Hypothesis: ‘Vasocrine’ signalling from perivascular fat - a mechanism linking insulin resistance and vascular disease

Adipose tissue expresses cytokines which inhibit insulin signalling pathways in liver and muscle. Obesity also results in impairment of endothelium-dependent vasodilatation to insulin. We propose a vasoregulatory role for local deposits of fat around the origin of arterioles supplying skeletal muscle. Isolated first order arterioles from rat cremaster muscle are under dual regulation by insulin, which activates both endothelin-1 mediated vasoconstriction and nitric oxide mediated vasodilatation. In obese rat arterioles, insulin-stimulated nitric oxide synthesis is impaired, resulting in unopposed vasoconstriction. We propose this to be the consequence of production of the adipocytokine tumour necrosis factor-α from the cuff of fat seen surrounding the origin of the arteriole in obese rats – a depot to which we ascribe a specialist vasoregulatory role. We suggest that this cytokine accesses the nutritive vascular tree to inhibit insulin-mediated capillary recruitment – a mechanism we term ‘vasocrine’ signalling. We also suggest a homology between this vasoactive periarteriolar fat and both periarterial and visceral fat, which may explain relationships between visceral fat, insulin resistance and vascular disease

Preventing cardiovascular events with empagliflozin: at what cost?

The EMPA-REG OUTCOME study,1 as the first randomised trial to show that a glucose-lowering intervention was associated with reduced cardiovascular events,2 raises important questions for policy makers. Chief among these questions is whether the detected effect size produces a cost-effective risk reduction from the studied pharmacological approach. The study has undoubtedly brought good news for the trial funders: analysts predict that its findings will propel empagliflozin ahead of other glucose-lowering drugs in sales

Innovation in Public Health: A Timely Methodological Opportunity to Reimagine and Operationalize Variables in Research

EditorialEditoria

Rethinking the appraisal and approval of drugs for type 2 diabetes

The process for approving new drugs for type 2 diabetes illustrates the significant shortcomings of the regulatory standards for licensing, reimbursing, and adopting new drugs. Regulatory reform is needed to improve the real-world therapeutic value of anti-diabetic drugs

Effects Of A Low Dose Of Fish Oil On Inflammatory Markers Of Brazilian Hiv-infected Adults On Antiretroviral Therapy: A Randomized, Parallel, Placebo-controlled Trial.

The benefits of antiretroviral therapy for HIV-infected subjects have been limited by an increased risk of metabolic and cardiovascular diseases. The objective of this study was to assess the effects of a low dose of marine omega-3 fatty acids on inflammatory marker concentrations in HIV-infected subjects under antiretroviral therapy (ART). This was a randomized, parallel, placebo-controlled trial that investigated the effects of 3 g fish oil/day (540 mg of eicosapentaenoic acid-EPA plus 360 mg of docosahexaenoic acid-DHA) or 3 g soy oil/day (placebo) for 24 weeks in 83 male and non-pregnant female HIV-infected adults on ART. There were no differences between groups for the measures at baseline. Multilevel analyses revealed no statistically significant relationship between the longitudinal changes in high sensitivity-C reactive protein (hs-CRP) (Wald Chi2 = 0.17, p = 0.918), fibrinogen (Wald Chi2 = 3.82, p = 0.148), and factor VIII (Wald Chi2 = 5.25, p = 0.073) with fish oil. No significant changes in interleukin-6 (IL6), interleukin-1 beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha) serum concentrations were observed with fish oil supplements for 12 weeks. Compared to placebo, a low dose of 900 mg omega-3 fatty acids (EPA plus DHA) in fish oil capsules did not change hs-CRP, fibrinogen, factor VIII, IL6, IL1-beta and TNF-alpha serum concentrations in HIV-infected subjects on ART. Further investigations should consider the assessment of more sensitive inflammatory markers or higher doses to evaluate the effects of marine omega-3 fatty acids in this population. Registered at the Nederlands Trial Register, Identifier no. NTR1798.76520-652

Effects of a low dose of fish oil on inflammatory markers of brazilian HIV-infected adults on antiretroviral therapy: a randomized, parallel, placebo-controlled trial

The benefits of antiretroviral therapy for HIV-infected subjects have been limited by an increased risk of metabolic and cardiovascular diseases. The objective of this study was to assess the effects of a low dose of marine omega-3 fatty acids on inflammatory marker concentrations in HIV-infected subjects under antiretroviral therapy (ART). Methods: This was a randomized, parallel, placebo-controlled trial that investigated the effects of 3 g fish oil/day (540 mg of eicosapentaenoic acid-EPA plus 360 mg of docosahexaenoic acid-DHA) or 3 g soy oil/day (placebo) for 24 weeks in 83 male and non-pregnant female HIV-infected adults on ART. Results: There were no differences between groups for the measures at baseline. Multilevel analyses revealed no statistically significant relationship between the longitudinal changes in high sensitivity-C reactive protein (hs-CRP) (Wald Chi2 = 0.17, p = 0.918), fibrinogen (Wald Chi2 = 3.82, p = 0.148), and factor VIII (Wald Chi2 = 5.25, p = 0.073) with fish oil. No significant changes in interleukin-6 (IL6), interleukin-1 beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha) serum concentrations were observed with fish oil supplements for 12 weeks. Conclusions: Compared to placebo, a low dose of 900 mg omega-3 fatty acids (EPA plus DHA) in fish oil capsules did not change hs-CRP, fibrinogen, factor VIII, IL6, IL1-beta and TNF-alpha serum concentrations in HIV-infected subjects on ART. Further investigations should consider the assessment of more sensitive inflammatory markers or higher doses to evaluate the effects of marine omega-3 fatty acids in this population. Registered at the Nederlands Trial Register, Identifier no. NTR17987865206528FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2008/50970-8; 2009/55532-

The association of hyperglycaemia with prevalent tuberculosis: a population-based cross-sectional study.

BACKGROUND: Systematic reviews suggest that the incidence of diagnosed tuberculosis is two- to- three times higher in those with diabetes mellitus than in those without. Few studies have previously reported the association between diabetes or hyperglycaemia and the prevalence of active tuberculosis and none in a population-based study with microbiologically-defined tuberculosis. Most have instead concentrated on cases of diagnosed tuberculosis that present to health facilities. We had the opportunity to measure glycaemia alongside prevalent tuberculosis. A focus on prevalent tuberculosis enables estimation of the contribution of hyperglycaemia to the population prevalence of tuberculosis. METHODS: A population-based cross-sectional study was conducted among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Prevalent tuberculosis was defined by the presence of a respiratory sample that was culture positive for M. tuberculosis. Glycaemia was measured by random blood glucose (RBG) concentration. Association with prevalent tuberculosis was explored across the whole spectrum of glycaemia. RESULTS: Among 27,800 Zambian and 11,367 Western Cape participants, 4,431 (15.9%) and 1,835 (16.1%) respectively had a RBG concentration ≥7.0 mmol/L, and 405 (1.5%) and 322 (2.8%) respectively had a RBG concentration ≥11.1 mmol/L. In Zambia, the prevalence of tuberculosis was 0 · 5% (142/27,395) among individuals with RBG concentration <11.1 mmol/L and also ≥11.1 mmol/L (2/405); corresponding figures for WC were 2 · 5% (272/11,045) and 4 · 0% (13/322). There was evidence for a positive linear association between hyperglycaemia and pulmonary prevalent tuberculosis. Taking a RBG cut-off 11.1 mmol/L, a combined analysis of data from Zambian and WC communities found evidence of association between hyperglycaemia and TB (adjusted odds ratio = 2 · 15, 95% CI [1 · 17-3 · 94]). The population attributable fraction of prevalent tuberculosis to hyperglycaemia for Zambia and WC combined was 0.99% (95% CI 0 · 12%-1.85%) for hyperglycaemia with a RBG cut-off of 11.1 mmol/L. CONCLUSIONS: This study demonstrates an association between hyperglycaemia and prevalent tuberculosis in a large population-based survey in Zambia and Western Cape. However, assuming causation, this association contributes little to the prevalence of TB in these populations

Reducing chronic disease through changes in food aid: A microsimulation of nutrition and cardiometabolic disease among Palestinian refugees in the Middle East

Background: Type 2 diabetes mellitus and cardiovascular disease and have become leading causes of morbidity and mortality among Palestinian refugees in the Middle East, many of whom live in long-term settlements and receive grain-based food aid. The objective of this study was to estimate changes in type 2 diabetes and cardiovascular disease morbidity and mortality attributable to a transition from traditional food aid to either (i) a debit card restricted to food purchases, (ii) cash, or (iii) an alternative food parcel with less grain and more fruits and vegetables, each valued at $30/person/month. Methods and findings: An individual-level microsimulation was created to estimate relationships between food aid delivery method, food consumption, type 2 diabetes, and cardiovascular disease morbidity and mortality using demographic data from the United Nations (UN; 2017) on 5,340,443 registered Palestinian refugees in Syria, Jordan, Lebanon, Gaza, and the West Bank, food consumption data (2011–2017) from households receiving traditional food parcel delivery of food aid (n = 1,507 households) and electronic debit card delivery of food aid (n = 1,047 households), and health data from a random 10% sample of refugees receiving medical care through the UN (2012–2015; n = 516,386). Outcome metrics included incidence per 1,000 person-years of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease events, microvascular events (end-stage renal disease, diabetic neuropathy, and proliferative diabetic retinopathy), and all-cause mortality. The model estimated changes in total calories, sodium and potassium intake, fatty acid intake, and overall dietary quality (Mediterranean Dietary Score [MDS]) as mediators to each outcome metric. We did not observe that a change from food parcel to electronic debit card delivery of food aid or to cash aid led to a meaningful change in consumption, biomarkers, or disease outcomes. By contrast, a shift to an alternative food parcel with less grain and more fruits and vegetables was estimated to produce a 0.08 per 1,000 person-years decrease in the incidence of hypertension (95% confidence interval [CI] 0.05–0.11), 0.18 per 1,000 person-years decrease in the incidence of type 2 diabetes (95% CI 0.14–0.22), 0.18 per 1,000 person-years decrease in the incidence of atherosclerotic cardiovascular disease events (95% CI 0.17–0.19), and 0.02 decrease per 1,000 person-years all-cause mortality (95% CI 0.01 decrease to 0.04 increase) among those receiving aid. The benefits of this shift, however, could be neutralized by a small (2%) increase in compensatory (out-of-pocket) increases in consumption of refined grains, fats and oils, or confectionaries. A larger alternative parcel requiring an increase in total food aid expenditure by 27% would be more likely to have a clinically meaningful improvement on type 2 diabetes and cardiovascular disease incidence. Conclusions: Contrary to the supposition in the literature, our findings do not robustly support the theory that transitioning from traditional food aid to either debit card or cash delivery alone would necessarily reduce chronic disease outcomes. Rather, an alternative food parcel would be more effective, even after matching current budget ceilings. But compensatory increases in consumption of less healthy foods may neutralize the improvements from an alternative food parcel unless total aid funding were increased substantially. Our analysis is limited by uncertainty in estimates of modeling long-term outcomes from shorter-term trials, focusing on diabetes and cardiovascular outcomes for which validated equations are available instead of all nutrition-associated health outcomes, and using data from food frequency questionnaires in the absence of 24-hour dietary recall data

The hypertension cascade of care in the midst of conflict: the case of the Gaza Strip

Although hypertension constitutes a substantial burden in conflict-affected areas, little is known about its prevalence, control, and management in Gaza. This study aims to estimate the prevalence and correlates of hypertension, its diagnosis and control among adults in Gaza. We conducted a representative, cross-sectional, anonymous, household survey of 4576 persons older than 40 years in Gaza in mid-2020. Data were collected through face-to-face interviews, anthropometric, and blood pressure measurements. Hypertension was defined in anyone with an average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg from two consecutive readings or a hypertension diagnosis. The mean age of participants was 56.9 ± 10.5 years, 54.0% were female and 68.5% were Palestinian refugees. The prevalence of hypertension was 56.5%, of whom 71.5% had been diagnosed. Hypertension was significantly higher among older participants, refugees, ex-smokers, those who were overweight or obese, and had other co-morbidities including mental illnesses. Two-thirds (68.3%) of those with hypertension were on treatment with one in three (35.6%) having their hypertension controlled. Having controlled hypertension was significantly higher in females, those receiving all medications for high blood pressure and those who never or rarely added salt to food. Investing in comprehensive but cost-effective initiatives that strengthen the prevention, early detection and timely treatment of hypertension in conflict settings is critical. It is essential to better understand the underlying barriers behind the lack of control and develop multi-sectoral programs to address these barriers