Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM. METHODS: PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots. RESULTS: Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = -1.53, 95%CI (-2.14,-0.93), p < 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = -0.68, 95%CI (-1.34, -0.01), p = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = -0.86, 95%CI (-2.65, 0.93), p = 0.34), and interleukin-6 (SMD = -0.04, 95%CI (-1.08, 1.01), p = 0.95) was observed. CONCLUSION: Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

Endothelial dysfunction, a predictor of cardiovascular disease in HIV patients on antiretroviral therapy: A systematic review and meta-analysis.

Aim Although antiretroviral therapy (ART) is available, the rate of new HIV infections is alarming. With this trend, it is anticipated that the use of ART will continue to rise, potentially resulting in associated vascular disorders. Therefore, we aimed to examine the impact of ART on endothelial function in people living with HIV (PLHIV), a predictor of cardiovascular diseases. METHOD: A comprehensive search for evidence was made on PubMed and Scopus on May 06, 2023, following the Preferred Reporting Items for Systematic Review and Meta-analysis. Cochrane and Newcastle-Ottawa quality assessment scales were used to evaluate quality, while the metaHun web tool and Review Manager version 5.4.1 were used for analysis. Subgroup, sensitivity, and publication bias were conducted for each outcome measure. RESULTS: We identified 37 studies, including a sample size of 3700 with 2265 individuals on ART. The analyzed evidence showed a large significant effect of ART on vascular cell adhesion molecule-1, with a standardized mean difference (SMD) of -1.23 (95 % CI: -1.72, -0.74; p = 0.0013). Similarly, a significant medium effect of ART was observed on intercellular cell adhesion molecule-1 in PLHIV, with an SMD of -1.28 (95 % CI: -2.00, -0.56; p = 0.0231) compared to the control group. Furthermore, ART exhibited a significant but small effect on flow-mediated dilation (FMD) with an SMD of -0.40 (95 % CI: -0.62, -0.19, p = 0.0159). CONCLUSION: Our findings show an improved endothelial function in PLHIV on ART, as demonstrated by reduced adhesion molecules; however, ART exhibited a small effect on FMD, thus suggesting PLHIV on ART may still be at risk of endothelial dysfunction and further cardiovascular diseases.

Association of carotid intima-media thickness and dyslipidaemia in patients with type 2 diabetes: a protocol for systematic review and meta-analysis.

INTRODUCTION: Patients with diabetes mellitus (DM) often present with comorbidities such as hypertension, dyslipidaemia, insulin resistance, obesity and hyperglycaemia, which increases their risk of cardiovascular diseases (CVDs)-related mortality. Carotid intima-media thickness (CIMT), a biomarker for subclinical atherosclerosis, has been associated with overall CVD, especially in type 2 DM (T2DM). Hence, this protocol for systematic review and meta-analysis aims to review existing literature on the association of CIMT and dyslipidaemia in patients with T2DM. METHODS AND ANALYSIS: The proposed systematic review and meta-analysis will be conducted according to an updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guideline. A comprehensive search of peer-reviewed studies on Google Scholar, PubMed, Science Direct and Web of Sciences databases will be conducted up to 30 June 2023. A meta-analysis of data extracted from selected studies will be performed to explore the association between dyslipidaemia and CIMT in patients with diabetes. The effect estimates will be reported as standardised mean differences/Cohen's d and 95% CIs. A random effect model will be used in case of high heterogeneity whereas fixed-effect model will be used in the absence of heterogeneity. All statistical analysis will be performed using SPSS V.29.0 software. In cases of high heterogeneity, subgroup analysis will be performed based on study design, countries of publication and body mass index to identify potential sources of heterogeneity. Publication bias will be assessed graphically via funnel plots and statistically using Egger's regression test. Sensitivity analysis will also be performed to evaluate the stability of the overall effect size and the grading of recommendations assessment, development and evaluation will be used to grade the quality of analysed evidence. ETHICS AND DISSEMINATION: As the proposed study will use secondary published data, approval will not be sought from the ethics committee. PROSPERO REGISTRATION NUMBER: CRD42023451731.

Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia.

BACKGROUND: Evidence from preclinical studies has found a correlation between the development of type 2 diabetes (T2D) and vitamin D deficiency. However, evidence from randomized controlled trials (RCTs) revealed inconclusive results on vitamin D supplementation. We explored the effect of vitamin D on inflammation and dyslipidemia in T2D. METHODS: We comprehensively searched for RCTs evaluating the effect of vitamin D in T2D on PubMed. Data were analyzed using Review Manager 5.3 and reports, such as standardized mean difference (SMD) and 95% confidence intervals (CI) at a 5% significant level using a random effect model. RESULTS: This study revealed a significant reduction in tumor necrosis factor-alpha (TNF-α) SMD = (-0.51, 95%CI (-0.93, -0.09); p = 0.02), high sensitivity C-reactive protein (hs-CRP) SMD = (-1.06, 95%CI (-1.67, -0.45); p < 0.05) in vitamin D compared to placebo. Additionally, interleukin-6 (IL-6) exhibited a marginal effect SMD = (-0.52, 95%CI (-1.05, 0.01), p = 0.05). Furthermore, a significant reduction in the level of triglycerides SMD = (-0.65, 95%CI (-1.11, -0.18), p < 0.05) was observed, concomitant to a significantly increased high-density lipoprotein (HDL) level SMD = (0.53, 95%CI (0.08, 0.98), p = 0.02). However, no statistically significant changes were observed in total cholesterols SMD = (-0.16, 95%CI (-0.57, 0.24), p = 0.43) and low-density lipoprotein (LDL) SMD = (-0.06, 95%CI (-0.37, 0.24), p = 0.67). CONCLUSIONS: These findings suggest that vitamin D supplementation may be beneficial in ameliorating inflammation and dyslipidemia in T2D patients.

Uncontrolled Hypertension, Treatment, and Predictors among Hypertensive Out-Patients Attending Primary Health Facilities in Johannesburg, South Africa.

Hypertension is a poorly controlled risk factor for cardiovascular disease in South Africa, particularly among patients receiving care in the public sector who are mostly from low socioeconomic backgrounds. This cross-sectional study investigated uncontrolled hypertension, treatment, and predictors among hypertensive out-patients attending primary health care facilities in Johannesburg, South Africa. The WHO STEPwise approach to the surveillance of non-communicable diseases was used to collect data, including sociodemographic and lifestyle factors, health status, and measurements for anthropometry and blood pressure along with self-reported adherence to treatment, estimated through the general medication adherence scale. Uncontrolled hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg in diagnosed patients receiving anti-hypertensive treatment. Overweight and obesity were defined as a body mass index ≥25 and ≥30 kg/m2, respectively. Logistic regression models were used to assess the predictors of uncontrolled hypertension. Four hundred (n = 400) hypertensive out-patients (mean age: 50 ± 8 years) participated in this study, with most living in poor sociodemographic environments. The prevalence rate of uncontrolled hypertension was 57%. Obesity (62% vs. 42%, p ≤ 0.0001), salt consumption (90% vs. 55%, p ≤ 0.0001), alcohol intake (42% vs. 19%, p ≤ 0.0001), a smoking habit (23% vs. 4%, p ≤ 0.0001), alternative medicine use (51% vs. 40%, p = 0.043), and comorbidities (64% vs. 36%, p ≤ 0.0001) were higher in the uncontrolled group than the controlled group, whereas the prevalence of physical activity (38% vs. 15%, p ≤ 0.0001) was high in the controlled group vs. the uncontrolled. Overall, 85% of the patients moderately adhered to treatment, only 2% exhibited high adherence, and 13% demonstrated low adherence; over half of the patients received tri-therapy treatment. The predictors of uncontrolled hypertension are a number of prescribed antihypertensive therapies [adjusted odds ration = 2.39; 95% confidence interval: 1.48-3.87], treatment adherence [0.46; 0.21-0.97], salt consumption [28.35; 7.87-102.04], physical activity [0.22; 0.13-0.37], current alcohol use [2.10; 1.22-3.61], and current cigarette smoking [4.79; 1.88-12.18]. The high prevalence of uncontrolled hypertension in this study suggests a need to optimize prescriptions, adherence to BP-lowering medications, and lifestyle modifications. The management of comorbidities such as diabetes could offer considerable benefits in controlling blood pressure.

Multimorbidity, Treatment, and Determinants among Chronic Patients Attending Primary Health Facilities in Tshwane, South Africa.

The growing burden of non-communicable diseases amidst the largest burden of HIV in South Africa leads to disease combinations of multimorbidity with the complexity of care. We conducted a cross-sectional study to assess multimorbidity, medication adherence, and associated factors among out-patients with chronic diseases in primary health care (PHC) facilities in Tshwane, South Africa. A structured questionnaire was used to collect data on comorbidities and medication adherence, along with socio-demographic and lifestyle factors. Logistic regression models were used to analyse the determinants of multimorbidity and medication adherence. In all 400 patients with chronic diseases (mean age: 47 ± 12 years) living in poor environments, common chronic conditions were hypertension (62%), diabetes (45%), HIV (44%), TB (33%), hypercholesterolemia (18%), and gout (13%). The proportion of concordant comorbidity (i.e., diseases with similar risk profiles and management) was 72%, more than 28% of discordant comorbidity (i.e., diseases not related in pathogenesis or management). Most patients had two coexisting chronic conditions (75%), while few had more than two chronic conditions (23%) and single-occurring conditions (2%). Prevalence rates for common multimorbidity patterns were 25% (HIV and TB), 17% (hypertension and diabetes), 9% (hypertension, diabetes, and hypercholesterolemia), and 2% (hypertension diabetes and HIV), while medication adherence was estimated at 74%. In multivariate analysis, multimorbidity was associated with an older age and lower socio-economic status, while medication non-adherence was associated with a younger age and socio-economic factors. The study highlights the presence of multimorbidity among primary care patients attributed to hypertension, diabetes, HIV, and TB in South Africa with non-adherence to medication in one-third of patients. Policies are needed for education on multimorbidity with a need to optimize lifestyle modifications, perhaps proactive outreach or nursing contact with high-risk patients with public-health-sensitive conditions, such as HIV and/or TB, as well as patients with a history of non-adherence to medications. Considerations should be given to the development of a medication adherence scale for multiple chronic conditions beyond assessing adherence to a single index medication.

Comprehensive Overview of the Effects of Amaranthus and Abelmoschus esculentus on Markers of Oxidative Stress in Diabetes Mellitus.

The use of medicinal plants in the management of diabetes mellitus (DM) is extensively reported. However, there is still very limited information on the role of these plants as markers of oxidative stress in DM. This current review evaluated the effect of Amaranthus spinosus, Amaranthus hybridus, and Abelmoschus esculentus on markers of oxidative stress in rodent models of DM. Current findings indicate that these plants have the potential to reduce prominent markers of oxidative stress, such as serum malondialdehyde and thiobarbituric acid-reactive substances, while increasing enzymes that act as antioxidants, such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase. This may reduce reactive oxygen species and further ameliorate oxidative stress in DM. Although the potential benefits of these plants are acknowledged in rodent models, there is still a lack of evidence showing their efficacy against oxidative stress in diabetic patients. Therefore, we recommend future clinical studies in DM populations, particularly in Africa, to evaluate the potential effects of these plants. Such studies would contribute to enhancing our understanding of the significance of incorporating these plants into dietary practices for the prevention and management of DM.

The Impact of Punica granatum Linn and Its Derivatives on Oxidative Stress, Inflammation, and Endothelial Function in Diabetes Mellitus: Evidence from Preclinical and Clinical Studies.

Diabetes mellitus is recognized as the leading contributor to cardiovascular disease and associated mortality rates worldwide. Despite the use of pharmaceutical drugs to treat diabetes, its prevalence continues to rise alarmingly. Therefore, exploring remedies with a lower toxicity profile is crucial while remaining safe and effective in addressing this global public health crisis. Punica granatum Linn (pomegranate), known for its properties and safety profile, has been investigated in applied research and preclinical and clinical trials. However, conflicting reports still exist regarding its effects in diabetes. According to our knowledge, no systematic review has been conducted to critically analyze evidence from preclinical and clinical trials simultaneously, explicitly focusing on oxidative stress, inflammation, and endothelial function in diabetes. Therefore, in this systematic review, we searched for evidence on the impact of pomegranate in diabetes using databases such as PubMed, Scopus, and Google Scholar. Our inclusion criteria were limited to studies published in English. Of the 170 retrieved studies, 46 were deemed relevant and underwent critical analysis. The analyzed evidence suggests that pomegranate has the potential to alleviate oxidative stress, inflammation, and endothelial dysfunction in diabetes. Although a beneficial impact was noted in these markers, the endothelial function evidence still requires validation through further clinical trials with a powered sample size.

A Systematic Review on Cardiometabolic Risks and Perinatal Outcomes among Pregnant Women Living with HIV in the Era of Antiretroviral Therapy.

Antiretroviral therapy (ART) regimens have been shown to cause metabolic changes in people living with HIV (PLWH), predisposing them to cardiometabolic disease (CVMD). However, such evidence is less established in pregnant women living with HIV (pWLWH) on ART. Pregnancy-induced cardiometabolic risks (CMR) can predispose to unfavourable pregnancy outcomes and further persist in the postpartum period, resolve, and recur in subsequent pregnancies, or emerge as newly diagnosed chronic diseases of ageing. Therefore, this systematic review aimed at synthesizing evidence on CMR and perinatal outcomes among pWLWH in the era of ART. We considered prospective and retrospective cohorts, case-control, cross-sectional, and interventional studies published in English. Specific keywords were used to conduct a thorough literature search on PubMed-Medline and Scopus following the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. Two investigators independently screened the search outputs and reviewed full texts of potentially eligible articles. Data extraction was conducted by one investigator and verified by the second investigator. Thirty-one relevant studies conducted on 20,904 pWLWH on ART across Africa, Asia, Europe, and America were included. Studies demonstrate inconclusive findings, especially on perinatal outcomes, but significant risks of gestational hypertension and dyslipidemia were reported in pWLWH on ART compared to the control group. Therefore, future studies should focus more on these perinatal outcomes, and their impact on postpartum maternal health and growth trajectories of uninfected infants born from pWLWH who are either on ART or ART-naïve in comparison to infants born of HIV-negative mothers over the life course, especially in HIV-burdened African countries.

A Systematic Review and Meta-Analysis on the Impact of Statin Treatment in HIV Patients on Antiretroviral Therapy.

The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin-placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (-0.59, 95% confidence intervals (CI): (-1.38, 0.19), p = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (-0.01, 95%CI: (-0.25, 0.23), p = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), p = 0.65). Additionally, we found a significant increase in CD8+CD38+HLA-DR+ T-cells (SMD (1.10, 95% CI: (0.93, 1.28), p < 0.00001) and CD4+CD38+HLA-DR+ T-cells (SMD (0.92, 95% CI: (0.32, 1.52), p = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (-2.87, 95% CI: (-4.08, -1.65), p < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins' effect on CD4 count and viral load, especially in virally suppressed patients.

Immunological Imbalances Associated with Epileptic Seizures in Type 2 Diabetes Mellitus.

PURPOSE OF THE REVIEW: Type 2 diabetes mellitus (T2DM) is a global health burden that leads to an increased morbidity and mortality rate arising from microvascular and macrovascular complications. Epilepsy leads to complications that cause psychological and physical distress to patients and carers. Although these conditions are characterized by inflammation, there seems to be a lack of studies that have evaluated inflammatory markers in the presence of both conditions (T2DM and epilepsy), especially in low-middle-income countries where T2DM is epidemic. Summary findings: In this review, we describe the role of immunity in the seizure generation of T2DM. Current evidence shows an increase in the levels of biomarkers such as interleukin (IL-1ß, IL-6, and IL-8), tumour necrosis factor-α (TNF-α), high mobility group box-1 (HMGB1), and toll-like receptors (TLRs) in epileptic seizures and T2DM. However, there is limited evidence to show a correlation between inflammatory markers in the central and peripheral levels of epilepsy. CONCLUSIONS: Understanding the pathophysiological mechanism behind epileptic seizures in T2DM through an investigation of immunological imbalances might improve diagnosis and further counter the risks of developing complications. This might also assist in delivering safe and effective therapies to T2DM patients affected, thus reducing morbidity and mortality by preventing or reducing associated complications. Moreover, this review also provides an overview approach on inflammatory cytokines that can be targeted when developing alternative therapies, in case these conditions coexist.

Self-Management of Diabetes and Associated Factors among Patients Seeking Chronic Care in Tshwane, South Africa: A Facility-Based Study.

The burden of diabetes continues to increase in South Africa and a significant number of diabetes patients present at public primary healthcare facilities with uncontrolled glucose. We conducted a facility-based cross-sectional study to determine the diabetes self-management practices and associated factors among out-patients in Tshwane, South Africa. An adapted validated questionnaire was used to collect data on sociodemography, diabetes knowledge, and summaries of diabetes self-management activities measured in the previous seven days, and over the last eight weeks. Data were analysed using STATA 17. A final sample of 402 diabetes out-patients was obtained (mean age: 43 ± 12 years) and over half of them were living in poor households. The mean total diabetes self-management of score was 41.5 ± 8.2, with a range of 21 to 71. Almost two thirds of patients had average self-management of diabetes, and 55% had average diabetes knowledge. Twenty-two percent of patients had uncontrolled glucose, hypertension (24%) was the common comorbidity, and diabetic neuropathy (22%) was the most common complication. Sex [male: AOR = 0.55, 95% CI: 0.34-0.90], race [Coloured: AOR = 2.84, 95% CI: 1.69-4.77 and White: AOR = 3.84, 95% CI: 1.46-10.1], marital status [divorced: AOR = 3.41, 95% CI: 1.13-10.29], social support [average: AOR = 2.51, 95% CI: 1.05-6.00 and good: AOR = 4.49, 95% CI: 1.61-7.57], body mass index [obesity: AOR = 0.31, 95% CI: 0.10-0.95], diabetes knowledge [average: AOR = 0.58, 95% CI: 0.33-0.10 and good: AOR = 1.86, 95% CI: 0.71-4.91], and uncontrolled glucose [AOR = 2.97, 95% CI: 1.47-5.98] were factors independently predictive of diabetes self-management. This study emphasizes that the self-management of diabetes was mostly on average among patients and was associated with the aforementioned factors. Innovative approaches are perhaps needed to make diabetes education more effective. Face-to-face sessions delivered generally during clinic visits should be better tailored to the individual circumstances of diabetes patients. Considerations should be given to the options of leveraging information technology to ensure the continuity of diabetes education beyond clinic visits. Additional effort is also needed to meet the self-care needs of all patients.

Okra ameliorates hyperglycaemia in pre-diabetic and type 2 diabetic patients: A systematic review and meta-analysis of the clinical evidence.

Background: Despite the use of available pharmaceutical drugs, high rates of metabolic diseases and cardiovascular disorders are alarming. This calls for alternative therapies that can attenuate these complications. Therefore, we investigated the beneficial effects of okra on glycaemic control in pre-diabetes and type 2 diabetes mellitus (T2D). Methods: MEDLINE and Scopus were searched for relevant studies. Collected data were analysed using RevMan and reported as mean difference and 95% confidence intervals (CI). Eight studies, including 331 patients with pre-diabetes or T2D, were eligible. Results: Our findings showed that okra treatment reduced the levels of fasting blood glucose: mean difference (MD) = -14.63 mg/dL; 95% CI (-25.25, -4.00, p = 0.007); I 2 = 33%, p = 0.17 compared to placebo. Glycated haemoglobin, however, did not differ significantly between the groups: MD = 0.01%; 95%CI (-0.51, 0.54, p = 0.96); I 2 = 23%, p = 0.28. Conclusion: this systematic review and meta-analysis found that okra treatment improves glycaemic control in patients with pre-diabetes or T2D. The findings suggest that okra may be used as a supplemental dietary nutrient, especially in pre-diabetic and T2D patients due to its potential to regulate hyperglycaemia.

Corchorus olitorius extract exhibit anti-hyperglycemic and anti-inflammatory properties in rodent models of obesity and diabetes mellitus.

Obesity and type 2 diabetes (T2D) are chronic conditions with detrimental impacts on the overall health of individuals. Presently, the use of pharmacological agents in obesity and T2D offers limited benefits and pose side effects. This warrant studies on remedies that are less toxic and inexpensive while effective in ameliorating secondary complications in obesity and T2D. Plant-based remedies have been explored increasingly due to their remarkable properties and safety profile. We searched for pre-clinical evidence published from inception until 2023 on PubMed, Scopus, Google, and Semantic scholar on Corchorus olitorius (C. olitorius) in both obesity and T2D. Our focus was to understand the beneficial impact of this plant-based remedy on basic glycemic, lipid, inflammatory, and biomarkers of oxidative stress. The evidence gathered in this review suggests that C. olitorius treatment may significantly reduce blood glucose, body weight, total cholesterol, triglycerides, and low-density lipoprotein (LDL) in concomitant with increasing high-density lipoprotein-cholesterol (HDL-c) in rodent models of obesity and T2D. Interestingly, this effect was consistent with the reduction of malonaldehyde, superoxide dismutase and catalases, tumor necrosis factor-alpha, interleukins, and leptin. Some of the mechanisms by which C. olitorius reduces blood glucose levels is through stimulation of insulin secretion, increasing ß-cell proliferation, thus promoting insulin sensitivity; the process which is mediated by ascorbic acid present in this plant. C. olitorius anti-hyperlipidemia is attributable to the content of ferulic acid found in this plant, which inhibits 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors and thus results in reduced synthesis of cholesterol and increased hepatic LDL-c receptor expression, respectively. The present review provides extensive knowledge and further highlights the potential benefits of C. olitorius on basic metabolic parameters, lipid profile, inflammation, and oxidative stress in rodent models of obesity and T2D.

The Effect of Vitamin D on Inflammation and Dyslipidemia in Type 2 Diabetes Mellitus: Protocol for a Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Type 2 diabetes mellitus is a chronic disease that contributes to an increasing global burden on the health system. It has a high chance of leading to macrovascular complications and cardiovascular disease. As an inflammatory condition, it would be essential to target inflammatory pathways when developing therapeutic drugs for type 2 diabetes mellitus. OBJECTIVE: We aimed to evaluate the effect of vitamin D on markers of inflammation and lipid profile among adult patients with diabetes. METHODS: A systematic review will seek studies published on Embase, Google Scholar, PubMed, Web of Science, and Science Direct. This planned systematic review and meta-analysis will be limited to randomized controlled trials; moreover, the search will include published studies regarding the effects of vitamin D on pro-inflammatory cytokines and lipid profiles. The review will include studies published from inception until December 30, 2022. The study identification and selection will be based on the eligibility criteria by 2 independent reviewers. Additionally, a meta-analysis will only be performed if more than 2 studies are available and explore the same outcomes, and this will be analyzed using RevMan (version 5.4.1). The quality and risk of bias will be assessed following the Cochrane risk of bias tool and Jadad checklist. RESULTS: The process for searching literature review has already started, and this is conducted independently by 2 reviewers using a predefined eligibility and "participants, intervention, comparator, and outcome" criteria. This systematic review and meta-analysis will not require any direct involvement of patients and the public; thus, no ethical approval was required. CONCLUSIONS: The findings obtained from the proposed study will be presented in scientific seminars, journal clubs, and conferences and published in peer-reviewed journals. TRIAL REGISTRATION: International Platform of Registered Systematic Review and Meta-analysis Protocols INPLASY202260022; https://inplasy.com/?s=INPLASY202260022. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/42193.

Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials.

Background: Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)-related outcomes in patients with diabetes or metabolic syndrome. Methods: To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Results: Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or increased blood flow in these subjects. Predominantly effective doses were 1,000 mg/daily for 4 weeks up to 12 months. The included RCTs presented with the high quality of evidence. Conclusion: Clinical evidence on the beneficial effects of vitamin C intake or its impact on improving prominent markers of inflammation and oxidative stress in patients with diabetes is still limited. Thus, more RCTs are required to solidify these findings, which is essential to better manage diabetic patients at increased risk of developing CVD.

Exploring the effectiveness of vitamin B12 complex and alpha-lipoic acid as a treatment for diabetes mellitus/neuropathy: a protocol for systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Diabetic neuropathy (DN) is common in patients diagnosed with diabetes mellitus. This often causes peripheral nerve damage. For many years vitamin B12 and alpha-lipoic acid (ALA) have been regarded as components that can be used in reducing markers of inflammation and oxidative stress. In this study, we will explore the effectiveness of vitamin B12 and ALA as a possible treatment for diabetic mellitus/neuropathy, emphasising markers of inflammation, lipid profile, and glucose metabolism. METHODS AND ANALYSIS: We will conduct a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P). The search strategies and information sources for the literature will be PubMed, Google Scholar, Web of Science and Science direct. The literature search will include studies published from inception until 30 June 2022. All included studies will be evaluated for quality and risk of bias according to the Cochrane guidelines. To investigate the stability of the results, we will conduct a sensitivity analysis of the outcomes. All data analysis will be performed using Review Manager V.5. 4. ETHICAL AND DISSEMINATION: This systematic review and meta-analysis will not require ethical approval from an institution committee as it does not have direct participants. We will obtain all our data from previous studies. The findings will be disseminated through publications in peer-reviewed journals and presented at local and international seminars and conferences.

Activated monocytes as a therapeutic target to attenuate vascular inflammation and lower cardiovascular disease-risk in patients with type 2 diabetes: A systematic review of preclinical and clinical studies.

Low grade inflammation is associated with the progression of atherosclerosis. Patients with type 2 diabetes (T2D) have altered cholesterol levels, which are targeted by free radicals to promote lipid peroxidation. Elevated levels of monocyte-associated cytokines such as interleukin (IL)-6, monocyte chemoattractant protein 1 (MCP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and tumor necrosis factor-alpha (TNF-α), subsequently drive endothelial tissue injury. In fact, the levels of circulating platelet-monocyte aggregates in patients with T2D is a robust marker for atherosclerosis and a cardiovascular disease (CVD)-risk factor. To identify eligible studies, we searched the major online databases using PubMed and Google Scholar. The cumulative evidence synthesized in the current review suggests that, traditional therapies which include thiazolidinediones, statins and some calcium channel blockers can be useful in the primary prevention of atherosclerosis by inhibiting the formation of monocyte-derived microparticles, and pro-inflammatory cytokines such as IL-6, TNF-α, MCP-1, and NF-κB in patients with T2D. Future studies are needed to ascertain whether the combination of dietary interventions and glucose or lipid lowering agents can provide an enhanced cardioprotection in patients with T2D.

Pharmacological effects of statins in adult patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis.

BACKGROUND: Due to contradicting findings on impact of statins on endothelial function in type 2 diabetes mellitus especially across the randomized controlled trials (RCTs). With this systematic review, we aim to evaluate whether the use of statins improves endothelial function in adults with type 2 diabetes. We will further highlight if these biomarkers are ideal therapeutic targets for risk for atherosclerosis and cardiovascular disease. METHODS: This protocol was carried out according to the preferred reporting items for systematic review and meta-analysis protocols-2015 guideline. The online databases, such as MEDLINE, Scopus, and Web of Sciences, will be targeted using the medical subject heading terms (MeSH) and text words. The review will include clinical studies on the effect of statins on markers of endothelial function in type 2 diabetes. The Cochrane risk of bias guideline will be used to assess the quality and risk of bias. We are planning to use the grading of recommendation assessment, development, and evaluation approach to evaluate the strength and quality of evidence. RESULTS: This study will not involve human samples and patient data; hence ethics approval will not be required. The findings will be presented in journal clubs and conferences and published in peer-reviewed journals.