Evaluation of the Tubular Effects of Dapagliflozin Using 1HNMR Spectroscopy

Fifty patients with type 2 diabetes on metformin monotherapy with HbA1c \> 7% and blood pressure \> 140/90 mmHg will be included. All eligible patients will be given dapagliflozin 10 mg qd for 3 months. Routine laboratory parameters that will be measured on each visit include: 1) for serum samples: glucose, urea, creatinine, uric acid, electrolytes (sodium, potassium, chloride, calcium, phosphate and magnesium and 2) for urine samples: glucose, urea, creatinine, uric acid, electrolytes (sodium, potassium, chloride, calcium, phosphate and magnesium) and alpha-1 microglobulin. It is well known that alpha-1 microglobulin is a low-molecular weight protein that is normally filtered by renal glomeruli and reabsorbed by the proximal tubular cells. Increased excretion of alpha1-microglobulin has been proposed as a non-invasive marker for the diagnosis and monitoring of early tubular disorders such as diabetic nephropathy. In addition, the fractional excretion values (FE) of the electrolytes will be calculated using the formula: FEA(%) = (UrineA/SerumA) /(UrineCr/SerumCr) × 100. The 1HΝMR spectra of urine samples will be recorded on a 500 MHz spectrometer. In the present study, the main low molecular weight (LMW) constituents of urine that will be quantified are 1) metabolites such as glucose, creatinine, creatine, choline, taurine, dimethylamine, betaine, trimethylaminoxide 2) amino acids such as glycine, valine, alanine, leucine, histidine, lysine, threonine and 3) organic acids such as citrate, hippurate, lactate, acetate, succinate, and formate. In addition, 1HNMR methodology allows for the detection of changes in the concentrations of hundreds of metabolites. These substances are normally present in traces, whereas in pathological conditions their concentrations can be found increased.