Association of C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 Serum Levels with Coronary Artery Disease in Subjects with and without Type 2 Diabetes Mellitus

<div><p>C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 are two newly discovered adipokines regulating glucose and lipid metabolism. But their role in type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) is still in infancy. The aim of this study was to investigate the associations of gene expression and serum levels of CTRP3 and CTRP13 with CAD, metabolic and inflammatory markers in patients with and without T2DM. Serum levels of CTRP3, CTRP13, adiponectin and inflammatory cytokines and their gene expression in peripheral blood mononuclear cells (PBMCs) were determined in 172 subjects categorized as group I (without T2DM and CAD), group II (with CAD but no T2DM), group III (with T2DM but no CAD) and group IV (with T2DM and CAD). Serum levels and gene expression of CTRP3, CTRP13 and adiponectin in the group I were higher compared to other groups. Inflammatory cytokines in the control group were lower than other groups too. CTRP3 serum levels have an independent association with BMI, smoking and CTRP3 gene expression; also CTRP13 serum levels has an independent association with BMI, HDL-C, insulin, HOMA-IR, HbA1c and TNF-α. Decreased serum levels of CTRP3 and CTRP13 were also associated with CAD. It appears that the decreased levels of CTRP3 and especially CTRP13 were associated with increased risk of T2DM and CAD. These findings suggest an emerging role of these adipokines in the pathogenesis of CAD, but further studies are necessary to establish this concept.</p></div

Univariate and multivariate analysis of the association between CTRP3 serum levels with correlated parameters.

<p>Univariate and multivariate analysis of the association between CTRP3 serum levels with correlated parameters.</p

Univariate and multivariate analysis of the association between CTRP13 serum levels with correlated parameters.

<p>Univariate and multivariate analysis of the association between CTRP13 serum levels with correlated parameters.</p

PBMCs gene expression of TNF-α, IL-6, CTRP3, CTRP13 and adiponectin.

<p>(A) PBMCs gene expression of TNF-α was higher in groups II, III and IV compared to the group I (all, p < .001). (B) IL-6 PBMCs gene expression was higher in groups II, III, IV compared with the group I (all, p < .001), Also gene expression of IL-6 was higher in group IV compared with group III (p < .05). (C) PBMCs gene expression of CTRP3 was higher in control group compared with CAD group (p < .05), T2DM (p < .05) and CAD+T2DM (< .01). (D) PBMCs gene expression of CTRP13 were higher in control group compared to the CAD+T2DM group (p < .05). (E) PBMCs gene expression of adiponectin was decreased in group IV compared with group I (p < .001).</p

Odds ratios of CAD incident in Non-T2DM patients and T2DM patients according to CTRP3 and CTRP13 serum levels.

<p>Odds ratios of CAD incident in Non-T2DM patients and T2DM patients according to CTRP3 and CTRP13 serum levels.</p

Clinical Biochemical Characteristics of Study population.

<p>Clinical Biochemical Characteristics of Study population.</p

Odds ratios of 3-vessels disease according to CTRP13 serum levels.

<p>Odds ratios of 3-vessels disease according to CTRP13 serum levels.</p

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the Global Burden of Disease Study 2017

Background: Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods: We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings: The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation: By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. Funding: Bill & Melinda Gates Foundation

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the Global Burden of Disease Study 2017

Background: Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods: We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings: The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation: By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. Funding: Bill & Melinda Gates Foundation