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CONTEXT: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. OBJECTIVE: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. DESIGN: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. RESULTS: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10-9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10-9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. CONCLUSION: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.
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Glucosa/farmacología , Secreción de Insulina/genética , Células Secretoras de Insulina/efectos de los fármacos , Adulto , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/estadística & datos numéricos , Intolerancia a la Glucosa/epidemiología , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Secreción de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiología , Masculino , Persona de Mediana Edad , Pruebas de Función Pancreática/estadística & datos numéricos , Polimorfismo de Nucleótido Simple , Estado Prediabético/epidemiología , Estado Prediabético/genética , Estado Prediabético/metabolismoRESUMEN
OBJECTIVE: To assess the variability in levels of glycosylated haemoglobin (HbA(1c)) during the first six years after diagnosis of clinical type 2 diabetes in relation to possible predictors. MATERIAL AND METHODS: Data were from a population-based sample from general practice of 581 newly diagnosed diabetic patients aged 40 or over. Estimation of HbA(1c) was centralized. The changes in levels of HbA(1c) were described by HbA(1c) at diagnosis and a regression line fitted to the HbA(1c) measurements after 1-year follow-up for each patient. The predictive effect of patient characteristics for changes in HbA(1c) was investigated in a multivariate mixed model. RESULTS: During the first year after diabetes diagnosis, HbA(1c) dropped to near normal average level and then started rising almost linearly. A sharp rise in long-term glycaemic level was observed in approximately a quarter of the patients, especially the relatively young. Of 581 patients, 156 (26.9%) patients, however, experienced a fall in HbA(1c) after 1-year follow-up and another quarter showed constant or only slowly rising HbA(1c). The changes in levels of HbA(1c) were only predicted by diagnostic HbA(1c) and age. CONCLUSIONS: During the first 6 years after the diagnosis of clinical type 2 diabetes, changes in levels of HbA(1c) show considerable inter-individual variability with age as the only long-term predictor. The results indicate that it is important to monitor changes in HbA(1c) more closely and intensify treatment of those often relatively young patients who actually experience the beginning of an apparently relentless deterioration of their glycaemic control.
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Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina Glucada/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: Self-rated general health (SRH) predicts future mortality. SRH may change, and these changes may alter the mortality risk. All-cause mortality until the age of 68 and its association with changes in SRH from the age of 40-45, 45-51, and 51-60 years was examined in a cohort of Danes. DESIGN: Prospective population study started in 1976 with follow-up in 1981, 1987, and 1996. SETTING: Suburban area of Copenhagen. SUBJECTS: A total of 1198 individuals born in 1936. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Among participants with two consecutive SRH ratings the mortality rate per 1000 observation years was 7.6 (95% CI 6.4; 8.9), 8.5 (95% CI 7.1; 10.2), and 8.9 (95% CI 6.4; 10.3) after the 45-, 51-, and 60-year examination. Decline in SRH between two time-points was in bivariate Cox regression analyses associated with an increased mortality risk, the association increasing as participants grew older. Multivariate analysis of the effect of changes of SRH on mortality gave similar results: hazard ratios for declined SRH were (reference: "unchanged good") 1.55 (95% CI 0.93-2.58), 1.96 (95% CI 1.09-3.53), and 2.22 (95% CI 0.97-5.09) at the 40-45, 45-51, and 51-60-year intervals. However, unchanged poor and improved SRH (at the 40-45-year interval) were also associated with an increase, and additional analyses showed that just rating SRH as poor at one rating was associated with increased risk. CONCLUSION: Changes in SRH are associated with higher mortality risks than unchanged good SRH.
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Estado de Salud , Mortalidad , Adulto , Anciano , Causas de Muerte , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Autoimagen , Encuestas y CuestionariosRESUMEN
OBJECTIVES: The aim of this study is to explore the contribution of genetically driven cardiometabolic risk factors for development of carotid arterial thickening in patients with type 2 diabetes. METHODS: In total, 12 genetic risk scores for blood pressure, blood lipids and glycaemic traits were constructed. The genetic risk scores were tested for association with carotid intima-media thickness and plaques in patients with type 2 diabetes ( n = 401) and in non-diabetic individuals ( n = 648) and for association with glucose levels in two population-based cohorts ( n = 1328 and n = 6161). RESULTS: In patients with type 2 diabetes, the genetic risk scores for pulse pressure were positively associated with plaque formation ( ß = 0.036 ± 0.01 standard deviation/allele, p = 0.003). The genetic risk score for diastolic blood pressure was negatively associated with carotid intima-media thickness ( ß = -0.037 ± 0.01 standard deviation/allele, p = 0.005), although not significant after correction for multiple testing ( p < 0.0042). In a meta-analysis of individuals with and without type 2 diabetes, the high-density lipoprotein genetic risk scores showed a trend towards an inverse association with carotid intima-media thickness and plaques, while the low-density lipoprotein genetic risk scores showed a trend towards a positive association with plaque formation but did reach the statistical threshold. CONCLUSION: Genetic loci for pulse pressure are associated with plaque formation among patients with type 2 diabetes, suggesting an underlying genetic contribution to arterial stiffening and atherosclerosis.
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Presión Sanguínea/genética , Enfermedades de las Arterias Carótidas/genética , Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 2/genética , Hipertensión/genética , Placa Aterosclerótica , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: Insulin resistance and impaired beta-cell function are key elements in the pathogenesis of type 2 diabetes. We aimed to develop valid algorithms for estimation of the insulin sensitivity index (S(I)) and acute insulin response (AIR) derived from simple and cheap physiological measurements that could be used in large-scale metabolic, genetic, and epidemiological studies. RESEARCH DESIGN AND METHODS: For our purpose, data from an oral glucose tolerance test (OGTT) (18 samples during 240 min) and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) (33 samples during 180 min) from 258 individuals with fasting plasma glucose <7 mmol/l and 2-h plasma glucose <7.8 mmol/l were used for model development and internal validation. Data from an additional 28 individuals were used for external validation. Bergman's minimal model was used to calculate S(I), and the trapezoidal method was used to calculate AIR(0-8 min). Multiple linear regression was applied to derive predictive equations of log(S(I)) and log(AIR(0-8 min)) using data on sex, BMI, plasma glucose, and serum insulin levels obtained during the OGTT. RESULTS: We demonstrate that it is possible to obtain estimates of S(I) (BIGTT-S(I)) and AIR (BIGTT-AIR) that are highly correlated to IVGTT-derived values of S(I) (R(2) = 0.77) and AIR (R(2) = 0.54). In the two validation datasets we obtained similar results. CONCLUSIONS: Data from OGTTs can provide accurate measures of insulin sensitivity and beta-cell function, which can be used in large scale metabolic, genetic, and epidemiological studies.
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Glucemia/metabolismo , Prueba de Tolerancia a la Glucosa , Células Secretoras de Insulina/fisiología , Insulina/sangre , Anciano , Intolerancia a la Glucosa/sangre , Homeostasis , Humanos , Hipoglucemiantes/uso terapéutico , Persona de Mediana Edad , Reproducibilidad de los Resultados , TolbutamidaRESUMEN
INTRODUCTION: There is no evidence on how motor function is best evaluated in children in a low-risk setting. The method used in the Danish Preventive Child Health Examination Programme (DPCHEP) in general practise has not been validated. The objective of this review was to identify existing motor function tests for 0-2-year-old children that were validated for use in the background population and which are suitable for use in the DPCHEP. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. A systematic literature search was performed in PubMed, Embase, SwedMed, PsycInfo and CINAHL in accordance with the inclusion and exclusion criteria. RESULTS: Five motor function tests were identified. The Alberta Infant Motor Scale (AIMS) exclusively assesses motor function, the Harris Infant Neuromotor Assessment also assesses cognition and the Early Motor Questionnaire (EMQ) additionally assesses perception-action integration skills. The Ages and Stages Questionnaire (ASQ) and The Brigance Infant and Toddler Screen include further aspects of development. All test methods, except for the AIMS, are based on parent involvement. CONCLUSIONS: For implementation in the DPCHEP, five motor function tests were potentially adequate. However, the time consumption and extensive use of tools render three of the five tests unsuitable for implementation in the existing programme. The two remaining tests, the ASQ and the EMQ, are parent questionnaires. We suggest that these should be pilot tested with a view to their subsequent implementation in the DPCHEP. It may be considered to present the test elements in a more manageable and systematic way, possibly with illustrations.
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Prueba de Esfuerzo/métodos , Destreza Motora , Examen Físico/métodos , Antropometría/métodos , Desarrollo Infantil , Preescolar , Humanos , Lactante , Recién Nacido , Trastornos de la Destreza Motora/diagnósticoRESUMEN
OBJECTIVE: Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (pSP-D) and SP-D gene (SFTPD) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis. METHODS: We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima-media thickness (IMT) and protruding plaques in the right carotid artery. Associations between cardiovascular traits and the levels of pSP-D (n = 687) or two coding SFTPD SNPs rs3088308 and rs721917 (n = 396) were investigated using multiple linear regressions and logistic regressions. RESULTS: There was no significant association between pSP-D and the presence of plaques or IMT. The SFTPD SNP rs3088308 was nominally associated with the presence of plaques, and rs721917 was nominally associated with IMT. The directions of effects of associations were markedly dependent on current smoking status. CONCLUSIONS: The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely to be mediated by structural variant SP-D modulation of effects of tobacco smoking and are independent of pSP-D levels. The data warrant confirmation in larger cohorts.
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Enfermedades de las Arterias Carótidas/genética , Polimorfismo de Nucleótido Simple , Proteína D Asociada a Surfactante Pulmonar/genética , Enfermedades Asintomáticas , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Distribución de Chi-Cuadrado , Dinamarca , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fenotipo , Placa Aterosclerótica , Proteína D Asociada a Surfactante Pulmonar/sangre , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversosRESUMEN
The separate and combined effects of the PPARG Pro(12)Ala polymorphism and the KCNJ11 Glu(23)Lys polymorphisms on risk of type 2 diabetes were investigated in relatively large-scale, case-control studies. Separate effects of the variants were examined among 1187/1461 type 2 diabetic patients and 4791/4986 middle-aged, glucose-tolerant subjects. The combined analysis involved 1164 type 2 diabetic patients and 4733 middle-aged, glucose-tolerant subjects. In the separate analyses, the K allele of the KCNJ11 Glu(23)Lys associated with type 2 diabetes (odds ratio, 1.19; P = 0.0002), whereas the PPARG Pro(12)Ala showed no significant association with type 2 diabetes. The combined analysis indicated that the two polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and we found no evidence for a synergistic interaction between them. Analysis of a model with equal additive effects of the two variants showed that the odds ratio for type 2 diabetes increased with 1.14/risk allele (P = 0.003). Together, the two polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. In conclusion, our results showed no evidence of a synergistic interaction between the KCNJ11 Glu(23)Lys and PPARG Pro(12)Ala polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes.
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Sustitución de Aminoácidos , Diabetes Mellitus Tipo 2/genética , Variación Genética , Mutación Missense , PPAR gamma/genética , Canales de Potasio de Rectificación Interna/genética , Adulto , Alanina , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Glutamina , Humanos , Lisina , Masculino , Persona de Mediana Edad , Prolina , Factores de RiesgoRESUMEN
The SLC2A10 gene encodes the GLUT10 facilitative glucose transporter, which is expressed in high amounts in liver and pancreas. The gene is mapped to chromosome 20q12-q13.1, a region that has been shown to be linked to type 2 diabetes. The gene was examined in 61 Danish type 2 diabetic patients, and a total of six variants (-27C-->T, Ala206Thr, Ala272Ala, IVS2 + 10G-->A, IVS4 + 18T-->G, and IVS4 + 26G-->A) were identified and investigated in an association study, which included 503 type 2 diabetic patients and 510 glucose-tolerant control subjects. None of the variants were associated with type 2 diabetes. Interestingly, carriers of the codon 206 Thr allele had 18% lower fasting serum insulin levels (P = 0.002) and 20% lower insulinogenic index (P = 0.03) than homozygous carriers of the Ala allele. These results suggest that variation in the coding region of SLC2A10 does not contribute substantially to the pathogenesis of type 2 diabetes in the examined study population. However, the codon 206 polymorphism may be related to the interindividual variation in fasting and oral glucose-induced serum insulin levels.
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Diabetes Mellitus Tipo 2/genética , Variación Genética , Proteínas de Transporte de Monosacáridos/genética , Anciano , Femenino , Frecuencia de los Genes , Genotipo , Proteínas Facilitadoras del Transporte de la Glucosa , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
In the present study, we tested the hypothesis that variability in the protein tyrosine phosphatase-1B (PTP-1B) gene is associated with type 2 diabetes. Using single-strand conformational polymorphism analysis, we examined cDNA of PTP-1B from 56 insulin-resistant patients with type 2 diabetes as well as cDNA from 56 obese patients. Four silent variants, (NT CGA-->CGG) R199R, (NT CCC-->CCT) P303P, 3'UTR+104insG, and 3'UTR+86T-->G, and one missense variant, P387L, were found. Subsequent analysis on genomic DNA revealed two intron variants, IVS9+57C-->T and IVS9+58G-->A, and two missense variants, G381S and T420M. The G381S and 3'UTR+104insG insertion variants were not associated with type 2 diabetes. In an association study, the P387L variant was found in 14 of 527 type 2 diabetic subjects (allelic frequency 1.4%, 0.4-2.4 CI) and in 5 of 542 glucose-tolerant control subjects (allelic frequency 0.5%, CI 0.1-1.1), showing a significant association to type 2 diabetes (P = 0.036). In vitro, p34 cell division cycle (p34(cdc2)) kinase-directed incorporation of [gamma-(32)P]ATP was reduced in a mutant peptide compared with native peptide (387P: 100% vs. 387L: 28.4 +/- 5.8%; P = 0.0012). In summary, a rare P387L variant of the PTP-1B gene is associated with a 3.7 (CI 1.26-10.93, P = 0.02) genotype relative risk of type 2 diabetes in the examined population of Danish Caucasian subjects and results in impaired in vitro serine phosphorylation of the PTP-1B peptide.
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Diabetes Mellitus Tipo 2/genética , Variación Genética , Fosfoserina/metabolismo , Proteínas Tirosina Fosfatasas/genética , Serina/metabolismo , Sustitución de Aminoácidos , Animales , Diabetes Mellitus Tipo 2/enzimología , Femenino , Genotipo , Humanos , Masculino , Ratones , Persona de Mediana Edad , Fosforilación , Reacción en Cadena de la Polimerasa , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteínas Tirosina Fosfatasas/metabolismo , Valores de ReferenciaRESUMEN
The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release. In a study comprising 519 unrelated glucose-tolerant subjects, we addressed the question as to whether the E23K variant was related to reduced serum insulin release during an oral glucose tolerance test (OGTT). Furthermore, the polymorphism was examined in a case-control study comprising 803 type 2 diabetic patients and 862 glucose-tolerant control subjects. The E23K variant was associated with significant reductions in the insulinogenic index (P = 0.022) and serum insulin levels under the response curve during an OGTT (0-120 min) (P = 0.014) as well as with an increase in BMI (P = 0.013). In the present study, the association of the E23K polymorphism with type 2 diabetes was not significant (P = 0.26). However, the K23K genotype significantly associated with type 2 diabetes in a meta-analysis of white case and control subjects (n = 2,824, odds ratio [OR] 1.49, P = 0.00022). In conclusion, the widespread E23K polymorphism may have a diabetogenic effect by impairing glucose-induced insulin release and increasing BMI.
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Diabetes Mellitus Tipo 2/epidemiología , Variación Genética , Intolerancia a la Glucosa/genética , Insulina/sangre , Insulina/metabolismo , Canales de Potasio de Rectificación Interna/genética , Sustitución de Aminoácidos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Genotipo , Prueba de Tolerancia a la Glucosa , Humanos , Secreción de Insulina , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.
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Citocromo-B(5) Reductasa/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Animales , Mapeo Cromosómico , Cromosomas Humanos Par 6/genética , Citocromo-B(5) Reductasa/deficiencia , Femenino , Variación Genética , Humanos , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Embarazo , Población BlancaRESUMEN
The aim of the study was to investigate whether genetic variation in the peroxisome proliferator-activated receptor-alpha (PPARalpha) is associated with type 2 diabetes and altered lipid or carbohydrate metabolism in glucose tolerant subjects. Mutation analyses of PPARalpha were performed in 56 type 2 diabetic patients. Six variants were identified: IVS3 + 76T>C, IVS3-19C>T, IVS4 + 35C>T, Leu162Val, Arg178Gly and Ala268Val. In a case-control study comprising 738 type 2 diabetic patients and 524 glucose tolerant subjects, the three exon variants did not show any significant differences in allele frequencies between type 2 diabetic patients and control subjects. The functional Leu162Val polymorphism was further investigated in genotype-phenotype studies involving 340 young, healthy subjects and 502 middle-aged glucose tolerant subjects. The young, healthy subjects who were heterozygous for the Leu162Val variant had, on average, a 20% decrease in fasting serum triglyceride levels (P=0.014). This finding was replicated in middle-aged subjects (P=0.023). The Leu162Val polymorphism was not related to alterations in insulin sensitivity, insulin release or level of glycaemia. In conclusion, the Leu162Val polymorphism of PPARalpha is associated with a decreased level of fasting serum triglyceride in glucose tolerant white subjects.
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Diabetes Mellitus Tipo 2/genética , Ayuno , Polimorfismo Genético , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genética , Triglicéridos/sangre , Adulto , Anciano , Alelos , Glucemia/metabolismo , Constitución Corporal , Estudios de Casos y Controles , Análisis Mutacional de ADN , Dinamarca , Femenino , Frecuencia de los Genes , Variación Genética , Prueba de Tolerancia a la Glucosa , Heterocigoto , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Mutación Puntual , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Valina/genética , Valina/metabolismo , Población Blanca/genéticaRESUMEN
BACKGROUND: To describe the frequency, in some European populations, of the World Health Organisation (WHO) defined metabolic syndrome and to compare the frequency of this syndrome with an alternative definition for non-diabetic subjects, called the insulin resistance syndrome proposed by the European Group for the Study of Insulin Resistance (EGIR). METHODS: Investigators of eight European studies contributed, according to a written protocol, the frequencies of abnormalities of these two syndromes, by sex and age class, as well as the overall frequencies of the syndromes and the average number of abnormalities: 8200 men and 9363 women were included. RESULTS: The frequency of both syndromes increased with age and was almost always higher in men than women for a given age. In non-diabetic subjects the frequency of the WHO syndrome varied between 7% and 36% for men 40 to 55 years; for women of the same age, between 5% and 22%. The EGIR syndrome was less frequent than the WHO syndrome (1% to 22% in men, 1% to 14% in women 40-55 years), and in men this was mainly due to the differing definitions of central obesity, as the WHO definition included overall obesity, BMI > or = 30 kg/m(2). CONCLUSIONS: There is great variability in the frequency of the syndrome between different populations, due to the differing frequencies of the abnormalities and no doubt to the differing methodologies of measurement. Prospective studies and advances in the knowledge of physio-pathological mechanisms are required to determine the most appropriate and practical definition of the syndrome.
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Resistencia a la Insulina , Síndrome Metabólico/epidemiología , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/epidemiología , Hiperinsulinismo/complicaciones , Hiperinsulinismo/epidemiología , Hiperlipidemias/complicaciones , Hiperlipidemias/epidemiología , Masculino , Síndrome Metabólico/clasificación , Obesidad/complicaciones , Obesidad/epidemiología , Caracteres Sexuales , Organización Mundial de la SaludRESUMEN
UNLABELLED: This review should be cited as: Renders CM, Valk GD, Griffin S. Wagner EH, Eijk JThM van, Assendelft WJJ. Interventions to improve the management of diabetes mellitus in primary care, outpatient and community settings (Cochrane Review). In: The Cochrane Library, Issue 2, 2001. Oxford: Update Software. A substantive amendment to this systematic review was last made on 29 June 2000. Cochrane reviews are regularly checked and updated if necessary. BACKGROUND: Diabetes is a common chronic disease that is increasingly managed in primary care. Different systems have been proposed to manage diabetes care. OBJECTIVES: To assess the effects of different interventions, targeted at health professionals or the structure in which they deliver care, on the management of patients with diabetes in primary care, outpatient and community settings. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, the Cochrane Controlled Trials Register (Issue 4 1999), MEDLINE (1966-1999), EMBASE (1980-1999), Cinahl (1982-1999), and reference lists of articles. SELECTION CRITERIA: Randomised trials (RCTs), controlled clinical trials (CCTs), controlled before and after studies (CBAs) and interrupted time series (ITS) analyses of professional, financial and organisational strategies aimed at improving care for people with Type 1 or Type 2 diabetes. The participants were health care professionals, including physicians, nurses and pharmacists. The outcomes included objectively measured health professional performance or patient outcomes, and self-report measures with known validity and reliability. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Forty-one studies were included involving more than 200 practices and 48,000 patients. Twenty-seven studies were RCTs, 12 were CBAs, and two were ITS. The studies were heterogeneous in terms of interventions, participants, settings and outcomes. The methodological quality of the studies was often poor. In all studies the intervention strategy was multifaceted. In 12 studies the interventions were targeted at health professionals, in nine they were targeted at the organization of care, and 20 studies targeted both. In 15 studies patient education was added to the professional and organisational interventions. A combination of professional interventions improved process outcomes. The effect on patient outcomes remained less clear as these were rarely assessed. Arrangements for follow-up (organisational intervention) also showed a favourable effect on process outcomes. Multiple interventions in which patient education was added or in which the role of the nurse was enhanced also reported favourable effects on patients' health outcomes. REVIEWERS' CONCLUSION: Multifaceted professional interventions can enhance the performance of health professionals in managing patients with diabetes. Organisational interventions that improve regular prompted recall and review of patients (central computerised tracking systems or nurses who regularly contact the patient) can also improve diabetes management. The addition of patient-oriented interventions can lead to improved patient health outcomes. Nurses can play an important role in patient-oriented interventions, through patient education or facilitating adherence to treatment.
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Centros Comunitarios de Salud/normas , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Servicio Ambulatorio en Hospital/normas , Atención Dirigida al Paciente , Gestión de la Calidad Total/métodos , Centros Comunitarios de Salud/organización & administración , Ensayos Clínicos Controlados como Asunto , Bases de Datos Bibliográficas , Diabetes Mellitus Tipo 1/enfermería , Diabetes Mellitus Tipo 2/enfermería , Medicina Basada en la Evidencia , Humanos , Metaanálisis como Asunto , Servicio Ambulatorio en Hospital/organización & administración , Educación del Paciente como Asunto/organización & administración , Educación del Paciente como Asunto/normas , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: The prevalence of diabetes in Denmark is unknown. The purpose of the present article was to describe the possibilities of developing a method to identify individuals with diagnosed diabetes in Denmark on the basis of existing national registers. MATERIAL AND METHODS: Record linkage of data from The Danish National Hospital Register, The Danish National Health Service Register and The Register of Medicinal Product Statistics. RESULTS: A minimum of 130,000 individuals in Denmark are estimated to have diabetes as on December 31, 1999. DISCUSSION: The possibility of developing a monitoring programme from existing data in registers seems to be present. If a validated monitoring programme is developed, this can not only be used to estimate the prevalence of diabetes, but also for a continuous monitoring of diabetes-related services.
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Diabetes Mellitus/epidemiología , Registro Médico Coordinado/métodos , Glucemia/análisis , Dinamarca/epidemiología , Humanos , Prevalencia , Sistema de RegistrosRESUMEN
The organization of treatment and control of type 2 diabetic patients in Denmark has undergone a major development within the last decade. From being based on local hospital guidelines, treatment and control have moved towards a more organized collaboration between primary and secondary care based on common national guidelines. Quality indicators from primary and secondary care are collected routinely, and gradually an increasingly precise depiction is documented in the National Indicator Project.
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Diabetes Mellitus Tipo 2 , Manejo de la Enfermedad , Planificación en Salud/organización & administración , Vías Clínicas , Dinamarca , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Humanos , Modelos Organizacionales , Garantía de la Calidad de Atención de Salud , Indicadores de Calidad de la Atención de SaludRESUMEN
Chronic exposure to glucocorticoids (GCs) has many side effects including glucose intolerance and diabetes and may accelerate the occurrence of cardiovascular disease and increase mortality. We studied the 14-year clinical development of diabetes in patients diagnosed with diabetes during GC treatment. A population-based sample of 1369 people newly diagnosed with clinical type 2 diabetes underwent a clinical examination at diagnosis, and surviving patients were followed up 6 and 14 years later. Patients receiving oral GC treatment at diagnosis were compared with the other patients. Of 1369 patients, 35 (2.6%) were treated with oral GCs at diabetes diagnosis. At that point, patients on GC therapy were older (69.9 versus 65.3 years, p = 0.007, sex-adjusted) and tended to have lower BMI (26.1 versus 29.1 kg/m(2) , p = 0.023), also 6 years after diagnosis (24.8 versus 28.4, p = 0.011), than patients not being treated with GCs. In a univariate Cox regression model, GC treatment at diagnosis increased all-cause mortality with a hazard ratio (95% confidence interval) of 2.01 (1.39-2.89, p = 0.0002, n = 1369), while this decreased to 1.41 (0.98-2.04, p = 0.065, n = 1369) when adjusted for age and sex and to 1.39 (0.92-2.11, p = 0.12, n = 1086) when risk factors, complications and cancer were added to the model. Apart from differences in age and overweight, patients in this relatively small sample of those diagnosed with clinical type 2 diabetes during GC treatment were comparable at diagnosis and during 14 years of follow-up with those not treated with GCs, including with regard to the adjusted mortality rate.
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Diabetes Mellitus Tipo 2/complicaciones , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Sobrepeso/complicaciones , Anciano , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de RiesgoRESUMEN
BACKGROUND: European studies on quality of diabetes care in an unselected primary care diabetes population are scarce. RESEARCH QUESTION: To test the feasibility of the set-up and logistics of a cross-sectional EUropean study on Care and Complications in patients with type 2 diabetes (T2DM) in Primary Care (EUCCLID) in 12 European countries. METHOD: One rural and one urban practice from each country participated. The central coordinating centre randomly selected five patients from each practice. Patient characteristics were assessed including medical history, anthropometric measures, quality indicators, UKPDS-risk engine, psychological and general well-being. RESULTS: We included 103 participants from 22 GPs in 11 countries. Central data and laboratory samples were successfully collected. Of the participants 54% were female, mean age was 66 years and mean duration of diabetes was 9.6 years. Besides, 18% were using insulin, 31% had a history of cardiovascular disease, mean HbA1c was 7.1% (range 6.6-8.0), mean systolic blood pressure was 133.7 mmHg (range 126.1-144.4) and mean total cholesterol was 4.9 mmol/l (range 4.0-6.2). CONCLUSION: A European study on care and complications in a random selection of people with T2DM is feasible. There are large differences in indicators of metabolic control and wellbeing between countries.