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  • 1
    Keywords: Germany ; human ; MODEL ; COHORT ; RISK ; GENE ; ASSOCIATION ; polymorphism ; VARIANTS ; SEXUAL DIMORPHISM ; resistance ; WOMEN ; MEN ; OBESITY ; REDUCED RISK ; BODY ; TYPE-2 ; TRENDS ; DIETARY-FAT ; EPIC-GERMANY ; insulin ; MASS INDEX ; REGRESSION ; VARIANT ; INHERITANCE ; INSULIN-RESISTANCE ; metabolic syndrome ; GENDER ; BMI ; type 2 diabetes ; A54T polymorphism ; ABORIGINAL CANADIANS ; ALA54THR POLYMORPHISM ; FATTY-ACID-BINDING ; intestinal fatty acid binding protein ; POSTPRANDIAL RESPONSES ; PROTEIN-2 GENE
    Abstract: The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95%CI: 0.07-0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA(1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study
    Type of Publication: Journal article published
    PubMed ID: 16718632
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  • 2
    Keywords: CANCER ; Germany ; human ; MODEL ; INFORMATION ; screening ; TOOL ; COHORT ; cohort study ; HISTORY ; POPULATION ; RISK ; METABOLISM ; FAMILY ; RISK-FACTORS ; score ; lifestyle ; DESIGN ; AGE ; WOMEN ; MEN ; risk factors ; smoking ; POPULATIONS ; DIETARY ; HYPERTENSION ; meat ; nutrition ; TYPE-2 ; EPIC-GERMANY ; BETA-CELL FUNCTION ; insulin ; MELLITUS ; REGRESSION ; FAMILIES ; PHYSICAL-ACTIVITY ; RELATIVE VALIDITY ; development ; methods ; metabolic syndrome ; prospective ; correlation ; MEAT INTAKE ; RISK-FACTOR ; type 2 diabetes ; PREDICT ; type-2-diabetes ; FASTING GLUCOSE ; IMPAIRED GLUCOSE-TOLERANCE ; INSULIN SECRETORY DYSFUNCTION ; WHOLE-GRAIN INTAKE
    Abstract: OBJECTIVE - We aimed to develop a precise risk score for the screening of large populations for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study populations. RESEARCH DESIGN AND METHODS - A prospective cohort study (European Prospective Investigation into Cancer and Nutrition [EPIC]-Potsdam study) of 9,729 men and 15,438 women aged 35-65 years was used to derive a risk score predicting incident type 2 diabetes. Multivariate Cox regression model coefficients were used to weigh each variable in the. calculation of the score. Data from the EPIC-Heidelberg, the Tubingen Family Study for Type 2 Diabetes (T F), and the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study were used to validate this score. RESULTS - information on age, waist circumference, height, history of hypertension, physical activity, smoking, and consumption of red meat, whole-grain bread, coffee, and alcohol formed the German Diabetes Risk Score (mean 446 points [range 118-983]). The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3% for 300 to 23.2% for 750 score points. The area under the receiver-operator characteristic (ROC) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies. Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were -0.56 in the TUF and -0.45 in the MeSyBePo studies. ROC values for undiagnosed diabetes were 0.83 in the TUF and 0.75 in the MeSyBePo studies. CONCLUSIONS - The German Diabetes Risk Score (available at www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes
    Type of Publication: Journal article published
    PubMed ID: 17327313
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  • 3
    Keywords: PEPTIDE ; RECEPTOR ; CELLS ; EXPRESSION ; Germany ; human ; MODEL ; COMMON ; COHORT ; DISEASE ; RISK ; SITE ; GENE ; GENES ; PROTEIN ; RELEASE ; RISK-FACTORS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; ACID ; NO ; AGE ; MUTATION ; SNP ; OBESITY ; risk factors ; REGION ; REGIONS ; EPIC-GERMANY ; insulin ; ASSOCIATIONS ; RE ; VARIANT ; ALLELE ; SNPs ; CARDIOVASCULAR-DISEASE ; AMINO-ACID ; interaction ; pancreatic ; GENOTYPE ; metabolic syndrome ; RISK-FACTOR ; cardiovascular disease ; EPIC-Potsdam ; DEPENDENT INSULINOTROPIC POLYPEPTIDE ; diabetes type 2 ; GASTRIC-INHIBITORY POLYPEPTIDE ; GIP receptor ; gluocose-dependent insulinotropic peptide
    Abstract: Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin release via interaction with its pancreatic receptor (GIP receptor (GIPR)). GIP also acts as vasoactive protein. To investigate whether variations in GIP and GIPR genes are associated with risk factors of the metabolic syndrome we sequenced gene regions and identified two coding SNPs (GIP Ser103Gly, GIPR Glu354Gln) and one splice site SNP (GIP rs2291726) in 47 subjects. Interestingly, in silico analyses revealed that splice site SNP rs2291726 results in a truncated protein and classified GIPR variant Glu354Gln as a functional amino acid change. Association analyses were performed in a case-cohort study of incident cardiovascular disease (CVD) nested in the EPIC-Potsdam cohort. No significant associations between incident CVD and GIP Ser103Gly and rs2291726 were found. For GIPR Glu354Gln, we obtained a nominal association of heterozygous minor allele carrier with CVD in a codominant model adjusted for BMI, sex, and age (OR: 0.67, Cl: 0.50-0.91,p = 0.01) or additional covariates of CVD (OR: 0.72, Cl: 0.52-0.97,p = 0.03). In conclusion, we identified a common splice site mutation (rs2291726) of the GIP gene which results in a truncated protein and provide preliminary evidence for an association of the heterozygous GIPR Glu354Gln genotype with CVD
    Type of Publication: Journal article published
    PubMed ID: 17624916
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 333 (1993), S. 315-318 
    ISSN: 0014-5793
    Keywords: Calmodulin ; Isoform ; Protein kinase
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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