The Role of Glucose and Fatty Acid Metabolism in the Development of Insulin Resistance in Skeletal Muscle

The rapid rise in the prevalence of obesity and diabetes has significantly contributed to the increasing global burden of noncommunicable diseases. Insulin resistance is a major underpinning etiology of both obesity and type 2 diabetes. Insulin resistance is characterized by a reduced response of skeletal, liver, and fat tissues to the actions of insulin hormone. Although detailed mechanisms implicated in the development of insulin resistance remain plausible, skeletal muscles have been identified to play an integral role in the improvement of insulin sensitivity in the diseased state. The effective modulation of glucose and fatty acid metabolism in the skeletal muscle through exercise or by certain therapeutics has been associated with reversal of insulin resistance and amelioration of diabetes associated complications such as inflammation and oxidative stress. This chapter will briefly discuss the role of glucose and fatty acid metabolism in the development of insulin resistance in the skeletal muscle

Skeletal Muscle as a Therapeutic Target for Natural Products to Reverse Metabolic Syndrome

Natural compounds, especially polyphenols have become a popular area of research mainly due to their apparent health benefits. Increasing the phenolic content of a diet, apart from its antioxidant benefit, has a beneficial effect on signaling molecules involved in carbohydrate and lipid metabolism. These effects could potentially protect against metabolic syndrome, a cluster of metabolic complications such as obesity, insulin resistance and type 2 diabetes that is characterized by a dysregulated carbohydrate, and lipid metabolism. Research continues to investigate various natural compounds for their amelioration of impaired signaling mechanisms that may lead to dysregulated metabolism to find means to improve the life expectancy of patients with metabolic syndrome. In this chapter, a systematic search through major databases such as MEDLINE/PubMed, EMBASE, and Google Scholar of literature reporting on the ameliorative potential of commonly investigated natural products that target skeletal muscle to ameliorate metabolic syndrome associated complications was conducted. The selected natural products that are discussed include apigenin, aspalathin, berberine, curcumin, epigallocatechin gallate, hesperidin, luteolin, naringenin, quercetin, resveratrol, rutin, and sulforaphane

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Abstract: Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential

Barriers and facilitators to combined ART initiation in pregnant women with HIV: lessons learnt from a PMTCT B+ pilot program in Swaziland

In January 2013, Swaziland launched a PMTCT B+ implementation study in rural Shiselweni. We aimed to identify patient and health service determinants of combined antiretroviral therapy (ART) initiation, to help guide national implementation of PMTCT B+

Effectiveness of a combination strategy for linkage and retention in adult HIV care in Swaziland: The Link4Health cluster randomized trial

Background: Gaps in the HIV care continuum contribute to poor health outcomes and increase HIV transmission. A combination of interventions targeting multiple steps in the continuum is needed to achieve the full beneficial impact of HIV treatment. Methods and findings: Link4Health, a cluster-randomized controlled trial, evaluated the effectiveness of a combination intervention strategy (CIS) versus the standard of care (SOC) on the primary outcome of linkage to care within 1 month plus retention in care at 12 months after HIV-positive testing. Ten clusters of HIV clinics in Swaziland were randomized 1:1 to CIS versus SOC. The CIS included point-of-care CD4+ testing at the time of an HIV-positive test, accelerated antiretroviral therapy (ART) initiation for treatment-eligible participants, mobile phone appointment reminders, health educational packages, and noncash financial incentives. Secondary outcomes included each component of the primary outcome, mean time to linkage, assessment for ART eligibility, ART initiation and time to ART initiation, viral suppression defined as HIV-1 RNA < 1,000 copies/mL at 12 months after HIV testing among patients on ART ≥6 months, and loss to follow-up and death at 12 months after HIV testing. A total of 2,197 adults aged ≥18 years, newly tested HIV positive, were enrolled from 19 August 2013 to 21 November 2014 (1,096 CIS arm; 1,101 SOC arm) and followed for 12 months. The median participant age was 31 years (IQR 26–39), and 59% were women. In an intention-to-treat analysis, 64% (705/1,096) of participants at the CIS sites achieved the primary outcome versus 43% (477/1,101) at the SOC sites (adjusted relative risk [RR] 1.52, 95% CI 1.19–1.96, p = 0.002). Participants in the CIS arm versus the SOC arm had the following secondary outcomes: linkage to care regardless of retention at 12 months (RR 1.08, 95% CI 0.97–1.21, p = 0.13), mean time to linkage (2.5 days versus 7.5 days, p = 0.189), retention in care at 12 months regardless of time to linkage (RR 1.48, 95% CI 1.18–1.86, p = 0.002), assessment for ART eligibility (RR 1.20, 95% CI 1.07–1.34, p = 0.004), ART initiation (RR 1.16, 95% CI 0.96–1.40, p = 0.12), mean time to ART initiation from time of HIV testing (7 days versus 14 days, p < 0.001), viral suppression among those on ART for ≥6 months (RR 0.97, 95% CI 0.88–1.07, p = 0.55), loss to follow-up at 12 months after HIV testing (RR 0.56, 95% CI 0.40–0.79, p = 0.002), and death (N = 78) within 12 months of HIV testing (RR 0.80, 95% CI 0.46–1.35, p = 0.41). Limitations of this study include a small number of clusters and the inability to evaluate the incremental effectiveness of individual components of the combination strategy. Conclusions: A combination strategy inclusive of 5 evidence-based interventions aimed at multiple steps in the HIV care continuum was associated with significant increase in linkage to care plus 12-month retention. This strategy offers promise of enhanced outcomes for HIV-positive patients

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

Results of the Sukuma Ndoda (“Stand up, Man”) HIV Self-Screening and Assisted Linkage to Care Project in Johannesburg: A Quasi-Experimental Pre–Post Evaluation

BackgroundHIV testing rates among South African men lag behind rates for women and national targets. Community-based HIV self-screening (HIVSS) distribution and follow-up by community health workers (CHWs) is a scalable option to increase testing coverage, diagnosis, and treatment initiation. We provided HIVSS and assisted linkage to care to men not recently tested (within the past 12 months) residing in high-HIV-burden areas of Johannesburg.MethodsCHWs distributed HIVSS in 6 clinic catchment areas. Follow-up to encourage confirmatory testing and antiretroviral therapy initiation was conducted through personal support (PS) or an automated short message service (SMS) follow-up and linkage system in 3 clinic areas each. Using a quasi-experimental pre-post design, we compared differences in the proportion of men testing in the clinic catchment areas during the HIVSS campaign (June-August 2019) to the 3 months prior (March-May 2019) and compared treatment initiations by assisted linkage strategy.ResultsAmong 4793 participants accepting HIVSS, 62% had never tested. Among 3993 participants with follow-up data, 90.6% reported using their HIVSS kit. Testing coverage among men increased by 156%, from under 4% when only clinic-based HIV testing services were available to 9.5% when HIVSS and HIV testing services were available (z = -11.6; P &lt; 0.01). Reported test use was higher for men followed through PS (99% vs. 68% in SMS); however, significantly more men reported reactive self-test results in the SMS group compared with PS (6.4% vs. 2.0%), resulting in more antiretroviral therapy initiations in the SMS group compared with PS (23 vs. 9; P &lt; 0.01).ConclusionsCHW HIVSS distribution significantly increases testing among men. While PS enabled personalized follow-up, reporting differences indicate SMS is more acceptable and better aligned with expectations of privacy associated with HIVSS

Impacts of COVID-19 on Diverse Farm Systems in Tanzania and South Africa

Emerging information on the interactions between the COVID-19 pandemic and global food systems have highlighted how the pandemic is accentuating food crises across Africa. Less clear, however, are how the impacts differ between farming systems. Drawing on 50 key informant interviews with farmers, village leaders and extension officers in South Africa and Tanzania, we identify the effects of COVID-19 and associated measures to curb the spread of the disease on farming production systems, the coping mechanisms adopted by farmers, and explore their longer-term plans for adaptation. We focus on a diverse range of production systems, from small-scale mixed farming systems in Tanzania to large-scale corporate farms in South Africa. Our findings highlight how COVID-19 restrictions have interrupted the supply chains of agricultural inputs and commodities, increasing the storage time for produce, decreasing income and purchasing power, and reducing labour availability. Farmers’ responses were heterogeneous, with highly diverse small-scale farming systems and those less engaged with international markets least affected by the associated COVID-19 measures. Large-scale farmers were most able to access capital to buffer short-term impacts, whereas smaller-scale farms shared labour, diversified to subsistence produce and sold assets. However, compounded shocks, such as recent extreme climate events, limited the available coping options, particularly for smaller-scale and emerging farmers. The study highlights the need to understand the characteristics of farm systems to better equip and support farmers, particularly in contexts of uncertainty. We propose that policy actions should focus on (i) providing temporary relief and social support and protection to financially vulnerable stakeholders, (ii) job assurance for farmworkers and engaging an alternative workforce in farming, (iii) investing in farming infrastructure, such as storage facilities, digital communication tools and extension services, and (iv) supporting diversified agroecological farming systems

Mortality under early access to antiretroviral therapy vs Eswatini’s national standard of care : the MaxART clustered randomized stepped‐wedge trial

Objectives Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others. MaxART is the first implementation trial of this strategy embedded within a government-managed health system, and assesses mortality as a secondary outcome. Because primary findings strongly supported scale-up of the 'treat all' strategy (hereafter Treat All), this analysis examines mortality as an additional indicator of its impact. Methods MaxART was conducted in 14 Eswatinian health clinics through a clinic-based stepped-wedge design, by transitioning clinics from then-national standard of care (SoC) to the Treat All intervention. All-cause, disease-related, and HIV-related mortality were analysed using the Cox proportional hazards model, censoring SoC participants at clinic transition. Median follow-up time among study participants was 292 days. There were 36/2034 deaths in SoC (1.77%) and 49/1371 deaths in Treat All (3.57%). Results Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and Treat All interventions, respectively, the multivariable-adjusted 12-month all-cause mortality rates were 1.42% [95% confidence interval (CI): 0.66-2.17] and 1.60% (95% CI: 0.78-2.40), disease-related mortality rates were 1.02% (95% CI: 0.40-1.64) and 1.10% (95% CI: 0.46-1.73), and HIV-related mortality rates were 1.03% (95% CI: 0.40-1.65) and 0.99% (95% CI: 0.40-1.58). Treat All had no impact on all-cause [hazard ratio (HR) = 1.12, 95% CI: 0.58-2.18, P = 0.73], disease-related (HR = 1.04, 95% CI: 0.52-2.11, P = 0.90), or HIV-related mortality (HR = 0.93, 95% CI: 0.46-1.87, P = 0.83). Conclusion There was no immediate benefit of the Treat All strategy on mortality, nor evidence of harm. Longer follow-up of participants is needed to establish long-term consequences