Dataset Information

Trajectories in estimated glomerular filtration rate in youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study.

ABSTRACT:

Aims

We sought to characterize the direction and associated factors of eGFR change following diagnosis of youth-onset type 1 and type 2 diabetes.

Methods

We assessed the direction of eGFR change at two visits (mean 6.6 years apart) in SEARCH, a longitudinal cohort study of youth-onset type 1 and type 2 diabetes. We used the CKiD_Cr-CysC equation to estimate GFR and categorized 'rising' and 'declining' eGFR as an annual change of ≥3 ml/min/1.73 m² in either direction. Multivariable logistic regression evaluated factors associated with directional change in eGFR.

Results

Estimated GFR declined in 23.8% and rose in 2.8% of participants with type 1 diabetes (N = 1225; baseline age 11.4 years), and declined in 18.1% and rose in 15.6% of participants with type 2 diabetes (N = 160; baseline age 15.0 years). Factors associated with rising and declining eGFR (versus stable) in both type 1 and type 2 diabetes included sex, age at diagnosis, baseline eGFR and difference in fasting glucose between study visits. Additional factors in type 1 diabetes included time from baseline visit, HbA1c and body mass index.

Conclusions

Over the first decade of diabetes, eGFR decline is more common in type 1 diabetes whereas eGFR rise is more common in type 2 diabetes.

SUBMITTER: Westreich KD

PROVIDER: S-EPMC7855388 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Trajectories in estimated glomerular filtration rate in youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study.

Westreich Katherine D KD Isom Scott S Divers Jasmin J D'Agostino Ralph R Lawrence Jean M JM Kanakatti Shankar Roopa R Dolan Lawrence M LM Imperatore Giuseppina G Dabelea Dana D Mayer-Davis Elizabeth J EJ Mottl Amy K AK

Journal of diabetes and its complications 20201023 2

<h4>Aims</h4>We sought to characterize the direction and associated factors of eGFR change following diagnosis of youth-onset type 1 and type 2 diabetes.<h4>Methods</h4>We assessed the direction of eGFR change at two visits (mean 6.6 years apart) in SEARCH, a longitudinal cohort study of youth-onset type 1 and type 2 diabetes. We used the CKiD<sub>Cr-CysC</sub> equation to estimate GFR and categorized 'rising' and 'declining' eGFR as an annual change of ≥3 ml/min/1.73 m<sup>2</sup> in either dir ...[more]

PMID: 33168393

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Project description:AimsTo replicate the association of genetic variants with estimated glomerular filtration rate (GFR) and albuminuria, which has been found in recent genome-wide studies in patients with Type 2 diabetes.MethodsWe evaluated 16 candidate single nucleotide polymorphisms for estimated GFR in 3028 patients with Type 2 diabetes sampled from clinics across Tayside, Scotland, UK, who were included in the Genetics of Diabetes Audit and Research Tayside (GoDARTs) study. These single nucleotide polymorphisms were tested for their association with estimated GFR at entry to the study, with albuminuria, and with time to stage 3B chronic kidney disease (estimated GFR<45 ml/min/1.73 m(2)). We also stratified the effects on estimated GFR in patients with (n = 2096) and without albuminuria (n = 613).Resultsrs1260326 in GCKR (β=1.30, P = 3.23E-03), rs17319721 in SHROOM3 (β = -1.28, P-value = 3.18E-03) and rs12917707 in UMOD (β = 2.0, P-value = 8.84E-04) were significantly associated with baseline estimated GFR. Analysis of effects on estimated GFR, stratified by albuminuria status, showed that in those without albuminuria (normoalbuminura; n = 613), UMOD had a significantly stronger effect on estimated GFR (β(normo) = 4.03 ± 1.23 vs β(albuminuria) = 1.72 ± 0.76, P = 0.002) compared with those with albuminuria, while GCKR (β(normo) = 0.45 ± 0.89 vs β(albuminuria) = 1.12 ± 0.55, P = 0.08) and SHROOM3 (β(normo) = -0.07 ± 0.89 vs β(albuminuria) = -1.43 ± 0.53, P = 0.003) had a stronger effect on estimated GFR in those with albuminuria. UMOD was also associated with a lower rate of transition to stage 3B chronic kidney disease (hazard ratio = 0.83[0.70, 0.99], P = 0.03).ConclusionThe genetic variants that regulate estimated GFR in the general population tend to have similar effects in patients with Type 2 diabetes and in this latter population, it is important to adjust for albuminuria status while investigating the genetic determinants of renal function.

Project description:BackgroundAn impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.MethodsIn the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits.ResultsOver a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates.ConclusionsThe long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815 and NCT00360893.).

Project description:ObjectiveEstimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR.MethodsGenome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula.ResultsThe non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome.ConclusionThe present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

Dataset Information

Trajectories in estimated glomerular filtration rate in youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study.

Aims

Methods

Results

Conclusions

Publications

Trajectories in estimated glomerular filtration rate in youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study.

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