Availability and readiness of diabetes health facilities to manage tuberculosis in Tanzania: a path towards integrating tuberculosis-diabetes services in a high burden setting?

BACKGROUND: The burden of tuberculosis (TB) and diabetes mellitus (DM) is rising and substantially affecting the low-income countries, including Tanzania. Integrated management of TB and DM is becoming of importance in TB high burden countries. In this study, we sought to assess the availability and readiness of diabetes facilities to manage TB in Tanzania. METHODS: The present study was based on a secondary analysis of the 2014-2015 Tanzania Service Provision Assessment Survey data. We calculated the service availability as a percentage of diabetes facilities offering TB services: diagnosis and treatment. Regarding the readiness of diabetes facilities to provide TB management, we calculated based on the three domains: staff training and guideline, diagnostics, and medicines as identified by World Health Organization-Service Availability and Readiness Assessment (SARA) manual. A score of at least half (≥50%) of the indicators listed in each of the three domains was considered as high readiness. We used a descriptive statistics to present our findings. RESULTS: There were 619 DM facilities all over the country of which only 238 (38.4%) had TB services.72.6 and 62.6% of these DM facilities with TB services were publicly owned and located in rural settings respectively. Generally, DM facilities had low readiness to manage TB; 12·6%. More specifically, all DM facilities had low readiness in terms of trained staff and guidelines. However, in the domain of diagnostics and medications, higher levels of care (hospitals) had a comparatively higher level of readiness to manage TB. CONCLUSION: Most of the DM facilities had low availability and readiness to manage TB. The findings of our study display an urgent need to mobilize important resources to enhance the integration of TB services in DM facilities. This includes medications, management guidelines, diagnostics, and health professionals who have received refresher training on TB/DM co-management. However, presently, few DM facilities may be allowed to start managing TB as per the Strategic and Action Plan for the Prevention and Control of Non-Communicable Diseases in Tanzania 2016-2020.

Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet-induced obese mice.

AIMS/INTRODUCTION: The mechanisms underlying the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on aortic endothelial dysfunction in diet-induced obesity are not clearly understood. This study investigated whether SGLT2 inhibition by luseogliflozin improved free fatty acid (FFA)-induced endothelial dysfunction in high-fat diet (HFD)-induced obese mice. MATERIALS AND METHODS: Mice were fed a control diet or high-fat diet for 8 weeks, and then each diet with or without luseogliflozin was provided for an additional 8 weeks under free or paired feeding. Afterward, the thoracic aortas were removed and utilized for the experiments. RESULTS: Luseogliflozin treatment decreased body weight, fasting blood glucose, insulin, and total cholesterol in HFD-fed mice only under paired feeding but not under free feeding. Endothelial-dependent vasodilation under FFA exposure conditions was significantly lower in HFD-fed mice than in control diet-fed mice, and luseogliflozin treatment ameliorated FFA-induced endothelial dysfunction. Reactive oxygen species (ROS) production induced by FFA was significantly increased in HFD-induced obese mice. Luseogliflozin treatment increased the expression of superoxide dismutase 2 (SOD2), an antioxidative molecule, and reduced FFA-induced ROS production in the thoracic aorta. Superoxide dismutase reversed FFA-induced endothelial dysfunction in HFD-fed mice. CONCLUSIONS: It was shown that caloric restriction is important for the effect of luseogliflozin on metabolic parameters and endothelial dysfunction. Furthermore, SGLT2 inhibition by luseogliflozin possibly ameliorates FFA-induced endothelial dysfunction by increasing SOD2 expression and decreasing reactive oxygen species production in the thoracic aorta.

Dietary obesity and glycemic excursions cause a parallel increase in STEAP4 and pro-inflammatory gene expression in murine PBMCs.

Background: The balance between pro-atherogenic and anti-atherogenic factors is very crucial in the development of atherosclerotic lesions. Although the expression of the six-transmembrane epithelial antigen of the prostate 4 (STEAP4) in myeloid cells is known to be atheroprotective, there is not a single study reporting on the status of STEAP4 expression in circulating monocytes in the early stages of diet-induced obesity or in events of glycemic excursions. Methods: We induced glycemic spikes twice daily for a 1-week duration to rats fed on regular chow and western diet, and analyzed gene expression changes in the peripheral blood mononuclear cells (PBMCs). We also conducted experiments on RAW 264.7 cells to gain insight into some of our in vivo findings. Results: Diet-induced obesity and glycemic excursions independently caused a significant increase in STEAP4 mRNA expression in PBMCs. This was also accompanied by an induction of a substantial number of pro-inflammatory cytokines, chemokines, and chemokine receptors. However, the combined effect of western diet and hyperglycemic spikes was subtle and non-additive. In the in vitro setting, either glucose spikes, persistent hyperglycemia, or a combination of palmitic acid and insulin resulted in a parallel increase in expression of STEAP4 and pro-inflammatory genes. This was, however, significantly abrogated with 4-octyl itaconate or attenuated by inhibitors of p38MAPK and NF-kB. Conclusions: STEAP4 expression in mononuclear cells is induced by increasing inflammation or oxidative stress. The observed increase in STEAP4 expression in circulating monocytes due to visceral obesity or glycemic excursions is a compensatory response. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00542-1.

Correction to: Dietary obesity and glycemic excursions cause a parallel increase in STEAP4 and pro-inflammatory gene expression in murine PBMCs.

[This corrects the article DOI: 10.1007/s13340-021-00542-1.].

Repeated glucose spikes and insulin resistance synergistically deteriorate endothelial function and bardoxolone methyl ameliorates endothelial dysfunction.

BACKGROUND: Both insulin resistance and postprandial glucose spikes are known for their potential to induce vascular endothelial dysfunction in individuals with metabolic syndrome. However, these factors are inextricable, and therefore, their relative contributions to inducing endothelial dysfunction remain elusive. In this study, we aimed to disentangle the effects of these factors and clarify whether bardoxolone methyl (CDDO-Me), a novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator, protects against glucose spike-induced endothelial dysfunction. METHODS: We induced glucose spikes twice daily for a duration of 1 week to rats fed a standard/control diet (CD) and Western-type diet (WTD). Endothelium-dependent relaxation (EDR) was evaluated using isolated thoracic aortas. Gene expression and dihydroethidium (DHE)-fluorescence studies were carried out; the effect of CDDO-Me on aortic endothelial dysfunction in vivo was also evaluated. RESULTS: Neither WTD-induced insulin resistance nor pure glucose spikes significantly deteriorated EDR. However, under high-glucose (20 mM) conditions, the EDR of thoracic aortas of WTD-fed rats subjected to glucose spikes was significantly impaired. In this group of rats, we observed significantly enhanced DHE fluorescence as a marker of reactive oxygen species, upregulation of an oxidative stress-related gene (NOX2), and downregulation of an antioxidant gene (SOD2) in the thoracic aortas. As expected, treatment of the thoracic aorta of this group of rats with antioxidant agents significantly improved EDR. We also noted that pretreatment of aortas from the same group with CDDO-Me attenuated endothelial dysfunction, accompanied by a correction of the redox imbalance, as observed in gene expression and DHE fluorescence studies. CONCLUSIONS: For the first time, we showed that insulin resistance and glucose spikes exert a synergistic effect on aortic endothelial dysfunction. Furthermore, our study reveals that CDDO-Me ameliorates endothelial dysfunction caused by glucose spikes in a rat model of metabolic syndrome.

Readiness of healthcare facilities with tuberculosis services to manage diabetes mellitus in Tanzania: A nationwide analysis for evidence-informed policy-making in high burden settings.

INTRODUCTION: Double disease burden such as Tuberculosis and Diabetes mellitus comorbidity is evident and on rising especially in high burden settings such as Tanzania. There is limited information about the availability of tuberculosis/diabetes integrated healthcare services in Tanzania. Therefore, this study explored the availability and examined the readiness of healthcare facilities with tuberculosis services to manage diabetes mellitus in Tanzania. METHODS: We abstracted data from the 2014-2015 Tanzania Service Provision Assessment Survey datasets. The service availability was assessed by calculating the proportion of tuberculosis facilities reported to manage diabetes mellitus. There were four domains; each domain with some indicators for calculating the readiness index. High readiness was considered if the tuberculosis facilities scored at least half (≥50%) of the indicators listed in each of the four domains (staff training and guideline, diagnostics, equipment, and medicines) as is recommended by the World Health Organization-Service Availability and Readiness Assessment manual while low readiness for otherwise. RESULTS: Out of 341 healthcare facilities with tuberculosis services included in the current study, 238 (70.0%) reported providing management for diabetes mellitus. The majority of the facilities were dispensaries and clinics 48.1%; publicly owned 72.6%; and located in rural 62.6%. Overall, the readiness of tuberculosis facilities to manage diabetes was low (10.8%). Similarly, the readiness was low based on the domain-specific readiness of trained staff and guidelines. CONCLUSION: Although the majority of the healthcare facilities with tuberculosis services had diabetes mellitus services the overall readiness was low. This finding provides a piece of evidence to inform the policymakers in high burden and low resource countries to strengthen the co-management of tuberculosis and diabetes.

Strategies to ameliorate endothelial dysfunction associated with metabolic syndrome, where are we?

There is a paucity of aggregated clinical trials on strategies of ameliorating endothelial dysfunction associated with Metabolic Syndrome (MS). We reviewed clinical trials conducted between 2008 and 2017, reporting on strategies of improving endothelial function in patients with MS. A comprehensive search of published articles by the Google Scholar and PubMed were carried out. Only studies involving non-invasive, objective measurement of endothelial function were included. Thirty (30) studies were selected for analysis, in which physical exercise training, diet modification, calcium channel blockers + alpha-lipoic acid, bezafibrate, allopurinol, mesoglycan, and l-arginine supplementation significantly improved Endothelial-Dependent Vasodilation (EDV) in patients with MS but without cardiovascular diseases. Large multicenter clinical trials are required to address the question of generalizability of these findings.