On the non-linear association between serum uric acid levels and all-cause mortality rate in patients with type 2 diabetes mellitus.
High levels of serum uric acid (SUA) are associated with increased mortality risk in the general population. Contrasting results are available in people with diabetes. The aim of our study was to investigate the association and its functional form between SUA and all cause-mortality in patients with type 2 diabetes mellitus (T2DM).



We studied three cohorts of patients with T2DM: Gargano Mortality Study, Foggia Mortality Study, Pisa Mortality Study. All-cause mortality rate was the end point of this study.



The most reliable relationship between SUA levels and all-cause mortality rate was quadratic, with such model being well approximated by SUA tertiles. Both tertiles 1 and 3 were at higher risk of mortality as compared to tertile 2: Hazard Ratio (HR) [95% Confidence Interval (CI)] = 1.34 (1.07-1.68) and 1.61 (1.29-1.99), respectively. In the pseudo-sample, created from the real pooled sample, the best relationship between SUA and all-cause mortality rate was quadratic. In a tree-based Recursive Partitioning and Regression Tree analysis two subgroups at increased risk of mortality were identified, namely those with SUA levels ≥7.28 mg/dl and with SUA levels <4.16 mg/dl as compared to patients with intermediate SUA levels (i.e. 4.16-7.28), thus providing further evidence on the J-shaped relationship between SUA levels and mortality rate.



SUA was not linearly associated with all-cause mortality rate in patients with T2DM. For clinical and public health purposes such association is J-shaped.
Unit of Endocrinology and Diabetology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Olga
O
Lamacchia
Unit of Biostatistics, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
Andrea
A
Fontana
Unit of Internal Medicine, Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
Antonio
A
Pacilli
Unit of Biostatistics, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. Electronic address: m.copetti@operapadrepio.it.
Massimiliano
M
Copetti
Unit of Endocrinology and Diabetology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Stefania
S
Fariello
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Monia
M
Garofolo
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Giuseppe
G
Penno
Research Unit of Diabetes and Endocrine Diseases, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy; Mendel-Laboratory, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy; Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
Vincenzo
V
Trischitta
Unit of Internal Medicine, Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. Electronic address: s.decosmo@operapadrepio.it.
Salvatore
S
De Cosmo
Unit of Endocrinology and Diabetology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. Electronic address: mauro.cignarelli@unifg.it.
Mauro
M
Cignarelli
D015415:Biomarkers / Q000097:blood; D002423:Cause of Death / Q000639:trends; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D014527:Uric Acid / Q000097:blood*
D015415:Biomarkers; D014527:Uric Acid
Diabetic complications; Oxidative stress; Risk factors