Impact of Gender on Chronic Complications in Participants With Type 2 Diabetes: Evidence From a Cross-Sectional Study.

INTRODUCTION: This study aimed to assess and compare the prevalence of diabetes complications between men and women with Type 2 diabetes (T2D), as well as how gender relates to these complications. METHODS: In this cross-sectional study, complications of diabetes, including coronary artery disease (CAD), retinopathy, neuropathy and diabetic kidney disease (DKD), were evaluated in 1867 participants with T2D. Additionally, baseline characteristics of the individuals, including anthropometric measurements, metabolic parameters and the use of dyslipidaemia drugs and antihyperglycaemic agents, were assessed. Gender differences in complications were examined using the chi-squared test. Multivariate logistic regression was employed to investigate the relationship between gender and T2D complications, with and without adjusting for the characteristics of the studied population. RESULTS: In the studied population, 62.1% had at least one complication, and complications were 33.5% for DKD, 29.6% for CAD, 22.9% for neuropathy and 19.1% for retinopathy. The prevalence of CAD and neuropathy was higher in men. However, DKD and retinopathy were more prevalent among women. Odds ratios of experiencing any complication, CAD and retinopathy in men compared with women were 1.57 (95% CI: 1.27-2.03), 2.27 (95% CI: 1.72-2.99) and 0.72 (95% CI: 0.52-0.98), respectively, after adjusting for demographic factors, anthropometric measures, metabolic parameters and the consumption of dyslipidaemia drugs and antihyperglycaemic agents. CONCLUSION: The prevalence of diabetes complications was significantly higher in men with diabetes, highlighting the need for better treatment adherence. CAD was associated with the male gender, whereas retinopathy was associated with the female gender. Men and women with diabetes should be monitored closely for CAD and retinopathy, respectively, regardless of their age, diabetes duration, anthropometric measures, laboratory findings and medications.

Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.

Resveratrol (RSV) has garnered significant attention in recent years due to its potential benefits against chronic diseases. However, its effects and safety in older adults have not been comprehensively studied. This study aimed to determine the effects and safety of RSV supplementation in older adults. MEDLINE/PubMed, Scopus, and Web of Science databases were comprehensively searched for eligible studies. Studies were enrolled if they were randomized clinical trials and had incorporated RSV supplementation for older adults. Two independent authors conducted the literature search, and eligibility was determined according to the PICOS framework. Study details, intervention specifics, and relevant outcomes were collected during the data collection. The Cochrane RoB-2 tool was used to evaluate the risk of bias. This review included 10 studies. The combination of RSV and exercise improved exercise adaptation and muscle function in healthy older adults and physical performance and mobility measures in individuals with functional limitations. RSV showed potential neuroprotective effects in patients with Alzheimer's disease. In overweight individuals, RSV demonstrated a positive impact on cognitive function, but it increased some biomarkers of cardiovascular disease risk at high doses. In older adults with diabetes and those with peripheral artery disease (PAD), RSV was not more effective than placebo. No study reported significant adverse events following RSV treatment. RSV can improve various health parameters in age-related health conditions. However, the optimal dosage, long-term effects, and potential interactions with medications still need to be investigated through well-designed RCTs.

Association of neutrophil to lymphocyte ratio with bone mineral density in post-menopausal women: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to compare the neutrophil lymphocyte ratio (NLR) levels between women with post-menopausal osteopenia or osteoporosis to those with normal bone mineral density (BMD). METHODS: We used Web of Science, PubMed, and Scopus to conduct a systematic search for relevant publications published before June 19, 2022, only in English language. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used the Newcastle-Ottawa scale for quality assessment. RESULTS: Overall, eight articles were included in the analysis. Post-menopausal women with osteoporosis had elevated levels of NLR compared to those without osteoporosis (SMD = 1.03, 95% CI = 0.18 to 1.88, p = 0.017, I2 = 98%). In addition, there was no difference between post-menopausal women with osteopenia and those without osteopenia in neutrophil lymphocyte ratio (NLR) levels (SMD = 0.58, 95% CI=-0.08 to 1.25, p = 0.085, I2 = 96.8%). However, there was no difference between post-menopausal women with osteoporosis and those with osteopenia in NLR levels (SMD = 0.75, 95% CI=-0.01 to 1.51, p = 0.05, I2 = 97.5%, random-effect model). CONCLUSION: The results of this study point to NLR as a potential biomarker that may be easily introduced into clinical settings to help predict and prevent post-menopausal osteoporosis.

Correlates of normal and decreased HDL cholesterol levels in type 2 diabetes: a cohort-based cross-sectional study.

BACKGROUND: The literature describes an inverse association between the values of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). This survey was designed to exhibit the features of people with type 2 diabetes (T2D) who display this inverse association and identify potential contributing factors to having normal HDL-C values. METHODS: A total of 6127 persons with T2D were assigned to the present survey. Demographic features and clinical status data were compared between subjects with a substantial inverse association of TG and HDL-C and those without. Logistic regressions were performed to ascertain the role of different factors related to normal HDL-C. Moreover, the restricted cubic spline (RCS) functions were conducted to scrutinize the underlying relationships between the studied variables and low HDL-C levels. RESULTS: Patients with high TG (150 ≤ TG < 400) compared to patients with normal TG (TG < 150) were less likely to have normal HDL-C. Younger age, narrow hip, lower levels of blood pressure, two-hour postprandial glucose (2hPP), fasting blood sugar (FBS), hemoglobinA1C (HbA1C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and non-HDL-C, higher atherogenic index of plasma (AIP), and TG/HDL-C ratio correlate with an inverse connection between the values of HDL-C and TG (all P < 0.05). Age greater than 65 years (odds ratio (OR) 1.260, 95% confidence intervals (CI) 1.124-1.413) had a positive association, whereas female sex (OR 0.467, CI 0.416-0.523) , 25 kg/m2 < body mass index (BMI) (OR 0.786, CI 0.691-0.894), and higher serum creatinine levels (OR 0.481, CI 0.372-0.621) had an inverse association with having normal HDL-C. CONCLUSIONS: Patients with an inverse connection between TG and HDL-C values had considerably different anthropometric features, lipid profiles, and glucose indices compared to those without this relationship. Furthermore, patients who aged less than 65 years, had female gender, BMI more than 25 kg/m2, and higher serum creatinine levels were less likely to exhibit normal HDL-C levels.

The lack of association between different LDL-C levels and oxidized LDL in patients with type 2 diabetes.

Background: High concentrations of low-density lipoprotein cholesterol (LDL-C) have been a known risk factor for cardiovascular diseases. Also, the role of oxidized LDL (ox-LDL) in forming atherosclerosis plaque has been proven. However, it has not yet been proven that atherogenic LDL-C by-products like ox-LDL will decrease by keeping the LDL levels at the desired level. This study aimed to examine the relationship between LDL-C and ox-LDL in different LDL-C values in patients with type 2 diabetes (T2D). Methods: In this cross-sectional study, 347 patients with T2D who received statins were enrolled. LDL-C values were defined into four groups as LDL-C < 55 mg/dL, 55 mg/dL ≤ to <70 mg/dL, 70 mg/dL ≤ to <100 mg/dL and LDL-C ≥ 100 mg/dL. Total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and ox-LDL were studied in the four defined groups. Results: Ox-LDL levels were not different among the four groups (p = 0.30). In addition, LDL-C and ox-LDL levels had no significant correlation (r = 0.480, p = 0.376). Additionally, based on this study analysis, ox-LDL levels were significantly correlated with TG levels (r = 0.119, p < 0.05) and TG/HDL ratio (r = 0.390, p < 0.01). Conclusions: It is concluded that ox-LDL levels were not associated with different LDL-C level categories from <55 mg/dL to >100 mg/dL in patients with T2D. However, the revealed association of ox-LDL with TG level and TG/HDL ratio may be considered in the clinic.

Decreasing trend of blood lipid profile in type 2 diabetes: Not a promising change in HDL-C, a serial cross-sectional study.

BACKGROUND: The prevalence of dyslipidemia in patients with type 2 diabetes (T2D) has been reported to be relatively high. The current study aimed to investigate the trend of serum lipid levels and the prevalence of dyslipidemia in patients with T2D. METHODS: Data were extracted from a cohort of patients with T2D who had regular follow-ups every year for three years. TG, TC, LDL-C, HDL-C, and non-HDL-C were analyzed. The atherogenic index of plasma (AIP) was calculated using log (TG/HDL-C). RESULTS: A total of 747 patients with T2D were included in this study, consisting of 469 (62.8%) women and 278 (37.2%) men. There was a significant downward trend in mean TG, TC, LDL-C, non-HDL-C, and AIP levels. The trend of mean HDL-C levels showed no significant change. The prevalence of high TG, high TC, high LDL-C, and high non-HDL-C significantly decreased from the first to the last visit. There was no significant change in the trend of prevalence of low HDL-C. The prevalence of high AIP significantly decreased in women and showed no significant changes in men. CONCLUSIONS: A decreasing trend was observed in the mean levels and prevalence of TG, TC, LDL-C, non-HDL-C, and AIP. HDL-C did not change significantly. The success rate in achieving a complete normal lipid profile during follow-up years was not promising and continues to be challenging.

Doxorubicin-loaded Niosomes functionalized with gelatine and alginate as pH-responsive drug delivery system: A 3D printing approach.

Despite many efforts, breast cancer remains one of the deadliest cancers and its treatment faces challenges related to cancer drug side effects and metastasis. Combining 3D printing and nanocarriers has created new opportunities in cancer treatment. In this work, 3D-printed gelatin-alginate nanocomposites containing doxorubicin-loaded niosomes (Nio-DOX@GT-AL) were recruited as an advanced potential pH-sensitive drug delivery system. Morphology, degradation, drug release, flow cytometry, cell cytotoxicity, cell migration, caspase activity, and gene expression of nanocomposites and controls (Nio-DOX and Free-DOX) were evaluated. Results show that the obtained niosome has a spherical shape and size of 60-80 nm. Sustained drug release and biodegradability were presented by Nio-DOX@GT-AL and Nio-DOX. Cytotoxicity analysis revealed that the engineered Nio-DOX@GT-AL scaffold had 90 % cytotoxicity against breast cancer cells (MCF-7), whereas exhibited <5 % cytotoxicity against the non-tumor breast cell line (MCF-10A), which was significantly more than the antitumor effect of the control samples. Scratch-assay as an indicator cell migration demonstrated a reduction of almost 60 % of the covered surface. Gene expression could provide an explanation for the antitumor effect of engineered nanocarriers, which significantly reduced metastasis-promoting genes (Bcl2, MMP-2, and MMP-9), and significantly enhanced the expression and activity of genes that promote apoptosis (CASP-3, CASP-8, and CASP-9). Also, considerable inhibition of metastasis-associated genes (Bax and p53) was observed. Moreover, flow-cytometry data demonstrated that Nio-DOX@GT-AL decreased necrosis and enhanced apoptosis drastically. The findings of this research can confirm that employing 3D-printing and niosomal formulation can be an effective strategy in designing novel nanocarriers for efficient drug delivery applications.

Correlation between different levels and patterns of dyslipidemia and glomerular filtration rate in patients with type 2 diabetes: A cross-sectional survey of a regional cohort.

BACKGROUND: Due to the high cardiovascular risk in patients with diabetic nephropathy, more attention should be paid to lipid levels and dyslipidemia in these patients. The current study investigated the association between single and mixed dyslipidemia patterns, estimated glomerular filtration rate (eGFR), and different chronic kidney disease (CKD) stages. METHODS: This cross-sectional study evaluated 4059 patients with type 2 diabetes (T2D). TG, TC, LDL-C, and HDL-C were measured. Non-HDL-C and AIP were calculated. We estimated eGFR using the CKD-EPI equation. RESULTS: With the progression of the kidney failure stage, mean levels of TG, LDL-C, non-HDL-C, and AIP decreased. HDL-C levels decreased with the advance of the CKD stage in men but did not change significantly in women. The prevalence of single dyslipidemia, including high LDL-C and high non-HDL-C, decreased with the advancing CKD stage. The prevalence of mixed dyslipidemia patterns, including high AIP and high LDL-C, high AIP and high non-HDL-C, showed a significant downward tendency. TG and AIP levels were negatively, and HDL-C levels were positively correlated with eGFR after adjusting for the risk factors. Also, CKD stage 3 was positively related to the risk of high TG and low HDL-C. CONCLUSION: This study shows that blood lipids decreased with the progression of renal failure in patients with T2D. However, after adjustment, TG and AIP levels had negative, and HDL-C levels had a positive correlation with eGFR, which could be consistent with the hypothesis that eGFR decreases with increasing TG or AIP levels or decreasing HDL-C levels.

Comparison of insulin resistance indices in predicting albuminuria among patients with type 2 diabetes.

PURPOSE: Diabetes is the leading cause of kidney disease. Up to 40% of the population with diabetes experience diabetic kidney disease (DKD). The correlation of DKD with insulin resistance (IR) indices has been shown in previous studies. In this study, the objective was to evaluate surrogate IR indices, including the Triglyceride-Glucose (TyG) index, Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to find the most valuable index for the correlation between albuminuria and IR in the type 2 diabetes (T2D) population. Albuminuria is defined as urine albumin excretion of > 30 mg/day. METHODS: In this cross-sectional study, 2934 participants were enrolled and evaluated for urinary albumin excretion, and albuminuria was detected in 526 of the entries. The logistic regression models and Receiver Operating Characteristic (ROC) curve analysis were performed to assess the relationship of TyG index, VAI, LAP, and HOMA-IR's with albuminuria in patients with T2D. RESULTS: The TyG index had the highest association (OR 1.67) with the presence of albuminuria in patients with T2D, followed by HOMA-IR (OR 1.127), VAI (OR 1.028), and LAP (OR 1.004). These four indices remained independent after adjustment for multiple confounders. Based on the ROC curve, TyG revealed the best area under the curve (AUC) for revealing albuminuria with sufficient accuracy (AUC: 0.62) in comparison with other measured indices. The calculated TyG index cut-off point for the presence of albuminuria was 9.39. CONCLUSION: Among the indices, TyG index had the most significant correlation with albuminuria in patients with T2D.

3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation.

Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60-80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.

Lipid accumulation product (LAP) index for the diagnosis of nonalcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis.

BACKGROUND: Lipid accumulation product (LAP) is an index calculated by waist circumference (WC) and triglyceride (TG), which reflects lipid toxicity. This study aims to investigate the association between the LAP index and nonalcoholic fatty liver disease (NAFLD) in a systematic review and meta-analysis. METHODS AND RESULTS: PubMed, Scopus, and Web of Science online databases were searched for eligible studies that investigated the association of the LAP index and NAFLD. Sixteen observational studies with 96,101 participants, including four cohort studies, one case‒control study and 11 cross-sectional studies with baseline data, were entered into this analysis. Fourteen studies reported a significant association between the LAP index and NAFLD, and two reported that this relation was not significant; two different meta-analyses (1- mean difference (MD) and 2- bivariate diagnostic test accuracy [DTA]) were conducted using Stata version 14. The LAP index was compared in subjects with and without NAFLD, and the difference was significant with 34.90 units (CI 95: 30.59-39.31, P < 0.001) of the LAP index. The DTA meta-analysis was conducted and showed that the LAP index pooled sensitivity and specificity for screening of NAFLD were 94% (CI95: 72%-99%, I2 = 99%, P < 0.001) and 85% (CI95: 62%-96%, I2 = 99%, P < 0.001), respectively. CONCLUSION: The LAP Index is an inexpensive, sensitive, and specific method to evaluate NAFLD and may be valuable for NAFLD screening.

The accuracy of triglyceride-glucose (TyG) index for the screening of metabolic syndrome in adults: A systematic review and meta-analysis.

AIMS: To investigate the relationship between the triglyceride-glucose (TyG) index, a novel surrogate index of insulin resistance (IR), and metabolic syndrome (MetS) in a systematic review and meta-analysis. DATA SYNTHESIS: Studies that report the TyG index in adult subjects with and without MetS were included. Thirteen observational articles were included in this study, with a total of 49,325 participants. Two different categories of meta-analyses were performed. First, the means of the TyG index were compared in participants with and without MetS. The pooled mean difference (MD) of the TyG index between groups was 0.83 units (CI 95: 0.74-0.92, I2 = 98, P-value < 0.001), and the subgroup analyses showed MD significantly differed based on the MetS diagnostic criteria. The pooled MD were 0.80 units (CI 95: 0.70-0.91, I2 = %88, P-value < 0.001) and 0.82 units (CI 95: 0.79-0.86, I2 = %0, P-value > 0.767) for studies reported data for males and females individual, respectively. Second bivariate diagnostic test accuracy (DTA) meta-analysis was performed and determined that the TyG index's pooled sensitivity and specificity for screening of MetS were 80% (CI95: 75%-84%, I2 = 87%, P-value < 0.001) and 81% (CI95: 77%-84%, I2 = 90.45%, P-value < 0.001), respectively. Summary receiver-operating characteristics (sROC) curves were also plotted with the area under the sROC curve of 0.87 (CI 95: 0.84-0.90). CONCLUSIONS: The TyG index is a sensitive and specific index for MetS and may be valuable for MetS screening. PROSPERO: CRD42022316209.

Neutrophil to Lymphocyte Ratio and Spontaneous Bacterial Peritonitis among Cirrhotic Patients: A Systematic Review and Meta-analysis.

Background: The goal of this systematic review and meta-analysis was analyzing published studies on the role of neutrophil to lymphocyte ratio (NLR) in infection and spatially spontaneous bacterial peritonitis (SBP) among cirrhotic patients. Methods: PubMed, Web of Science, and Scopus were searched until May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment. Results: Of 14 studies included in our study, six studies were on infection with 2786 hospitalized cirrhotic patients, of whom 934 developed an infection. Other studies were on SBP with 1573 cirrhotic patients with ascites, of whom 557 developed SBP. The pooled results showed that there was no difference in NLR levels between hospitalized cirrhotic patients who developed infection compared to those who did not (random-effects model: SMD = 0.63, 95% CI = -0.01-1.27, p=0.054). However, cirrhotic patients with ascites who developed SBP had elevated levels of NLR compared to those who did not (random-effects model: SMD = 1.05, 95% CI = 0.52-1.57,p < 0.001). This difference remained significant in prospective studies (SMD = 0.94, 95% CI = 0.51-1.38,p < 0.001) but not in retrospective studies (SMD = 1.37, 95% CI = -0.56-3.29,p=0.165), in the subgroup analysis according to the study design. The pooled sensitivity of NLR was 92.07% (95% CI = 74.85%-97.84%) and the pooled specificity was 72.58% (95% CI = 57.72%-83.69%). The pooled positive likelihood ratio, negative likelihood ratio, DOR of NLR were 3.35(95%CI = 2.06-5.46), 0.10 (95%CI = 0.03-0.38), and 30.78 (95%CI = 7.01-135.04), respectively. Conclusion: Our results support NLR to be a valid biomarker that can be readily integrated into clinical settings to help in the prevention and prediction of SBP among cirrhotic patients.

Cerebellar Microstructural Abnormalities in Parkinson's Disease: a Systematic Review of Diffusion Tensor Imaging Studies.

Diffusion tensor imaging (DTI) is now having a strong momentum in research to evaluate the neural fibers of the CNS. This technique can study white matter (WM) microstructure in neurodegenerative disorders, including Parkinson's disease (PD). Previous neuroimaging studies have suggested cerebellar involvement in the pathogenesis of PD, and these cerebellum alterations can correlate with PD symptoms and stages. Using the PRISMA 2020 framework, PubMed and EMBASE were searched to retrieve relevant articles. Our search revealed 472 articles. After screening titles and abstracts, and full-text review, and implementing the inclusion criteria, 68 papers were selected for synthesis. Reviewing the selected studies revealed that the patterns of reduction in cerebellum WM integrity, assessed by fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity measures can differ symptoms and stages of PD. Cerebellar diffusion tensor imaging (DTI) changes in PD patients with "postural instability and gait difficulty" are significantly different from "tremor dominant" PD patients. Freezing of the gate is strongly related to cerebellar involvement depicted by DTI. The "reduced cognition," "visual disturbances," "sleep disorders," "depression," and "olfactory dysfunction" are not related to cerebellum microstructural changes on DTI, while "impulsive-compulsive behavior" can be linked to cerebellar WM alteration. Finally, higher PD stages and longer disease duration are associated with cerebellum white matter alteration depicted by DTI. Depiction of cerebellar white matter involvement in PD is feasible by DTI. There is an association with disease duration and severity and several clinical presentations with DTI findings. This clinical-imaging association may eventually improve disease management.