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  • 1
    Online Resource
    Online Resource
    Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus
    Springer Science and Business Media LLC ; 2020
    In:  Diabetologia Vol. 63, No. 3 ( 2020-03), p. 636-647
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 63, No. 3 ( 2020-03), p. 636-647
    Abstract: The aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes. Methods We used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records. Results Median age was 44.1 years and diabetes duration 20.9 years. The prevalence of CKD stages G1, G2, G3 and G4 and end-stage renal disease (ESRD) was 64.0%, 29.3%, 5.4%, 0.6%, 0.7%, respectively. Micro/macroalbuminuria prevalence was 8.6% and 3.0%, respectively. The incidence rate of ESRD was 2.5 (95% CI 1.9, 3.2) per 1000 person-years. The majority (59%) of those with chronic kidney disease stages G3–G5 did not have albuminuria on the day of recruitment or previously. Over 11.6 years of observation, the median annual decline in eGFR was modest at −1.3 ml min −1 [1.73 m] −2  year −1 (interquartile range [IQR]: −2.2, −0.4). However, 14% experienced a more significant loss of at least 3 ml min −1 [1.73 m] −2 . These decliners had more cardiovascular disease (OR 1.9, p  = 5 × 10 −5 ) and retinopathy (OR 1.3 p  = 0.02). Adding HbA 1c , prior cardiovascular disease, recent mean eGFR and prior trajectory of eGFR to a model with age, sex, diabetes duration, current eGFR and ACR maximised the prediction of final eGFR ( r 2 increment from 0.698 to 0.745, p   〈  10 −16 ). Attempting to model nonlinearity in eGFR decline or to detect latent classes of decliners did not improve prediction. Conclusions These data show much lower levels of kidney disease than historical estimates. However, early identification of those destined to experience significant decline in eGFR remains challenging.
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-019-05052-z
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1458993-X
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  • 2
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    Online Resource
    Comparison of serum and urinary biomarker panels with albumin/creatinine ratio in the prediction of renal function decline in type 1 diabetes
    Springer Science and Business Media LLC ; 2020
    In:  Diabetologia Vol. 63, No. 4 ( 2020-04), p. 788-798
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 63, No. 4 ( 2020-04), p. 788-798
    Abstract: We examined whether candidate biomarkers in serum or urine can improve the prediction of renal disease progression in type 1 diabetes beyond prior eGFR, comparing their performance with urinary albumin/creatinine ratio (ACR). Methods From the population-representative Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) we sampled 50% and 25% of those with starting eGFR below and above 75 ml min −1 [1.73 m] −2 , respectively ( N  = 1629), and with median 5.1 years of follow-up. Multiplexed ELISAs and single molecule array technology were used to measure nine serum biomarkers and 13 urine biomarkers based on our and others’ prior work using large discovery and candidate studies. Associations with final eGFR and with progression to 〈 30 ml min −1 [1.73] m −2 , both adjusted for baseline eGFR, were tested using linear and logistic regression models. Parsimonious biomarker panels were identified using a penalised Bayesian approach, and their performance was evaluated through tenfold cross-validation and compared with using urinary ACR and other clinical record data. Results Seven serum and seven urine biomarkers were strongly associated with either final eGFR or progression to 〈 30 ml min −1 [1.73 m] −2 , adjusting for baseline eGFR and other covariates (all at p 〈 2.3 × 10 −3 ). Of these, associations of four serum biomarkers were independent of ACR for both outcomes. The strongest associations with both final eGFR and progression to 〈 30 ml min −1 [1.73 m] −2 were for serum TNF receptor 1, kidney injury molecule 1, CD27 antigen, α-1-microglobulin and syndecan-1. These serum associations were also significant in normoalbuminuric participants for both outcomes. On top of baseline covariates, the r 2 for prediction of final eGFR increased from 0.702 to 0.743 for serum biomarkers, and from 0.702 to 0.721 for ACR alone. The area under the receiver operating characteristic curve for progression to 〈 30 ml min −1 [1.73 m] −2 increased from 0.876 to 0.953 for serum biomarkers, and to 0.911 for ACR alone. Other urinary biomarkers did not outperform ACR. Conclusions/interpretation A parsimonious panel of serum biomarkers easily measurable along with serum creatinine may outperform ACR for predicting renal disease progression in type 1 diabetes, potentially obviating the need for urine testing.
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-019-05081-8
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1458993-X
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  • 3
    Online Resource
    Online Resource
    Quantitative levels of serum N -glycans in type 1 diabetes and their association with kidney disease
    Oxford University Press (OUP) ; 2021
    In:  Glycobiology Vol. 31, No. 5 ( 2021-06-03), p. 613-623
    Details
    In: Glycobiology, Oxford University Press (OUP), Vol. 31, No. 5 ( 2021-06-03), p. 613-623
    Abstract: We investigated associations of quantitative levels of N-glycans with hemoglobin A1c (HbA1c), renal function and renal function decline in type 1 diabetes. We measured 46 total N-glycan peaks (GPs) on 1565 serum samples from the Scottish Diabetes Research Network Type 1 Bioresource Study (SDRNT1BIO) and a pool of healthy donors. Quantitation of absolute abundance of each GP used 2AB-labeled mannose-3 as a standard. We studied cross-sectional associations of GPs and derived measures with HbA1c, albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR), and prospective associations with incident albuminuria and final eGFR. All GPs were 1.4 to 3.2 times more abundant in SDRTN1BIO than in the healthy samples. Absolute levels of all GPs were slightly higher with higher HbA1c, with strongest associations for triantennary trigalactosylated disialylated, triantennary trigalactosylated trisialylated structures with core or outer arm fucose, and tetraantennary tetragalactosylated trisialylated glycans. Most GPs showed increased abundance with worsening ACR. Lower eGFR was associated with higher absolute GP levels, most significantly with biantennary digalactosylated disialylated glycans with and without bisect, triantennary trigalactosylated trisialylated glycans with and without outer arm fucose, and core fucosylated biantennary monogalactosylated monosialylated glycans. Although several GPs were inversely associated prospectively with final eGFR, cross-validated multivariable models did not improve prediction beyond clinical covariates. Elevated HbA1c is associated with an altered N-glycan profile in type 1 diabetes. Although we could not establish GPs to be prognostic of future renal function decline independently of HbA1c, further studies to evaluate their impact in the pathogenesis of diabetic kidney disease are warranted.
    Type of Medium: Online Resource
    ISSN: 1460-2423
    URL: Article
    DOI: 10.1093/glycob/cwaa106
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1478140-2
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