Metabolic basis for low urine pH in type 2 diabetes

Background and objectives: Type 2 diabetes is associated with excessively low urine pH, which increases the risk for uric acid nephrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes. Design, setting, participants, & measurements: Nine non-stone-forming patients who had type 2 diabetes and low urine pH and 16 age- and body mass index-matched non-stone-forming volunteers without type 2 diabetes were maintained on a constant metabolic diet for 7 days, and 24-hour urine was collected on the last 2 days of the diet. Results: Urine dietary markers (potassium, sulfate, phosphorus, and urea nitrogen) were not different between the two groups. Patients with type 2 diabetes exhibited a significantly lower 24-hour urine pH (5.45 ± 0.27 versus 5.90 ± 0.42; P < 0.01) and higher net acid excretion (NAE; 57 ± 12 versus 38 ± 18 mEq/d; P < 0.01) compared with control subjects. The proportion of NAE excreted as ammonium (NH₄⁺/NAE) was significantly lower in patients with type 2 diabetes than in control subjects (0.70 ± 0.12 versus 0.94 ± 0.36; P < 0.01); however, the greater NAE in patients with type 2 diabetes was not accounted for by the differences in unmeasured urinary anions. Conclusions: The overly acidic urine in patients with type 2 diabetes persists after controlling for dietary factors, body size, and age. The lower pH is due to a combination of greater NAE and lower use of ammonia buffers in patients with diabetes, which predisposes them to uric acid urolithiasis.