Epigenetic control of the post-bariatric phenotype: the role of microRNAs

The rising obesity pandemic and the concomitant rise in its co-morbidities are leading causes of global morbidity and mortality. Bariatric surgery is a form of gastrointestinal surgery that leads to sustained weight loss, diabetes resolution, reduction in cancer risk and other improvements in health. MicroRNAs are a family of small, endogenous, non-coding RNAs that regulate gene expression at the post-transcriptional level. MicroRNAs control expression of over half the human transcriptome and are involved in processes fundamental to both normal physiology and disease, including obesity and diabetes. This study hypothesizes that microRNAs are biomarkers for health improvements following bariatric surgery. Using quantitative PCR, a microRNA baseline was established in the serum and urine of an obese human population and increases in three anti-fibrotic microRNAs were found in urine following bariatric surgery. Circulating microRNA profiles were characterised in Roux-en-Y gastric bypass patients preoperatively and at 5 timepoints postoperatively. Roux-en-Y gastric bypass significantly altered circulating microRNA profiles in a time dependent manner. Relative to preoperative levels, of the 159 circulating microRNAs assayed 2 were significantly deregulated 1 month postoperatively, 5 were deregulated at 3 months, 10 at 6 months, 28 at 9 months and 31 at 12 months. Target prediction and pathway analysis revealed that these differentiated microRNAs regulate biological pathways that are involved in obesity and that microRNAs may contribute to the development of the beneficial post-bariatric phenotype. Both circulating and urinary post-bariatric microRNA levels correlated with measured clinical biomarkers such as BMI and blood glucose. These results indicate that bariatric operations fundamentally alter microRNA expression both in urine and in circulation and suggest that microRNAs represent not only potentially novel biomarkers for improvements in health following surgery, but are possible biological effectors that contribute to the mechanisms behind bariatric surgery. MicroRNA expression profiles could potentially be used to monitor operative outcomes and understanding the role of these differentially expressed microRNAs could shed light behind the mechanism by which bariatric surgery improves health.Open Acces

Prevalence and predictors of diabetes distress and depression in people with type 1 diabetes

BackgroundPeople living with diabetes often encounter psychosocial challenges, including diabetes distress and depression. Despite this, little research has focused on the co-occurrence of these conditions. This study aimed to explore the prevalence of depressive symptoms and diabetes distress in people with type 1 diabetes in Kuwait and to identify clinical and demographic factors associated with these conditions.MethodsA total of 832 people with type 1 diabetes (females: 54.1%, mean age: 29 ± 8.5 years), were invited to participate in Dose Adjustment for Normal Eating (DAFNE) course. Diabetes distress was measured using the Problem Areas in Diabetes (PAID) scale and depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Depressive symptoms were defined as PHQ-9 scores ≥10. Data on biomedical outcomes, lifestyle factors, and sociodemographic information were collected.ResultsThe prevalence rates of diabetes distress and depressive symptoms were 27.8% and 38.3%, respectively. Notably, 19.6% of people experienced both conditions. In the regression analysis, PAID scale and PHQ-9 scores were significantly associated, patients with higher score on depressive symptoms scale were more likely to suffer diabetes distress (B= 2.65, p < 0.001). Female sex (odds ratio [OR]= 2.2, 95% CI= 1.5, 3.2), higher hemoglobin A1c levels (OR= 1.6, 95% CI= 1.0, 2.5), obesity (OR= 1.7, 95% CI= 1.1, 2.8), inactivity (OR= 2.4, 95% CI= 1.6, 3.6), microvascular complications (OR= 2.8, 95% CI= 1.5, 5.4), and lipohypertrophy (OR= 1.7, 95% CI= 1.1, 2.5) were associated with greater odds for the co-occurrence of diabetes distress and depressive symptoms (p< 0.05 for all).ConclusionThe majority of people with type 1 diabetes in Kuwait experience both diabetes distress and depressive symptoms. The strong correlation between diabetes distress and depressive symptoms suggests mutual predictability. The co-occurrence of both symptoms is associated with many sociodemographic and clinical factors

Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function

Background: Obesity and diabetes cause chronic kidney disease with a common pathophysiology that is characterized by the accumulation of collagen in the extracellular matrix. Recent evidence has implicated the epithelial-to-mesenchymal transition (EMT) as a key step in this pathology with regulation by microRNAs. Weight loss leads to improvements in renal function; therefore, this study hypothesized that bariatric-surgery aided weight loss would lead to changes in urinary microRNAs involved in the regulation of renal function.Materials and methods: Twenty-four bariatric patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy donated urine pre-operatively and at 2–6 months and 1–2 years post-operatively. Urine samples were also obtained from 10 healthy weight and 7 morbidly obese non-surgical controls. Expression levels of kidney microRNAs were assessed in urine and the function of microRNAs was assessed through the in vitro transfection of HK-2 cells, a kidney proximal tubule cell line.Results: Levels of miR 192, miR 200a, and miR 200b were upregulated in urine following bariatric surgery. This increase was consistent across surgical type and diabetes status and was maintained and enhanced with time. Bariatric surgery alters urinary miR 192 expression from levels seen in morbidly obese patients to levels seen in healthy weight control patients. In mechanistic studies, the transfection of miR 192 in HK-2 cells increased miR 200a expression and decreased ZEB2, a key transcriptional promoter of kidney fibrosis.Conclusions: Bariatric surgery increased miR 192 and miR 200 urinary levels, key anti-fibrotic microRNAs that could contribute to a renal-protective mechanism and may be of value as urinary biomarkers following surgery. These findings suggest that urinary microRNAs may represent potential novel biomarkers for obesity-associated renal function

Photocatalytic Degradation Of Phenolic Compounds

A great challenge for this century lies in cleaning-up the wastewater generated during industrial, domestic and agricultural activities before being released, into the aquatic environment, or reused for another purpose e.g. irrigation. Phenolic compounds among the various organic contaminates found in wastewater require special attention because of their toxic effect on humans and the environment. Their presence has been confirmed in many different industrial wastewaters. These phenolic compounds are refractory ones and the efficiency of their traditional treatment techniques is low. Therefore, the use of an effective and economic elimination technique for phenolic compounds in wastewater becomes an urgent demand. Advanced oxidation processes (AOPs) represents the most recent technology in wastewater treatment. TiO2 is known to be an excellent photocatalyst. However, there are some challenges regarding using TiO2 in the industrial scale. Significant attention is directed towards using carbonaceous nanomaterials as support to enhance photocatalytic behavior of TiO2 due to their unique and controllable structural and electrical properties. In this work, low percentage of reduced graphene oxide (RGO) and graphene oxide (GO) were supported on TiO2 seeking a better catalytic performances. These composites were tested for degrading some phenolic compounds using UV as photoexcitation source in presence of some oxidants e.g. H2O2. It was found that small loadings of GO and RGO decreased the band gap energy for TiO2 and increased the efficiency and decreased the time needed for the photodegradation of phenolic compounds.qscienc

Erratum to: Is Social Deprivation Associated with Weight Loss Outcomes Following Bariatric Surgery? A 10-Year Single Institutional Experience

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Bariatric surgery modulates urinary levels of microRNAs involved in the regulation of renal function

Background: Obesity and diabetes cause chronic kidney disease with a common pathophysiology that is characterized by the accumulation of collagen in the extracellular matrix. Recent evidence has implicated the epithelial-to-mesenchymal transition (EMT) as a key step in this pathology with regulation by microRNAs. Weight loss leads to improvements in renal function; therefore, this study hypothesized that bariatric-surgery aided weight loss would lead to changes in urinary microRNAs involved in the regulation of renal function.Materials and methods: Twenty-four bariatric patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy donated urine pre-operatively and at 2–6 months and 1–2 years post-operatively. Urine samples were also obtained from 10 healthy weight and 7 morbidly obese non-surgical controls. Expression levels of kidney microRNAs were assessed in urine and the function of microRNAs was assessed through the in vitro transfection of HK-2 cells, a kidney proximal tubule cell line.Results: Levels of miR 192, miR 200a, and miR 200b were upregulated in urine following bariatric surgery. This increase was consistent across surgical type and diabetes status and was maintained and enhanced with time. Bariatric surgery alters urinary miR 192 expression from levels seen in morbidly obese patients to levels seen in healthy weight control patients. In mechanistic studies, the transfection of miR 192 in HK-2 cells increased miR 200a expression and decreased ZEB2, a key transcriptional promoter of kidney fibrosis.Conclusions: Bariatric surgery increased miR 192 and miR 200 urinary levels, key anti-fibrotic microRNAs that could contribute to a renal-protective mechanism and may be of value as urinary biomarkers following surgery. These findings suggest that urinary microRNAs may represent potential novel biomarkers for obesity-associated renal function

Improved physiology and metabolic flux after Roux-en-Y gastric bypass is associated with temporal changes in the circulating microRNAome: A longitudinal study in humans

BackgroundThe global pandemic of obesity and the metabolic syndrome are leading causes of mortality and morbidity. Bariatric surgery leads to sustained weight loss and improves obesity-associated morbidity including remission of type 2 diabetes. MicroRNAs are small, endogenous RNAs that regulate gene expression post-transcriptionally, controlling most of the human transcriptome and contributing to the regulation of systemic metabolism. This preliminary, longitudinal, repeat sampling study, in which subjects acted as their own control, aimed to assess the temporal effect of bariatric surgery on circulating microRNA expression profiles.MethodsWe used Exiqon’s optimized circulating microRNA panel (comprising 179 validated miRNAs) and miRCURY locked nucleic acid plasma/serum Polymerase Chain Reaction (PCR) to assess circulating microRNA expression. The microRNAome was determined for Roux-en-Y gastric bypass (RYGB) patients examined preoperatively and at 1 month, 3 months, 6 months, 9 months and 12 months postoperatively. Data was analysed using multivariate and univariate statistics.ResultsCompared to the preoperative circulating microRNA expression profile, RYGB altered the circulating microRNAome in a time dependent manner and the expression of 48 circulating microRNAs were significantly different. Importantly, these latter microRNAs are associated with pathways involved in regulation and rescue from metabolic dysfunction and correlated with BMI, the percentage of excess weight loss and fasting blood glucose levels.ConclusionsThe results of this pilot study show that RYGB fundamentally alters microRNA expression in circulation with a time-dependent progressive departure in profile from the preoperative baseline and indicate that microRNAs are potentially novel biomarkers for the benefits of bariatric surgery

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial

Objective: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. Methods: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 μSiemens) and estimated glomerular filtration rate (eGFR). Results: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). Conclusions: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.This research was funded by European Commission, FP7 EC-GA No. 279074; Boehringher Ingelheim, Ingelheim am Rhein, Germany (IIS Program. Grant number 1218.166); Merck Healthcare KGaA, Darmstadt, Germany (IIS number: EMR200084_621), Instituto de Salud Carlos III, Spain PI11/01653. The study funders were not involved in the design of the study, the collection, analysis and interpretation of data or writing the report and did not impose any restrictions regarding the publication of the report.S

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance