to group assignment. The primary outcome was a change in the innate immune phenotype (monocyte subsets and in vitro cytokine production). Secondary outcomes were changes in blood markers of islet autoimmunity (cell counts, lymphocyte stimulation indices and CD8 quantum dot assays), glucose and lipid metabolism, beta cell function (by mixed-meal test), gut microbiota and faecal SCFA. The data was collected at the Amsterdam University Medical Centers. All 30 participants were analysed. Faecal butyrate and propionate levels were significantly affected by oral butyrate supplementation and butyrate treatment was safe. However, this modulation of intestinal SCFAs did not result in any significant changes in adaptive or innate immunity, or in any of the other outcome variables. In our discussion, we elaborate on this important discrepancy with previous animal work. Oral butyrate supplementation does not significantly affect innate or adaptive immunity in humans with longstanding type 1 diabetes. Netherlands Trial Register: NL4832 (www.trialregister.nl). Raw sequencing data are available in the European Nucleotide Archive repository (https://www.ebi.ac.uk/ena/browse) under study PRJEB30292. The study was funded by a Le Ducq consortium grant, a CVON grant, a personal ZONMW-VIDI grant and a Dutch Heart Foundation grant.

Multiple markers contribute to risk of progression from normal to mild cognitive impairment

ObjectiveTo identify a parsimonious set of markers that optimally predicts subsequent clinical progression from normal to mild cognitive impairment (MCI). Methods250 clinically normal adults (mean age = 73.6 years, SD = 6.0) from the Harvard Aging Brain Study were assessed at baseline on a wide set of markers, including magnetic resonance imaging markers of gray matter thickness and volume, white matter lesions, fractional anisotropy, resting state functional connectivity, positron emission tomography markers of glucose metabolism and β-amyloid (Aβ) burden, and a measure of vascular risk. Participants were also tested annually on a battery of clinical and cognitive tests (median follow-up = 5.0 years, SD = 1.66). We applied least absolute shrinkage and selection operator (LASSO) Cox models to determine the minimum set of non-redundant markers that predicts subsequent clinical progression from normal to MCI, adjusting for age, sex, and education. Results23 participants (9.2%) progressed to MCI over the study period (mean years of follow-up to diagnosis = 3.96, SD = 1.89). Progression was predicted by several brain markers, including reduced entorhinal thickness (hazard ratio, HR = 1.73), greater Aβ burden (HR = 1.58), lower default network connectivity (HR = 1.42), and smaller hippocampal volume (HR = 1.30). When cognitive test scores were added to the model, the aforementioned neuroimaging markers remained significant and lower striatum volume as well as lower scores on baseline memory and processing speed tests additionally contributed to progression. ConclusionAmong a large set of brain, vascular and cognitive markers, a subset of markers independently predicted progression from normal to MCI. These markers may enhance risk stratification by identifying clinically normal individuals who are most likely to develop clinical symptoms and would likely benefit most from therapeutic intervention.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression.

Effect of α-linolenic acid on vascular function and metabolic risk markers during the fasting and postprandial phase: A randomized placebo-controlled trial in untreated (pre-)hypertensive individuals.

Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals. In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60±8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10g of refined cold-pressed flaxseed oil, providing 4.7g ALA (n=29), or 10g of high-oleic sunflower (control) oil (n=30) for 12 weeks. As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58μmol/L (P=0.02) and 0.14pg/mL (P=0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake. A high intake of ALA, about 3-5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals.

Metabolomics analysis in adults with high bone mass identifies a relationship between bone resorption and circulating citrate which replicates in the general population.

ObjectiveBone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross‐sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z‐score ≥+3.2).Designβ‐C‐terminal telopeptide of type‐I collagen (β‐CTX), procollagen type‐1 amino‐terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis‐related metabolites, were measured using nuclear magnetic resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using generalized estimating equation linear regression, accounting for within‐family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use).ResultsA total of 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% were female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted ββ‐CTX = 0.050 (95% CI 0.024, 0.076), P = 1.71 × 10−4, βosteocalcin = 6.54 × 10−4 (1.87 × 10−4, 0.001), P = .006 and βP1NP = 2.40 × 10−4 (6.49 × 10−5, 4.14 × 10−4), P = .007 (β = increase in citrate (mmol/L) per 1 µg/L BTM increase). Inverse relationships of β‐CTX (β = −0.276 [−0.434, −0.118], P = 6.03 × 10−4) and osteocalcin (−0.004 [−0.007, −0.001], P = .020) with triglycerides were also identified. We explored the generalizability of these associations in 3664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between β‐CTX and citrate (adjusted βwomen = 0.020 [0.013, 0.026], P = 1.95 × 10−9) and an inverse association of similar magnitude between β‐CTX and triglycerides (β = −0.354 [−0.471, −0.237], P = 3.03 × 10−9).ConclusionsBone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates.

Association of Serum Total Osteocalcin Concentrations With Endogenous Glucocorticoids and Insulin Sensitivity Markers in 12-Year-Old Children: A Cross-Sectional Study.

Background: Osteocalcin (OC) is an osteoblast-derived marker of bone turnover that has recently been linked to glucose metabolism, glucocorticoid action, and cardiovascular risk.Objective: We determined whether serum total OC (tOC) is associated with cardiometabolic factors, such as insulin sensitivity (IS) markers and endogenous glucocorticoids in 12-year-old children. In addition, we assessed whether low birth weight or exposure to maternal preeclampsia affect tOC concentrations.Methods: In this cross-sectional study, 192 children (109 girls) were studied at 12 years of age. Seventy of them had been born small (SGA), 78 appropriate for gestational age (AGA), and 44 from preeclamptic pregnancies (PRE) as AGA. Blood pressure was measured, and fasting blood samples were collected for markers of glucose metabolism, osteoblast, adipocyte, and adrenocortical function. IS was estimated by Quantitative Insulin Sensitivity Check Index (QUICKI). Free cortisol index (FCI) was calculated as serum cortisol/corticosteroid binding globulin.Results: The highest tOC concentrations were detected in midpubertal children (Tanner B/G stage 3). The children in the highest tOC quartile (n = 48) had lower body mass index (BMI), waist-to-height ratio, diastolic blood pressure, leptin, cortisol/cortisone ratio and FCI, and higher insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and alkaline phosphatase (ALP) than those in the lower tOC quartiles (p < 0.02 for all). QUICKI was similar in these subgroups. In logistic regression analysis, pubertal developmental stages 2 and 3, high ALP, IGF-I, and low FCI and BMI (p < 0.02 for all) were associated independently with higher tOC. The means of serum tOC and IS markers were similar in the SGA, AGA, and PRE subgroups.Conclusions: In both sexes, the highest tOC levels were detected in midpubertal children reflecting the fast pubertal growth phase. Higher tOC levels were associated with lower BMI and FCI, whereas no association was found with IS. Birth weight or exposure to preeclampsia had no effect on tOC concentrations.

Roux-en-Y gastric bypass surgery improves hepatic glucose metabolism and reduces plasma kisspeptin levels in morbidly obese patients with type 2 diabetes.

Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery.NEW & NOTEWORTHY Our manuscript is the first, to the best of our knowledge, to present data showing that Roux-en-Y gastric bypass surgery (RYGB) lowers fasting kisspeptin levels in patients who are obese with type 2 diabetes. This lowering of kisspeptin is important because it could link improvements in liver glucose metabolism after RYGB with increased insulin responsiveness also seen after surgery.

Healthy lifestyle moderates the relationship between cardiovascular disease with blood pressure, body composition, carotid intima-media thickness, and glycated hemoglobin among adults.

We investigate whether the adherence to healthy lifestyle recommendations (regular physical activity, healthy diet, reduced alcohol consumption, nonsmoking) moderates the relationship between cardiovascular disease (CVD) and its risk factors (obesity, diabetes, dyslipidemia, and hypertension) with clinical variables among adults. This cross-sectional population-based study comprised 862 adults (39.3 ± 11.4 years, 46.4% men) from Florianópolis, Brazil. Clinical variables were systolic (SBP) and diastolic blood pressure, waist circumference, body mass index (BMI), percentage of body fat, muscular strength, carotid intima-media thickness (IMT), high sensitive C-reactive protein, and lipid and glucose metabolism markers. Multiple linear regression adjusted for confounding factors was used. Reduced IMT and HbA1c were observed in males with CVD or its risk factors who adopted healthy lifestyle recommendations (p < 0.001), and lower SBP levels were observed in females without CVD or its risk factors (p = 0.034). Females with CVD or its risk factors who followed healthy lifestyle recommendations showed higher BMI (p = 0.035). Adherence to number of healthy lifestyle recommendations moderated cardiovascular health in adults with CVD and without CVD. Novelty The adherence to healthy lifestyle recommendations moderated the relationship between IMT and HbA1c with CVD or its risk factors among males. The lower values of SBP among females without CVD or its risk factors were moderated by the adherence to healthy lifestyle recommendations.

Probiotics in Adolescent Prediabetes: A Pilot RCT on Glycemic Control and Intestinal Bacteriome.

Dysbiosis of intestinal ecology could be implicated in prediabetes. The aim of this pilot randomized controlled trial (RCT) was to collect preliminary data on the effects of probiotic supplementation (Vivomixx©) on markers of glucose metabolism, intestinal microbiome composition, and intestinal health indices, of prediabetic adolescents. The intervention group was administered probiotic sachets twice daily for 4 months, while both intervention and control groups received weekly consultation sessions for a healthier lifestyle. Thirty-two participants were recruited (1.3 participants per month) and were randomized (16 in control and 16 in intervention group). Fifteen of them signed the inform consent and never entered the study (6 in control and 9 in intervention group). Thus, seventeen participants completed the study (10 in control and 7 in intervention group), with no serious adverse events. After the 4-month intervention, no difference was observed in the markers of glycemic control between the two groups, although a minor effect was observed for fasting glucose at 1-month, probably due to the initial higher adherence to the probiotic supplements. Modifications of the protocol procedures are warranted because of the high attrition rates and suboptimal compliance that were noted. Future studies and further RCTs with larger samples need to be conducted to fully elucidate the potential effects of probiotics in the glycemic control of prediabetic adolescents.

Higher Weight and Weight Gain after 4 Years of Age Rather than Weight at Birth Are Associated with Adiposity, Markers of Glucose Metabolism, and Blood Pressure in 5-Year-Old Ethiopian Children

Fetal and early life growth is associated with adult risk of obesity and cardiometabolic disease. However, little is known about the relative importance of birth weight and successive periods of weight gain on markers of cardiometabolic risk in childhood in low-income populations. The objective was to study associations of birth weight and weight gain velocities in selected age intervals from birth to 60 mo with height, fat-free mass (FFM), and markers of adiposity and cardiometabolic risk at 60 mo. In a prospective cohort study of 375 Ethiopian children aged 60 mo, we estimated individual weight gain velocities in the periods between birth and 3, 6, 24, 48, and 60 mo using linear-spline mixed-effects modeling. Subsequently, we analyzed associations of birth weight, weight gain velocities, and current weight with height, FFM, and markers of adiposity and cardiometabolic risk. Weight gain from 48 to 60 mo and weight at 60 mo rather than birth weight were the strongest correlates of insulin, C-peptide, HOMA-IR, blood pressure, height, FFM, waist circumference, and fat mass at 60 mo. For instance, 1 SD higher (1 SD=50 g/mo) weight accretion from 48 to 60 mo was associated with a higher insulin of 23.3% (95% CI: 9.6%, 38.8%), C-peptide of 11.4% (2.7%, 20.8%), systolic blood pressure of 1.4 mm Hg (0.6, 2.3 mm Hg), fat mass of 0.72 kg (0.59, 0.85 kg), and FFM of 0.70 kg (0.56, 0.85 kg). Weight gain from 0 to 3 mo was positively associated with LDL cholesterol, systolic blood pressure, height, and the body composition indices, and weight gain from 24 to 48 mo was inversely associated with blood glucose. In 60-mo-old Ethiopian urban children, weight gain and weight after 48 mo rather than weight at birth may represent a sensitive period for variations in markers of adiposity and glucose metabolism. The birth cohort is registered at https://www.isrctn.com/ as ISRCTN46718296.

Season, Terrestrial Ultraviolet Radiation, and Markers of Glucose Metabolism in Children Living in Perth, Western Australia.

Seasonality in glucose metabolism has been observed in adult populations; however, little is known of the associations between season and glucose metabolism in children. In this study, we examined whether markers of glucose metabolism (fasting glucose, insulin and HbA1c) varied by season in a paediatric population (6–13 years of age) located in Perth (Western Australia, n = 262) with data categorised by weight. Linear regression was used to analyse the nature of the relationships between mean daily levels of terrestrial ultraviolet radiation (UVR) (prior to the day of the blood test) and measures of glucose metabolism. Fasting blood glucose was significantly lower in autumn compared to spring, for children in combined, normal and obese weight categories. Fasting insulin was significantly lower in autumn and summer compared to winter for individuals of normal weight. HbA1c was significantly higher in summer (compared with winter and spring) in overweight children, which was in the opposite direction to other published findings in adults. In children with obesity, a strong inverse relationship (r = −0.67, p = 0.002) was observed for fasting glucose, and daily terrestrial UVR levels measured in the previous 6 months. Increased safe sun exposure in winter therefore represents a plausible means of reducing fasting blood sugar in children with obesity. However, further studies, using larger paediatric cohorts are required to confirm these relationships.

Calpain Activity in Leukocytes Is Associated with Diabetes Biochemical Markers

CAPN10 gene is associated with type 2 diabetes (T2D). Specific members of the calpain system (CAPN1, CAPN2 and CAPN10) are implicated in glucose metabolism. The aim of this study was to evaluate the calpain activity in leukocytes of control subjects and patients with T2D and its association with the calpain family members involved in glucose metabolism and with biochemical parameters that are altered in T2D. Calpain activity under extracellular glucose concentrations (70-280mg/dL) was evaluated in leukocytes from subjects with and without T2D. Protein and mRNA levels of CAPN1, CAPN2 and CAPN10 were evaluated. Calpain inhibitors assays were performed in leukocytes from subjects without T2D to evaluate glucose uptake. Calpain activity at 100mg/dL glucose was correlated with biochemical parameters by multivariate regression. Calpain activity in control subjects increased with extracellular glucose concentration in a dose-dependent manner, showing a negative association with HbA1c levels and total amount of CAPN10 protein. In contrast, calpain activity is decreased in patients with T2D and do not respond to changes in glucose concentration. A reduction of CAPN1 autolytic fragments were observed in the subjects with diabetes. Calpain inhibitors decreased calpain activity but did not altered glucose uptake in leukocytes. Calpain activity induced by glucose in leukocytes was associated with biochemical markers of glucose metabolism and with CAPN10 protein abundance. Calpain activity is low in subjects with T2D. Thus, calpain activity induced by extracellular glucose in leukocytes could be a potential marker for T2D early risk detection.

Systematic Review of the Effects of Ultraviolet Radiation on Markers of Metabolic Dysfunction.

Emerging findings suggest that exposure to ultraviolet wavelengths of sunlight modulates metabolic function. Here we review the metabolic effects of exposure to ultraviolet radiation (UVR), focusing on the effects of phototherapies (that administer UVR), and advice to increase sun exposure in individuals enrolled in clinical trials and intervention studies. We identified 25 studies in which the effects of UVR on metabolic outcomes were examined, including: narrowband ultraviolet B phototherapy (nbUVB, n = 12); psoralen ultraviolet A phototherapy (n = 4); other types of UVR phototherapy (n = 5); and sun exposure advice (n = 5). Most studies recruited a small number of participants (≤100), who were middle-aged individuals undergoing treatment for psoriasis flare, with phototherapy or sun exposure advice administered for ≤12 weeks. Data obtained at baseline were usually compared with an endpoint following treatment with UVR, for a limited number of outcomes. There were few studies in which markers of glucose metabolism were assessed, with some beneficial effects of sun exposure (but not phototherapy) reported. LDL-cholesterol levels were lower in individuals receiving sun exposure advice, while treatment with nbUVB reduced blood concentrations of inflammatory markers (C-reactive protein and interleukin-6). Future studies should focus on determining whether the effects of these interventions change with time, and if they are dependent on the source of UVR (i.e. phototherapy or sun exposure) and wavelength(s) of light administered. Furthermore, studies need to measure a variety of (clinical) markers of glucose metabolism, adiposity and inflammation, control for factors such as skin type and sex, and stratify participants for metabolic disease diagnosis.

Retinal and peripheral vascular function in healthy individuals with low cardiovascular risk

ObjectiveTo assess retinal and peripheral microvascular function in individuals with low cardiovascular risk. Methods and resultsRetinal microvascular function was assessed using the dynamic vessel analyser (DVA) and peripheral vascular reactivity was measured using the digital thermal monitor (DTM) in 136 healthy participants. In addition, systemic blood pressure (BP) profiles, blood analyses for glucose and lipid metabolism markers (CHOL, HDL-c, LDL-c), as well as the Framingham Risk Score (FRS) were assessed in all participants.Based on peripheral vascular reactivity scores, participants were separated into 3 groups: high, intermediate and low risk. Participants with high risk showed a significant higher retinal arteriolar time to reach maximum dilation (tMD) than those with intermediate and low risk (p < 0.001). In addition, retinal arterial dilation amplitude (DA), and constriction slope (SlopeAC) were higher in subjects with low risk (p = 0.006, p = 0.019). Only in high risk participants, peripheral vascular reactivity parameters correlated with retinal arterial functional parameters DA, (r = 0.3800, p = 0.029) and tMD (r = −0.5904, p < 0.001). ConclusionWe conclude that signs of abnormal vascular function are similarly present and detectable in various microvascular beds, despite existing differences in their anatomical and physiological properties.

Prospective Longitudinal Trends in Body Composition and Clinical Outcomes 3Years Following Sleeve Gastrectomy.

Longitudinal assessment of body composition following bariatric surgery allows monitoring of health status. Our aim was to elucidate trends of anthropometric and clinical outcomes 3years following sleeve gastrectomy (SG). A prospective cohort study of 60 patients who underwent SG. Anthropometrics including body composition analysis measured by multi-frequency bioelectrical impedance analysis, blood tests, liver fat content measured by abdominal ultrasound and habitual physical activity were evaluated at baseline and at 6 (M6), 12 (M12), and 36 (M36) months post-surgery. Sixty patients (55% women, age 44.7 ± 8.7years) who completed the entire follow-up were included. Fat mass (FM) was reduced significantly 1year post-surgery (55.8 ± 11.3 to 26.7 ± 8.3kg; P < 0.001) and then increased between 1 and 3years post-operatively, but remained below baseline level (26.7 ± 8.3 to 33.1 ± 11.1kg; P < 0.001). Fat free mass (FFM) decreased significantly during the first 6months (64.7 ± 14.3 to 56.9 ± 11.8kg; P < 0.001), slightly decreased between M6 and M12 and then reached a plateau through M36. Weight loss "failure" (< 50% excess weight loss) was noticed in 5.0% and 28.3% of patients at M12 and M36, respectively. Markers of lipid and glucose metabolism changed thereafter in parallel to the changes observed in FM, with the exception of HDL-C, which increased continuingly from M6 throughout the whole period analyzed (45.0 ± 10.2 to 59.5 ± 15.4mg/dl; P < 0.001) and HbA1c which continued to decrease between M12 and M36 (5.5 ± 0.4 to 5.3 ± 0.4%; P < 0.001). There were marked within-person variations in trends of anthropometric and clinical parameters during the 3-year follow-up. Weight regain primarily attributed to FM with no further decrease in FFM occurs between 1 and 3years post-SG. FM increase at mid-term may underlie the recurrence of metabolic risk factors and can govern clinical interventions.

Pretreatment Prevotella-to-Bacteroides ratio and markers of glucose metabolism as prognostic markers for dietary weight loss maintenance.

Pre-treatment gut microbial Prevotella-to-Bacteroides (P/B) ratio and markers of glucose metabolism (i.e., fasting glucose and insulin) have been suggested as biomarkers for optimal weight management. However, both biomarkers need further validation, and the interactions between them for optimal weight management are largely unknown. To investigate differences in weight loss maintenance between subjects with low and high P/B ratio and the potential interactions with markers of glucose metabolism and dietary fiber intake. Following an 8-week weight loss period using meal replacement products, subjects losing ≥ 8% of their initial body weight were randomized to one of three protein supplements or maltodextrin for a 24-week weight maintenance period. Habitual diet was consumed along with the supplements expected to constitute 10-15% of total energy. For this analysis we stratified the participants into low and high strata based on median values of pre-intervention P/B ratio, pre-weight loss Homeostatic model assessment of insulin resistance (HOMA-IR) (<2.33 or > 2.33), and dietary fiber intake during the intervention (< 28.5 or > 28.5 g/10 MJ). Regardless of weight maintenance regimen, subjects with high P/B ratio (n = 63) regained 1.5 (95% CI 0.4, 2.7) kg body weight (P = 0.007) more than subjects with low P/B ratio (n = 63). The regain among subjects with high P/B ratio was particular evident if HOMA-IR was high and dietary fiber intake was low. Consequently, in the high P/B strata, subjects with high HOMA-IR and low fiber intake (n = 17) regained 5.3 (95% CI 3.3, 7.3) kg (P < 0.001) more body weight compared with participants with low HOMA-IR and high fiber intake (n = 16). Subjects with high P/B ratio were more susceptible to regain body weight compared with subjects with low P/B ratio, especially when dietary fiber intake was low and glucose metabolism was impaired. These observations underline that both the P/B ratio and markers of glucose metabolism should be considered as important biomarkers within personalized nutrition for optimal weight management.