Higher serum levels of uric acid are associated with a reduced insulin clearance in non-diabetic individuals
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Decreased insulin clearance has been reported to be associated with insulin resistance-related disorders and incident type 2 diabetes. The aim of this study was to evaluate whether higher levels of uric acid (UA), a known risk factor of type 2 diabetes, are associated with a reduced insulin clearance.
440 non-diabetic individuals were stratified in tertiles according to serum UA levels. Insulin clearance and skeletal muscle insulin sensitivity were assessed by euglycemic hyperinsulinemic clamp. Hepatic insulin resistance was estimated by the liver IR index.
Subjects with higher levels of UA displayed an unfavorable metabolic phenotype with a worse lipid profile, increased levels of 2-h post-load glucose levels, fasting, and 2-h post-load insulin levels, hsCRP, liver IR index, and lower levels of eGFR and skeletal muscle insulin sensitivity, in comparison to individuals with lower UA levels. Moreover, subjects with higher UA concentrations exhibited decreased levels of insulin clearance even after adjustment for age, gender, BMI, eGFR, and skeletal muscle insulin sensitivity. In a multivariate regression analysis model including several confounding factors, UA concentration was an independent predictor of insulin clearance (β = − 0.145; P = 0.03). However, when liver IR index was included in the model, the independent association between UA levels and insulin clearance was not retained. Accordingly, in a mediation analysis, liver IR index was a mediator of the negative effects of UA levels on insulin clearance (t = − 2.55, P = 0.01).
Higher serum levels of UA may affect insulin clearance by impairing hepatic insulin sensitivity.
KeywordsUric acid Insulin clearance Hepatic insulin resistance Diabetes risk Skeletal muscle insulin sensitivity
T.V.F. researched and analyzed data, and wrote and edited the manuscript; E.S, E.P, F.A, and A.S. researched data and reviewed the manuscript; M.L.H. and F.P. contributed to the discussion and reviewed the manuscript; G.S. designed the study, contributed to analyze the data, and reviewed the manuscript. All authors have read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human and animal rights
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Comitato Etico Azienda Ospedaliera “Mater Domini”, Italy) and with the Helsinki Declaration of 1975.
Informed consent was obtained from all patients for being included in the study.
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