Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus.

Abstract

AIMS:

Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro- or macroalbuminuria.

METHODS:

Patients with Type 2 diabetes (n = 90) and hypertension (n = 150) were selected from the community-cohort 'Prevention of REnal and Vascular End-stage Disease' (PREVEND) and the Steno Diabetes Center for this case-control study. Cases transitioned in albuminuria stage (from normo- to microalbuminuria or micro- to macroalbuminuria). Controls, matched for age, gender, and baseline albuminuria stage, remained in normo- or microalbuminuria stage during follow-up. Median follow-up was 2.9 years. Metabolomics were performed on plasma and urine. The predictive performance of a metabolite for albuminuria transition was assessed by the integrated discrimination index.

RESULTS:

In patients with Type 2 diabetes with normoalbuminuria, no metabolites discriminated cases from controls. In patients with Type 2 diabetes with microalbuminuria, plasma histidine was lower (fold change = 0.87, P = 0.02) and butenoylcarnitine was higher (fold change = 1.17, P = 0.007) in cases vs. controls. In urine, hexose, glutamine and tyrosine were lower in cases vs. controls (fold change = 0.20, P < 0.001; 0.32, P < 0.001; 0.51, P = 0.006, respectively). Adding the metabolites to a model of baseline albuminuria and estimated glomerular filtration rate metabolites improved risk prediction for macroalbuminuria transition (plasma integrated discrimination index = 0.28, P < 0.001; urine integrated discrimination index = 0.43, P < 0.001). These metabolites did not differ between hypertensive cases and controls without Type 2 diabetes.

CONCLUSIONS:

Type 2 diabetes-specific plasma and urine metabolites were discovered that predict the development of macroalbuminuria beyond established renal risk markers. These results should be confirmed in a large, prospective cohort.

• Authors: M J Pena, H J Lambers Heerspink, M E Hellemons, T Friedrich, G Dallmann, M Lajer, S J L Bakker, R T Gansevoort, P Rossing, D de Zeeuw, S S Roscioni
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 31 Issue 9 Pg. 1138-47 (Sep 2014) ISSN: 1464-5491 [Electronic] England
• PMID: 24661264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Chemical References

• Biomarkers

Topics

• Aged
• Albuminuria (metabolism, physiopathology)
• Biomarkers (metabolism)
• Case-Control Studies
• Diabetes Mellitus, Type 2 (metabolism, physiopathology)
• Diabetic Nephropathies (metabolism, physiopathology)
• Early Diagnosis
• Female
• Glomerular Filtration Rate
• Humans
• Hypertension (metabolism, physiopathology)
• Male
• Middle Aged
• Predictive Value of Tests
• Prospective Studies