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1.
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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31390012

RESUMO

OBJECTIVE: Impaired glucose tolerance (IGT) is one of the pre-symptomatic states of type 2 diabetes mellitus and requires an oral glucose tolerance test (OGTT) for diagnosis. Our aims were two-fold: 1) characterize signatures of small molecules predicting the OGTT-response and 2) identify metabolic subgroups of participants with IGT. METHODS: Plasma samples from 827 participants of the Study of Health in Pomerania free of diabetes were measured utilizing mass spectrometry and proton-nuclear magnetic resonance spectroscopy. Linear regression analyses were used to screen for metabolites significantly associated with the OGTT-response after two hours adjusting for baseline glucose and insulin levels, as well as important confounders. A signature predictive for IGT was established using regularized logistic regression. All IGT cases (N=159) were selected and subjected to unsupervised clustering using a k-means approach. RESULTS AND CONCLUSION: In total, 99 metabolites and 22 lipoprotein measures were significantly associated with either 2-hour glucose or 2-hour insulin levels. Those comprised variations in baseline concentrations of branched-chain amino keto-acids, acylcarnitines, lysophospholipids or phosphatidylcholines largely confirming previous studies. By the use of these metabolites, IGT-subjects segregated into two distinct groups. Our IGT prediction model combining both clinical and metabolomics traits achieved an AUC of 0.84, slightly improving the prediction based on established clinical measures. The present metabolomics approach revealed molecular signatures associated directly to the response of the OGTT and to IGT in line with previous studies. However, clustering of IGT subjects revealed distinct metabolic signatures of otherwise similar individuals pointing towards the possibility of metabolomics for patient stratification.

3.
Sci Rep ; 9(1): 9439, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263163

RESUMO

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10-8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

4.
Sci Rep ; 9(1): 9693, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273286

RESUMO

The present study evaluated the ability of the visceral adiposity index (VAI), the lipid accumulation product (LAP), and product of triglycerides and glucose (TyG), three novel, insulin resistance-related markers, to discriminate prediabetes/diabetes in the general German population. Altogether 2,045 Germans (31-72 years, 53.3% women) without known diabetes and a history of Myocardial Infarction (MI)/stroke from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study were eligible. The discriminatory accuracy of the markers for oral glucose tolerance test (OGTT)-defined prediabetes/diabetes according to the American Diabetes Association (ADA) criteria was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). The Youden Index (YI) was used to determine optimal cut-off values, and a non-parametric ROC regression was used to examine whether the discriminatory accuracy varied by sex and age. 365 men (38.2%) and 257 women (23.6%) were newly diagnosed with prediabetes/diabetes. AUCs for TyG, LAP and VAI were 0.762 (95% CI 0.740-0.784), 0.743 (95% CI 0.720-0.765), and 0.687 (95% CI 0.662-0.712), respectively. The optimal cut-off values for the LAP and TyG were 56.70 and 8.75 in men, and 30.40 and 8.53 in women. In conclusion, TyG and LAP provide good discrimination of persons with prediabetes/diabetes.

5.
Pharmacoeconomics ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31350720

RESUMO

BACKGROUND AND OBJECTIVE: Accurate prediction of relevant outcomes is important for targeting therapies and to support health economic evaluations of healthcare interventions in patients with diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) risk equations are some of the most frequently used risk equations. This study aims to analyze the calibration and discrimination of the updated UKPDS risk equations as implemented in the UKPDS Outcomes Model 2 (UKPDS-OM2) for predicting cardiovascular (CV) events and death in patients with type 2 diabetes mellitus (T2DM) from population-based German samples. METHODS: Analyses are based on data of 456 individuals diagnosed with T2DM who participated in two population-based studies in southern Germany (KORA (Cooperative Health Research in the Region of Augsburg)-A: 1997/1998, n = 178; KORA-S4: 1999-2001, n = 278). We compared the participants' 10-year observed incidence of mortality, CV mortality, myocardial infarction (MI), and stroke with the predicted event rate of the UKPDS-OM2. The model's calibration was evaluated by Greenwood-Nam-D'Agostino tests and discrimination was evaluated by C-statistics. RESULTS: Of the 456 participants with T2DM (mean age 65 years, mean diabetes duration 8 years, 56% male), over the 10-year follow-up time 129 died (61 due to CV events), 64 experienced an MI, and 46 a stroke. The UKPDS-OM2 significantly over-predicted mortality and CV mortality by 25% and 28%, respectively (Greenwood-Nam-D'Agostino tests: p < 0.01), but there was no significant difference between predicted and observed MI and stroke risk. The model poorly discriminated for death (C-statistic [95% confidence interval] = 0.64 [0.60-0.69]), CV death (0.64 [0.58-0.71]), and MI (0.58 [0.52-0.66]), and failed to discriminate for stroke (0.57 [0.47-0.66]). CONCLUSIONS: The study results demonstrate acceptable calibration and poor discrimination of the UKPDS-OM2 for predicting death and CV events in this population-based German sample. Those limitations should be considered when using the UKPDS-OM2 for economic evaluations of healthcare strategies or using the risk equations for clinical decision-making.

6.
Environ Int ; 129: 221-228, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31132656

RESUMO

BACKGROUND: Associations between several persistent organic pollutants (POPs) and type 2 diabetes have been found in humans, but the relationship has rarely been investigated in the general population. The current nested case-control study examined internal exposure to polychlorinated biphenyls (PCB) and pesticides and the incidence of type 2 diabetes among participants of two population-based German cohort studies. METHODS: We retrospectively selected 132 incident cases of type 2 diabetes and 264 age- and sex-matched controls from the CARdiovascular Living and Aging in Halle (CARLA) study (2002-2006, East Germany) and the Cooperative Health Research in the Region of Augsburg (KORA) study (1999-2001, South Germany) based on diabetes status at follow-up examinations in 2007-2010 and 2006-08, respectively (60% male, mean age 63 and 54 years). We assessed the association between baseline POP concentrations and incident diabetes by conditional logistic regression adjusted for cohort, BMI, cholesterol, alcohol, smoking, physical activity, and parental diabetes. Additionally, we examined effect modification by sex, obesity, parental diabetes and cohort. RESULTS: In both cohorts, diabetes cases showed a higher BMI, a higher frequency of parental diabetes, and higher levels of POPs. We observed an increased chance for incident diabetes for PCB-138 and PCB-153 with an odds ratio (OR) of 1.50 (95%CI: 1.07-2.11) and 1.53 (1.15-2.04) per interquartile range increase in the respective POP. In addition, explorative results suggested higher OR for women and non-obese participants. CONCLUSIONS: Our results add to the evidence on diabetogenic effects of POPs in the general population, and warrant both policies to prevent human exposure to POPs and additional research on the adverse effects of more complex chemical mixtures.

7.
Eur J Nutr ; 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089867

RESUMO

PURPOSE: Inter-individual metabolic differences may be a reason for previously inconsistent results in diet-diabetes associations. We aimed to investigate associations between dietary intake and diabetes for metabolically homogeneous subgroups ('metabotypes') in a large cross-sectional study. METHODS: We used data of 1517 adults aged 38-87 years from the German population-based KORA FF4 study (2013/2014). Dietary intake was estimated based on the combination of a food frequency questionnaire and multiple 24-h food lists. Glucose tolerance status was classified based on an oral glucose tolerance test in participants without a previous diabetes diagnosis using American Diabetes Association criteria. Logistic regression was applied to examine the associations between dietary intake and diabetes for two distinct metabotypes, which were identified based on 16 biochemical and anthropometric parameters. RESULTS: A low intake of fruits and a high intake of total meat, processed meat and sugar-sweetened beverages (SSB) were significantly associated with diabetes in the total study population. Stratified by metabotype, associations with diabetes remained significant for intake of total meat (OR 1.67, 95% CI 1.04-2.67) and processed meat (OR 2.23, 95% CI 1.24-4.04) in the metabotypes with rather favorable metabolic characteristics, and for intake of fruits (OR 0.83, 95% CI 0.68-0.99) and SSB (OR:1.21, 95% CI 1.09-1.35) in the more unfavorable metabotype. However, only the association between SSB intake and diabetes differed significantly by metabotype (p value for interaction = 0.01). CONCLUSIONS: Our findings suggest an influence of metabolic characteristics on diet-diabetes associations, which may help to explain inconsistent previous results. The causality of the observed associations needs to be confirmed in prospective and intervention studies.

8.
Diabetes Res Clin Pract ; 151: 20-32, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30904743

RESUMO

AIMS: To describe the characteristics and treatment of patients with type 2 diabetes mellitus initiating a second-line glucose-lowering therapy in the global DISCOVER study programme. METHODS: DISCOVER comprises two similar 3-year prospective observational studies (NCT02322762 and NCT02226822), involving 15,992 patients initiating a second-line glucose-lowering therapy in 38 countries across six regions (Africa, Americas, South-East Asia, Eastern Mediterranean, Europe and Western Pacific). RESULTS: Overall, 54.2% of patients were male (across region range [ARR]: 37.7-58.6%). At baseline, mean age and time since diagnosis of type 2 diabetes mellitus were 57.2 (ARR: 53.1-61.9)and 5.6 (ARR: 4.6-6.9) years, respectively. Median glycated haemoglobin (HbA1c) was 63.9 mmol/mol (8.0%; ARR: 7.6-8.3%). Microvascular and macrovascular complications were reported in 18.9% (ARR: 14.5-23.5%) and 12.7% (ARR: 5.0-26.6%) of patients, respectively. First-line treatments were mostly metformin monotherapy (55.6%; ARR: 42.5-83.6%) and combinations of metformin with a sulfonylurea (14.4%; ARR: 5.8-31.1%). The most commonly prescribed second-line therapies were combinations of metformin with a dipeptidyl peptidase-4 inhibitor (23.5%; ARR: 2.2-29.6%) or a sulfonylurea (20.9%; ARR: 13.6-57.1%). CONCLUSIONS: DISCOVER demonstrates considerable global variation in the treatment of type 2 diabetes mellitus, and a need for more aggressive risk factor control.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Saúde Global , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-30892596

RESUMO

AIMS: Serum uromodulin has recently emerged as promising biomarker for kidney function and was suggested to be associated with type 2 diabetes (T2D) in coronary patients. Here, we analyzed the association of serum uromodulin with T2D in the population-based KORA F4/FF4 study. METHODS: In 1119 participants of the KORA F4 study aged 62 - 81 years, serum uromodulin was measured and the association of serum uromodulin with T2D was assessed using logistic and linear regression models stratified for sex. After a mean follow-up time of 6.5 years, 635 participants where reevaluated. Glucose tolerance status was determined by oral glucose tolerance test at baseline and at the follow-up examination except in cases of known T2D. RESULTS: Serum uromodulin was inversely associated with T2D in the crude analysis and after adjustment for age and BMI in men (p < 0.001) and in women (p < 0.05). After further adjustment for estimated glomerular filtration rate, serum uromodulin was significantly inversely associated with T2D in men (p < 0.001), but not in women. Serum uromodulin was not associated with prediabetes after multivariate adjustment and did not predict T2D in men or in women after the follow-up time of 6.5 ± 0.3 years. CONCLUSIONS: In participants of the KORA F4 study, serum uromodulin is independently associated with T2D in men, but is no predictor of future development of T2D.

10.
J Clin Endocrinol Metab ; 104(8): 3192-3202, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30865224

RESUMO

CONTEXT: Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and metabolic risks. Recent studies report glucocorticoid cosecretion as a relevant phenotype of PA, which could contribute to associated risks, including type 2 diabetes mellitus (T2DM). The relationship between autonomous cortisol secretion (ACS) and glucose metabolism in PA has not been investigated. OBJECTIVE: To evaluate the prevalence of impaired glucose homeostasis in patients with PA according to cortisol cosecretion. DESIGN: We performed oral glucose tolerance tests (OGTTs) and complete testing for hypercortisolism [1-mg dexamethasone suppression test (DST), late-night salivary cortisol, 24-hour urinary free cortisol] in 161 newly diagnosed patients with PA of the German Conn Registry. Seventy-six of 161 patients were reevaluated at follow-up. We compared our results to a population-based sample from the Cooperative Health Research in the Region of Augsburg (KORA)-F4 study matched to the participants with PA (3:1) by sex, age, and body mass index. RESULTS: At the time of diagnosis, 125 patients (77.6%) had a pathological response in at least one of the Cushing screening tests; T2DM was diagnosed in 6.4% of these 125 cases. Patients with a pathological DST exhibited significantly higher 2-hour plasma glucose in OGTTs and were significantly more often diagnosed with T2DM than were patients with a normal DST (20% vs 0.8%, P < 0.0001) and matched controls from the KORA study (20.6% vs 5.9%, P = 0.022). Patients with PA without ACS tended to have higher homeostatic model assessment of insulin resistance levels than did KORA control subjects (P = 0.05). CONCLUSION: ACS appears frequently in patients with PA and is associated with impaired glucose metabolism, which could increase the risk of T2DM. PA itself seems to enhance insulin resistance.

11.
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
12.
Br J Radiol ; 92(1096): 20180562, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30633543

RESUMO

OBJECTIVE:: To analyze the associations between epicardial and paracardial fat and impaired glucose tolerance as well as left ventricular (LV) alterations. METHODS:: 400 subjects underwent 3 T MRI and fat depots were delineated in the four chamber-view of the steady-state free precession cine sequence (repetition time: 29.97 ms; echo time 1.46 ms). LV parameters were also derived from MRI. Oral glucose tolerance tests were performed. RESULTS:: Epi- and paracardial fat was derived in 372 (93%) subjects (220 healthy controls, 100 persons with prediabetes, 52 with diabetes). Epi- and paracardial fat increased from normal glucose tolerance (NGT) to prediabetes and diabetes (7.7 vs 9.2 vs 10.3 cm2 and 14.3 vs 20.3 vs 27.4 cm2, respectively; all p < 0.001). However, the association between impaired glucose metabolism and cardiac fat attenuated after adjustment, mainly confounded by visceral adipose tissue (VAT). 93 subjects (27%) had LV impairment, defined as late gadolinium enhancement, ejection fraction < 55% or LV concentricity index > 1.3 g ml-1 . Mean epicardial fat was higher in subjects with LV impairment (11.0 vs 8.1 cm2, p < 0.001). This association remained independent after adjustment for traditional risk factors and VAT [ß: 1.13 (0.22; 2.03), p = 0.02]. CONCLUSION:: Although epicardial and paracardial fat are increased in prediabetes and diabetes, the association is mostly confounded by VAT. Epicardial fat is independently associated with subclinical LV impairment in subjects without known cardiovascular disease. ADVANCES IN KNOWLEDGE:: This study contributes to the picture of epicardial fat as a pathogenic local fat depot that is independently associated with MR-derived markers of left ventricular alterations.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Glucose/metabolismo , Ventrículos do Coração/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Pericárdio/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Disfunção Ventricular Esquerda/fisiopatologia
14.
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.

15.
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.

16.
J Thorac Imaging ; 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30570523

RESUMO

PURPOSE: Myocardial strain analysis is a promising tool for the detection of subtle but relevant alterations of left ventricular function, also in asymptomatic subjects. Thus, we determined the feasibility of cardiac magnetic resonance-based 2D global strain analysis using feature tracking and its association with cardiovascular risk factors in a sample from the general population. MATERIALS AND METHODS: Subjects without a history of cardiocerebrovascular disease were enrolled in a substudy of the population-based KORA (Cooperative Health Research in the Region of Augsburg) cohort. In all participants with the absence of late gadolinium enhancement, longitudinal and circumferential global strains were measured on Cine SSFP imaging (TR: 29.97 ms, TE: 1.46 ms, ST: 8 mm), using a semiautomatic segmentation algorithm (CVI42, Circle, Canada). Differences in strain values according to age, sex, body mass index, hypertension, diabetes mellitus, and hyperlipidemia were derived using linear regression analysis. RESULTS: Among 360 subjects (mean age, 56.2±9.2 y, 57% male), the average global systolic radial strain was 40.1±8.2%, circumferential 19.9±2.7%, and longitudinal 19.8±3.2%. Male sex was associated with decreased global strain values, independent of the strain direction (all P<0.001). Although many cardiovascular risk factors were correlated with strain in univariate analysis, mainly waist-to-hip ratio and HbA1c remained associated with decreased radial and circumferential strains in fully adjusted models. Similarly, higher radial and circumferential strains were observed in older subjects (ß=0.14, P=0.01 and ß=0.11, P=0.04, respectively). CONCLUSIONS: Strain analysis using magnetic resonance feature tracking is feasible in population-based cohort studies and shows differences with respect to age and sex as well as an independent association with markers of metabolic syndrome.

17.
Diabetologia ; 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413829

RESUMO

AIMS/HYPOTHESIS: The aim of this study was to investigate the modifying effect of the glucose transporter (GLUT2) gene SLC2A2 (rs8192675) variant on the glycaemic response to metformin in individuals recently diagnosed with type 2 diabetes. METHODS: Individuals with type 2 diabetes (n = 508) from the prospective German Diabetes Study (age [mean ± SD] 53 ± 10 years; 65% male; BMI 32 ± 6 kg/m2, metformin use 57%) underwent detailed metabolic characterisation (hyperinsulinaemic-euglycaemic clamp, IVGTT) during the first year after diagnosis. Participants provided self-reported data from the time of diagnosis. The change in fasting glucose was assessed in relation to SLC2A2 genotype and glucose-lowering treatment using two-way ANCOVA with gene×treatment interactions adjusted for age, sex, BMI and diabetes duration. RESULTS: The C variant allele of rs8192675 was associated with a higher prevalence of diabetes symptoms at diabetes diagnosis. In the metformin monotherapy group only, patients with a C allele showed a larger adjusted blood glucose reduction during the first year after diabetes diagnosis than patients with the TT genotype (6.3 mmol/l vs 3.9 mmol/l; genotype difference 2.4 mmol/l, p = 0.02; p value for genotype interaction [metformin monotherapy vs non-pharmacological therapy] <0.01). The greater decline in fasting glucose (CC/CT vs TT) in metformin monotherapy persisted after further adjusting for glucose values at diagnosis (genotype difference 1.0 mmol/l, p = 0.01; genotype×treatment interaction p = 0.06). CONCLUSIONS/INTERPRETATION: The variant rs8192675 in the SLC2A2 gene (C allele) is associated with an improved glucose response to metformin monotherapy during the first year after diagnosis in type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01055093.

18.
Cardiovasc Diabetol ; 17(1): 150, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30486889

RESUMO

BACKGROUND: The global prevalence of type 2 diabetes-related complications is not well described. We assessed prevalence of vascular complications at baseline in DISCOVER (NCT02322762; NCT02226822), a global, prospective, observational study program of 15,992 patients with type 2 diabetes initiating second-line therapy, conducted across 38 countries. METHODS: Patients were recruited from primary and specialist healthcare settings. Data were collected using a standardized case report form. Prevalence estimates of microvascular and macrovascular complications at baseline were assessed overall and by country and region, and were standardized for age and sex. Modified Poisson regression was used to assess factors associated with the prevalence of complications. RESULTS: The median duration of type 2 diabetes was 4.1 years (interquartile range [IQR]: 1.9-7.9 years), and the median glycated hemoglobin (HbA1c) level was 8.0% (IQR: 7.2-9.1%). The crude prevalences of microvascular and macrovascular complications were 18.8% and 12.7%, respectively. Common microvascular complications were peripheral neuropathy (7.7%), chronic kidney disease (5.0%), and albuminuria (4.3%). Common macrovascular complications were coronary artery disease (8.2%), heart failure (3.3%) and stroke (2.2%). The age- and sex-standardized prevalence of microvascular complications was 17.9% (95% confidence interval [CI] 17.3-18.6%), ranging from 14.2% in the Americas to 20.4% in Europe. The age- and sex-standardized prevalence of macrovascular complications was 9.2% (95% CI 8.7-9.7%), ranging from 4.1% in South-East Asia to 18.8% in Europe. Factors positively associated with vascular complications included age (per 10-year increment), male sex, diabetes duration (per 1-year increment), and history of hypoglycemia, with rate ratios (95% CIs) for microvascular complications of 1.14 (1.09-1.19), 1.30 (1.20-1.42), 1.03 (1.02-1.04) and 1.45 (1.25-1.69), respectively, and for macrovascular complications of 1.41 (1.34-1.48), 1.29 (1.16-1.45), 1.02 (1.01-1.02) and 1.24 (1.04-1.48), respectively. HbA1c levels (per 1.0% increment) were positively associated with microvascular (1.05 [1.02-1.08]) but not macrovascular (1.00 [0.97-1.04]) complications. CONCLUSIONS: The global burden of microvascular and macrovascular complications is substantial in these patients with type 2 diabetes who are relatively early in the disease process. These findings highlight an opportunity for aggressive early risk factor modification, particularly in regions with a high prevalence of complications. Trial registration ClinicalTrials.gov; NCT02322762. Registered 23 December 2014. https://clinicaltrials.gov/ct2/show/NCT02322762 . ClinicalTrials.gov; NCT02226822. Registered 27 August 2014. https://clinicaltrials.gov/ct2/show/NCT02226822.

19.
BMC Endocr Disord ; 18(1): 72, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326888

RESUMO

BACKGROUND: Little evidence exists on the impact of diabetes risk scores, e.g. on physicians and patient's behavior, perceived risk of persons, shared-decision making and particularly on patient's health. The aim of this study is to investigate the impact of a non-invasive type 2 diabetes risk prediction model in the primary health care setting as component of routine health checks on change in physical activity. METHODS: Parallel group cluster randomized controlled trial including 30 primary care physicians (PCPs) and 300 participants in the region of Düsseldorf and surrounding urban and rural municipalities, West Germany. On cluster level, PCPs will be randomized into intervention or control group using a biased coin minimization technique. Participants in the control group are going to have a routine health check "Check-up 35" which is recommended biannually for all people ≥35 years of age in Germany. In the intervention group, the routine health check is expanded by usage of a non-invasive diabetes risk prediction model (German Diabetes Risk Score). Primary outcome is change in physical activity after 1 year. Secondary outcomes include aspects of targeted counseling, motivation of participant's to change lifestyle, perceived and objectively measured diabetes risk, acceptance of diabetes risk scores, quality of life, depression and anxiety. Patients will be followed over 12 months. Hierarchical or mixed models will be conducted, including a random intercept to adjust for cluster, the respective baseline value, and covariates to compare the groups. DISCUSSION: This pragmatic cluster randomized controlled trial will enhance our knowledge on the clinical impact of diabetes risk scores for the first time in the real-life primary health care setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT03234322 , registered on July 28, 2017.

20.
Int J Clin Pharmacol Ther ; 56(10): 459-466, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30168417

RESUMO

PURPOSE: The aim of this study was to evaluate the representativeness of diagnoses in the Disease Analyzer (DA) database for major chronic diseases (cancer, dementia, diabetes). MATERIALS AND METHODS: DA contains anonymized longitudinal data on drug prescriptions, diagnoses as well as medical and demographic data directly obtained from the computer system of a representative sample of practices throughout Germany. DA contains data from 2,498 practices with 7.8 million patients (2017). The distribution and sex-specific incidence of various cancer subsites among new cancer cases, the age- and sex-specific prevalence of dementia, and the prevalence of diabetes were assessed. National reference data were obtained from official sources. RESULTS: Mean age (43 years) and sex distribution (47% men) of primary care patients in DA were similar to the German population. Among incident cancer cases, there was good agreement between DA data and national data with respect to the various cancer subsites (e.g., breast cancer: DA 17%; reference: 15%). Furthermore, sex distribution was largely similar. The age distribution of prevalent dementia was similar to national reference data, both in men (80 - 84 years: DA: 26.8%; reference: 27.0%) and in women (80 - 84 years: DA: 24.6%; reference: 24.1%). Diabetes prevalence in the DA (10.7%) was higher than in claims data from physicians (9.8%) or patients from statutory health insurances (9.9%). CONCLUSION: There was a good agreement of the incidence or prevalence of major chronic diseases in the outpatient DA with German reference data. The higher diabetes prevalence in the DA is due to the increased number of outpatient visits of diabetes patients.
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Assuntos
Bases de Dados Factuais , Farmacoepidemiologia/métodos , Padrões de Prática Médica/estatística & dados numéricos , Demografia , Métodos Epidemiológicos , Alemanha , Humanos , Médicos/estatística & dados numéricos , Fatores de Risco
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