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  • 1
    Online Resource
    Online Resource
    Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes
    American Diabetes Association ; 2016
    In:  Diabetes Vol. 65, No. 3 ( 2016-03-01), p. 803-817
    Details
    In: Diabetes, American Diabetes Association, Vol. 65, No. 3 ( 2016-03-01), p. 803-817
    Abstract: Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10–7) and 13% for RAB38/CTSC (P = 5.8 × 10−7). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db15-1313
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2016
    detail.hit.zdb_id: 80085-5
    detail.hit.zdb_id: 1501252-9
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  • 2
    Online Resource
    Online Resource
    Associations of Diet Quality and All-Cause Mortality Across Levels of Cardiometabolic Health and Disease: A 7.6-Year Prospective Analysis From the Dutch Lifelines Cohort
    American Diabetes Association ; 2021
    In:  Diabetes Care Vol. 44, No. 5 ( 2021-05-01), p. 1228-1235
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 44, No. 5 ( 2021-05-01), p. 1228-1235
    Abstract: To simultaneously investigate the association of diet quality and all-cause mortality in groups with varying cardiometabolic diseases (CMDs) at baseline. RESEARCH DESIGN AND METHODS From the population-based Lifelines cohort, 40,892 non-underweight participants aged ≥50 years with data on diet quality and confounding factors were included (enrollment 2006–2013). From food-frequency questionnaire data, tertiles of the Lifelines Diet Score were calculated (T1 = poorest, T3 = best diet quality). Four CMD categories were defined: 1) CMD free, 2) type 2 diabetes, 3) one cardiovascular disease (CVD), 4) two or more CMDs. Months when deaths occurred were obtained from municipal registries up until November 2019. Multivariable Cox proportional hazards models were applied for the total population and stratified by CMD categories. RESULTS After a median follow-up of 7.6 years, 1,438 participants died. Diet quality and CMD categories were independently associated with all-cause mortality in crude and adjusted models (P & lt; 0.001). A dose-response relationship of diet quality with all-cause mortality was observed in the total population (Ptrend & lt; 0.001, T2 vs. T3 = 1.22 [1.07–1.41], T1 vs. T3 = 1.57 [1.37–1.80] ). In stratified analyses, the association was significant for CMD-free individuals (T1 vs. T3 = 1.63 [1.38–1.93]) and for patients with type 2 diabetes (1.87 [1.17–3.00] ) but not for patients with one CVD (1.39 [0.93–2.08]) or multiple CMDs (1.19 [0.80–1.76] ). CONCLUSIONS A high-quality diet can potentially lower all-cause mortality risk in the majority of the aging population. Its effect may be greatest for CMD-free individuals and patients with type 2 diabetes. Tailored dietary guidelines may be required for patients with extensive histories of CMDs.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc20-2709
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
    detail.hit.zdb_id: 1490520-6
    detail.hit.zdb_id: 441231-X
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  • 3
    Online Resource
    Online Resource
    Association Between CNDP1 Genotype and Diabetic Nephropathy Is Sex Specific
    American Diabetes Association ; 2010
    In:  Diabetes Vol. 59, No. 6 ( 2010-06-01), p. 1555-1559
    Details
    In: Diabetes, American Diabetes Association, Vol. 59, No. 6 ( 2010-06-01), p. 1555-1559
    Abstract: The 5-5 homozygous CNDP1 (carnosinase) genotype is associated with a reduced risk of diabetic nephropathy. We investigated whether this association is sex specific and independent of susceptibility for type 2 diabetes. RESEARCH DESIGN AND METHODS Three separate groups of 114, 90, and 66 patients with type 2 diabetes and diabetic nephropathy were included in this study and compared with 93 patients with type 2 diabetes for & gt;15 years without diabetic nephropathy and 472 population control subjects. The diabetes control group was used to determine an association in the three patient groups separately, and the population control group was used to estimate the genotype risk [odds ratio (CI)] for the population in a pooled analysis. The population control subjects were also compared with 562 patients with type 2 diabetes without diabetic nephropathy to determine whether the association was independent of type 2 diabetes. The CNDP1 genotype was determined by fragment analysis after PCR amplification. RESULTS The frequency of the 5-5 homozygous genotype was 28, 36, and 41% in the three diabetic nephropathy patient groups and 43 and 42% in the diabetic and population control subjects, respectively. The 5-5 homozygous genotype occurred significantly less frequently in women in all three patient groups compared with diabetic control subjects. The genotype risk for the population was estimated to be 0.5 (0.30–0.68) in women and 1.2 (0.77–1.69) in men. The 562 patients with type 2 diabetes without diabetic nephropathy did not differ from the general population (P = 0.23). CONCLUSIONS This study suggests that the association between the CNDP1 gene and diabetic nephropathy is sex specific and independent of susceptibility for type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db09-1377
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2010
    detail.hit.zdb_id: 80085-5
    detail.hit.zdb_id: 1501252-9
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