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.

Co-administration of "L-Lysine, Vitamin C, and Zinc" increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats.

PURPOSE: We previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats. METHODS: The streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats. RESULTS: The determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone. CONCLUSIONS: The results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.

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.

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.

Bilateral inferior petrosal sinus sampling: validity, diagnostic accuracy in lateralization of pituitary microadenoma, and treatment in eleven patients with Cushing's syndrome - a single-center retrospective cohort study.

BACKGROUND: This single-center retrospective cohort study aimed to describe the findings and validity of Bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of patients with ACTH-dependent Cushing's syndrome (CS). METHODS: Eleven patients underwent BIPSS due to equivocal biochemical tests and imaging results. Blood samples were taken from the right inferior petrosal sinus (IPS), left IPS, and a peripheral vein before and after stimulation with desmopressin (DDAVP). ACTH and prolactin levels were measured. The diagnosis was based on the ACTH ratio between the IPS and the peripheral vein. Also, lateralization of pituitary adenoma in patients with Cushing's disease (CD) was predicted. No significant complications were observed with BIPSS. RESULTS: Based on the pathology report, eight patients had CD, and three had ectopic ACTH syndrome (EAS). Unstimulated BIPSS resulted in a sensitivity of 87.5%, specificity of 100%, PPV of 100%, NPV of 75%, and accuracy of 91%. Stimulated BIPSS resulted in a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and accuracy of 100%. However, pituitary magnetic resonance imaging (MRI) had a lower diagnostic accuracy (sensitivity:62.5%, specificity:33%, PPV:71%, NPV:25%, accuracy:54%). BIPSS accurately demonstrated pituitary adenoma lateralization in 75% of patients with CD. CONCLUSIONS: This study suggests that BIPSS may be a reliable and low-complication technique in evaluating patients with ACTH-dependent CS who had inconclusive imaging and biochemical test results. The diagnostic accuracy is improved by DDAVP stimulation. Pituitary adenoma lateralization can be predicted with the aid of BIPSS.

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.

Vitamin C supplementation lowers advanced glycation end products (AGEs) and malondialdehyde (MDA) in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial.

This study evaluated how daily vitamin C administration impacts systemic oxidative stress and inflammation and its safety in T2D patients. This randomized, double-blinded, placebo-controlled, parallel-arm clinical trial included 70 patients with T2D. They were allocated to receive either 500 mg/day of vitamin C or a matching placebo for 8 weeks. Of the 70 subjects assigned to the trial, 57 were included in the statistical analysis (vitamin C: n = 32, placebo: n = 25). Inflammatory and oxidative markers, including advanced glycation end products (AGEs), malondialdehyde (MDA), advanced oxidation protein products (AOPP), oxidized low-density lipoprotein (ox-LDL), highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and ferric reducing ability of plasma (FRAP) were measured at baseline and the end of the trial. In addition, vitamin C tolerance was evaluated. A nutritionist visited all participants for a standard diabetic regimen. Following vitamin C supplementation, the serum levels of MDA (p-value < .001) and AGEs (p-value = .002) demonstrated a significant decrease after controlling for multiple confounders, including age, blood pressure, waist circumference, HbA1C, TG, and LDL-C, while no significant changes were observed for AOPP (p-value = .234) and ox-LDL (p-value = .480). The FRAP showed an increasing trend as an antioxidant marker but was not statistically significant (p-value = .312). The hs-CRP and TNF-α had no significant changes (p-value: .899 and .454, respectively). Also, no major adverse events were observed. Vitamin C supplementation may be beneficial in reducing AGEs and MDA in patients with T2D.

Lipid profile, ox-LDL, and LCAT activity in patients with endometrial carcinoma and type 2 diabetes: The effect of concurrent disease based on a case-control study.

Background and Aim: The role of lecithin: cholesterol acyltransferase (LCAT) and oxidized low-density lipoprotein (ox-LDL) in endometrial cancer (EC) or EC with concurrent type 2 diabetes is still unclear. This study investigated the LCAT activity, ox-LDL, and lipid profile in EC patients with or without type 2 diabetes and compared them with healthy individuals and patients with type 2 diabetes alone. Methods: In this cross-sectional, case-control study, 93 female participants were recruited. The participants were divided into four groups, including EC with type 2 diabetes (n = 19), EC without type 2 diabetes (n = 17), type 2 diabetes (n = 31), and healthy controls (n = 26). Sociodemographic information, the LCAT activity, triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and ox-LDL levels were collected. One-way analysis of variance and analysis of covariance, Student's t-test, Mann-Whitney U-test, and χ 2-test were used to compare demographic features and laboratory results among studied groups. Regression analyses were also performed to evaluate the interaction effect between EC and type 2 diabetes on serum LCAT activity. Results: The LCAT activity was significantly lower, and ox-LDL levels were significantly higher in all patient groups compared to the healthy controls (p < 0.001). EC patients had significantly lower LCAT activity and higher ox-LDL levels than type 2 diabetes and healthy groups (p < 0.05). Higher levels of TG and lower levels of HDL-C were observed in all patient groups compared to the healthy group (all p < 0.001). Patients with EC and concomitant type 2 diabetes had significantly lower serum LDL-C levels than healthy and type 2 diabetes groups (p < 0.05). Conclusions: The combination of EC and type 2 diabetes had a subadditive effect on LCAT activity and ox-LDL level. The lowest LCAT activity and the highest ox-LDL levels were observed in patients with EC and concurrent type 2 diabetes.

Challenges and solutions in clinical research during the COVID-19 pandemic: A narrative review.

Background and Aims: The COVID-19 pandemic has presented significant challenges to clinical research, necessitating the adoption of innovative and remote methods to conduct studies. This study aimed to investigate these challenges and propose solutions for conducting clinical research during the pandemic. Methods: A narrative review was conducted (approval ID: IR.AMS.REC.1401.029), utilizing keyword searches in PubMed and Web of Science (WOS) citation index expanded (SCI-EXPANDED) from January 2020 to January 2023. Keywords included COVID-19, clinical research, barriers, obstacles, facilitators and enablers. Results: Out of 2508 records retrieved, 43 studies were reviewed, providing valuable insights into the challenges and corresponding solutions for conducting clinical research during the COVID-19 pandemic. The identified challenges were categorized into four main groups: issues related to researchers or investigators, issues related to participants and ethical concerns, administrative issues, and issues related to research implementation. To address these challenges, multiple strategies were proposed, including remote monitoring through phone or video visits, online data collection and interviews to minimize in-person contact, development of virtual platforms for participant interaction and questionnaire completion, consideration of financial incentives, adherence to essential criteria such as inclusion and exclusion parameters, participant compensation, and risk assessment for vulnerable patients. Conclusion: The COVID-19 pandemic has significantly impacted clinical research, requiring the adaptation and enhancement of existing research structures. Although remote methods and electronic equipment have limitations, they hold promise as effective solutions during this challenging period.

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.

Organ-based clues for diagnosis of inborn errors of immunity: A practical guide for clinicians.

Inborn errors of immunity (IEI) comprise a group of about 490 genetic disorders that lead to aberrant functioning or the development of distinct immune system components. So far, a broad spectrum of IEI-related manifestations has been noted in the literature. Due to overlapping signs and symptoms of IEI, physicians face challenges in appropriately diagnosing and managing affected individuals. The last decade has witnesses improving in the molecular diagnosis of IEI patients. As a result, it can be the mainstay of diagnostic algorithms, prognosis, and possibly therapeutic interventions in patients with IEI. Furthermore, reviewing IEI clinical complications demonstrates that the manifestations and severity of the symptoms depend on the involved gene that causes the disease and its penetrance. Although several diagnostic criteria have been used for IEI, not every patient can be explored in the same way. As a result of the failure to consider IEI diagnosis and the variety of diagnostic capabilities and laboratory facilities in different regions, undiagnosed patients are increasing. On the other hand, early diagnosis is an almost essential element in improving the quality of life in IEI patients. Since there is no appropriate guideline for IEI diagnosis in different organs, focusing on the clues in the patient's chief complaint and physical exams can help physicians narrow their differential diagnosis. This article aims to provide a practical guide for IEI diagnosis based on the involved organ. We hope to assist clinicians in keeping IEI diagnosis in mind and minimizing possible related complications due to delayed diagnosis.

Therapeutic effects of resveratrol and Omega-3 in mice atherosclerosis: focus on histopathological changes.

BACKGROUND: Resveratrol and omega-3 have been shown to prevent atherosclerosis. However, histopathological changes and their comparison have not been studied well. This study investigated the therapeutic effects of resveratrol and omega-3 in experimental atherosclerosis of mice. METHODS: We divided sixty 6-week-old male C57BL/6 mice into six groups and followed for 10 weeks: (1) standard diet, (2) atherogenic diet, (3) atherogenic diet along with resveratrol from the start of the sixth week, (4) atherogenic diet along with omega-3 from the start of the sixth week, (5) standard diet along with resveratrol from the start of the sixth week, (6) standard diet along with omega-3 from the start of the sixth week. RESULTS: The mice fed on an atherogenic diet had a larger fat area and a thicker aortic wall thickness than mice fed on a standard diet. The use of omega-3 and resveratrol in the mice with an atherogenic diet resulted in a significantly reduced fat area (p-value = 0.003), and resveratrol had a significantly higher effect. Omega-3 or resveratrol induced a significant reduction in aortic wall thickness in mice on an atherogenic diet, and there was no significant difference between them. Among the mice with a standard diet, this study did not observe any significant changes in the fat area or the aortic wall thickness with the consumption of omega-3 or resveratrol. CONCLUSIONS: Resveratrol and omega-3 had a regressive and therapeutic role in atherosclerosis, with a more significant effect in favor of resveratrol.

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.