RESUMEN
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.
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Estudios Prospectivos , Masculino , Humanos , Femenino , Estudios de Cohortes , Alemania/epidemiología , Encuestas y Cuestionarios , AutoinformeRESUMEN
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.
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Herpes Zóster/epidemiología , Neuralgia Posherpética/epidemiología , Autoinforme , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Femenino , Alemania/epidemiología , Herpes Zóster/etiología , Herpes Zóster/prevención & control , Herpes Zóster/virología , Herpesvirus Humano 3 , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neuralgia Posherpética/etiología , Neuralgia Posherpética/prevención & control , Neuralgia Posherpética/virología , Reproducibilidad de los Resultados , Factores Sexuales , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Loss of adequate insulin secretion for the prevailing insulin resistance is critical for the development of type 2 diabetes and has been suggested to result from circulating lipids (triacylglycerols [TG] or free fatty acids) and/or adipocytokines or from ectopic lipid storage in the pancreas. This study aimed to address whether circulating lipids, adipocytokines or pancreatic fat primarily associates with lower insulin secretion. SUBJECTS/METHODS: Nondiabetic persons (n=73), recruited from the general population, underwent clinical examinations, fasting blood drawing to measure TG and adipocytokines and oral glucose tolerance testing (OGTT) to assess basal and dynamic insulin secretion and sensitivity indices. Magnetic resonance imaging and 1H-magnetic resonance spectroscopy were used to measure body fat distribution and ectopic fat content in liver and pancreas. RESULTS: In age-, sex- and BMI-adjusted analyses, total and high-molecular-weight adiponectin were the strongest negative predictors of fasting beta-cell function (BCF; ß=-0.403, p=0.0003 and ß=-0.237, p=0.01, respectively) and adaptation index (AI; ß=-0.210, p=0.006 and ß=-0.133, p=0.02, respectively). Circulating TG, but not pancreatic fat content, related positively to BCF (ß=0.375, p<0.0001) and AI (ß=0.192, p=0.003). Similar results were obtained for the disposition index (DI). CONCLUSIONS: The association of serum lipids and adiponectin with beta-cell function may represent a compensatory response to adapt for lower insulin sensitivity in nondiabetic humans.
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Células Secretoras de Insulina/fisiología , Insulina/metabolismo , Lípidos/fisiología , Triglicéridos/sangre , Adiponectina/sangre , Anciano , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Resistencia a la Insulina , Secreción de Insulina , Masculino , Persona de Mediana EdadRESUMEN
Objective: Hepatic energy metabolism negatively relates to insulin resistance and liver fat content in patients with type 2 diabetes, but its role in metabolically healthy humans is unclear. We hypothesized that intrahepatocellular γ-adenosine triphosphate (γATP) and inorganic phosphate (Pi) concentrations exhibit similar associations with insulin sensitivity in nondiabetic, nonobese volunteers. Design: A total of 76 participants underwent a four-point sampling, 75-g oral glucose tolerance test (OGTT), as well as in vivo31P/1H magnetic resonance spectroscopy. In 62 of them, targeted plasma metabolomic profiling was performed. Pearson correlation analyses were performed for the dependent variables γATP and Pi. Results: Adjusted for age, sex, and body mass index (BMI), hepatic γATP and Pi related to 2-hour OGTT glucose (r = 0.25 and r = 0.27, both P < 0.05), and Pi further associated with nonesterified fatty acids (NEFAs; r = 0.28, P < 0.05). However, neither γATP nor Pi correlated with several measures of insulin sensitivity. Hepatic γATP correlated with circulating leucine (r = 0.42, P < 0.001) and Pi with C16:1 fatty acids palmitoleic acid and C16:1w5 (r = 0.28 and 0.30, respectively, P < 0.01), as well as with δ-9-desaturase index (r = 0.33, P < 0.05). Only the association of γATP with leucine remained important after correction for multiple testing. Leucine and palmitoleic acid, together with age, sex, and BMI, accounted for 26% and for 15% of the variabilities in γATP and Pi, respectively. Conclusions: Specific circulating amino acids and NEFAs, but not measures of insulin sensitivity, partly affect hepatic phosphorus metabolites, suggesting mutual interaction between hepatic energy metabolism and circulating metabolites in nondiabetic humans.
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Aminoácidos/metabolismo , Ácidos Grasos/metabolismo , Salud , Hígado/metabolismo , Fósforo/metabolismo , Adulto , Anciano , Estudios de Cohortes , Metabolismo Energético/fisiología , Estudios de Factibilidad , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Metaboloma , Persona de Mediana Edad , Adulto JovenRESUMEN
Metformin is the first-line oral medication to increase insulin sensitivity in patients with type 2 diabetes (T2D). Our aim was to investigate the pleiotropic effect of metformin using a nontargeted metabolomics approach. We analyzed 353 metabolites in fasting serum samples of the population-based human KORA (Cooperative Health Research in the Region of Augsburg) follow-up survey 4 cohort. To compare T2D patients treated with metformin (mt-T2D, n = 74) and those without antidiabetes medication (ndt-T2D, n = 115), we used multivariable linear regression models in a cross-sectional study. We applied a generalized estimating equation to confirm the initial findings in longitudinal samples of 683 KORA participants. In a translational approach, we used murine plasma, liver, skeletal muscle, and epididymal adipose tissue samples from metformin-treated db/db mice to further corroborate our findings from the human study. We identified two metabolites significantly (P < 1.42E-04) associated with metformin treatment. Citrulline showed lower relative concentrations and an unknown metabolite X-21365 showed higher relative concentrations in human serum when comparing mt-T2D with ndt-T2D. Citrulline was confirmed to be significantly (P < 2.96E-04) decreased at 7-year follow-up in patients who started metformin treatment. In mice, we validated significantly (P < 4.52E-07) lower citrulline values in plasma, skeletal muscle, and adipose tissue of metformin-treated animals but not in their liver. The lowered values of citrulline we observed by using a nontargeted approach most likely resulted from the pleiotropic effect of metformin on the interlocked urea and nitric oxide cycle. The translational data derived from multiple murine tissues corroborated and complemented the findings from the human cohort.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Citrulina/sangre , Diabetes Mellitus Tipo 2/sangre , Ayuno/sangre , Humanos , Resistencia a la Insulina/fisiología , Estudios Longitudinales , Masculino , Ratones , Modelos Biológicos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismoRESUMEN
Type 1 diabetes has been recently linked to nonalcoholic fatty liver disease (NAFLD), which is known to associate with insulin resistance, obesity, and type 2 diabetes. However, the role of insulin resistance and hyperglycemia for hepatic energy metabolism is yet unclear. To analyze early abnormalities in hepatic energy metabolism, we examined 55 patients with recently diagnosed type 1 diabetes. They underwent hyperinsulinemic-normoglycemic clamps with [6,6-(2)H2]glucose to assess whole-body and hepatic insulin sensitivity. Hepatic γATP, inorganic phosphate (Pi), and triglyceride concentrations (hepatocellular lipid content [HCL]) were measured with multinuclei magnetic resonance spectroscopy ((31)P/(1)H-MRS). Glucose-tolerant humans served as control (CON) (n = 57). Whole-body insulin sensitivity was 44% lower in patients than in age- and BMI-matched CON. Hepatic γATP was 15% reduced (2.3 ± 0.6 vs. 2.7 ± 0.6 mmol/L, P < 0.001), whereas hepatic Pi and HCL were similar in patients when compared with CON. Across all participants, hepatic γATP correlated negatively with glycemia and oxidized LDL. Carriers of the PPARG G allele (rs1801282) and noncarriers of PPARGC1A A allele (rs8192678) had 21 and 13% lower hepatic ATP concentrations. Variations in genes controlling oxidative metabolism contribute to a reduction in hepatic ATP in the absence of NAFLD, suggesting that alterations in hepatic mitochondrial function may precede diabetes-related liver diseases.
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Adenosina Trifosfato/metabolismo , Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 1/genética , Metabolismo Energético/genética , Hígado/metabolismo , Adulto , Alelos , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Resistencia a la Insulina/genética , Metabolismo de los Lípidos/genética , Hígado/patología , Masculino , Estrés Oxidativo/fisiología , PPAR gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Fosfatos/metabolismo , Triglicéridos/metabolismoRESUMEN
CONTEXT: Insulin resistance reflects the inadequate insulin-mediated use of metabolites and predicts type 2 diabetes (T2D) but is also frequently seen in long-standing type 1 diabetes (T1D) and represents a major cardiovascular risk factor. OBJECTIVE: We hypothesized that plasma metabolome profiles allow the identification of unique and common early biomarkers of insulin resistance in both diabetes types. DESIGN, SETTING, AND PATIENTS: Two hundred ninety-five plasma metabolites were analyzed by mass spectrometry from patients of the prospective observational German Diabetes Study with T2D (n = 244) or T1D (n = 127) and known diabetes duration of less than 1 year and glucose-tolerant persons (CON; n = 129). Abundance of metabolites was tested for association with insulin sensitivity as assessed by hyperinsulinemic-euglycemic clamps and related metabolic phenotypes. MAIN OUTCOMES MEASURES: Sixty-two metabolites with phenotype-specific patterns were identified using age, sex, and body mass index as covariates. RESULTS: Compared with CON, the metabolome of T2D and T1D showed similar alterations in various phosphatidylcholine species and amino acids. Only T2D exhibited differences in free fatty acids compared with CON. Pairwise comparison of metabolites revealed alterations of 28 and 49 metabolites in T1D and T2D, respectively, when compared with CON. Eleven metabolites allowed differentiation between both diabetes types and alanine, α-amino-adipic acid, isoleucin, and stearic acid showed an inverse association with insulin sensitivity in both T2D and T1D combined. CONCLUSION: Metabolome analyses from recent-onset T2D and T1D patients enables identification of defined diabetes type-specific differences and detection of biomarkers of insulin sensitivity. These analyses may help to identify novel clinical subphenotypes diabetes.
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Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Resistencia a la Insulina/fisiología , Metaboloma , Adolescente , Adulto , Anciano , Aminoácidos/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Masculino , Metabolómica , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
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.
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Adiponectina/sangre , Glucemia , Proteína C-Reactiva/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Inflamación/diagnóstico , Proteínas de Fase Aguda/metabolismo , Anciano , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Fibrinógeno/metabolismo , Humanos , Inflamación/sangre , Inflamación/complicaciones , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteína Amiloide A Sérica/metabolismoRESUMEN
AIMS: To estimate the national incidence rate and trend of type 1 diabetes (T1DM) in Germany from 1999 to 2008 and the national prevalence in 2008 in the age group 0-14 years. METHODS: Data were taken from a nationwide registry for incident cases of T1DM in the ages 0-4 years and 3 regional registries (North-Rhine-Westphalia, Baden-Wuerttemberg and Saxony) for incident cases of T1DM in the ages 0-14 years covering 41% of the child population in Germany. The degree of ascertainment was ≥ 97% in all registries. Incident and prevalent cases were grouped by region, sex, age (0-4, 5-9, 10-14 years), and, for incident data, additionally by two 5-year periods (1999-2003, 2004-2008). Poisson regression models were fitted to the data to derive national estimates of incidence rate trends and prevalence in the age groups 5-9, 10-14 and 0-14 years. We used direct age-standardization. RESULTS: The estimated national incidence rate in 0-14-year-olds increased significantly by 18.1% (95%CI: 11.6-25.0%, p<0.001) from 1999-2003 to 2004-2008, independent of sex, corresponding to an average annual increase of 3.4% (95%-CI: 2.2-4.6%). The overall incidence rate was estimated at 22.9 per 100,000 person-years and we identified a within-country west-east-gradient previously unknown. The national prevalence in the ages 0-14 years on 31/12/2008 was estimated to be 148.1 per 100,000 persons. CONCLUSIONS: The national incidence rate of childhood T1DM in Germany is higher than in many other countries around the world. Importantly, the estimated trend of the incidence rate confirms the international data of a global increase of T1DM incidences.
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Diabetes Mellitus Tipo 1/epidemiología , Sistema de Registros , Adolescente , Distribución por Edad , Niño , Preescolar , Femenino , Alemania/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Prevalencia , Distribución por SexoRESUMEN
BACKGROUND: This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control. METHODS: In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9) for symptoms of depression and severity of depressive symptoms (PHQ-9 score). Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c. RESULTS: A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation) was 5.3 (4.4) among women and 3.9 (3.6) among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (ßwomen 3.8, p<0.001). However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (ßmen 0.14, p=0.006). CONCLUSIONS: Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes.
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Depresión/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Adolescente , Adulto , Edad de Inicio , Estudios de Casos y Controles , Niño , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Modelos Lineales , Masculino , Tamizaje Masivo , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Adulto JovenRESUMEN
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.
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Pruebas de Función Hepática/métodos , Hígado/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Fosfatidilcolinas/metabolismo , Fosfoenolpiruvato/metabolismo , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isótopos de Fósforo/farmacocinética , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución TisularRESUMEN
OBJECTIVE: This study sought to evaluate the associations between metabolic control and each DSM-5 (Diagnostic and Statistical Manual, fifth edition) symptom of depression among young women and men with early-onset long-duration type 1 diabetes. METHODS: The data of 202 18-21-year-old patients with type 1 diabetes from a population-based, nationwide survey (40.1% male) with a mean age of 19.4 (standard deviation 0.9) years, a mean HbA1c level of 8.3% (1.6%) (i.e., 67 [17.5]mmol/mol), and a mean diabetes duration of 15.7 (1.0) years were included. The German version of the Patient Health Questionnaire (PHQ-9) was used to assess depression symptoms. For each PHQ-9 depressive symptom, the mean HbA1c values of screening-positive and screening-negative patients were compared via t-test. The associations between HbA1c levels and depressive symptoms were analyzed using multiple linear regression analyses and stepwise adjustments for individual, socioeconomic and health-related covariates. RESULTS: Exactly 43.0% and 33.3% of female and male participants reported at least one depressive symptom, and 5.0% and 2.5% met the DSM-5 criteria for major depressive syndrome. HbA1c levels increased with psychomotor agitation/retardation (women), overeating/poor appetite (men/women), lethargy (men), and sleep difficulty (men). Overeating/poor appetite, lethargy, and total PHQ-9 score (per score increase by one) were associated with increased HbA1c levels of 1.10, 0.96 and 0.09 units (%), respectively. CONCLUSIONS: The associations between depressive symptoms and HbA1c levels vary by symptom and sex. Differentiating the symptoms of depression and targeted interventions might help to improve metabolic outcomes in young adults with early-onset type 1 diabetes and depression.
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Depresión/psicología , Trastorno Depresivo Mayor/psicología , Diabetes Mellitus Tipo 1/psicología , Hemoglobina Glucada/metabolismo , Adolescente , Anorexia/metabolismo , Anorexia/psicología , Depresión/metabolismo , Trastorno Depresivo Mayor/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Humanos , Hiperfagia/metabolismo , Hiperfagia/psicología , Letargia/metabolismo , Letargia/psicología , Masculino , Agitación Psicomotora/metabolismo , Agitación Psicomotora/psicología , Trastornos Psicomotores/metabolismo , Trastornos Psicomotores/psicología , Trastornos del Inicio y del Mantenimiento del Sueño/metabolismo , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Adulto JovenRESUMEN
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.
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Complicaciones de la Diabetes , Diabetes Mellitus/epidemiología , Infarto del Miocardio/mortalidad , Sistema de Registros/estadística & datos numéricos , Adulto , Anciano , Estudios de Casos y Controles , Causas de Muerte/tendencias , Angiopatías Diabéticas/mortalidad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/complicaciones , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
OBJECTIVE: We provide a population-based overview of health behaviours of children and adolescents with type 1 diabetes in comparison to the general population, and analyse their relevance for glycaemic control and self-rated health status. METHODS: Data from questionnaires of 11- to 17-year-old children and adolescents with diabetes (n = 629) were compared to a representative sample (n = 6,813). RESULTS: Children and adolescents with type 1 diabetes had a significantly increased odds of infrequent physical activity (adjusted OR 1.56), short overall duration of physical activity per week (OR 1.55, difference -1.3 hours/week), and high daily computer use (OR 2.51). They had a lower odds of active and passive smoking (OR 0.31 and OR 0.29), and high daily television time (OR 0.68). The odds of an at least good and excellent self-rated health status was increased with intense physical activity, and decreased with active smoking and prolonged daily use of computer and television. Active smoking and prolonged daily use of computer were associated with higher HbA1c. CONCLUSIONS: Children and adolescents with type 1 diabetes showed a different profile of health behaviour. Their overall health may improve if their education stresses specifically frequent physical activity with longer overall duration and less frequent television or computer use.
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Diabetes Mellitus Tipo 1 , Conductas Relacionadas con la Salud , Adolescente , Glucemia/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Femenino , Estado de Salud , Humanos , Lactante , Recién Nacido , Masculino , Encuestas y CuestionariosRESUMEN
Chronic diseases impose a tremendous global health problem of the 21st century. Epidemiological and public health models help to gain insight into the distribution and burden of chronic diseases. Moreover, the models may help to plan appropriate interventions against risk factors. To provide accurate results, models often need to take into account three different time-scales: calendar time, age, and duration since the onset of the disease. Incidence and mortality often change with age and calendar time. In many diseases such as, for example, diabetes and dementia, the mortality of the diseased persons additionally depends on the duration of the disease. The aim of this work is to describe an algorithm and a flexible software framework for the simulation of populations moving in an illness-death model that describes the epidemiology of a chronic disease in the face of the different times-scales. We set up a discrete event simulation in continuous time involving competing risks using the freely available statistical software R. Relevant events are birth, the onset (or diagnosis) of the disease and death with or without the disease. The Lexis diagram keeps track of the different time-scales. Input data are birth rates, incidence and mortality rates, which can be given as numerical values on a grid. The algorithm manages the complex interplay between the rates and the different time-scales. As a result, for each subject in the simulated population, the algorithm provides the calendar time of birth, the age of onset of the disease (if the subject contracts the disease) and the age at death. By this means, the impact of interventions may be estimated and compared.
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Enfermedad Crónica/epidemiología , Simulación por Computador , Muerte , Modelos Teóricos , Edad de Inicio , Algoritmos , Estudios de Cohortes , Femenino , Humanos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Having shown in a recent randomized controlled trial that evidence-based patient information (EBPI) significantly increased knowledge on primary prevention of diabetes compared to standard patient information, we now investigated interaction between socioeconomic status (SES) and the effect of an EBPI. FINDINGS: 1,120 visitors (aged 40-70 years, without known diabetes) to the "Techniker Krankenkasse" and the "German Diabetes Center" websites were randomized. The intervention group received a newly developed on-line EBPI, the control group standard on-line information. The primary outcome measure was knowledge, classified as "good/average/poor". We analyzed associations of knowledge with socioeconomic variables (education, vocational training, employment, subjective social status) combined with intervention effect including interactions, adjusted for possible confounding by knowledge before intervention, self-reported blood glucose measurements, blood pressure, blood lipid levels, age and gender. Logistic regression models were fitted to the subpopulation (n = 647) with complete values in these variables.Education (high vs. low) was significantly associated with knowledge (good vs. average/poor); however, there was no significant interaction between education and intervention. After adjustment, the other socioeconomic variables were not significantly associated with knowledge. CONCLUSIONS: Socioeconomic variables did not significantly change the effect of the intervention. There was a tendency towards a lower effect where lower educated individuals were concerned. Possibly the power was too low to detect interaction effects. Larger studies using SES-specific designs are needed to clarify the effect of SES. We suggest considering the socioeconomic status when evaluating a decision aid, e.g. an EBPI, to ensure its effectiveness not only in higher socioeconomic groups. TRIAL REGISTRATION: Current Controlled Trials ISRCTN22060616 (Date assigned: 12 September 2008).
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Diabetes Mellitus Tipo 2/prevención & control , Práctica Clínica Basada en la Evidencia , Factores Socioeconómicos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevención PrimariaRESUMEN
Food frequency questionnaires (FFQs) provide an inexpensive tool for dietary assessment. Given the scarcity of data on their validity for nutritional analysis in persons with overt diabetes mellitus or with increased risk of diabetes (relatives of patients with diabetes), this study tests the hypothesis that an FFQ, adapted to local dietary habits, yields a reliable estimate of nutrient intake when compared with 7-day food record (7DR) in healthy, prediabetes, and diabetes cohorts. One hundred three volunteers (50 persons with overt diabetes mellitus, 24 relatives of patients with diabetes, and 29 nondiabetic individuals without a family history of diabetes) completed both FFQ and 7DR. A second FFQ was completed by 100 of these volunteers after 3 months to evaluate its reproducibility. Data were compared by correlation and Bland-Altman analyses. Across the entire group, estimates for gram intakes of nutrients and total energy were associated with wide limits of agreement between FFQ and 7DR (correlation coefficients, 0.23-0.72; P < .02). Compared with 7DR, the FFQ overestimated intakes of saturated fat in the entire group (+6.6 ± 14 g; P < .001) and in persons with overt diabetes mellitus (+7.6 ± 15 g; P < .001) but underestimated protein intake in relatives of patients with diabetes (-16.36 ± 31 g; P = .01). The repeated FFQ revealed variable agreement (correlation coefficients, 0.34-0.72; P < .001) and underestimated (P < .01) macronutrient and total energy intakes, with slightly better performance in persons with overt diabetes mellitus and relatives of patients with diabetes than in nondiabetic individuals without a family history of diabetes. Hence, the FFQ allows measuring intakes of total energy and macronutrients in prediabetes and diabetes cohorts but reveals limitations when assessing dietary composition.
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Diabetes Mellitus , Encuestas sobre Dietas/normas , Dieta , Conducta Alimentaria , Encuestas y Cuestionarios/normas , Adulto , Austria , Registros de Dieta , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
CONTEXT: Hepatic steatosis, defined as increased hepatocellular lipid content (HCL), associates with visceral obesity and glucose intolerance. As exact HCL quantification by 1H-magnetic resonance spectroscopy (1H-MRS) is not generally available, various clinical indices are increasingly used to predict steatosis. OBJECTIVE: The purpose of this study was to test the accuracy of NAFLD liver fat score (NAFLD-LFS), hepatic steatosis index (HSI) and fatty liver index (FLI) against 1H-MRS and their relationships with insulin sensitivity and secretion. DESIGN, SETTING AND PARTICIPANTS: Ninety-two non-diabetic, predominantly non-obese humans underwent clinical examination, 1H-MRS and an oral glucose tolerance test (OGTT) to calculate insulin sensitivity and ß-cell function. Accuracy of indices was assessed from the area under the receiver operating characteristic curve (AROC). RESULTS: Median HCL was 2.49% (0.62;4.23) and correlated with parameters of glycemia across all subjects. NAFLD-LFS, FLI and HSI yielded AROCs of 0.70, 0.72, and 0.79, respectively, and related positively to HCL, insulin resistance, fasting and post-load ß-cell function normalized for insulin resistance. Upon adjustment for age, sex and HCL, regression analysis revealed that NAFLD-LFS, FLI and HSI still independently associated with both insulin sensitivity and ß-cell function. CONCLUSION: The tested indices offer modest efficacy to detect steatosis and cannot substitute for fat quantification by 1H-MRS. However, all indices might serve as surrogate parameters for liver fat content and also as rough clinical estimates of abnormal insulin sensitivity and secretion. Further validation in larger collectives such as epidemiological studies is needed.
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Adiposidad , Hígado Graso/diagnóstico , Resistencia a la Insulina , Hígado/patología , Consumo de Bebidas Alcohólicas , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Células Secretoras de Insulina/patología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Response rates in epidemiologic studies vary widely. This study examines response rates of potential study participants according to foreign versus German background and investigates effects of recruitment strategies. METHODS: Response rates and characteristics of recruitment procedures from feasibility studies for a large cohort study conducted in 2011 were analyzed. RESULTS: Among 1,235 participants the proportion of recruited individuals with a foreign background was 17.3% (95% confidence interval 15.3-19.5%), significantly lower than in the sampling frame (23.1%). The difference between observed and expected proportion was high among individuals with Turkish background and smaller among ethnic Germans from the Former Soviet Union and other foreign background groups. Common recruitment strategies to increase the response had positive effects in all groups. For the planned recruitment strategy in the forthcoming German National Cohort, we estimate an overall response of approximately 50%. CONCLUSIONS: Individuals with Turkish background may need particular efforts to be adequately represented in a population-based cohort in Germany. Other foreign background groups are relatively well represented using standard procedures. An adequate response can be obtained under carefully planned recruitment strategies.
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Emigrantes e Inmigrantes/estadística & datos numéricos , Estudios Epidemiológicos , Selección de Paciente , Grupos de Población/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Estudios de Cohortes , Femenino , Alemania , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.