Dataset Information

Metabolomic Profile Predicts Development of Microalbuminuria in Individuals with Type 1 Diabetes.

ABSTRACT: Elevated urinary albumin excretion (microalbuminuria) is an early marker of diabetic nephropathy, but there is an unmet need for better biomarkers that capture the individuals at risk with higher accuracy and earlier than the current markers do. We performed an untargeted metabolomic study to assess baseline differences between individuals with type 1 diabetes who either developed microalbuminuria or remained normoalbuminuric. A total of 102 individuals progressed to microalbuminuria during a median follow-up of 3.2 years, whereas 98 sex-, age- and body mass index (BMI) matched non-progressors remained normoalbuminuric during a median follow-up of 7.1 years. Metabolomic screening identified 1,242 metabolites, out of which 111 differed significantly between progressors and non-progressors after adjustment for age of diabetes onset, baseline glycosylated hemoglobin A1c (HbA_1c), and albumin excretion rate (AER). The metabolites that predicted development of microalbumiuria included several uremic toxins and carnitine metabolism related molecules. Iterative variable selection indicated erythritol, 3-phenylpropionate, and N-trimethyl-5-aminovalerate as the best set of variables to predict development of microalbuminuria. A metabolomic index based on these metabolites improved the prediction of incident microalbuminuria on top of the clinical variables age of diabetes onset, baseline HbA_1c and AER (ROC_AUC?=?0.842 vs 0.797), highlighting their ability to predict early-phase diabetic nephropathy.

SUBMITTER: Haukka JK

PROVIDER: S-EPMC6138633 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Metabolomic Profile Predicts Development of Microalbuminuria in Individuals with Type 1 Diabetes.

Haukka Jani K JK Sandholm Niina N Forsblom Carol C Cobb Jeffrey E JE Groop Per-Henrik PH Ferrannini Ele E

Scientific reports 20180914 1

Elevated urinary albumin excretion (microalbuminuria) is an early marker of diabetic nephropathy, but there is an unmet need for better biomarkers that capture the individuals at risk with higher accuracy and earlier than the current markers do. We performed an untargeted metabolomic study to assess baseline differences between individuals with type 1 diabetes who either developed microalbuminuria or remained normoalbuminuric. A total of 102 individuals progressed to microalbuminuria during a me ...[more]

PMID: 30217994

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Project description:ObjectiveWe tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals.Research design and methodsWe studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients' relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2-51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial-Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables.ResultsHigher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06-1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS >0.295, 95% CI 1.47-3.51; P = 0.0002).ConclusionsThe T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.

Project description:ObjectiveTo investigate the prevalence of microalbuminuria (MAU) among Chinese individuals without diabetes and the relationship between MAU and metabolic factors, individual socioeconomic status (SES), and regional economic development level.DesignCross-sectional study of prevalence of MAU.Setting152 urban street districts and 112 rural villages from northeast, north, east, south central, northwest and southwest China.Participants46 239 participants were recruited using a multistage stratified sampling design from 2007 to 2008. A total of 41 290 participants without diabetes determined by oral glucose tolerance test were included in the present study. Urine albumin/creatinine ratio results of 35 430 individuals were available.Primary and secondary outcome measuresPositive detection of MAU was determined using an ACR of 22.1-299.9 mg/g in men 30.9-299.9 mg/g in women.ResultsThe prevalence of MAU in men was 22.4% and 24.5% in women. In developed, intermediate-developed and under-developed areas, the prevalence of MAU in men was 20.7%, 21.9% and 32.5%, respectively; in women the prevalence was 19.6%, 26.0% and 29.5%, respectively. The prevalence of MAU increased as the number of metabolic disorders present increased, and as the number of lower SES components increased (farmer, below university education level and low income). Prevalence of MAU in developed and intermediate developed areas had adjusted risk ratios of 0.52 (95% CI 0.42 to 0.60) and 0.65 (95% CI 0.57 to 0.76), respectively. Multivariate logistic analyses demonstrated MAU was strongly associated with older age, high-blood pressure, higher blood glucose low education level, low occupational level and residence in under-developed region.ConclusionsSeveral factors had independent correlations to MAU in China: older age, metabolic abnormalities, lower SES level and living in economically under-developed areas, which encourage the development of strategies to lower the risk for MAU in these susceptible populations.

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Metabolomic Profile Predicts Development of Microalbuminuria in Individuals with Type 1 Diabetes.

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Metabolomic Profile Predicts Development of Microalbuminuria in Individuals with Type 1 Diabetes.

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