Hyperuricemia Is Independently Associated with Coronary Heart Disease and Renal Dysfunction in Patients with Type 2 Diabetes Mellitus
et al. (2011) Hyperuricemia Is Independently Associated with Coronary Heart Disease and Renal
Dysfunction in Patients with Type 2 Diabetes Mellitus. PLoS ONE 6(11): e27817. doi:10.1371/journal.pone.0027817
Hyperuricemia Is Independently Associated with Coronary Heart Disease and Renal Dysfunction in Patients with Type 2 Diabetes Mellitus
Hiroyuki Ito 0
Mariko Abe 0
Mizuo Mifune 0
Koshiro Oshikiri 0
Shinichi Antoku 0
Yuichiro Takeuchi 0
Michiko 0
Giorgio Sesti, Universita Magna-Graecia di Catanzaro, Italy
0 Department of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital , Tokyo , Japan
Aims: To investigate the relationship between hyperuricemia (HUA) and the clinical backgrounds in Japanese patients with type 2 diabetes mellitus. Methods: After a cross-sectional study evaluating the association of HUA with the clinical characteristics in 1,213 patients with type 2 diabetes mellitus, the estimated glomerular filtration rate (eGFR) and the incidence of diabetic macroangiopathies was investigated in a prospective observational study in 1,073 patients during a 3.5 year period. HUA was defined by serum uric acid levels .327 mmol/L or as patients using allopurinol. Results: The frequency of HUA was significantly higher in the diabetic patients (32% in men and 15% in women) than in the normal controls (14% in men and 1% in women). In total, HUA was found in 299 (25%) of the patients during the crosssectional study. Even after adjusting for sex, drinking status, treatment for diabetes mellitus, body mass index, hypertension, use of diuretics, hyperlipidemia, HbA1c and/or the eGFR, the HUA was independently associated with some diabetic complications. The eGFR was significantly reduced in HUA patients compared to those with normouricemia in the 12 months after observation was started. HUA was also an independent risk factor for coronary heart disease even after adjustment in the Cox proportional hazard model. Conclusions: HUA is a associated with diabetic micro- and macroangiopathies. HUA is a predictor of coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus. However, the influence of HUA is considered to be limited.
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It has been reported that hyperuricemia (HUA) is an independent
risk factor for the progression of renal dysfunction [1,2] and
cardiovascular events [110], as well as gout. Type 2 diabetes
mellitus is also well-known as a major risk factor for chronic kidney
disease (CKD) and atherosclerotic disease. Although the serum uric
acid level was previously shown to be higher in patients with diabetes
mellitus than in the population without glucose intolerance [10], it
was also elevated in the individuals with impaired glucose tolerance
other than type 2 diabetes [1114]. However, HUA has been
reported to be associated with the onset of diabetes mellitus or
metabolic syndrome [1520]. Although several studies have reported
the relationship between HUA and diabetic macroangiopathies,
such as coronary heart disease, stroke and peripheral arterial disease,
the conclusions have been controversial [2127]. Furthermore, the
changes in kidney function associated with the HUA have not yet
been sufficiently studied in the patients with type 2 diabetes mellitus.
The aim of this study was to investigate the relationship between
the HUA and the clinical background including diabetic
complications and the glomerular filtration rate (GFR), in a
cross-sectional study, and to determine the incidences of diabetic
macroangiopathies and the changes in the eGFR according to a
prospective observational study in Japanese patients with type 2
diabetes mellitus.
Ethics statement
This study was conducted according to the principles expressed
in the Declaration of Helsinki. The Ethics Committees of
Edogawa Hospital approved the protocol of this study and waived
the need for written informed consent because the data were
analyzed anonymously for this observation study based on the data
stored in the hospital database.
Study population and methods
First, a cross-sectional study was performed in a population of
1,213 patients diagnosed with type 2 diabetes mellitus who
underwent consecutive evaluations, including urinalysis, and
determination of the serum creatinine and uric acid levels in the
Department of Diabetes, Metabolism and Kidney Disease of
Edogawa Hospital, Tokyo, Japan between April 2008 and March
2009. The patients with end-stage renal disease receiving
maintenance dialysis were excluded from this study. Subjects
who underwent physical health examinations were also entered
into the study as normal controls (age-matched, 156 men and 116
women). The control did not have diabetes mellitus or a history of
myocardial and/or cerebral infarction.
Second, a prospective observational study was performed in the
population of the cross-sectional study. The estimated GFR
(eGFR) and new onset of diabetic micro- and macroangiopathies
were estimated in 1,073 of the patients with type 2 diabete (...truncated)