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.

Metformin and heart failure-related outcomes in patients with or without diabetes: a systematic review of randomized controlled trials.

Metformin is considered a safe anti-hyperglycemic drug for patients with type 2 diabetes (T2D); however, information on its impact on heart failure-related outcomes remains inconclusive. The current systematic review explored evidence from randomized clinical trials (RCTs) reporting on the impact of metformin in modulating heart failure-related markers in patients with or without T2D. Electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible studies. Included studies were those assessing the use of metformin as an intervention, and also containing the comparison group on placebo, and all articles had to report on measurable heart failure-related indices in individuals with or without T2D. The modified Downs and Black checklist was used to evaluate the risk of bias. Overall, nine studies met the inclusion criteria, enrolling a total of 2486 patients. Although summarized evidence showed that metformin did not affect left ventricular function, this antidiabetic drug could improve myocardial oxygen consumption concomitant to reducing prominent markers of heart failure such as n-terminal pro-brain natriuretic peptide and low-density lipoprotein levels, inconsistently between diabetic and nondiabetic patients. Effective modulation of some heart failure-related outcomes with metformin treatment was related to its beneficial effects in ameliorating insulin resistance and blocking pro-inflammatory markers such as the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11). Overall, although such beneficial effects were observed with metformin treatment, additional RCTs are necessary to improve our understanding on its modulatory effects on heart failure-related outcomes especially in diabetic patients.

Adipokines as a therapeutic target by metformin to improve metabolic function: A systematic review of randomized controlled trials.

Metformin is a widely used glucose-lowering drug, although its impact on adipose tissue function remains elusive. Adipose tissue-derived molecules regulate diverse physiological mechanisms, including energy metabolism, insulin sensitization, and inflammatory response. Alternatively, it has remained relevant to understand the therapeutic regulation of adipokines in efforts to alleviate inflammation in conditions associated with the metabolic syndrome. The current qualitative analysis of available literature focused on randomized clinical trials (RCTs) assessing the association between administration of metformin and adipokine regulation in individuals with metabolic syndrome. The major electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible RCTs. Overall, 13 RCTs met the inclusion criteria, with a total of 4605 participants. Patients with metabolic syndrome were characterized by a state of obesity, impaired glucose tolerance, insulin resistance, and type 2 diabetes. Cumulative evidence from these RCTs supported the blood glucose lowering effects of metformin, in addition to promoting weight loss, ameliorating insulin resistance, and reducing pro-inflammatory markers such as interleukin-6 and tumor necrosis factor-α in patients with metabolic syndrome. Importantly, these therapeutic effects are associated with the upregulation of adiponectin and suppression of leptin and resistin.

Natural killer cell levels in adults living with type 2 diabetes: a systematic review and meta-analysis of clinical studies.

BACKGROUND: Chronic immune activation and hyperglycaemia are a hallmark of type 2 diabetes mellitus (T2D) while natural killer (NK) cells are involved in the pathogenesis of T2D. Dysregulated NK cell responses are associated with an increased risk of cardiovascular disease in patients living with T2D. OBJECTIVE: To provide a comprehensive and systematic evidence-based estimate on the levels of NK cells in patients living with T2D. RESULTS: This systematic review and meta-analysis included 13 studies reporting on 491 adult patients with T2D and 1064 nondiabetic controls. The pooled effect estimates showed increased levels of NK cells in adult patients with T2D compared to controls (MD: 0.03 [- 3.20, 3.26], I2 = 97%, p < 0.00001). CONCLUSION: Overall, the evidence presented in this systematic review shows that the changes in NK cells in patients living with T2D are still unclear and further studies are needed.

Platelet activation in adult HIV-infected patients on antiretroviral therapy: a systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment. METHODS: Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model. RESULTS: We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfected controls (Hedges' g 2.00 [95%CI 1.05, 2.94]; z = 4.12, p < 0.0001). These remained elevated despite successful ART (Hedges' g 2.05 [95%CI 0.58, 3.52]; z = 2.71, p = 0.0067). CONCLUSION: The levels of platelet activation are elevated in treatment-naïve HIV-infected patients, and these persist during successful ART. Further studies should assess the clinical relevance of monitoring the levels of platelet activation in HIV-infected patients on ART.

Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Evidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: -0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: -0.31 [95% CI: -0.54, -0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.

A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy.

Evidence on the beneficial effects of resveratrol supplementation on cardiovascular disease-related profiles in patients with type 2 diabetes (T2D) is conflicting, while its impact on renal function and blood pressure measurements remains to be established in these patients. The current meta-analysis included randomized controlled trials (RCTs) reporting on the impact of resveratrol supplementation on markers of renal function and blood pressure in patients with T2D on hypoglycemic medication. Electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible studies from inception up to June 2020. The random and fixed effects model was used in the meta-analysis. A total of five RCTs met the inclusion criteria and involved 388 participants with T2D. Notably, most of the participants were on metformin therapy, or metformin in combination with other hypoglycemic drugs such as insulin and glibenclamide. Pooled estimates showed that resveratrol supplementation in patients with T2D lowered the levels of fasting glucose (SMD: -0.06 [95% CI: -0.24, 0.12]; I2 = 4%, p = 0.39) and insulin (SMD: -0.08 [95% CI: -0.50, 0.34], I2 = 73%, p = 0.002) when compared to those on placebo. In addition, supplementation significantly lowered systolic blood pressure (SMD: -5.77 [95% CI: -8.61, -2.93], I2 = 66%, p = 0.02) in these patients. Although resveratrol supplementation did not affect creatinine or urea levels, it reduced the total protein content (SMD: -0.19 [95% CI: -0.36, -0.02]; I2 = 91%, p = 0.001). In all, resveratrol supplementation in hypoglycemic therapy improves glucose control and lowers blood pressure; however, additional evidence is necessary to confirm its effect on renal function in patients with T2D.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.