52 research outputs found
Treatment with high dose salicylates improves cardiometabolic parameters: Meta-analysis of randomized controlled trials
No full textThere is conflicting evidence regarding the efficacy of high dose salicylates in improving cardiometabolic risk in healthy and type 2 diabetes patients. We aimed to determine whether treatment with salicylates at an anti-inflammatory dose (≥1g daily) would improve cardiometabolic risk in healthy individuals and type 2 diabetes patients, compared to placebo.Medline, Medline-in-process, Embase, and all EBM databases were searched for studies published up to December 2016. Twenty-eight articles from 24 studies comprising 1591 participants were included. Two reviewers independently assessed the risk of bias and extracted data from included studies. Meta-analyses using random-effects model were used to analyze the data.High dose salicylates (≥3g/d) decreased fasting glucose (MD -0.4mmol/l, 95% CI -0.54, -0.27) and glucose area under the curve (MD -0.41mmol/l, 95% CI -0.81, -0.01). Salicylates (≥3g/d) also increased fasting insulin (MD 2.4 μU/ml, 95% CI 0.3, 4.4), 2-h insulin (MD 25.4 μU/ml, 95% CI 8.2, 42.6), insulin secretion (MD 79.2, 95% CI 35, 123) but decreased fasting C-peptide (MD -0.11nmol/l, 95% CI -0.2, -0.04), insulin clearance (MD -0.26l/min, 95% CI -0.36, -0.16) and triglycerides (MD -0.36mmol/l, 95% CI -0.51, -0.21) and increased total adiponectin (MD 1.97μg/ml, 95% CI 0.99, 2.95). A lower salicylate dose (1-2.9g) did not change any cardiometabolic parameters (p>0.1). No significant difference was observed between those receiving salicylates and placebo following withdrawal due to adverse events.High dose salicylates appear to improve cardiometabolic risk factors in healthy individuals and type 2 diabetes patients.CRD42015029826.Estifanos Baye, Negar Naderpoor, Marie Misso, Helena Teede, Lisa J. Moran,
Barbora de Courte
Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
No full textBackground: Vitamin D has been proposed to have anti-inflammatory properties; however, the effect of vitamin D supplementation on inflammation in type 2 diabetes has not been established. Objective: The aim of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on inflammatory markers in patients with type 2 diabetes and to identify relevant gaps in knowledge. Data sources MEDLINE, CINAHL, Embase, and EBM Reviews were searched systematically from inception to January 25, 2017. Study selection Randomized controlled trials (RCTs) investigating the effects of vitamin D supplementation (any form, route, and duration, and with any cosupplementation) compared with placebo or usual care on inflammatory markers in patients with type 2 diabetes were selected. Data extraction: Study and sample characteristics and aggregate outcome data were extracted, risk of bias was determined, and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Twenty-eight RCTs were included, 20 of which had data available for pooling. In meta-analyses of 20 RCTs (n = 1270 participants), vitamin D–supplemented groups had lower levels of C-reactive protein (standardized mean difference [SMD] −0.23; 95%CI, −0.37 to −0.09; P = 0.002) and tumor necrosis factor α (SMD −0.49; 95%CI, −0.84 to −0.15; P = 0.005), a lower erythrocyte sedimentation rate (SMD −0.47; 95%CI, −0.89 to −0.05; P = 0.03), and higher levels of leptin (SMD 0.42; 95%CI, 0.04–0.81; P = 0.03) compared with control groups. No differences were observed for adiponectin, interleukin 6, or E-selectin (all P > 0.05). In meta-regression and subgroup analyses, age, sex, body mass index, duration of diabetes, baseline vitamin D status, and dose and duration of supplementation did not alter the results. Conclusions: This meta-analysis provides level 1 evidence that vitamin D supplementation may reduce chronic low-grade inflammation in patients with type 2 diabetes. Systematic Review RegistrationAya Mousa, Negar Naderpoor, Helena Teede, Robert Scragg and Barbora de Courte
Modulation of insulin resistance in conditions associated with high insulin resistance
No full textInsulin resistance is a key factor in the development of diabetes. My thesis focuses on modulation of insulin resistance in obesity and polycystic ovary syndrome, two conditions characterised by insulin resistance. I explore the relationships between insulin resistance and kidney and liver function as well as faecal microbiota in overweight or obese individuals. I also show that vitamin D supplementation has no effect on insulin resistance in this population. Furthermore, I review the literature on the effect of obesity on polycystic ovary syndrome, the most common endocrine disease in reproductive-aged women. Finally, I compare the effect of combined lifestyle modification and metformin with lifestyle modification alone, on insulin resistance and other outcomes in polycystic ovary syndrome
Relationship between vitamin D and gestational diabetes in overweight or obese pregnant women may be mediated by adiponectin
No full textScope: Maternal vitamin D deficiency has been implicated in adverse pregnancy outcomes. However, the association between vitamin D and inflammation, particularly adipokines, remains unexplored in pregnancy. Methods and results: In 102 overweight or obese pregnant women at high-risk of gestational diabetes mellitus (GDM), we investigated relationships between maternal 25-hydroxyvitamin D (25(OH)D) concentrations at 12–15 wk gestation (baseline) and serum lipids, inflammatory markers, novel adipokines (omentin-1, visfatin, high molecular weight (HMW) adiponectin), and subsequent pregnancy outcomes (GDM, preeclampsia, preterm birth [PTB]). After adjustment for maternal factors (age, BMI, parity, ethnicity, and smoking status), baseline 25(OH)D concentrations were inversely associated with total cholesterol and triglycerides, and positively associated with HMW-adiponectin. Higher baseline 25(OH)D concentrations were associated with decreased fasting and 1-h post-OGTT glucose and reduced risk of GDM at 26–28 wk, as well as with longer gestation and reduced risk of PTB upon additional adjustment for caesarean section. Adding HMW-adiponectin to the multivariable models attenuated most associations, and HMW-adiponectin was a significant predictor in the models. Conclusion: Our findings suggest that lower maternal 25(OH)D concentrations in overweight/ obese pregnant women at high-risk of GDM are associated with increased cardiometabolic risks during pregnancy and adverse pregnancy outcomes, and that these associations may be mediated by HMW-adiponectin.Aya Mousa, Sally K Abell, Soulmaz Shorakae, Cheryce L Harrison, Negar Naderpoor, Danielle Hiam, Alba Moreno-Asso, Nigel K Stepto, Helena J Teede and Barbora de Courte
Vitamin D supplementation has no effect on insulin sensitivity or secretion in Vitamin D-deficient, overweight or obese adults: A randomized placebo-controlled trial
No full textBackground: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion.Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo.Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)].Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m2): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg-1 · min-1, respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake (P > 0.1).Conclusions: Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults, despite using high-dose vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient populations. This trial was registered at clinicaltrials.gov as NCT02112721.Aya Mousa, Negar Naderpoor, Maximilian PJ de Courten, Helena Teede, Nicole Kellow, Karen Walker, Robert Scragg and Barbora de Courte
Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial
No full textDespite Australia's sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity.Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers.The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes.Clinicaltrials.gov ID: NCT02112721 .Barbora de Courten, Aya Mousa, Negar Naderpoor, Helena Teede, Maximilian P J de Courten and Robert Scrag
The gut microbiota and inflammation: an overview
No full textThe gut microbiota encompasses a diverse community of bacteria that carry out various functions influencing the overall health of the host. These comprise nutrient metabolism, immune system regulation and natural defence against infection. The presence of certain bacteria is associated with inflammatory molecules that may bring about inflammation in various body tissues. Inflammation underlies many chronic multisystem conditions including obesity, atherosclerosis, type 2 diabetes mellitus and inflammatory bowel disease. Inflammation may be triggered by structural components of the bacteria which can result in a cascade of inflammatory pathways involving interleukins and other cytokines. Similarly, by-products of metabolic processes in bacteria, including some short-chain fatty acids, can play a role in inhibiting inflammatory processes. In this review, we aimed to provide an overview of the relationship between the gut microbiota and inflammatory molecules and to highlight relevant knowledge gaps in this field. Based on the current literature, it appears that as the gut microbiota composition differs between individuals and is contingent on a variety of factors like diet and genetics, some individuals may possess bacteria associated with pro-inflammatory effects whilst others may harbour those with anti-inflammatory effects. Recent technological advancements have allowed for better methods of characterising the gut microbiota. Further research to continually improve our understanding of the inflammatory pathways that interact with bacteria may elucidate reasons behind varying presentations of the same disease and varied responses to the same treatment in different individuals. Furthermore, it can inform clinical practice as anti-inflammatory microbes can be employed in probiotic therapies or used to identify suitable prebiotic therapies
Increased inflammation and cardiometabolic risk in individuals with low AMY1 copy numbers
No full textLower copy number variations (CNVs) in the salivary amylase gene (AMY1) have been associated with obesity and insulin resistance; however, the relationship between AMY1 and cardiometabolic risk has not been fully elucidated. Using gold-standard measures, we aimed to examine whether AMY1 CNVs are associated with cardiometabolic risk factors in an overweight or obese, otherwise healthy population. Fifty-seven adults (58% male) aged 31.17 +/- 8.44 years with a body mass index (BMI) >= 25 kg/m(2) were included in the study. We measured AMY1 CNVs (qPCR); anthropometry (BMI; body composition by dual-energy X-ray absorptiometry); cardiovascular parameters (blood pressure, serum lipids by ELISA); insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), insulin secretion (intravenous glucose tolerance test), and serum inflammation markers (multiplex assays). Based on previous studies and median values, participants were divided into low (<= 4) and high (>4) AMY1 CNV groups. Low AMY1 carriers (n = 29) had a higher fat mass (40.76 +/- 12.11 versus 33.33 +/- 8.50 kg, p = 0.009) and LDL-cholesterol (3.27 +/- 0.80 versus 2.87 +/- 0.69 mmol/L, p = 0.038), and higher serum levels of interleukin [IL]-6, IL-1 beta, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1) (all p < 0.05) compared with high AMY1 carriers (n = 28), but there were no differences in glycaemic measures, including insulin sensitivity or secretion (all p > 0.1). Except for MCP-1, the results remained significant in multivariable models adjusted for age, sex, and fat mass (all p < 0.05). Our findings suggest that low AMY1 CNVs are associated with increased cardiovascular disease risk and inflammation, but not glucose metabolism, in overweight or obese adults
Vitamin D-binding protein in pregnancy and reproductive health
No full textVitamin D-binding protein (VDBP), the main carrier of vitamin D, has recently been implicated in reproductive health and pregnancy outcomes including endometriosis, polycystic ovary syndrome (PCOS), pre-eclampsia, and gestational diabetes mellitus (GDM). Improved methods for measuring VDBP and an increased understanding of its role in biological processes have led to a number of newly published studies exploring VDBP in the context of pregnancy. Here, we synthesize the available evidence regarding the role of VDBP in reproductive health and pregnancy, and we highlight areas requiring further study. Overall, low levels of maternal serum VDBP concentrations have been associated with infertility, endometriosis, PCOS and spontaneous miscarriage, as well as adverse pregnancy outcomes including GDM, pre-eclampsia, preterm birth and fetal growth restriction. However, increased VDBP concentration in cervicovaginal fluid has been linked to unexplained recurrent pregnancy loss and premature rupture of membranes. Some genetic variants of VDBP have also been associated with these adverse outcomes. Further studies using more accurate VDBP assays and accounting for ethnic variation and potential confounders are needed to clarify whether VDBP is associated with reproductive health and pregnancy outcomes, and the mechanisms underlying these relationships.</p
Altered gut microbiota composition is associated with back pain in overweight and obese individuals
No full textBackground:\ua0Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses.Aims and Methods:\ua0We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity.Results:\ua0Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with (n\ua0= 14) or without (n\ua0= 22) back pain. Individuals with back pain had a higher abundance of the genera\ua0Adlercreutzia\ua0(p\ua0= 0.0008; FDR = 0.027), Roseburia\ua0(p\ua0= 0.0098; FDR = 0.17), and\ua0Uncl. Christensenellaceae\ua0(p\ua0= 0.02; FDR = 0.27) than those without back pain.\ua0Adlercreutzia\ua0abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year.\ua0Adlercreutzia\ua0was positively correlated with BMI (rho = 0.35,\ua0p\ua0= 0.03), serum adipsin (rho = 0.33,\ua0p\ua0= 0.047), and serum leptin (rho = 0.38,\ua0p\ua0= 0.02).Conclusions:\ua0Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering\ua0Adlercreutzia\ua0abundance to treat back pain
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