Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 489
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-31672450

RESUMO

BACKGROUND AND AIMS: Data on the prospective relationship of alcohol consumption at more moderate levels with systolic and diastolic function are scarce. We aimed to examine the prospective association of alcohol consumption with echocardiographic measures of cardiac structure and function, in individuals with and without type 2 diabetes (T2DM). METHODS AND RESULTS: We included 778 participants from the Hoorn Study (aged 68.4 ± 7.2 years, 49% women), a population-based prospective cohort study, oversampled for people with impaired glucose metabolism or T2DM. Self-reported alcohol consumption was collected at baseline with a validated food-frequency questionnaire and categorized into: none (0/week), light (>0-≤30 g/week), light-to-moderate (>30-≤70 g/week), moderate (>70-≤140 g/week), and heavy drinkers (>140 g/week). Echocardiography was performed at baseline (N = 778) and after 8 years follow-up (N = 404). Multiple linear regression was used to study the association between alcohol consumption and echocardiographic measures (left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI)), adjusted for confounders. Moderate and heavy alcohol consumption were associated with a decreased LVEF of -3.91% (CI: -7.13;-0.69) for moderate and -4.77% (-8.18;-1.36) for heavy drinkers compared to light drinkers. No associations were found between alcohol consumption, LVMI and LAVI. Modified Poisson regression showed a trend that higher alcohol consumption amounts were associated with a higher risk of incident systolic dysfunction (LVEF≤50%) (P-for-trend 0.058). CONCLUSION: The findings provide longitudinal evidence that moderate and heavy alcohol consumption are associated with decreased LVEF and trend towards a higher risk of incident LV systolic dysfunction, compared to light drinkers.

2.
Biol Psychiatry ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31635762

RESUMO

BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.

3.
Diabetes ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492661

RESUMO

Obesity-related insulin resistance (IR) may develop in multiple organs, representing different etiologies towards cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in relation to liver or muscle IR by means of RNA sequencing in overweight/obese participants of the DiOGenes cohort (n=368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, whilst genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, CODAM (n=325) and the Maastricht Study (n=685), an increased systemic low-grade inflammation profile was specifically related to muscle IR, but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases. DiOGenes was registered at clinicaltrials.gov as NCT00390637.

4.
Eur J Nutr ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486878

RESUMO

PURPOSE: Artificially sweetened and sugar-sweetened beverage consumptions have both been reported to be associated with type 2 diabetes mellitus (T2D) risk. The aim of the current study was to investigate the potential underlying associations with dynamic pancreatic ß-cell function (BCF) and insulin sensitivity. METHODS: We evaluated cross-sectional associations in 2240 individuals (mean ± SD age 59.6 ± 8.18, 49.4% male, 21.9% T2D) participating in a diabetes-enriched population-based cohort. Artificially sweetened and sugar-sweetened soft drinks and juice consumption were assessed by a food-frequency questionnaire. Glucose metabolism status, insulin sensitivity, and BCF were measured by a seven-point oral glucose tolerance test. Regression analyses were performed to assess associations of artificially and sugar-sweetened beverage consumption with measures of glucose homeostasis. Associations were adjusted for potential confounders, and additionally with and without total energy intake and BMI, as these variables could be mediators. RESULTS: Moderate consumption of artificially sweetened soft drink was associated with lower ß-cell glucose sensitivity [standardized beta (95% CI), - 0.06 (- 0.11, - 0.02)], total insulin secretion [ß - 0.06 (- 0.10, - 0.02)], and with lower ß-cell rate sensitivity [odds ratio (95% CI), 1.29 (1.03, 1.62)] compared to abstainers. Daily artificially sweetened soft drink consumption was associated with lower ß-cell glucose sensitivity [ß - 0.05 (- 0.09, 0.00)], and total insulin secretion [ß - 0.05 - 0.09, - 0.01)] compared to abstainers. CONCLUSIONS: Moderate and daily consumption of artificially sweetened soft drinks was associated with lower BCF, but not with insulin sensitivity. No evidence was found for associations of sugar-sweetened soft drink and juice consumption with BCF or insulin sensitivity in this middle-aged population. Prospective studies are warranted to further investigate the associations of artificially and sugar-sweetened beverage consumption with non-fasting insulin sensitivity and multiple BCF aspects.

5.
Clin J Am Soc Nephrol ; 14(11): 1626-1633, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31540930

RESUMO

BACKGROUND AND OBJECTIVES: Higher serum phosphate is associated with cardiovascular events and all-cause mortality. Explanations of this association have focused on large vessel calcification and stiffness. Studies suggest that a higher serum phosphate induces microvascular dysfunction, but relationships in humans with direct measures of microvascular function are lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a cross-sectional analysis of 3189 community-living participants that underwent skin capillaroscopy, laser-Doppler flowmetry, and flicker light-induced retinal vessel responses. We used linear regression to assess the association between serum phosphate and each microvascular outcome. The primary outcome was skin capillary recruitment during postocclusive peak reactive hyperemia by capillaroscopy. Secondary outcomes included capillary recruitment during venous congestion, heat-induced skin hyperemic response, flicker light-induced retinal arteriolar, and venular dilation. RESULTS: The mean age of the cohort was 59±8 years, 48% were women, 7% had an eGFR <60 ml/min per 1.73 m2, and the mean serum phosphate concentration was 3.2±0.5 mg/dl. A 1 mg/dl higher serum phosphate was independently associated with a 5.0% lower postocclusive capillary recruitment (95% CI, -10.0% to -0.1%). Results were similar for capillary recruitment with venous congestion (-4.5%; 95% CI, -9.8% to 0.7%). A 1 mg/dl higher serum phosphate was also independently associated with a 0.23% lower retinal venular dilation in response to flicker light (95% CI, -0.44% to -0.02%). A higher serum phosphate was not associated with change in flicker light-induced retinal arteriolar dilation or heat-induced skin hyperemic response, however a higher serum phosphate was associated with a lower heat-induced skin hyperemic response among men (-149% [95% CI, -260 to -38] per 1 mg/dl higher serum phosphate) but not women (P interaction, 0.01). CONCLUSIONS: Higher serum phosphate concentrations, even within the normal range, are associated with microvascular dysfunction in community-living individuals. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_20_CJN02610319.mp3.

6.
Am J Clin Nutr ; 110(2): 437-450, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165884

RESUMO

BACKGROUND: Folate and vitamin B-12 are essential micronutrients involved in the donation of methyl groups in cellular metabolism. However, associations between intake of these nutrients and genome-wide DNA methylation levels have not been studied comprehensively in humans. OBJECTIVE: The aim of this study was to assess whether folate and/or vitamin B-12 intake are asssociated with genome-wide changes in DNA methylation in leukocytes. METHODS: A large-scale epigenome-wide association study of folate and vitamin B-12 intake was performed on DNA from 5841 participants from 10 cohorts using Illumina 450k arrays. Folate and vitamin B-12 intakes were calculated from food-frequency questionnaires (FFQs). Continuous and categorical (low compared with high intake) linear regression mixed models were applied per cohort, controlling for confounders. A meta-analysis was performed to identify significant differentially methylated positions (DMPs) and regions (DMRs), and a pathway analysis was performed on the DMR annotated genes. RESULTS: The categorical model resulted in 6 DMPs, which are all negatively associated with folate intake, annotated to FAM64A, WRAP73, FRMD8, CUX1, and LCN8 genes, which have a role in cellular processes including centrosome localization, cell proliferation, and tumorigenesis. Regional analysis showed 74 folate-associated DMRs, of which 73 were negatively associated with folate intake. The most significant folate-associated DMR was a 400-base pair (bp) spanning region annotated to the LGALS3BP gene. In the categorical model, vitamin B-12 intake was associated with 29 DMRs annotated to 48 genes, of which the most significant was a 1100-bp spanning region annotated to the calcium-binding tyrosine phosphorylation-regulated gene (CABYR). Vitamin B-12 intake was not associated with DMPs. CONCLUSIONS: We identified novel epigenetic loci that are associated with folate and vitamin B-12 intake. Interestingly, we found a negative association between folate and DNA methylation. Replication of these methylation loci is necessary in future studies.

7.
Am J Clin Nutr ; 110(2): 358-366, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31240298

RESUMO

BACKGROUND: Advanced glycation endproducts (AGEs) and their precursors (dicarbonyls) are associated with the progression of diseases such as diabetes and cardiovascular disease. Plasma concentrations of dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) are increased after an oral glucose load indicating that consumption of diets high in carbohydrates may induce the endogenous formation of dicarbonyls and AGEs. OBJECTIVE: To examine the associations of dietary glycemic index (GI) and glycemic load (GL) with concentrations of dicarbonyls and AGEs in plasma and urine. METHODS: Cross-sectional analyses were performed in a human observational cohort [Cohort on Diabetes and Atherosclerosis Maastricht (CODAM), n = 494, 59 ± 7 y, 25% type 2 diabetes]. GI and GL were derived from FFQs. Dicarbonyls and AGEs were measured in the fasting state by ultra-performance liquid chromatography-tandem MS. MGO, GO, and 3-DG and protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and pentosidine were measured in plasma. Free forms of CML, CEL, and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured in both plasma and urine. Multiple linear regression was performed with dicarbonyls and AGEs as dependent variables, and dietary GI or GL as main independent variables (all standardized). Models were adjusted for health and lifestyle factors, dietary factors, and reciprocally for GI and GL. As this was an explorative study, we did not adjust for multiple testing. RESULTS: GI was not associated with any of the dicarbonyls or AGEs. GL was positively associated with free urinary MG-H1 (ß = 0.34; 95% CI: 0.12, 0.55). Furthermore, GL was positively associated with free plasma MG-H1 and free urinary CML (ß = 0.23; 95% CI: 0.02, 0.43; and ß = 0.28; 95% CI: 0.06, 0.50), but these associations were not independent of dietary AGE intake. CONCLUSIONS: A habitual diet higher in GL is associated with higher concentrations of free urinary MG-H1. This urinary AGE is most likely a reflection of AGE accumulation and degradation in tissues, where they may be involved in tissue dysfunction.

8.
Sci Rep ; 9(1): 9388, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253846

RESUMO

The Muscle Insulin Sensitivity Index (MISI) has been developed to estimate muscle-specific insulin sensitivity based on oral glucose tolerance test (OGTT) data. To date, the score has been implemented with considerable variation in literature and initial positive evaluations were not reproduced in subsequent studies. In this study, we investigate the computation of MISI on oral OGTT data with differing sampling schedules and aim to standardise and improve its calculation. Seven time point OGTT data for 2631 individuals from the Maastricht Study and seven time point OGTT data combined with a hyperinsulinemic-euglycaemic clamp for 71 individuals from the PRESERVE Study were used to evaluate the performance of MISI. MISI was computed on subsets of OGTT data representing four and five time point sampling schedules to determine minimal requirements for accurate computation of the score. A modified MISI computed on cubic splines of the measured data, resulting in improved identification of glucose peak and nadir, was compared with the original method yielding an increased correlation (ρ = 0.576) with the clamp measurement of peripheral insulin sensitivity as compared to the original method (ρ = 0.513). Finally, a standalone MISI calculator was developed allowing for a standardised method of calculation using both the original and improved methods.

9.
J Diabetes Res ; 2019: 6289831, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218233

RESUMO

Advanced glycation end products (AGEs) accumulate in fatty livers and may contribute to low-grade inflammation (LGI), potentially via their receptor, RAGE. It is unknown if the AGE accumulation in fatty livers results in elevated circulating AGEs. In a cohort study, we investigated the association of liver fat and hepatocellular damage with circulating AGEs and soluble RAGE (sRAGE) and subsequently the association of circulating AGEs and sRAGE with LGI. Cross-sectional associations of liver fat percentage (eLF%; ln-transformed) and liver enzymes (LE score; standardized) with circulating AGEs (free CML, CEL, and MG-H1 in nM and protein-bound CML, CEL, and pentosidine in nmol/mmol lysine; ln-transformed) and sRAGE (pg/ml, ln-transformed) and additionally of AGEs and sRAGE with LGI (standardized) were determined by multiple linear regression. eLF% was positively associated with circulating free CEL (ß = 0.090; 95% CI 0.041; 0.139) but inversely with protein-bound CML (ß = -0.071; 95% CI -0.108; -0.034). Similarly, the LE score was positively associated with free CML (ß = 0.044; 95% CI 0.012; 0.076) and CEL (ß = 0.040; 95% CI 0.009; 0.072) but inversely with protein-bound CML (ß = -0.037; 95% CI -0.060; -0.013). Free CML (ß = 0.297; 95% CI 0.049; 0.545) was positively associated with LGI, while protein-bound CML (ß = -0.547; 95% CI -0.888; -0.207) was inversely associated, although this association was absent after adjustment for BMI. eLF% and LE score were not associated with sRAGE and sRAGE not with LGI after adjustment for BMI. Liver fat and enzymes were positively associated with circulating free AGEs, which were associated with LGI. In contrast, inverse relations were observed of liver fat and enzymes with circulating protein-bound AGEs and of protein-bound AGEs with LGI. These data suggest that hepatic steatosis and inflammation affect the formation and degradation of hepatic protein-bound AGEs resulting in elevated circulating free AGE levels. These alterations in AGE levels might influence LGI, but this is likely independent of RAGE.

11.
J Sports Sci ; 37(15): 1746-1754, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30929574

RESUMO

Dynamic sitting, such as fidgeting and desk work, might be associated with health, but remains difficult to identify out of accelerometry data. We examined, in a laboratory study, whether dynamic sitting can be identified out of triaxial activity counts. Among 18 participants (56% men, 27.3 ± 6.5 years), up to 236 counts per minute were recorded in the anteroposterior and mediolateral axes during dynamic sitting using a hip-worn accelerometer. Subsequently, we examined in 621 participants (38% men, 80.0 ± 4.7 years) from the AGES-Reykjavik Study whether dynamic sitting was associated with cardio-metabolic health. Compared to participants who recorded the fewest dynamic sitting minutes (Q1), those with more dynamic sitting minutes had a lower BMI (Q2 = -1.39 (95%CI = -2.33;-0.46); Q3 = -1.87 (-2.82;-0.92); Q4 = -3.38 (-4.32;-2.45)), a smaller waist circumference (Q2 = -2.95 (-5.44;-0.46); Q3 = -3.47 (-6.01;-0.93); Q4 = -8.21 (-10.72;-5.71)), and a lower odds for the metabolic syndrome (Q2 = 0.74 [0.45;1.20] Q3 = 0.58 [0.36;0.95]; Q4 = 0.36 [0.22;0.59]). Our findings suggest that dynamic sitting might be identified using accelerometry and that this behaviour was associated with health. This might be important given the large amounts of time people spend sitting. Future studies with a focus on validation, causation and physiological pathways are needed to further examine the possible relevance of dynamic sitting.


Assuntos
Acelerometria/instrumentação , Metabolismo Energético , Exercício/fisiologia , Comportamento Sedentário , Postura Sentada , Adolescente , Adulto , Índice de Massa Corporal , Feminino , Monitores de Aptidão Física , Humanos , Masculino , Síndrome Metabólica , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
12.
Neurology ; 92(16): e1899-e1911, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30944236

RESUMO

OBJECTIVE: To identify a plasma metabolomic biomarker signature for migraine. METHODS: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS: Decreases in the level of apolipoprotein A1 (ß -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (ß -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (ß -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS: Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.

13.
J Clin Endocrinol Metab ; 104(11): 5056-5064, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901028

RESUMO

CONTEXT: There is an ongoing debate about whether and how fructose is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A recent experimental study showed an increased intrahepatic triglyceride (IHTG) content in mice deficient for aldolase B (aldo B-/-), the enzyme that converts fructose-1-phosphate to triose phosphates. OBJECTIVE: To translate these experimental findings to the human situation. DESIGN: Case-control study. SETTING: Outpatient clinic for inborn errors of metabolism. PATIENTS OR OTHER PARTICIPANTS: Patients with hereditary fructose intolerance, a rare inborn error of metabolism caused by a defect in aldolase B (n = 15), and healthy persons matched for age, sex, and body mass index (BMI) (n =15). MAIN OUTCOME MEASURE: IHTG content, assessed by proton magnetic resonance spectroscopy. RESULTS: IHTG content was higher in aldo B-/- patients than controls (2.5% vs 0.6%; P = 0.001) on a background of lean body mass (median BMI, 20.4 and 21.8 kg/m2, respectively). Glucose excursions during an oral glucose load were higher in aldo B-/- patients (P = 0.043). Hypoglycosylated transferrin, a surrogate marker for hepatic fructose-1-phosphate concentrations, was more abundant in aldo B-/- patients than in controls (P < 0.001). Finally, plasma ß-hydroxybutyrate, a biomarker of hepatic ß-oxidation, was lower in aldo B-/- patients than controls (P = 0.009). CONCLUSIONS: This study extends previous experimental findings by demonstrating that aldolase B deficiency also results in IHTG accumulation in humans. It suggests that the accumulation of fructose-1-phosphate and impairment of ß-oxidation are involved in the pathogenesis.

14.
Hypertension ; 73(4): 803-811, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30739535

RESUMO

An increasing number of individuals will face age-related cognitive difficulties because life expectancy has increased. It is, therefore, important to identify modifiable risk factors for cognitive impairment. Very short-term to mid-term blood pressure variability (BPV) may be such a factor because it may cause cerebral ischemia. To this end, we investigated whether greater systolic and diastolic BPV are cross-sectionally associated with memory function (n=1804), information processing speed (n=1793), and executive function (n=1780) in 40- to 75-year-old individuals from The Maastricht Study. A composite BPV-index was derived by standardizing within-visit, 24-hour, and 7-day BPV. We performed linear regression with adjustments for age, sex, educational level, 24-hour systolic or diastolic pressure, and cardiovascular risk factors. We found that a 1-SD greater systolic BPV was not associated with information processing speed (ß [SD difference], -0.10; 95% CI, -0.14 to 0.06), or executive function (-0.09; 95% CI, -0.20 to 0.02) but was marginally associated with lower memory function (-0.11; 95% CI, -0.21 to 0.00). A 1-SD greater diastolic BPV was associated with lower information processing speed (-0.10; 95% CI, -0.20 to -0.00) and executive function (-0.12; 95% CI, -0.22 to -0.01) and marginally associated with lower memory function (-0.09; 95% CI, -0.20 to 0.01). These effects on cognitive performance are equivalent to ≈3 additional years of aging. In conclusion, greater very short-term to mid-term diastolic and, to a lesser extent, systolic BPV may be a modifiable risk factor for cognitive deterioration in 40- to 75-year-old, community-dwelling individuals.

15.
J Clin Endocrinol Metab ; 104(7): 2719-2727, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753672

RESUMO

CONTEXT: Hepatokines have emerged as potential mediators of obesity-associated comorbidities, such as type 2 diabetes, cardiovascular disease, fractures, and central hypogonadism. OBJECTIVE: To assess whether weight loss-induced changes in hepatokines are mediated by intrahepatic triglyceride (IHTG) content. DESIGN: Cross-sectional study and randomized controlled trial. SETTING: General community. PARTICIPANTS: Metabolically healthy, lean men (waist <94 cm; n = 25) and men with abdominal obesity (waist 102 to 110 cm; n = 52). INTERVENTION: Men with abdominal obesity were randomized to 8-week dietary weight loss or no weight loss. MAIN OUTCOME MEASURES: IHTG and serum hepatokines, that is, serum IGF1, IGF binding protein 1 (IGFBP1), SHBG, fibroblast growth factor 21 (FGF21), fetuin A, and plasma fetuin B. RESULTS: All hepatokines, except for fetuin B, were significantly different between lean men and men with obesity. After the weight-loss intervention (-10.3 kg; 95% CI, -11.4 to-9.2), serum IGF1, IGFBP1, SHBG, and fetuin A approached the values observed in lean men. Cross-sectional associations were observed between IHTG and IGF1 (ß = -0.51; 95% CI, -0.82 to -0.20), IGFBP1 (ß = -4.2; 95% CI, -7.7 to -0.7), and FGF21 (ß = 2.1; 95% CI, 1.3 to 2.9) in lean men and men with abdominal obesity combined. Weight loss resulted in a reduction of IHTG (treatment effect, -2.2%; 95% CI, -3.4% to -1.2%) that was associated with a change in IGF1 (ß = -0.9; 95% CI, -1.3 to -0.4), IGFBP1 (ß = -0.17; 95% CI, -0.31 to -0.03), and SHBG levels (ß = -0.18; 95% CI, -0.29 to -0.07). Mediation analyses showed that only the weight loss-induced change in serum IGF1 was mediated by IHTG (mediated effect, 32.7%; 95% CI, 4.6% to 79.2%). CONCLUSIONS: Dietary weight loss has differential effects on hepatokines. This study shows that the change in serum IGF1 levels after dietary weight loss is mediated by the change in IHTG content.

16.
Microbiome ; 7(1): 2, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30609941

RESUMO

BACKGROUND: The gut microbiota evolves from birth and is in early life influenced by events such as birth mode, type of infant feeding, and maternal and infant antibiotics use. However, we still have a gap in our understanding of gut microbiota development in older children, and to what extent early events and pre-school lifestyle modulate the composition of the gut microbiota, and how this impinges on whole body metabolic regulation in school-age children. RESULTS: Taking advantage of the KOALA Birth Cohort Study, a long-term prospective birth cohort in the Netherlands with extensive collection of high-quality host metadata, we applied shotgun metagenomics sequencing and systematically investigated the gut microbiota of children at 6-9 years of age. We demonstrated an overall adult-like gut microbiota in the 281 Dutch school-age children and identified 3 enterotypes dominated by the genera Bacteroides, Prevotella, and Bifidobacterium, respectively. Importantly, we found that breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age. The correlations between pre-school dietary lifestyle and metabolic phenotypes exhibited a striking enterotype dependency. Thus, an inverse correlation between high dietary fiber consumption and low plasma insulin levels was only observed in individuals with the Bacteroides and Prevotella enterotypes, but not in Bifidobacterium enterotype individuals in whom the gut microbiota displayed overall lower microbial gene richness, alpha-diversity, functional potential for complex carbohydrate fermentation, and butyrate and succinate production. High total fat consumption and elevated plasma free fatty acid levels in the Bifidobacterium enterotype are associated with the co-occurrence of Streptococcus. CONCLUSIONS: Our work highlights the persistent effects of breastfeeding duration and pre-school dietary lifestyle in affecting the gut microbiota in school-age children and reveals distinct compositional and functional potential in children according to enterotypes. The findings underscore enterotype-specific links between the host metabolic phenotypes and dietary patterns, emphasizing the importance of microbiome-based stratification when investigating metabolic responses to diets. Future diet intervention studies are clearly warranted to examine gut microbe-diet-host relationships to promote knowledge-based recommendations in relation to improving metabolic health in children.


Assuntos
Bactérias/classificação , Ácidos Graxos não Esterificados/sangue , Trato Gastrointestinal/microbiologia , Insulina/sangue , Metagenômica/métodos , Bactérias/genética , Aleitamento Materno/estatística & dados numéricos , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Fibras na Dieta/administração & dosagem , Fezes/microbiologia , Humanos , Estilo de Vida , Masculino , Fenótipo , Filogenia , Estudos Prospectivos
17.
J Hypertens ; 37(2): 365-371, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30640873

RESUMO

INTRODUCTION: Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid-femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)]. METHODS: We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ±â€Š7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by -1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness. RESULTS: Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: -0.04 (-0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (-0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient. CONCLUSION: We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.

18.
Curr Opin Nephrol Hypertens ; 28(1): 26-33, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30320620

RESUMO

PURPOSE OF REVIEW: Chronic kidney disease (CKD) remains a serious diabetic complication despite the use of widely employed interventions such as angiotensin-converting enzyme inhibitors and glucose-lowering treatments. Accumulation of methylglyoxal, a highly reactive glucose metabolite and a major precursor in the formation of advanced glycation end products, may link the hemodynamic, inflammatory, metabolic, and structural changes that drive diabetic CKD. Therefore, methylglyoxal may serve as a potential therapeutic target to prevent diabetic CKD. RECENT FINDINGS: Higher plasma methylglyoxal levels were shown to be associated with a decline in the estimated glomerular filtration rate. Furthermore, interventions that lower methylglyoxal levels reduced albuminuria in rodent models of diabetes. In addition, the glyoxalase system, which detoxifies methylglyoxal into D-lactate, has been identified as a key protective enzymatic system against diabetic CKD in both human and rodent studies. Recently, several promising treatments to lower methylglyoxal directly or to boost the glyoxalase system have been identified. SUMMARY: The review highlights the mechanisms through which methylglyoxal is formed in diabetes, and how methylglyoxal contributes to the mechanisms that drive CKD in diabetes. Furthermore, we discuss the role of glyoxalase-1 in diabetic CKD. Finally, we discuss recent data about treatments that lower methylglyoxal stress.


Assuntos
Nefropatias Diabéticas/etiologia , Lactoilglutationa Liase/fisiologia , Aldeído Pirúvico/metabolismo , Insuficiência Renal Crônica/etiologia , Nefropatias Diabéticas/metabolismo , Humanos , Aldeído Pirúvico/antagonistas & inibidores , Insuficiência Renal Crônica/metabolismo
19.
J Nutr ; 148(12): 1911-1916, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30398646

RESUMO

Background: Methylglyoxal (MGO) is the most potent precursor of advanced glycation end products (AGEs). MGO and AGEs have been associated with diabetes, its complications, and other age-related diseases. Experimental studies have shown that the flavonoids quercetin and epicatechin are able to scavenge MGO and lower AGE formation. Objective: Data on the effects of these flavonoids on MGO and AGE concentrations in humans are not yet available. We therefore investigated the effect of quercetin and epicatechin on the concentrations of MGO and AGEs in a post hoc analysis. Methods: Thirty-seven apparently healthy, nonsmoking adults with a systolic blood pressure between 125 and 160 mm Hg at screening were included in a randomized, double-blind, placebo-controlled crossover trial. Participants ingested (-)-epicatechin (100 mg/d), quercetin 3-glucoside (160 mg/d), or placebo capsules for periods of 4 wk separated by 4-wk washout periods. Fasting blood samples were collected at the start and end of each intervention period. Liquid chromatography-tandem mass spectrometry was used to determine plasma concentrations of the dicarbonyl compounds MGO, glyoxal (GO), and 3-deoxyglucosone (3-DG) and free and protein-bound AGEs. Gene expression of glyoxalase 1 (GLO1), the enzyme involved in the degradation of MGO, was determined by either microarray or quantitative reverse transcriptase-polymerase chain reaction. Results: The treatment effect (Δtreatment - Δplacebo) of quercetin on MGO was -40.2 nmol/L (95% CI: -73.6, -6.8 nmol/L; P = 0.019), a decrease of 11% from baseline values, whereas GO, 3-DG, and free and protein-bound AGEs did not change significantly. Epicatechin did not affect the concentrations of dicarbonyls and free and protein-bound AGEs. We did not find a significant change in expression of GLO1. Conclusions: In apparently healthy (pre)hypertensive men and women, quercetin but not epicatechin decreased plasma MGO concentrations. Quercetin may potentially form a new treatment strategy for diseases in which MGO plays a pivotal role. This study was registered at clinicaltrials.gov as NCT01691404.

20.
Atherosclerosis ; 280: 1-6, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30448567

RESUMO

BACKGROUND AND AIMS: Familial combined hyperlipidemia (FCHL) is a complex dyslipidemia associated with premature cardiovascular disease (CVD). The present study was conducted to 1) determine the incidence of CVD in FCHL in this era of protocolled, primary prevention; and 2) examine whether cardiovascular risk estimation based on the Systemic Coronary Risk Estimation (SCORE) chart, as proposed in the 2016 ESC/EAS guidelines for the management of dyslipidemia, is justified in FCHL. METHODS: FCHL patients, their normolipidemic (NL) relatives and spouses originally included in our baseline cohort in 1998-2005 (n = 596) were invited for a follow-up visit to determine the incidence of CVD, defined as (non-)fatal coronary artery disease, ischemic stroke and peripheral artery disease requiring invasive treatment. RESULTS: Follow-up data (median: 15 years) was acquired for 85% of the original cohort. The cumulative incidence of CVD was significantly higher in FCHL patients than in spouses (23.6% versus 4.7%; hazard ratio (HR): 5.4, 95%CI: 2.0-14.6; HR after adjustment for risk factors included in SCORE: 4.7, 95%CI: 1.6-13.8), but not in NL relatives compared to spouses (5.8% versus 4.7%). The SCORE chart tended to overestimate CVD risk in the spouses (observed [O]/expected [E] ratio:0.2, p = 0.01), but not in FCHL patients (O/E:1.3, p = 0.50). CONCLUSIONS: Risk of primary CVD is still substantially increased in FCHL patients, despite preventive measures. The overestimation of CVD risk by the SCORE chart - a nowadays frequently observed phenomenon thanks to improved primary prevention - was not seen in FCHL. These results suggest that more aggressive treatment is justified to avoid excessive CVD in FCHL.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA