Glucagon-like peptide (GLP)-1 receptor agonists are the cornerstone in the treatment of hyperglycemia in many people suffering from type 2 diabetes (T2D). These drugs have potent glucose-lowering actions and, additionally, lower body weight through satiety induction while reducing blood pressure and dyslipidemia. Partly through these actions, GLP-1 receptor agonism was shown to reduce cardiovascular disease (CVD) in people with T2D with previous CVD or at high-risk thereof. In these cardiovascular safety trials, in secondary or exploratory analyses, GLP-1 receptor agonists were also shown to reduce macro-albuminuria, an accepted surrogate marker for diabetic kidney disease (DKD), a condition that still represents a major unmet medical need. In this review we will discuss the evidence which suggests renoprotection induced by GLP-1 receptor agonists and the potential mechanisms that may be involved. These include mitigation of hyperglycemia, overweight and insulin resistance, systemic and glomerular hypertension, dyslipidemia, sodium retention, inflammation and renal hypoxia. The recently initiated large-sized FLOW trial investigating the effects of semaglutide on hard renal outcomes in patients with DKD will provide clarity whether GLP-1 receptor agonists may reduce the burden of DKD in addition to their other beneficial metabolic and cardiovascular effects.
OBJECTIVE Studies have shown a disparate association between body composition and the risk of type 2 diabetes. We assessed whether associations between differences in body composition and type 2 diabetes vary among ethnic groups with disparate cardiometabolic risk. RESEARCH DESIGN AND METHODS We used data from the Healthy Life in an Urban Setting (HELIUS) study, including individuals aged 18–70 years of African Surinamese (n = 3,997), South Asian Surinamese (n = 2,956), Turkish (n = 3,546), Moroccan (n = 3,850), Ghanaian (n = 2,271), and Dutch (n = 4,452) origin living in Amsterdam. Type 2 diabetes was defined using the World Health Organization criteria. Logistic regression was used to assess the relation between body composition and type 2 diabetes. Waist-to-hip ratio (WHR), waist circumference, BMI, and body fat percentage by bioelectrical impedance were used to estimate body composition. RESULTS Per unit change in BMI, only Ghanaian (odds ratio [OR] 0.94 [95% CI 0.89–0.99]) and Moroccan (0.94 [0.89–0.99]) women had a smaller increase in type 2 diabetes compared with the Dutch population, whereas the ORs for body fat percentage were 0.94 (0.89–1.00) for Ghanaian, 0.93 (0.88–0.99) for Moroccan, and 0.95 (0.90–1.00) for South Asian Surinamese women. There was no interaction between WHR and ethnicity on the risk of type 2 diabetes, and there were no differences in men. WHR had the highest precision in predicting type 2 diabetes in both men (C statistic = 0.78) and women (C statistic = 0.81). CONCLUSIONS The association between differences in body composition and type 2 diabetes is roughly the same in all ethnic groups. WHR seems the most reliable and consistent predictor of type 2 diabetes regardless of ethnic background.
Aim: To study the effects of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, the angiotensin receptor blocker (ARB) losartan, and their combination on blood pressure, while studying the mechanisms potentially involved.Methods: A total of 24 people with type 2 diabetes (T2D) (age: 66 ± 6 years; body mass index: 31.0 ± 3 kg/m 2 ; estimated glomerular filtration rate: 90 ml/min/1.73m 2 ) received a 1-week treatment with empagliflozin 10 mg once daily, losartan 50 mg once daily, their combination, and placebo, in a randomized double-blind crossover design, with 4-week washout periods in between. Blood pressure, arterial stiffness, autonomic nervous system activity and plasma volume, extracellular fluid and serum albumin were assessed.Results: Versus placebo (139 mmHg), empagliflozin reduced systolic blood pressure (SBP) by 8 mmHg (P = .001), losartan by 12 mmHg (P = .001) and empagliflozin + losartan by 15 mmHg (P < .001). Combination therapy had a larger SBP-lowering effect versus empagliflozin monotherapy (-7 [95% CI -12; -2] mmHg) and numerically larger effects versus losartan monotherapy (-3 [-8; 2] mmHg). Empagliflozin reduced sympathetic nervous system (SNS) activity, arterial stiffness and extracellular fluid, while increasing serum albumin. Losartan reduced SNS activity and arterial stiffness.Combination therapy induced volume contraction variables, together with a reduction in SNS activity and arterial stiffness. Conclusion:In people with T2D, SGLT2 inhibition in combination with an ARB had a larger blood pressure-lowering effect versus placebo than either of the drugs alone.
<b>Objective</b>: Studies have shown a disparate association between body composition and the risk of type 2 diabetes. We assessed whether associations between differences in body composition and type 2 diabetes vary among ethnic groups with disparate cardiometabolic risk. <p><b>Research Design and Methods: </b>We used data from the HELIUS study, including individuals aged 18-70 of<b> </b>African Surinamese (n=3997), South-Asian Surinamese (n=2956), Turkish (n=3546), Moroccan (n=3850), Ghanaian (n=2271) and Dutch (n=4452) origin living in Amsterdam. Type 2 diabetes was defined using the World Health Organization criteria. Logistic regression was used to assess the relation between body composition and type 2 diabetes. Waist-hip ratio, waist circumference, BMI and body fat percentage by bio-electrical impedance were used to estimate body composition.</p> <p><b>Results: </b>Per unit change in BMI only Ghanaian [OR 0.94 (95% CI 0.89-0.99)] and Moroccan [0.94 (0.89-0.99)] women had a smaller increase in type 2 diabetes per unit change in BMI compared to the Dutch population, while OR for body fat percentage were 0.94 (0.89-1.00) for Ghanaian, 0.93 (0.88-0.99) for Moroccan and 0.95 (0.90-1.00) for South-Asian Surinamese women. There was no interaction between WHR and ethnicity on the risk of type 2 diabetes, and there were no differences in men. WHR had the highest precision in predicting type 2 diabetes in both men (c-statistic=0.78) and women (c-statistic=0.81). </p> <b>Conclusions: </b>The<b> </b>association between differences in body composition and type 2 diabetes is roughly the same in all ethnic groups. WHR seems the most reliable and consistent predictor of type 2 diabetes regardless of ethnic background.<b> </b>
Background: evidence shows important ethnic differences in vascular dysfunction rates; however, the mechanisms driving these differences remain unclear. One potential factor is the ethnic differences in the role of inflammation in vascular injury. We tested the hypothesis that low-grade inflammation is unequally associated with vascular dysfunction in different ethnic groups. Methods: we included 5698 participants (similar-sized Dutch, African Surinamese, South-Asian Surinamese, Ghanaians, Turkish, and Moroccans) of the HELIUS study (the Netherlands) conducted between 2011 and 2015. Logistic regression was used to examine the associations of Z-score inflammatory biomarker concentration (high sensitivity C-reactive protein [hs-CRP], fibrinogen, and D-dimer) with vascular dysfunction (aortic stiffness, coronary artery disease [CAD], and peripheral artery disease [PAD]), with adjustments for age, sex, smoking (pack-years), BMI, hypertension, HbA1c, total cholesterol, and statin use Findings: in the fully adjusted models, higher Z-score hs-CRP was positively associated with CAD in Dutch [OR 1¢63, (95% CI 1¢21À2¢18)] and PAD in South Asians [1¢25(1¢03À1¢53)], respectively. Higher Z-score fibrinogen was positively associated with CAD in African Surinamese [1¢28(1¢03À1¢59)] while higher Z-score D-dimer was positively associated with PAD in Moroccans [1¢39(1¢01À1¢93)]. Higher Z-score hs-CRP [0¢71 (0¢54À0¢94)] and fibrinogen [0¢75(0¢58À0¢97)] concentrations were negatively associated with PAD in African Surinamese. Interpretation: our study shows that inflammatory biomarkers are unequally associated with vascular dysfunction in different ethnic groups. These observations provide opportunities for future studies aimed at assessing the predictive roles of inflammation on vascular disease in different ethnic groups.
Background Blood pressure (BP) is regulated by plasma metabolites from different neurohumoral and cardiometabolic systems. Since there are established differences in hypertension pathogenesis and treatment response between ethnicities, we hypothesized that plasma metabolites may be differently associated with BP across ethnic groups. Purpose To investigate associations between plasma metabolite profiles and BP in a multi-ethnic population-based cohort. Methods From the Healthy Living In an Urban Setting (HELIUS) study, 369 subjects (mean age 52±11 years, 51%F) of African and non-African descent were included. Office systolic (136±21 mmHg) and diastolic (83±12 mmHg) BP levels were recorded. Plasma metabolites were measured semi-quantitively with LC-MS (Metabolon) from fasting plasma samples. Associations between metabolite profiles and BP were assessed with machine learning prediction models using the XGBoost algorithm with nested cross-validation. Associations between the resulting best predictors and BP were assessed with linear regression models while adjusting for age, sex, estimated glomerular filtration rate and diabetes. Results Plasma metabolite profiles explained 14.1% of systolic BP variance and 10.6% of diastolic BP variance. These were attenuated to 3.1% and 1.4% respectively, when using residuals of BP after adjusting for age and sex. Top predictors for both systolic and diastolic BP included N-formylmethionine, several acylcarnitines and polyunsaturated fatty acids such as hexadecadienoate. These metabolites were significantly associated with higher systolic BP with estimates ranging from 3.0 to 4.5 mmHg per 1 SD increase in the adjusted models. Associations with hexadecadienoate, dihomolinoleate and catecholamine metabolites, including vanillactate had significant interactions (p<0.05) with ethnicity, and were only significant in subjects of non-African descent. Conclusions Plasma metabolome composition explained a large proportion of BP variance, but this association was attenuated when adjusting for confounders. Polyunsaturated fatty acids and catecholamine metabolites were only associated with BP in the non-African descent subjects. N-formylmethionine was the most consistent predictor for systolic BP across all subgroups. Future studies could focus on translating these findings in vitro in order to decipher the role of N-formylmethionine in BP regulation. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Dutch Heart Foundation, the Netherlands Organization for Health Research and Development, the European Integration Fund and the European Union (Seventh Framework Programme) Explained variances of machine learning Linear regression models
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