RESUMO
The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2-3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4-5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.
Assuntos
Estudos Prospectivos , Masculino , Humanos , Feminino , Estudos de Coortes , Alemanha/epidemiologia , Inquéritos e Questionários , AutorrelatoRESUMO
BACKGROUND: Until now, herpes zoster (HZ)-related disease burden in Germany has been estimated based on health insurance data and clinical findings. However, the validity of self-reported HZ is unclear. This study investigated the validity of self-reported herpes zoster (HZ) and its complication postherpetic neuralgia (PHN) using data from the pretest studies of the German National Cohort (GNC) in comparison with estimates based on health insurance data. METHODS: Data of 4751 participants aged between 20 and 69 years from two pretest studies of the GNC carried out in 2011 and 2012 were used. Based on self-reports of physician-diagnosed HZ and PHN, age- and sex-specific HZ incidence rates and PHN proportions were estimated. For comparison, estimates based on statutory health insurance data from the German population were considered. RESULTS: Eleven percent (95%-CI, 10.4 to 12.3, n = 539) of the participants reported at least one HZ episode in their lifetime. Our estimated age-specific HZ incidence rates were lower than previous estimates based on statutory health insurance data. The PHN proportion in participants older than 50 years was 5.9% (1.9 to 13.9%), which was in line with estimates based on health insurance data. CONCLUSION: As age- and sex-specific patterns were comparable with that in health insurance data, self-reported diagnosis of HZ seems to be a valid instrument for overall disease trends. Possible reasons for observed differences in incidence rates are recall bias in self-reported data or overestimation in health insurance data.
Assuntos
Herpes Zoster/epidemiologia , Neuralgia Pós-Herpética/epidemiologia , Autorrelato , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Herpes Zoster/etiologia , Herpes Zoster/prevenção & controle , Herpes Zoster/virologia , Herpesvirus Humano 3 , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/etiologia , Neuralgia Pós-Herpética/prevenção & controle , Neuralgia Pós-Herpética/virologia , Reprodutibilidade dos Testes , Fatores Sexuais , Inquéritos e Questionários , Adulto JovemRESUMO
AIMS/HYPOTHESIS: The role of biomarkers of subclinical inflammation in the early deterioration of glycaemia before type 2 diabetes is largely unknown. We hypothesised that increased levels of circulating proinflammatory biomarkers and decreased circulating adiponectin would be associated with 7 year increases of HbA(1c) in non-diabetic individuals. METHODS: This study was based on individuals who participated in the prospective Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999-2001) and the 7 year follow-up KORA F4 (2006-2008) survey. Individuals with type 2 diabetes at baseline or with a diagnosis of diabetes in the period between both surveys were excluded, which left a sample of 850 men and women. Multivariable linear regression analyses were performed to assess associations among baseline values of leucocyte count and levels of acute-phase proteins (high-sensitivity C-reactive protein [hsCRP], serum amyloid A [SAA] and fibrinogen), IL-6 and adiponectin with changes in HbA1c between baseline and follow-up. RESULTS: A high leucocyte count and high hsCRP, SAA and IL-6 levels were positively associated with changes in HbA(1c) after adjusting for age, sex, lifestyle factors and baseline HbA(1c). In contrast, the adiponectin level was inversely associated with changes in HbA(1c) (p value between <0.0001 and 0.020). The associations of leucocyte count and levels of hsCRP and SAA with HbA(1c) changes remained significant after additional adjustment for waist circumference and circulating lipids at baseline and for the 7 year change in waist circumference (p value between 0.004 and 0.045). CONCLUSIONS/INTERPRETATION: An elevated leucocyte count and elevated hsCRP and SAA were associated with early deterioration of glycaemia before the diagnosis of type 2 diabetes. These associations were largely independent of baseline abdominal adiposity and increases in waist circumference.
Assuntos
Adiponectina/sangue , Glicemia , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Inflamação/diagnóstico , Proteínas de Fase Aguda/metabolismo , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Fibrinogênio/metabolismo , Humanos , Inflamação/sangue , Inflamação/complicações , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteína Amiloide A Sérica/metabolismoRESUMO
High field MR scanners can resolve a metabolite resonating at 2.06 ppm in the in vivo proton-decoupled liver (31) P MR spectrum. Traditionally this peak has been assigned to phosphoenolpyruvate (PEP), the key metabolite for gluconeogenesis. However, recent evidence supported the assignment to biliary phosphatidylcholine (PtdCh), which is produced in the liver and stored in the gall bladder. To elucidate the respective contributions of PtdCh and PEP to the in vivo resonance at 2.06 ppm (PEP-PtdCh), we made phantom measurements that confirmed that both biliary PtdCh and PEP resonate approximately at 2 ppm. The absolute quantification of PEP-PtdCh yielded concentrations ranging from 0.6 to 2.0 mmol/l, with mean coefficients of variation of 4.8% for intraday and 7.2% for interday reproducibility in healthy volunteers. The T1 relaxation time of PEP-PtdCh was 0.97 ± 0.30 s in the liver and 0.44 ± 0.11 s in the gallbladder. Ingestion of a mixed meal decreased the concentration of PtdCh-PEP by approximately 12%. In the retrospective analysis, PEP-PtdCh was 68% higher in the liver of subjects with gallbladder infiltration of the volume of interest (VOI) compared with those without gallbladder infiltration. PEP-PtdCh was also significantly higher in the liver of cholecystectomy patients compared with volunteers without gallbladder infiltration, which suggests increased intrahepatic bile fluid as a compensation for gall bladder removal. These results show that liver PtdCh is the major component of the resonance at 2.06 ppm and that careful VOI positioning is mandatory to avoid interference from the gallbladder.
Assuntos
Testes de Função Hepática/métodos , Fígado/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Fosfatidilcolinas/metabolismo , Fosfoenolpiruvato/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isótopos de Fósforo/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição TecidualRESUMO
PURPOSE: The aims of this study were (i) to establish a robust and fast method to quantify hepatocellular phosphorus compounds in molar concentration on a 3T clinical scanner, (ii) to evaluate its reproducibility, and (iii) to test its feasibility for a use in large cohort studies. METHOD: Proton-decoupled (31) P magnetic resonance spectroscopy of liver (31) P compounds were acquired on 85 healthy subjects employing image selected in-vivo spectroscopy localization in 13 min of acquisition at 3T. Absolute quantification was achieved using an external reference and double-matching phantoms (inorganic phosphates and adenosine triphosphate (ATP) solutions). Reproducibility of the method was also examined. RESULTS: This method showed a high intra- and interday as well as inter- and intraobserver reproducibility (r > 0.98; P < 0.001), with a high signal to noise ratio (SNR) (i.e., mean SNR of γ-ATP: 16). The mean liver concentrations of 85 healthy subjects were assessed to be 1.99 ± 0.51 and 2.74 ± 0.55 mmol/l of wet tissue volume for Pi and γ-ATP, respectively. CONCLUSION: This method reliably quantified molar concentrations of liver (31) P compounds on 85 subjects with a short total examination time (â¼25 min) on a 3T clinical scanner. Thus, the current method can be readily utilized for a clinical study, such as a large cohort study.
Assuntos
Fígado/metabolismo , Fosfatos/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/instrumentação , Espectroscopia de Prótons por Ressonância Magnética/métodos , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Isótopos de Fósforo/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The aim of the study was to analyse mortality after a first myocardial infarction (MI) and its trends in people with diabetes compared to those without diabetes in Southern Germany, 1985-2009. Using data of the population-based MONICA/KORA Myocardial Infarction Registry, we ascertained all patients with a first fatal or non-fatal MI between 1985 and 2009 (n = 16,478, age 25-74 years, 71% male, 29% with diabetes). The impact of diabetes and calendar time on mortality was examined using multiple logistic and Cox regression. Survival improved with calendar time: The crude cumulative 5-year survival was 26.9 and 46.3% among diabetic and non-diabetic individuals (both sexes combined) with a first MI in the years 1985-1989, and 53.6 and 66.6% among those with a first MI in the years 2005-2009. This significant decrease of mortality was confirmed in multivariate analyses. The proportion of fatal first MIs was significantly higher in diabetic compared to non-diabetic patients [adjusted odds ratio (OR) 1.26; 95% confidence interval 1.17-1.36]. This association persisted in a similar manner between both sexes with no consistent change of OR over calendar time in which first MIs have been observed. Likewise, multiple adjusted risk of death after a non-fatal first MI was significantly higher among both diabetic men and women [hazard ratio (HR) 1.64; 1.47-1.82, 1.83; 1.55-2.14] with constant HR over calendar time. During the past 25 years, survival has improved in both diabetic and non-diabetic patients with incident MI in a similar manner. However, mortality after a first MI remained significantly higher in the diabetic population, particularly in women.
Assuntos
Complicações do Diabetes , Diabetes Mellitus/epidemiologia , Infarto do Miocárdio/mortalidade , Sistema de Registros/estatística & dados numéricos , Adulto , Idoso , Estudos de Casos e Controles , Causas de Morte/tendências , Angiopatias Diabéticas/mortalidade , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/complicações , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
OBJECTIVE: Despite modern therapeutic regimens, youths with Type 1 diabetes may be at increased risk of mental and behavioral disorders. In this study, the prevalence of disordered eating behavior (DEB) in intensely treated children and adolescents with early-onset Type 1 diabetes and peers from the general population was compared. METHOD: Data from 629 patients from a population-based, nationwide survey (54.1% male, mean age 15.3 years) with early-onset Type 1 diabetes of at least 10 years duration were compared with data from 6,813 participants of the German KiGGS study (51.3% male, mean age 14.6 years). The generic SCOFF questionnaire was used as screening instrument to identify participants with symptoms of DEB. Both groups were compared with multivariable regression analysis adjusting for sociodemographic covariates. RESULTS: 31.2% of the female and 11.7% of the male diabetic patients and 28.9% of the females and 15.2% of the males in the comparison group were SCOFF-positive (SCOFF score ≥2; p > .05). The odds for symptoms of eating disorders were 3.7% higher in female and 4.3% lower in male patients with diabetes than in the comparison group, but the differences were not significant. 20.5% of the female and 18.5% of the male diabetic patients reported insulin restriction at least three times per week. DISCUSSION: Children and adolescents with early-onset Type 1 diabetes of long duration do not seem to be more frequently SCOFF-positive than peers. However, as insulin restriction is practiced in a substantial portion of patients, attention for insulin restriction in diabetes care is essential.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Feminino , Alemanha/epidemiologia , Inquéritos Epidemiológicos , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Prevalência , Inquéritos e QuestionáriosRESUMO
OBJECTS: Hepatic and pancreatic fat content become increasingly important for phenotyping of individuals with metabolic diseases. This study aimed to (1) evaluate hepatic fat fractions (HFF) and pancreatic fat fractions (PFF) using (1)H magnetic resonance spectroscopy (MRS) and the recently introduced fast mDixon method, and to examine body fat effects on HFF and PFF, (2) investigate regional differences in HFF and PFF by mDixon. MATERIALS AND METHODS: HFF and PFF were quantified by mDixon with two flexible echo times and by single voxel (1)H MRS in 24 healthy subjects. The regional differences of PFF within the pancreas were assessed with mDixon. Abdominal visceral and subcutaneous fat was assessed by T1-weighted MRI at 3T. RESULTS: Both methods correlated well for quantification of HFF (r = 0.98, p < 0.0001) and PFF (r = 0.80, p < 0.0001). However, mDixon showed a higher low limit in HFF and PFF. PFF showed no regional differences using mDixon. In addition, both visceral and subcutaneous fat correlated with pancreatic fat, while only visceral fat correlated with liver fat, employing both (1)H MRS and mDixon. CONCLUSION: The novel and fast two-point mDixon exhibits a good correlation with the gold-standard (1)H MRS for assessment of HFF and PFF, with limited sensitivity for assessing lower fat content.
Assuntos
Tecido Adiposo/anatomia & histologia , Fígado/anatomia & histologia , Espectroscopia de Ressonância Magnética/métodos , Pâncreas/anatomia & histologia , Gordura Abdominal/anatomia & histologia , Feminino , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gordura Subcutânea/anatomia & histologia , Imagem Corporal TotalRESUMO
Type 2 diabetes (T2D) can be prevented in pre-diabetic individuals with impaired glucose tolerance (IGT). Here, we have used a metabolomics approach to identify candidate biomarkers of pre-diabetes. We quantified 140 metabolites for 4297 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) cohort. Our study revealed significant metabolic variation in pre-diabetic individuals that are distinct from known diabetes risk indicators, such as glycosylated hemoglobin levels, fasting glucose and insulin. We identified three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2) and acetylcarnitine) that had significantly altered levels in IGT individuals as compared to those with normal glucose tolerance, with P-values ranging from 2.4×10(-4) to 2.1×10(-13). Lower levels of glycine and LPC were found to be predictors not only for IGT but also for T2D, and were independently confirmed in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Using metabolite-protein network analysis, we identified seven T2D-related genes that are associated with these three IGT-specific metabolites by multiple interactions with four enzymes. The expression levels of these enzymes correlate with changes in the metabolite concentrations linked to diabetes. Our results may help developing novel strategies to prevent T2D.
Assuntos
Biomarcadores/metabolismo , Metabolômica/métodos , Estado Pré-Diabético/metabolismo , Idoso , Glicemia/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Jejum/sangue , Feminino , Alemanha , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
This article describes new relationships between the age-specific incidence of, the prevalence of and mortality from a chronic disease. We express these relationships in terms of an ordinary differential equation and form the methodological basis for a novel approach to estimating incidences from age-specific prevalence data. We examine practical aspects of the relationships and a comparison with a known stochastic method in a simulation study. Finally, we apply the novel method to a data set of renal replacement therapy recorded from patients with chronic kidney failure in a region of Germany with approximately 310,000 inhabitants from 2002 to 2010.
Assuntos
Doença Crônica/epidemiologia , Interpretação Estatística de Dados , Métodos Epidemiológicos , Adulto , Idoso , Doença Crônica/mortalidade , Simulação por Computador , Estudos Transversais , Alemanha/epidemiologia , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/mortalidade , Pessoa de Meia-Idade , PrevalênciaRESUMO
The objectives of this study are to estimate the recent population-based incidences of all-cause and cause-specific blindness in Germany and compare them with results from a similar study conducted in 1994-1998. All blindness allowance recipients newly registered between January 2008 and December 2009 in a region in southern Germany (population, approximately 3.5 million) were assessed and their ophthalmological reports reviewed. The main causes of blindness were identified and their incidences estimated. There were 572 newly registered cases of blindness allowance. The all-cause incidence of blindness (per 100,000 person-years) in the general population was 8.4 (95 % confidence interval, 7.8-9.2), and the highest incidences were for macular degeneration (3.4; 3.0-3.9), diabetic retinopathy (0.8; 0.6-1.1) and glaucoma (0.7; 0.5-0.9). During the last two decades, blindness incidences decreased for all the main causes (standardised to the West German population 1991: 12.3; 11.9-12.7 in 1994-1998 vs. 7.3; 6.7-8.0 in 2008-2009). The highest absolute decrease was for macular degeneration and the highest relative decrease was for cataract. The most frequent main causes of blindness in Germany remained macular degeneration, diabetic retinopathy and glaucoma. Our findings suggest a remarkable decrease in the incidences of blindness, probably because of new diagnostic options and effective treatments.
Assuntos
Cegueira/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Retinopatia Diabética/epidemiologia , Feminino , Alemanha/epidemiologia , Glaucoma/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
Low childhood socioeconomic status (SES) has been linked with insulin resistance (HOMA-IR) in adulthood. Our aim was to examine if maternal and paternal education, as indicators of childhood SES, equally contributed to increased HOMA-IR in later life. Of 5,115 adults from the Coronary Artery Disease Risk Development in Young Adults (CARDIA) Study aged 18-30 years in 1985-1986, data on 1,370 females and 1,060 males with baseline and 20 year follow-up data were used to estimate associations of maternal and paternal education with HOMA-IR, adjusting for personal education, BMI, lipids, blood pressure, and lifestyle factors. Parental education was determined as high with ≥ 12 years of schooling and classified as both high, only mother high, only father high, both low education. Distinct combinations of maternal and paternal education were associated with HOMA-IR across race and sex groups. Lowest year 20 HOMA-IR in European American (EA) females occurred when both parents were better educated, but was highest when only the father had better education. HOMA-IR was lowest in African American (AA) participants when the mother was better educated but the father had less education, but was highest when both parents were better educated. Parental education was unrelated to HOMA-IR in EA males. Associations of parental education with HOMA-IR are seen in AA females, AA males, and EA females but not in EA males. The distinct combinations of parental education and their associations with HOMA-IR especially in AA participants need to be addressed in further research on health disparities.
Assuntos
Disparidades nos Níveis de Saúde , Resistência à Insulina , Adolescente , Adulto , Negro ou Afro-Americano , Escolaridade , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Resistência à Insulina/etnologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pais , Autorrelato , Fatores Sexuais , Fatores Socioeconômicos , Estados Unidos , Saúde da População Urbana , População Branca , Adulto JovemRESUMO
OBJECTIVE: Insulin glulisine has a higher efficacy in reducing postprandial glucose excursions and in restoring normal postprandial microcirculation than rapid human insulin. The aim was to compare the incidence of macro- and microvascular outcomes in Type 2 diabetic patients treated with insulin glulisine or regular human insulin. MATERIALS: Computerized data from 952 glulisine (age: 61 ± 11 y) and 11,157 regular insulin (65 ± 11 y) users in general practices throughout Germany (Disease Analyzer, 11/2004 to 3/2010) were analyzed. METHODS: Hazard ratios (HR; Cox regression) for 3.5-year-risk of macro- or microvascular outcomes were adjusted for age, sex, diabetes duration, diabetologist care, hypertension, hyperlipidemia, depression, and comedication (basal insulin, oral antidiabetics). Furthermore, adjustment was carried out for baseline microvascular complications when analyzing macrovascular outcomes and vice versa. RESULTS: Overall, risk for macro- or microvascular outcomes was 20% lower for insulin glulisine users (p < 0.05). There was a decreased risk for coronary heart disease (HR; 95%CI: 0.78; 0.62 - 0.99), and an indication for a lower risk for incident myocardial infarction (HR: 0.66; 0.43 - 1.02). Also for microvascular complications, the adjusted hazard ratios for retinopathy, nephropathy and neuropathy were below 1.0, indicating a lower risk for the insulin glulisine group, however, which was significant for neuropathy only (HR: 0.74; 0.58 - 0.93). CONCLUSIONS: Prescription of the rapid-acting insulin analog glulisine was associated with a reduced incidence of macro- and microvascular outcomes in Type 2 diabetes under real-life conditions. Given that this was a retrospective database analysis, it is important to confirm this finding in a randomized controlled trial.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Microvasos/efeitos dos fármacos , Idoso , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/fisiopatologia , Intervalo Livre de Doença , Feminino , Medicina Geral , Alemanha/epidemiologia , Humanos , Incidência , Insulina/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Microcirculação/efeitos dos fármacos , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to examine the epidemiology and mortality risk of patients with incident end-stage renal disease (ESRD) in diabetic and non-diabetic individuals and to determine differences between sexes. METHODS: We used the claims data of a statutory health insurance company. Patients aged 30 years and older who started dialysis or had pre-emptive kidney transplantation between 1 April 2006 and 7 October 2008 were included. We estimated incidence rates of ESRD according to diabetes status, sex and age as well as relative and attributable risks due to diabetes. Using Cox regression, we studied survival and estimated time-dependent hazard ratios (HR). RESULTS: We included 623 patients with incident ESRD (n = 254 had diabetes); 477 (76.6%) were male, and the mean age was 66.5 years. Standardized to the German population, incidences of ESRD in patients with and without diabetes were 157.9 and 25.6 per 100,000 person-years respectively (6.2-fold increased risk). The impact of diabetes on mortality was time-dependent. Diabetics had an increased mortality risk after the first year. An interaction of diabetes with time (per additional year of follow-up) was found in the whole population (HR 2.01, 95% CI 1.21-3.33) and in females (HR 3.27, 95% CI 1.03-10.39); however, males did not reach statistical significance (HR 1.78, 95% CI 0.99-3.18). The fixed baseline effect of diabetes in these models was non-significant (HR ~ 0.7-0.8). CONCLUSIONS: Diabetes is an important risk factor for ESRD. We provide further evidence that the impact of diabetes on survival after ESRD is time-dependent and that differences between sexes might exist.
Assuntos
Complicações do Diabetes/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/mortalidade , Feminino , Seguimentos , Alemanha , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: This study was conducted to estimate incidences of renal replacement therapy (RRT) in the diabetic and non-diabetic populations in Germany, as well as relative and attributable risks of RRT due to diabetes. METHODS: Using the data of a regional dialysis centre (region population of 310 000), we assessed all incident RRT patients aged 30 years or older in 2002-08. We estimated sex- and age-specific and -standardized incidences of RRT in the diabetic and non-diabetic populations, which were estimated by applying diabetes prevalences from a population-based study, and relative and attributable risks due to diabetes. RESULTS: Of all subjects with incident RRT (n = 544), 49.6% had diabetes. Fifty-eight percent were male, mean age (SD) was 70.3 years (11.4 years). Incidences per 100 000 person-years (standardized to the 2004 German population) in the diabetic and the non-diabetic populations were 213.7 [95% confidence interval (95% CI), 159.5-267.8] and 26.9 (95% CI, 22.5-31.3) in men and 130.2 (95% CI, 65.6-194.9) and 16.4 (95% CI, 13.5-19.3) in women, respectively. Standardized relative risks were 7.9 (5.9-10.8) in men and 8.0 (4.7-13.5) in women. There was a significant interaction between age and diabetes, with lower relative risks in higher ages. Attributable risks among diabetic individuals were 0.87 in men and women, and population-attributable risks were 0.41 and 0.35 in men and women, respectively. CONCLUSIONS: In this population-based study in a German region, we found the relative risk of RRT in the estimated adult diabetic population to be 8-fold increased compared with the non-diabetic population. A high proportion of the RRT risk can be attributed to diabetes in the diabetic as well as in the whole population.
Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus/terapia , Falência Renal Crônica/complicações , Terapia de Substituição Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/mortalidade , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Diálise Renal , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We investigated the association of undiagnosed diabetes, previously known diabetes and prediabetes (WHO 1999 classification) with all-cause and cause-specific mortality in an older German population. Previous study results for mortality in patients with very low levels of HbA1c, fasting plasma glucose (FPG), and 2-h plasma glucose (2hPG) are still inconclusive. Thus we have extended the analyses to continuous measures of glycemia. A total of 1,466 subjects aged 55-74 years from the population-based KORA survey S4 (conducted from 1999 to 2001) were included in our observational mortality study (152 subjects with previously known diabetes, and 1,314 further subjects who underwent oral glucose tolerance tests). Mortality was followed up for a maximum of 10.0 years (median follow-up 8.8 years). A total of 180 (12.3%) of the 1,466 subjects have died during the follow-up period. The age- and sex-adjusted hazard ratios for all-cause mortality were 2.6 (95%CI, 1.7-3.8) for known diabetes, 2.8 (95%CI, 1.7-4.4) for undiagnosed diabetes, and 1.1 (95%CI, 0.8-1.7) for prediabetes [reference: normal glucose tolerance (NGT)]. After multivariable adjustment, undiagnosed diabetes was associated with 3.0-fold increased cancer mortality, 1.1-fold increased cardiovascular mortality, and 4.7-fold increased non-cancer, non-cardiovascular mortality compared with NGT. For HbA1c, FPG, and 2hPG, J-shaped associations with all-cause mortality were observed. Undiagnosed diabetes is associated with increased all-cause, cancer, and non-cancer non-cardiovascular mortality, but not with cardiovascular mortality in this older population. All-cause mortality in undiagnosed diabetes is similar to that in previously known diabetes but much higher than mortality in prediabetes and NGT.
Assuntos
Glicemia/metabolismo , Causas de Morte , Diabetes Mellitus Tipo 2/sangue , Estado Pré-Diabético/sangue , Idoso , Doenças Cardiovasculares/mortalidade , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Alemanha/epidemiologia , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/mortalidade , Modelos de Riscos Proporcionais , Medição de RiscoRESUMO
BACKGROUND: Population-based estimates of costs of renal replacement therapy are scarce in the literature. The aim of our study was to calculate the costs of long-term dialysis in 2006 on the basis of patient-specific data from a well-defined population in a region in western Germany (n = 310,757). METHODS: Cost estimation was performed from the perspective of the statutory health insurance. All dialysis patients from the study region (n = 344, 54% male, mean age (+/-SD) 69 +/- 13 years, 42% diabetic) were assessed for the costs of the dialysis procedures, dialysis-related hospital admissions, outpatient contacts outside of our dialysis center, dialysis-related medication, patient transportation and related costs (e.g. reimbursement fees on the basis of the German diagnosis-related group system, price scales). We estimated the cumulative cost per patient year in 2006 (in Euros), along with the 10th and 90th percentiles and the 95% confidence intervals (CI) by using bootstrapping procedures. RESULTS: The mean total dialysis-related cost in 2006 was 54,777 Euros (95% CI, 51,445-65,705) per patient year. The largest part of the costs (55%) was caused by the dialysis procedures, followed by the costs of medication (22%), hospitalization (14%) and transportation (8%). The total cost increased significantly with increasing age. No significant association was found between total cost and sex, dialysis strategy, end-stage renal disease duration and diabetes. CONCLUSIONS: We present for the first time a cost estimation of dialysis in Germany on the basis of patient-level data in a population-based sample. Except age, patient characteristics were not significantly associated with costs. The largest part of the costs was caused by the dialysis procedures themselves; however, other dialysis-specific health care utilization also strongly contributed to the total cost.
Assuntos
Custos de Cuidados de Saúde , Diálise Renal/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção à Saúde/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We study the link between two quality measures of SNP (single nucleotide polymorphism) data in genome-wide association (GWA) studies, that is, per SNP call rates (CR) and p-values for testing Hardy-Weinberg equilibrium (HWE). The aim is to improve these measures by applying methods based on realized randomized p-values, the false discovery rate and estimates for the proportion of false hypotheses. While exact non-randomized conditional p-values for testing HWE cannot be recommended for estimating the proportion of false hypotheses, their realized randomized counterparts should be used. P-values corresponding to the asymptotic unconditional chi-square test lead to reasonable estimates only if SNPs with low minor allele frequency are excluded. We provide an algorithm to compute the probability that SNPs violate HWE given the observed CR, which yields an improved measure of data quality. The proposed methods are applied to SNP data from the KORA (Cooperative Health Research in the Region of Augsburg, Southern Germany) 500 K project, a GWA study in a population-based sample genotyped by Affymetrix GeneChip 500 K arrays using the calling algorithm BRLMM 1.4.0. We show that all SNPs with CR = 100 per cent are nearly in perfect HWE which militates in favor of the population to meet the conditions required for HWE at least for these SNPs. Moreover, we show that the proportion of SNPs not being in HWE increases with decreasing CR. We conclude that using a single threshold for judging HWE p-values without taking the CR into account is problematic. Instead we recommend a stratified analysis with respect to CR.
Assuntos
Teorema de Bayes , Interpretação Estatística de Dados , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Doenças Cardiovasculares/genética , Frequência do Gene , Genótipo , Alemanha , Humanos , Pessoa de Meia-IdadeRESUMO
Active smoking is a risk factor for type 2 diabetes (T2DM), but it is unclear whether exposure to environmental tobacco smoke (ETS) is also associated with T2DM. The effect of passive and active smoking on the 7-year T2DM incidence was investigated in a population-based cohort in Southern Germany (KORA S4/F4; 1,223 subjects aged 55-74 years at baseline in 1999-2001, 887 subjects at follow-up). Incident diabetes was identified by oral glucose tolerance tests or by validated physician diagnoses. Among never smokers, subjects exposed to ETS had an increased diabetes risk in the total sample (odds ratio (OR) = 2.5; 95% confidence interval (CI): 1.1, 5.6) and in a subgroup of subjects having prediabetes at baseline (OR = 4.4; 95% CI: 1.5, 13.4) after adjusting for age, sex, parental diabetes, socioeconomic status, and lifestyle factors. Active smoking also had a statistically significant effect on diabetes incidence in the total sample (OR = 2.8; 95% CI: 1.3, 6.1) and in prediabetic subjects (OR = 7.8; 95% CI: 2.4, 25.7). Additional adjustment for components of the metabolic syndrome including waist circumference did not attenuate any of these associations. This study provides evidence that both passive and active smoking is associated with T2DM.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Fatores Etários , Idoso , Índice de Massa Corporal , Estudos de Coortes , Comorbidade , Exposição Ambiental/efeitos adversos , Feminino , Alemanha/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Circunferência da CinturaRESUMO
BACKGROUND: Evidence-based patient information (EBPI) has been recognised as important tool for informed choice in particular in the matter of preventive options. An objective, on the best scientific evidence-based consumer information about subthreshold elevated blood glucose levels (impaired fasting glucose and impaired glucose tolerance) and primary prevention of diabetes, is not available yet. Thus we developed a web-based EBPI and aim to evaluate its effects on informed decision making in people 50 years or older. METHODS/DESIGN: We conduct a web-based randomised-controlled trial to evaluate the effect of information about elevated blood glucose levels and diabetes primary prevention on five specific outcomes: (i) knowledge of elevated blood glucose level-related issues (primary outcome); (ii) attitudes to a metabolic testing; (iii) intention to undergo a metabolic testing; (iv) decision conflict; (v) satisfaction with the information. The intervention group receives a specially developed EBPI about subthreshold elevated blood glucose levels and diabetes primary prevention, the control group information about this topic, available in the internet.The study population consists of people between 50 and 69 years of age without known diabetes. Participants will be recruited via the internet page of the cooperating health insurance company, Techniker Krankenkasse (TK), and the internet page of the German Diabetes Centre. Outcomes will be measured through online questionnaires. We expect better informed participants in the intervention group. DISCUSSION: The design of this study may be a prototype for other web-based prevention information and their evaluation. TRIAL REGISTRATION: Current Controlled Trial: ISRCTN22060616.