Role of vitamin D in risk factors of patients with type 2 diabetes mellitus / Papel de la vitamina D en los factores de riesgo de los pacientes con diabetes mellitus tipo 2

Introduction and objectives: Previous observational studies have suggested that low vitamin D status is associated with high circulating C-reactive protein levels, as well as other plasma inflammatory cytokines. However, there is no study to explore the relationship between vitamin D status and Lp-PLA2, a new biomarker of vascular-specific inflammation. The aim of this study was to examine the association between vitamin D status and circulating Lp-PLA2 levels in subjects with type 2 diabetes mellitus. Material and methods: This descriptive cross-sectional study enrolled diabetic subjects who underwent physical examination at Taizhou People's Hospital between August 2016 and January 2017. Blood pressure, anthropometry, metabolic profiles, serum 25(OH)D levels and Lp-PLA2 mass levels were measured in all participants. Results: A total of 196 participants were recruited into this study. The vitamin D insufficiency group had higher serum LP-PLA2 levels than the vitamin D sufficiency group (t=−2.765, p=.005). A significant negative correlation was noted between Lp-PLA2 and 25(OH)D in the vitamin D insufficiency group (r=−0.364, p=0.009). However, no significant relationship between serum Lp-PLA2 concentration and 25(OH)D levels was observed in subjects with vitamin D sufficiency. Conclusions: From this cohort of patients with type 2 diabetes, regardless of traditional cardiovascular risk factors, we observed a statistically significant inverse relation between Lp-PLA2 and 25(OH)D at levels <30ng/mL

Introducción y objetivos: Los estudios observacionales previos han sugerido que la situación de los bajos niveles de la vitamina D está asociada a los altos niveles de la proteína C reactiva circulantes, así como a otras citoquinas inflamatorias en plasma. Sin embargo, no existe ningún estudio que explore la relación entre la situación de la vitamina D y la lipoproteína asociada a la fosfolipasa A2 (Lp-PLA2), un nuevo biomarcador de la inflamación específico vascular. El objetivo de este estudio fue examinar la asociación entre la situación de la vitamina D y los niveles circulantes de Lp-PLA2 en sujetos con diabetes mellitus tipo 2. Material y métodos: Estudio transversal descriptivo que incluyó sujetos diabéticos que fueron sometidos a un examen físico en el Hospital popular de Taizhou entre agosto de 2016 y enero de 2017. Se midieron en todos los participantes la presión arterial, la antropometría, los perfiles metabólicos, el suero de 25 (OH) niveles séricos de vitamina D y los niveles de masa de Lp-PLA2. Resultados: Un total de 196 participantes fueron reclutados para este estudio. El grupo de insuficiencia de la vitamina D reflejó unos niveles superiores de Lp-PLA2 que el grupo con suficiencia de vitamina D (T=−2,765; p=0,005). Se observó una correlación negativa significativa entre Lp-PLA2 y 25(OH)D en el grupo con insuficiencia de vitamina D (R=−0,364; p=0,009). Sin embargo, no se observó ninguna relación significativa entre la concentración sérica de Lp-PLA2 y 25(OH)D en sujetos con niveles de suficiencia de vitamina D. Conclusiones: A partir de esta cohorte de pacientes con diabetes tipo 2, independientemente de los factores de riesgo cardiovascular, se observó una relación inversa entre Lp-PLA2, estadísticamente significativa, en los niveles de 25(OH)D<30ng/ml

Role of vitamin D in risk factors of patients with type 2 diabetes mellitus.

INTRODUCTION AND OBJECTIVES: Previous observational studies have suggested that low vitamin D status is associated with high circulating C-reactive protein levels, as well as other plasma inflammatory cytokines. However, there is no study to explore the relationship between vitamin D status and Lp-PLA2, a new biomarker of vascular-specific inflammation. The aim of this study was to examine the association between vitamin D status and circulating Lp-PLA2 levels in subjects with type 2 diabetes mellitus. MATERIAL AND METHODS: This descriptive cross-sectional study enrolled diabetic subjects who underwent physical examination at Taizhou People's Hospital between August 2016 and January 2017. Blood pressure, anthropometry, metabolic profiles, serum 25(OH)D levels and Lp-PLA2 mass levels were measured in all participants. RESULTS: A total of 196 participants were recruited into this study. The vitamin D insufficiency group had higher serum LP-PLA2 levels than the vitamin D sufficiency group (t=-2.765, p=.005). A significant negative correlation was noted between Lp-PLA2 and 25(OH)D in the vitamin D insufficiency group (r=-0.364, p=0.009). However, no significant relationship between serum Lp-PLA2 concentration and 25(OH)D levels was observed in subjects with vitamin D sufficiency. CONCLUSIONS: From this cohort of patients with type 2 diabetes, regardless of traditional cardiovascular risk factors, we observed a statistically significant inverse relation between Lp-PLA2 and 25(OH)D at levels <30ng/mL.

miRNA-214 suppresses oxidative stress in diabetic nephropathy via the ROS/Akt/mTOR signaling pathway and uncoupling protein 2.

In the present study, the function of microRNA (miR)-214 on diabetic nephropathy (DN) and diabetes of proximal tubular cells was investigated. Reverse transcription-quantitative polymerase chain reaction was used measure the expression of miR-214 in rats with DN and ELISA was performed to measure oxidative stress and ROS levels. Results indicated that miR-214 expression in the peripheral blood was significantly decreased in rats with DN. The in vitro model of DN indicated that miR-214 upregulation significantly decreased oxidative stress and reactive oxygen species (ROS) levels, but significantly increased uncoupling protein 2 (UCP2), phosphorylated (p)-Akt and p-mammalian target of rapamycin (mTOR) protein expression levels. The administration of genipin, a UCP2 inhibitor, significantly attenuated the effects of miR-214 upregulation on oxidative stress in the in vitro DN model by regulating ROS, Akt and mTOR protein expression levels. Notably, Akt inhibitor suppressed p-Akt protein expression and attenuated the effects of miR-214 upregulation on oxidative stress in the in vitro DN model. Collectively, these data suggest that miR-214 regulates diabetes through a ROS/Akt/mTOR signaling pathway by UCP2 in proximal tubular cells.

Let­7a­5p may participate in the pathogenesis of diabetic nephropathy through targeting HMGA2.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM), and has been demonstrated as one of the major causes of renal failure. In a previous study, it was noted that microRNA let­7a­5p was downregulated in DN; however, the underlying mechanism requires additional investigation. The aim of the present study was to investigate the roles of let­7a­5p in the pathogenesis of DN and its associated mechanism. The renal tissues of db/db and db/m mice, and renal mesangial cells treated with high concentrations of glucose were obtained; reverse transcription­quantitative polymerase chain reaction, and western blot analysis were applied to detect the expression of let­7a­5p and high­mobility group AT­hook 2 (HMGA2) in vivo and in vitro. In addition, renal mesangial cells cultured under high­glucose conditions (20 and 30 mmol/l) were transfected with either let­7a­5p mimics or let­7a­5p inhibitors. The effects of let­7a­5p on the proliferation and apoptosis of renal mesangial cells were examined using CCK­8 and flow cytometry methods. Additionally, cells were collected and the expression of phosphoinositide 3­kinase (PI3K), phosphorylated protein kinase B (p­AKT) and HMGA2 was analyzed with western blot analysis. Finally, a dual luciferase reporter assay was performed to confirm whether HMGA2 was a direct target of let­7a­5p. Let­7a­5p was significantly downregulated and HMGA2 was markedly upregulated in the tissue samples of DN mice and renal mesangial cells cultured under high­glucose conditions. In addition, transfection of let­7a­5p mimics induced a significant decrease in the proliferation and increase in the apoptosis of renal mesangial cells cultured under high­glucose conditions; transfection of let­7a­5p inhibitors exhibited the opposite effects. Furthermore, transfection of let­7a­5p mimics also led to the inhibition of the PI3K­AKT signaling pathway; transfection of let­7a­5p inhibitors may activate the PI3K­AKT signaling pathway through the increase in PI3K and AKT levels. Finally, a dual luciferase reporter assay confirmed that HMGA2 is a direct target of let­7a­5p. Let­7a­5p was downregulated in DN and may participate in the pathogenesis of DN via regulating HMGA2 expression and the PI3K­AKT signaling pathway.

Long non-coding RNA HEIH contributes to diabetic retinopathy by regulating miR-939/VEGF axis.

Diabetes is one of the most prevalent metabolic diseases in the world. This study explored the role of long non-coding RNA HEIH in regulating the development of diabetic retinopathy (DR). The expression of HEIH gene was detected in the serum of patients with DR. Subsequently, high concentrations of D-glucose (HG) were used to stimulate ARPE-19 cells to construct a cell model of DR. HEIH was overexpressed and suppressed to further investigate the effects of HEIH on HG-induced ARPE-19 cell injury. Moreover, the regulatory relationship between HEIH and miR-939 was investigated, and a target relationship between miR-939 and VEGF in ARPE-19 cells was explored. We elucidated an association between HEIH/miR-939/VEGF axis and the PI3K/AKT pathway. HEIH was highly expressed in the serum of patients with DR. Moreover, HG-induced ARPE-19 cell injury and expression of HEIH. The overexpression of HEIE aggravated HG-induced ARPE-19 cell injury by significantly inhibiting cell viability, inducing apoptosis, promoting cytochrome C release from mitochondria to cytoplasm, and enhancing the caspase-3 activity, whereas suppression of HEIE had the opposite effects. In addition, the effects of the suppression of HEIH on HG-induced ARPE-19 cell injury were markedly reversed by inhibiting miR-939. miR-939 regulated HG-induced ARPE-19 cell injury by targeting VEGF. The suppression of HEIH reversed HG-induced activation of the PI3K/AKT signaling pathway. Our findings revealed that HEIH may contribute to DR by sponging miR-939 to target VEGF expression and by regulating the activation of the PI3K/AKT pathway. Inhibition of epidermal growth factor receptor and PI3K/Akt signaling suppresses cell proliferation and survival through regulation of Stat3 activation in human cutaneous squamous cell carcinoma. HEIH/miR-939/VEGF axis may provide a novel perspective for DR therapy.

SIRT5 regulates pancreatic ß-cell proliferation and insulin secretion in type 2 diabetes.

Impaired insulin secretion and insulin resistance are the primary characteristics of type 2 diabetes (T2D). However, the mechanisms underlying insulin secretion failure have yet to be elucidated. The present study demonstrated that sirtuin 5 (SIRT5) is upregulated in patients with T2D and in pancreatic ß-cell lines. It was also revealed that elevated SIRT5 expression is positively associated with age and blood glucose levels, and negatively associated with pancreatic and duodenal homeobox 1 (PDX1) expression. Colony formation and Cell Counting Kit-8 assays demonstrated that SIRT5 suppressed the proliferation of pancreatic ß-cells in vitro. In addition, downregulation of SIRT5 promoted the secretion of insulin. Additionally, SIRT5 ectopic expression downregulated the expression of PDX1 and the inhibition of SIRT5 upregulated PDX1 expression. Chromatin immunoprecipitation assay analysis demonstrated that SIRT5 may regulate the transcription of PDX1 via H4K16 deacetylation. In conclusion, the results of the present study indicate that SIRT5 may serve an important role in the pathogenesis of T2D, and may present a novel therapeutic target for the treatment of patients with T2D.

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.

Effect of probiotics on glucose metabolism in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

OBJECTIVE: Our aim was to investigate the effects of probiotics on glucose metabolism in patients with type 2 diabetes mellitus using a meta-analysis of randomized, controlled trials. MATERIALS AND METHODS: Online databases Embase, Web of Science, and PubMed were searched until August 2014 to identify eligible articles. Finally, 7 trials were included. RESULTS: Probiotic consumption significantly changed fasting plasma glucose (FPG) by -15.92mg/dL (95% confidence interval [CI], -29.75 to -2.09) and glycosylated hemoglobin (HbA1c) by -0.54% (95% CI, -0.82 to -0.25) compared with control groups. Subgroup analysis was conducted to trials with non-yogurts control. Meta-analysis of trials with multiple species of probiotics found a significant reduction in FPG (weighted mean difference [WMD]: -35.41mg/dL, 95% CI: -51.98 to -18.89). The duration of intervention for ≥8 weeks resulted in a significant reduction in FPG (WMD: -20.34mg/dL, 95% CI: -35.92 to -4.76). Subgroup analysis of trials with species of probiotics did not result in a significant meta-analysis effect. Furthermore, the duration of intervention <8 weeks did not result in a significant reduction in FPG. The results also showed that probiotic therapy significantly decreased homeostasis model assessment of insulin resistance (HOMA-IR) and insulin concentration (WMD: -1.08, 95% CI: -1.88 to -0.28; and WMD: -1.35mIU/L, 95% CI: -2.38 to -0.31, respectively). CONCLUSIONS: The present meta-analysis suggests that consuming probiotics may improve glucose metabolism by a modest degree, with a potentially greater effect when the duration of intervention is ≥8 weeks, or multiple species of probiotics are consumed.

Small­sized gold nanoparticles inhibit the proliferation and invasion of SW579 cells.

The present study reported on an intrinsic property of gold nanoparticles (Au­NPs), namely their ability to inhibit the proliferation and invasion of thyroid carcinoma cells. Au­NPs of various sizes (5­60 nm) were synthesized and their uptake into the SW579 human thyroid carcinoma cell line was verified using transmission electron microscopy (TEM). The viability, apoptosis, cell cycle distribution and invasive capacity of SW579 cells were assessed following treatment with Au­NPs using a Cell Counting Kit­8 assay, flow cytometric analysis and a Transwell as well as a fluorometric invasion assay. TEM demonstrated that all sizes of Au­NPs could be taken up by the SW579 cells. The results showed that small­sized Au­NPs (5 and 10 nm) significantly suppressed the proliferation and invasion of SW579 cells and induced apoptosis as well as cell cycle arrest in G0/G1 phase, while larger­sized gold nanoparticles (20­60 nm) did not exert these effects, therefore suggesting that the effects of Au­NPs on SW579 cells were highly associated with their particle size. The reduction of the invasive capacity of SW579 cells following treatment with Au­NPs may be attributed to decreases in the expression of matrix metalloproteinase­2 and ­9, which were observed using western blot and reverse­transcription quantitative polymerase chain reaction analyses. The present study was the first to demonstrate that small­sized Au­NPs inhibit the proliferation and invasion of thyroid carcinoma cells, which may contribute to the advancement of biomedical applications of Au­NPs.

Effect of probiotics on body weight and body-mass index: a systematic review and meta-analysis of randomized, controlled trials.

OBJECTIVE: To assess the efficacy of probiotic therapies on body weight and BMI using a meta-analysis of randomized, controlled trials. METHODS: Twenty studies with 25 trials (1931 participants with age over 18 years) were included. The pooled WMD was calculated by random effects model. RESULTS: Probiotic consumption significantly reduced body weight by 0.59 kg (95% CI, 0.30-0.87) and BMI by 0.49 kg/m(2) (95% CI, 0.24-0.74). A greater reduction in BMI was found with multiple species of probiotics. Subgroup analysis of trials with intervention duration ≥8 weeks found a more significant reduction in BMI. Limiting analysis to trials with a baseline BMI ≥25 kg/m(2) showed a greater reduction in BMI. CONCLUSION: Consuming probiotics could reduce body weight and BMI, with a potentially greater effect when multiple species of probiotics were consumed, the duration of intervention was ≥8 weeks, or the objects were overweight.