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1.
Diabetologia ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705160

RESUMO

AIMS/HYPOTHESIS: Higher concentrations of the adipokine omentin are associated with lower levels of cardiometabolic risk factors in experimental and cross-sectional studies, but with higher risk of type 2 diabetes and cardiovascular diseases in population-based cohort studies. However, it is unknown whether high omentin concentrations are associated with increased risk of cardiovascular events in people with established diabetes. Therefore, the present study investigated the association between serum omentin concentrations and the risk of cardiovascular events in individuals with diabetes. METHODS: This prospective study was based on participants of the German ESTHER cohort with diabetes and without previous cardiovascular event. The ESTHER cohort consists of individuals aged 50-75 years at baseline who were recruited by their general practitioners. After exclusion of individuals with serum C-reactive protein ≥10 mg/l (≥95.24 nmol/l), the final analysis population consisted of 933 individuals. At baseline, serum omentin concentrations were measured by ELISA. Cox regression models were fitted to estimate HRs and their corresponding 95% CIs for associations of omentin tertiles with a composite endpoint of cardiovascular events and separately with incident myocardial infarction, stroke and cardiovascular death. RESULTS: During 14 years of follow-up, 228 individuals experienced a primary cardiovascular event (myocardial infarction, stroke or cardiovascular death). After comprehensive adjustment for age, sex, BMI, metabolic and lifestyle factors and medication use, HRs (95% CIs) for the 2nd and 3rd tertile of omentin compared with the 1st tertile were: 1.24 (95% CI 0.86, 1.79) and 1.63 (1.15, 2.32) (ptrend = 0.005) for the composite cardiovascular endpoint; 1.39 (0.78, 2.47) and 1.71 (0.98, 2.99) (ptrend = 0.065) for incident myocardial infarction; 1.40 (0.78, 2.53) and 2.05 (1.17, 3.58) (ptrend = 0.010) for incident stroke; and 1.43 (0.85, 2.40) and 1.72 (1.04, 2.83) (ptrend = 0.040) for cardiovascular death. Effect estimates and p values were almost unaltered after additional adjustment for adiponectin. CONCLUSIONS/INTERPRETATION: Higher omentin concentrations are associated with an increased risk for cardiovascular events in individuals with diabetes after adjustment for multiple cardiovascular risk factors. Given data from preclinical studies, it appears possible that this association reflects a compensatory, but insufficient upregulation of omentin concentrations as a response to stimuli that increase cardiovascular risk.

2.
Nat Commun ; 10(1): 4179, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519890

RESUMO

The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity.

3.
Endocr Connect ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505464

RESUMO

OBJECTIVE: Metabolic syndrome and obesity are risk factors for chronic kidney disease. However, early kidney alterations may escape diagnosis in these conditions due to glomerular hyperfiltration. Uromodulin, a glycoprotein exclusively synthesized in tubular cells of the thick ascending limb of Henle's loop, is a novel tissue-specific biomarker for kidney function. In contrast to the commonly used markers creatinine and cystatin C, serum uromodulin does not primarily depend on glomerular filtration. We hypothesized that serum uromodulin is a marker for metabolic syndrome and related components. DESIGN: The analyses included 1088 participants of the population-based KORA F4 study aged 62-81 years. Metabolic syndrome was present in 554 participants. After a mean follow-up time of 6.5 years, 621 participants were reevaluated, of which 92 had developed incident metabolic syndrome. METHODS: The association of serum uromodulin with metabolic syndrome and its components were assessed using multivariable logistic regression models. RESULTS: Serum uromodulin was inversely associated with metabolic syndrome after adjustment for sex, age, estimated glomerular filtration rate, physical activity, smoking, alcohol consumption and high sensitivity C-reactive protein (OR 0.65; 95% CI 0.56-0.76 per standard deviation uromodulin; p<0.001). Serum uromodulin was inversely associated with all single components of metabolic syndrome. However, serum uromodulin was not associated with new-onset metabolic syndrome after the follow-up period of 6.5 ± 0.3 years (OR 1.18; 95% CI 0.86-1.60). CONCLUSIONS: Serum uromodulin is independently associated with prevalent, but not with incident metabolic syndrome. Low serum uromodulin may indicate a decreased renal reserve in the metabolic syndrome.

4.
Diabetes Care ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31540903

RESUMO

OBJECTIVE: To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS: EMPA treatment resulted in a placebo-corrected absolute of -1.8% (95% CI -3.4, -0.2%; P = 0.02) and relative change in LFC of -22% (-36, -7%; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change -2.5 kg [-3.7, -1.4 kg]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (-74 mol/L [-108, -42 mol/L]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60%]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS: EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.

5.
Circ Res ; 125(8): 773-782, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31476962

RESUMO

Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31461765

RESUMO

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have higher circulating levels of C-reactive protein, but the relationship between inflammation and endocrine function in PCOS remains poorly understood. Thus, this study aimed to investigate the association between low-grade inflammation and sex hormones in women with PCOS. DESIGN AND PATIENTS: A comprehensive panel of biomarkers of inflammation was measured in serum of 63 women with PCOS using proximity extension assay technology. Associations of 65 biomarkers with sex hormones were assessed without and with adjustment for age and body mass index (BMI). RESULTS: In the unadjusted analysis, 20 biomarkers were positively correlated with 17-OH-progesterone (17-OH-P), 14 with prolactin and 6 with free testosterone, whereas inverse associations were found for 16 biomarkers with sex hormone-binding globulin (SHBG), 6 with luteinizing hormone (LH) and 6 with estrogen (all p<0.05). Among the positive associations, correlations were mainly found for five chemokines (CXCL11, CCL4, MCP-4/CCL13, CXCL5, CXCL6) and for VEGF-A, LAP-TGFß1, TNFSF14 and MMP-1. Inverse associations with sex hormones were mainly present for two chemokines (CXCL1, MCP-2/CCL8), CDCP1, CST5 and CSF-1. Adjustment for age and BMI reduced the number of biomarker associations for SHBG and estrogen, but had hardly any impact on associations with 17-OH-P, prolactin, free testosterone and LH. CONCLUSION: Women with PCOS feature BMI-independent associations between biomarkers of inflammation and certain sex steroid and hypophyseal hormones. Most of these inflammation-related biomarkers were chemokines, which may be relevant as potential mediators of the increased cardiometabolic risk of women with PCOS.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31321442

RESUMO

OBJECTIVE: The aim of this study was to determine the effect of bariatric surgery on the incidence of RA in participants of the Swedish Obese Subjects (SOS) study. METHODS: The SOS is a longitudinal study aiming to assess the effect of bariatric surgery on mortality and obesity-related diseases. This report includes 2002 subjects with obesity who underwent bariatric surgery and 2034 matched controls; none of them had RA at baseline. Cases of incident RA were identified through the Swedish National Patient Register by searching for International Classification of Diseases codes. Both intention-to-treat analyses and per-protocol analyses are reported. In the per-protocol analysis, participants from the control group who underwent bariatric surgery later on during follow-up were censored at the time of surgery. RESULTS: During follow-up, 92 study participants developed RA. The median follow-up was 21 years (range 0-29). Bariatric surgery was neither associated with the incidence of RA in the intention-to-treat analysis [hazard ratio (HR) 0.92 (95% CI 0.59, 1.46), P = 0.74], nor in the per-protocol analysis [HR 0.86 (95% CI 0.54, 1.38), P = 0.53]. Weight change at the 2 year follow-up, expressed as the change in BMI compared with baseline, did not associate with the development of RA. Higher serum CRP levels and smoking associated with the future development of RA independent of other factors. CONCLUSIONS: We did not detect any association between bariatric surgery and the incidence of RA in subjects affected by obesity followed up for up to 29 years. CLINICALTRIALS.GOV: (http://clinicaltrials.gov): NCT01479452.

8.
Nat Commun ; 10(1): 2581, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197173

RESUMO

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.


Assuntos
Metilação de DNA/fisiologia , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Insulina/metabolismo , Obesidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Ilhas de CpG/genética , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética/fisiologia , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla/métodos , Homeostase/genética , Humanos , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto Jovem
9.
Eur J Nutr ; 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31154491

RESUMO

PURPOSE: Coffee is widely consumed and implicated in numerous health outcomes but the mechanisms by which coffee contributes to health is unclear. The purpose of this study was to test the effect of coffee drinking on candidate proteins involved in cardiovascular, immuno-oncological and neurological pathways. METHODS: We examined fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were analyzed using three multiplex proximity extension assays that, after quality control, measured a total of 247 proteins implicated in cardiovascular, immuno-oncological and neurological pathways and of which 59 were previously linked to coffee exposure. Repeated measures ANOVA was used to test the relationship between coffee treatment and each protein. RESULTS: Two neurology-related proteins including carboxypeptidase M (CPM) and neutral ceramidase (N-CDase or ASAH2), significantly increased after coffee intake (P < 0.05 and Q < 0.05). An additional 46 proteins were nominally associated with coffee intake (P < 0.05 and Q > 0.05); 9, 8 and 29 of these proteins related to cardiovascular, immuno-oncological and neurological pathways, respectively, and the levels of 41 increased with coffee intake. CONCLUSIONS: CPM and N-CDase levels increased in response to coffee intake. These proteins have not previously been linked to coffee and are thus novel markers of coffee response worthy of further study. CLINICAL TRIAL REGISTRY: http://www.isrctn.com/ISRCTN12547806 .

10.
Trends Endocrinol Metab ; 30(5): 286-298, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30935671

RESUMO

The most prevalent chronic complications of diabetes are diabetic neuropathies, among which distal sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) are the best studied. Their major clinical sequelae such as foot ulcers, neuropathic pain, and orthostatic hypotension are associated with lower quality of life and increased risk of mortality. Here we discuss the recent insights into DSPN and CAN focusing on two prospective cohorts; that is, the German Diabetes Study (GDS) including recent-onset diabetes patients and the population-based Cooperative Health Research in the Region of Augsburg, Germany (KORA) surveys. The insights from these studies investigating novel tools for early detection and prediction of (pre)diabetic neuropathy as well as biomarkers of oxidative stress and inflammation should ultimately culminate in improving the health care of patients affected by this serious condition.

11.
PLoS One ; 14(3): e0213650, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30921355

RESUMO

Previous studies reported that secreted frizzled-related protein-5 (Sfrp5) decreases beta cell proliferation and increases fasting insulin levels, but studies on direct effects of Sfrp5 on insulin secretion and its underlying mechanisms are missing. This study examined effects of Sfrp5 on (i) beta cell viability and proliferation, (ii) basal and glucose-stimulated insulin secretion and (iii) canonical and non-canonical Wnt signalling pathways. We incubated rat INS-1E cells with 0.1, 1 or 5 µg/ml recombinant Sfrp5 for 24h. We measured basal and glucose-stimulated insulin secretion at glucose concentrations of 2.5 and 20 mmol/l. Phosphorylated and total protein content as well as mRNA levels of markers of cell proliferation, canonical and non-canonical Wnt signalling pathways were examined using Western blotting and real-time PCR. Differences between treatments were analysed by repeated measurement one-way ANOVA or Friedman's test followed by correction for multiple testing using the Benjamini-Hochberg procedure. At 5 µg/ml, Sfrp5 reduced mRNA levels of cyclin-B1 by 25% (p<0.05). At 1 and 5 µg/ml, Sfrp5 increased glucose-stimulated insulin secretion by 24% and by 34% (both p<0.05), respectively, but had no impact on basal insulin secretion. Sfrp5 reduced the phosphorylation of the splicing forms p46 and p54 of JNK by 39% (p<0.01) and 49% (p<0.05), respectively. In conclusion, Sfrp5 reduced markers of cell proliferation, but increased in parallel dose-dependently glucose-stimulated insulin secretion in INS-1E cells. This effect is likely mediated by reduced JNK activity, an important component of the non-canonical Wnt signalling pathway.

12.
Semin Immunopathol ; 41(4): 477-489, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30778653

RESUMO

Depression is a frequent comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). Depression and diabetes are linked by a bidirectional relationship, but the underlying mechanisms are still incompletely understood. Experimental, observational and intervention studies showed that inflammatory processes contribute to the development of depression in animal models and humans. Given the high risk of morbidity and mortality in patients with the double burden of diabetes and depression, this review provides an overview of epidemiological studies that addressed the relationship between biomarkers of inflammation and depressive symptoms or depression in diabetes patients. In patients with T1D, there is some evidence that higher levels of high-sensitivity C-reactive protein (hsCRP), IL-6, IL-1 receptor antagonist (IL-1RA) and sICAM-1 may be related to depressive symptoms or (for hsCRP) lower treatment response. For T2D, hsCRP, IL-1RA, CCL2 and adiponectin or its isoforms were associated with depressive symptoms in at least two studies, whereas positive associations of IL-1ß, IL-6 and IL-18 with depressive symptoms or depression were reported from single cohorts. However, the number of studies is too low for any meaningful meta-analysis. Prospective life course studies including both patients with T1D and T2D, a comprehensive assessment of systemic inflammation and repeated assessment of depressive symptoms should represent a future research priority to clarify to what extent subclinical inflammation affects the risk of depression in patients with diabetes. A better understanding of the role of inflammatory processes may help to identify subtypes of depression with partly different pathogenesis, which could have consequences with respect to therapeutic options including immunomodulation.

13.
Eur J Epidemiol ; 34(4): 409-422, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30599058

RESUMO

The objective of the present study was to identify proteins that contribute to pathophysiology and allow prediction of incident type 2 diabetes or incident prediabetes. We quantified 14 candidate proteins using targeted mass spectrometry in plasma samples of the prospective, population-based German KORA F4/FF4 study (6.5-year follow-up). 892 participants aged 42-81 years were selected using a case-cohort design, including 123 persons with incident type 2 diabetes and 255 persons with incident WHO-defined prediabetes. Prospective associations between protein levels and diabetes, prediabetes as well as continuous fasting and 2 h glucose, fasting insulin and insulin resistance were investigated using regression models adjusted for established risk factors. The best predictive panel of proteins on top of a non-invasive risk factor model or on top of HbA1c, age, and sex was selected. Mannan-binding lectin serine peptidase (MASP) levels were positively associated with both incident type 2 diabetes and prediabetes. Adiponectin was inversely associated with incident type 2 diabetes. MASP, adiponectin, apolipoprotein A-IV, apolipoprotein C-II, C-reactive protein, and glycosylphosphatidylinositol specific phospholipase D1 were associated with individual continuous outcomes. The combination of MASP, apolipoprotein E (apoE) and adiponectin improved diabetes prediction on top of both reference models, while prediabetes prediction was improved by MASP plus CRP on top of the HbA1c model. In conclusion, our mass spectrometric approach revealed a novel association of MASP with incident type 2 diabetes and incident prediabetes. In combination, MASP, adiponectin and apoE improved type 2 diabetes prediction beyond non-invasive risk factors or HbA1c, age and sex.


Assuntos
Adiponectina/sangue , Apolipoproteínas E/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo , Estado Pré-Diabético/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteômica , Fatores de Risco
14.
J Clin Endocrinol Metab ; 104(6): 2295-2304, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30689904

RESUMO

CONTEXT AND OBJECTIVE: Not only type 2 diabetes (T2D), but also type 1 diabetes (T1D), can be associated with insulin resistance, as assessed using insulin-stimulated whole-body glucose disposal (M-value). We hypothesized that different factors would affect the M-value at the onset of T1D and T2D. DESIGN AND PATIENTS: We examined 132 patients with T1D or T2D matched for sex, age, and body mass index with a known diabetes duration of <12 months. Multivariable linear regression analyses were applied to test the associations between glycemic control, blood lipid levels, adiponectin, and proinflammatory immune mediators and the M-value, obtained from the hyperinsulinemic-euglycemic clamp. RESULTS: Despite comparable age, body mass index, and near-normoglycemic control, the mean M-value was lower in those with T2D than in those with T1D. Patients with T1D had a lower waist/hip ratio and serum triglycerides but higher serum adiponectin than patients with T2D. However, the circulating proinflammatory markers were not different. Even with adjustments for glucose-lowering treatments, the fasting blood glucose correlated negatively with the M-value in both groups. However, gamma-glutamyl transferase-independently of any treatments-correlated negatively only in T2D. In contrast, serum adiponectin correlated positively with the M-values. CONCLUSIONS: Fasting glycemia correlated with insulin-stimulated glucose disposal in both diabetes types. However, altered liver and adipose tissue function were associated with insulin-stimulated glucose disposal only in T2D, underpinning the specific differences between these diabetes types.

15.
Cardiovasc Diabetol ; 18(1): 9, 2019 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-30660185

RESUMO

BACKGROUND: Reports on body mass index (BMI) trajectories from childhood into late adolescence, their determinants, and subsequent cardiometabolic risk markers, particularly among European populations have been few. Moreover, sex-specific investigation is necessary considering the sex difference in BMI, and the sex-specific association between BMI and some cardiometabolic risk markers. METHODS: Using a sample from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study, we explored sex-specific trajectories of the BMI standard deviation score (SDS) from 4 to 18 years of age in 354 males and 335 females by latent (class) growth models. The determinants of trajectory were assessed by logistic regression. We identified cardiometabolic risk markers that were highly associated with BMI SDS trajectory by random forest regression, and finally we used generalized linear models to investigate differences in the identified cardiometabolic risk markers between pairs of trajectories. RESULTS: We observed four: 'low-normal weight', 'mid-normal weight', 'high-normal weight', and 'overweight', and three: ''low-normal weight', 'mid-normal weight', and 'high-normal weight' trajectories in males and females, respectively. Higher maternal prepregnancy BMI was associated with the 'overweight' trajectory, and with 'high-normal weight' trajectory in both sexes. In addition, employed mothers and first-born status were associated with 'high-normal weight' trajectory in females. BMI SDS trajectory was associated with high-density lipoprotein-cholesterol and interleukin-18 (IL-18) in males, and diastolic blood pressure and interleukin-6 (IL-6) in females. However, only males following the 'overweight' trajectory had significantly higher IL-18 when compared to their 'low-normal weight' counterpart. CONCLUSIONS: We identified sex-specific distinct trajectories of BMI SDS from childhood into late adolescence, higher maternal prepregnancy BMI as a common determinant of the 'high-normal weight' and 'overweight' trajectories, and 'overweight' trajectory being associated with elevated IL-18 in late adolescence-young adulthood. This study emphasizes the role of maternal prepregnancy BMI in overweight, and highlights IL-18 as a cardiometabolic signature of overweight across life.


Assuntos
Desenvolvimento do Adolescente , Índice de Massa Corporal , Desenvolvimento Infantil , Síndrome Metabólica/epidemiologia , Obesidade Pediátrica/epidemiologia , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Pressão Sanguínea , Peso Corporal , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Interleucina-18/sangue , Interleucina-6/sangue , Lipídeos/sangue , Estudos Longitudinais , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/fisiopatologia , Prevalência , Prognóstico , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
16.
Environ Int ; 124: 370-392, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30660850

RESUMO

BACKGROUND: While prior studies have linked air pollution (AP) to diabetes prevalence and incidence, few have investigated whether AP exposure is also associated with alterations in diabetes-related biomarkers in metabolically healthy adults. OBJECTIVE: To evaluate the associations between short-, medium-, and long-term AP and diabetes-related biomarkers (adiponectin, interleukin-1 receptor antagonist [IL-1RA], high sensitivity C-reactive protein [hsCRP], fibrinogen) in persons without diabetes. METHODS: Adiponectin, IL-1RA, hsCRP, and fibrinogen were measured in blood samples collected at the baseline (t0; 2000-2003) and first follow-up (t1; 2006-2008) examinations of the prospective Heinz Nixdorf Recall (HNR) cohort study in Germany. Participants' residential mean exposures to PM10, PM2.5, NO2, and accumulation mode particle number concentration (PNAM) were estimated for several time windows (1- to 365-day) prior to examination using a dispersion and chemistry transport model. We fitted covariate-adjusted linear mixed effects models using a random participant intercept and investigated effect modification by obesity status. RESULTS: We analyzed 6727 observations (nt0 = 3626, nt1 = 3101) from 4052 participants of the HNR study (52% women; ages 45-76 years at t0). For all air pollutants, medium-term exposures (60- to 120-day) were negatively associated with adiponectin (e.g., 91-day PNAM: -2.51% change [-3.40%, -1.53%] per interquartile [IQR] increase). Several short-, medium-, and long-term AP exposures were positively associated with IL-1RA (e.g., 365-day PM10: 2.64% change [1.25%, 4.22%] per IQR increase). Long-term exposures were positively associated with hsCRP level while no consistent patterns were observed for fibrinogen. Stronger associations for adiponectin were observed among non-obese participants. CONCLUSION: In persons without diabetes, we observed differing patterns of association between AP and diabetes-related biomarkers across a range of exposure windows, supporting the hypothesis that AP may play a role in the development of diabetes.


Assuntos
Poluição do Ar , Biomarcadores/sangue , Diabetes Mellitus/sangue , Glucose/metabolismo , Adiponectina , Idoso , Proteína C-Reativa/metabolismo , Estudos de Coortes , Exposição Ambiental/análise , Feminino , Fibrinogênio/metabolismo , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Diabetes Care ; 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30523031

RESUMO

OBJECTIVE: To investigate the associations between different anthropometric measurements and development of distal sensorimotor polyneuropathy (DSPN) considering interaction effects with prediabetes/diabetes and to evaluate subclinical inflammation as a potential mediator. RESEARCH DESIGN AND METHODS: This study was conducted among 513 participants from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort (aged 62-81 years). Anthropometry was measured at baseline. Incident DSPN was defined by neuropathic impairments using the Michigan Neuropathy Screening Instrument at baseline and follow-up. Associations between anthropometric measurements and DSPN were estimated by multivariable logistic regression. Potential differences by diabetes status were assessed using interaction terms. Mediation analysis was conducted to determine the mediation effect of subclinical inflammation in these associations. RESULTS: After a mean follow-up of 6.5 years, 127 cases with incident DSPN were detected. Both general and abdominal obesity were associated with development of DSPN. The odds ratios (95% CI) of DSPN were 3.06 (1.57; 5.97) for overweight, 3.47 (1.72; 7.00) for obesity (reference: normal BMI), and 1.22 (1.07; 1.38) for 5-cm differences in waist circumference, respectively. Interaction analyses did not indicate any differences by diabetes status. Two chemokines (C-C motif chemokine ligand 7 [CCL7] and C-X-C motif chemokine ligand 10 [CXCL10]) and one neuron-specific marker (Δ/Notch-like epidermal growth factor related receptor [DNER]) were identified as potential mediators, which explained a proportion of the total effect up to 11% per biomarker. CONCLUSIONS: General and abdominal obesity were associated with incident DSPN among individuals with and without diabetes, and this association was partly mediated by inflammatory markers. However, further mechanisms and biomarkers should be investigated as additional mediators to explain the remainder of this association.

19.
Nutrients ; 10(12)2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513727

RESUMO

Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry⁻mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p < 0.05 and q < 0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p < 0.05 and q > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.

20.
BMC Public Health ; 18(1): 1331, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509230

RESUMO

BACKGROUND: Previous studies found regional differences in the prevalence and incidence of type 2 diabetes between Northeast and South of Germany. The aim of this study was to investigate if regional variations are also present for macrovascular disease in people with type 2 diabetes and in the general population. A further aim was to investigate if traditional risk factors of macrovascular complications can explain these regional variations. METHODS: Data of persons aged 30-79 from two regional population-based studies, SHIP-TREND (Northeast Germany, 2008-2012, n = 2539) and KORA-F4 (South Germany, 2006-2008, n = 2932), were analysed. Macrovascular disease was defined by self-reported previous myocardial infarction, stroke or coronary angiography. Multivariable logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for prevalence of macrovascular disease in persons with type 2 diabetes and in the general population. RESULTS: The prevalence of macrovascular disease in persons with type 2 diabetes and in the general population was considerably higher in the Northeast (SHIP-TREND: 32.8 and 12.0%) than in the South of Germany (KORA-F4: 24.9 and 8.8%), respectively. The odds of macrovascular disease in persons with type 2 diabetes was 1.66 (95% CI: 1.11-2.49) in the Northeast in comparison to the South after adjustment for sex, age, body mass index, hypertension, hyperlipidemia and smoking. In the general population, SHIP-TREND participants also had a significantly increased odds of macrovascular disease compared to KORA-F4 participants (OR = 1.63, 95% CI: 1.33-2.00). After excluding coronary angiography (myocardial infarction or stroke only), the ORs for region decreased in all models, but the difference between SHIP-TREND and KORA-F4 participants was still significant in the age- and sex-adjusted model for the general population (OR = 1.34, 95% CI: 1.01-1.78). CONCLUSIONS: This study provides an indication for regional differences in macrovascular disease, which is not explained by traditional risk factors. Further examinations of other risk factors, such as regional deprivation or geographical variations in medical care services are needed.

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