Ethnic differences in cardiometabolic risk profile in an overweight/obese paediatric cohort in the Netherlands: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Differences in prevalence of cardiometabolic risk factors between different ethnic groups are largely unknown. We determined the variation in cardiometabolic risk profile according to ethnicity in a cohort overweight/obese Dutch children.</p> <p>Methods</p> <p>An oral glucose tolerance test was performed in 516 overweight/obese Dutch children of multi-ethnic origin, attending an obesity out-patient clinic of an urban general hospital (mean age 10.6 ± 3.2; 55.2% boys). Anthropometric parameters and blood samples were collected, and the prevalence of (components of) the metabolic syndrome (MetS) and insulin resistance were determined in each ethnic group.</p> <p>Results</p> <p>Major ethnic groups were Dutch native (18.4%), Turkish (28.1%), and Moroccan (25.8%). The remaining group (27.7%) consisted of children with other ethnicities. Turkish children had the highest mean standardized BMI compared to Dutch native children (<it>P </it>< 0.05). As compared to Moroccan children, they had a higher prevalence of MetS (22.8% vs. 12.8%), low HDL-cholesterol (37.9% vs. 25.8%), hypertension (29.7% vs. 18.0%) and insulin resistance (54.9% vs. 37.4%, all <it>P </it>< 0.05). Although Turkish children also had higher prevalences of forementioned risk factors than Dutch native children, these differences were not statistically significant. Insulin resistance was associated with MetS in the Turkish and Moroccan subgroup (OR 6.6; 95%CI, 2.4–18.3 and OR 7.0; 95%CI, 2.1–23.1, respectively).</p> <p>Conclusion</p> <p>In a Dutch cohort of overweight/obese children, Turkish children showed significantly higher prevalences of cardiometabolic risk factors relative to their peers of Moroccan descent. The prospective value of these findings needs to be established as this may warrant the need for differential ethnic-specific preventive measures.</p

Aortic microcalcification is associated with elastin fragmentation in Marfan syndrome

Marfan syndrome (MFS) is a connective tissue disorder in which aortic rupture is the major cause of death. MFS patients with an aortic diameter below the advised limit for prophylactic surgery (<5 cm) may unexpectedly experience an aortic dissection or rupture, despite yearly monitoring. Hence, there is a clear need for improved prognostic markers to predict such aortic events. We hypothesize that elastin fragments play a causal role in aortic calcification in MFS, and that microcalcification serves as a marker for aortic disease severity. To address this hypothesis, we analysed MFS patient and mouse aortas. MFS patient aortic tissue showed enhanced microcalcification in areas with extensive elastic lamina fragmentation in the media. A causal relationship between medial injury and microcalcification was revealed by studies in vascular smooth muscle cells (SMCs); elastin peptides were shown to increase the activity of the calcification marker alkaline phosphatase (ALP) and reduce the expression of the calcification inhibitor matrix GLA protein in human SMCs. In murine Fbn1C1039G/+ MFS aortic SMCs, Alpl mRNA and activity were upregulated as compared with wild-type SMCs. The elastin peptide-induced ALP activity was prevented by incubation with lactose or a neuraminidase inhibitor, which inhibit the elastin receptor complex, and a mitogen-activated protein kinase kinase-1/2 inhibitor, indicating downstream involvement of extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation. Histological analyses in MFS mice revealed macrocalcification in the aortic root, whereas the ascending aorta contained microcalcification, as identified with the near-infrared fluorescent bisphosphonate probe OsteoSense-800. Significantly, microcalcification correlated strongly with aortic diameter, distensibility, elastin breaks, and phosphorylated ERK1/2. In conclusion, microcalcification co-localizes with aortic elastin degradation in MFS aortas of humans and mice, where elastin-derived peptides induce a calcification process in SMCs via the elastin receptor complex and ERK1/2 activation. We propose microcalcification as a novel imaging marker to monitor local elastin degradation a

Differential impact of impaired fasting glucose versus impaired glucose tolerance on cardiometabolic risk factors in multi-ethnic overweight/obese children

We aimed to investigate the prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and their associations with cardiometabolic risk factors, according to ethnicity in a large obese paediatric cohort. A 75-g oral glucose tolerance test was performed in 1,007 overweight/obese Dutch children of multi-ethnic origin, referred to the obesity outpatient clinics of two Dutch hospitals in Amsterdam (mean age, 11.4 ± 3.2 years; 50.7% boys). Anthropometric parameters and blood samples were collected, and cardiometabolic risk factors were assessed. The cohort consisted of Dutch native (26.0%), Turkish (23.7%), Moroccan (18.8%) and children of ‘other’ (31.5%) ethnicity. The prevalence of IFG was significantly higher in Moroccan and Turkish children as compared to Dutch native children (25.4% and 19.7% vs. 11.8%, respectively, P < 0.05). IGT was most frequently present in Turkish and Dutch native children, relative to Moroccan children (6.3% and 5.3% vs. 1.6%, P < 0.05). Besides pubertal status and ethnicity, components of ‘metabolic syndrome’ (MetS) which were associated with IGT, independent of hyperinsulinaemia, were hypertension [odds ratio (OR), 2.3; 95% CI, 1.1–4.9] while a trend was seen for high triglycerides (OR, 2.0; 95% CI, 0.9–4.3). When analyzing components of MetS which were associated with IFG, only low high-density lipoprotein cholesterol was significantly associated (OR, 1.7; 95% CI, 1.2–2.5) independent of hyperinsulinaemia. In conclusion, in a Dutch multi-ethnic cohort of overweight/obese children, a high prevalence of IFG was found against a low prevalence of IGT, which differed in their associations with cardiometabolic risk factors

Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling.

BACKGROUND: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. METHODS: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. RESULTS: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59). CONCLUSIONS: Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk

Haalbaarheid en doelrealisatie van DivorceATLAS: Een kortdurende training voor preventieve ondersteuning van gescheiden ouders.

Preventive support can help prevent or limit problems for divorced parents and their children. The short-term Divorce ATLAS training, available in a face-to-face group variant and online variant, offers such support to parents during and after divorce. The feasibility and goal realization of DivorceATLAS were evaluated with information from the group trainers and participating parents: n = 141 in group training and n = 27 online. The results show that the Divorce ATLAS supports parents in an accessible way in their parenthood after divorce. Participants and trainers were enthusiastic. The Divorce ATLAS training gave parents new ideas for parenting after the divorce and an impulse to get started with thi

Feasibility and goal realization of ScheidingsATLAS:A short training for prevenitve support of divorced parents

Preventive support can help prevent or limit problems for divorced parents and their children. The short-term Divorce ATLAS training, available in a face-to-face group variant and online variant, offers such support to parents during and after divorce. The feasibility and goal realization of DivorceATLAS were evaluated with information from the group trainers and participating parents: n = 141 in group training and n = 27 online. The results show that the Divorce ATLAS supports parents in an accessible way in their parenthood after divorce. Participants and trainers were enthusiastic. The Divorce ATLAS training gave parents new ideas for parenting after the divorce and an impulse to get started with thi