Blood Pressure and Uric Acid in Diabetes Mellitus

The existence of a strong association between arterial hypertension and hyperuricemia has been recognized for more than a century. Initial data showed that hyperuricemia could be present in as many as 30% of untreated hypertensive patients, rising to around 60% in those receiving antihypertensive therapy, particularly diuretics.1 Recent studies have provided evidence for a casual role of hyperuricemia in the pathogenesis of hypertension,2 chronic kidney disease,3 and type 2 diabetes,4 favoring the possibility that uric acid may play a role in the epidemic of obesity, metabolic syndrome, and cardiorenal disease.5 Development of progressive renal damage as a result of any of the two most frequent causes of end‐stage renal disease, hypertension and diabetes mellitus, contributes to further increases in uric acid levels and its potential deletereous cardiorenal consequences.6

In this issue of the Journal of Clinical Hypertension, Bjornstad and colleagues7 describe the existence of a paradoxical situation consisting of an inverse relationship between serum uric acid and systolic blood pressure in patients with type 1 diabetes. This situation compares with the finding of the expected positive association between uric acid and systolic blood pressure observed in the control group of the nondiabetic population included in the Coronary Artery Calcification in Type 1 Diabetes Study. It is known that the levels of serum uric acid are lower in type 1 diabetic patients compared with the general population8; however, it has been demonstrated that in type 1 diabetes, serum uric acid levels are associated with microvascular endothelial dysfunction,9 with the development of microalbuminuria,10 which reflects early diabetic nephropathy, and also with the progression of subclinical coronary aterosclerosis.11 As nicely reviewed by the authors of the paper to which this commentary is devoted, the explanation of their finding is not easy and they make a very good review of possibilities. One of them is that serum uric acid levels can fall in diabetics as a consequence of glycosuria leading to proximal tubular dysfunction and enhanced uricosuria.12 In fact, serum uric acid levels are higher in patients with better diabetes control and less glycosuria.13 Recently, a new class of antidiabetic drugs is available in Europe and the United States, the sodium glucose cotransport‐2 (SGLT2 inhibitors to be used mainly in type 2 diabetic patients. The main mechanism of this class of drugs is the induction of glucosuria through which they obtain a significant reduction in hemoglobin A_1c and fasting plasma glucose.14 These effects are accompanied by a significant decrease in body weight, systolic and diastolic blood pressure, and, interestingly, serum uric acid levels. Further studies are needed, but glycosuria could be the main effector after the finding of decreased serum uric acid levels in type 1 diabetes and the presence of an inverse association between this parameter and systolic blood pressure at least before renal damage develops and progresses.