Clinical usefulness of measuring urinary polyol excretion by gas-chromatography/mass-spectrometry in type 2 diabetes to assess polyol pathway activity.

Introduction: Decreased myo-inositol levels and increased activity of the polyol pathway have been proposed to play a role in causing diabetic microvascular complications. There are few clinical methods for examining the activity of the polyol pathway in diabetic patients. We assessed the effect of changes in glycemic control on polyol pathway activity by measuring urinary polyol excretion.
Materials and Methods: Gas-chromatography/mass-spectrometry (GC/MS) was used to assess the urinary excretion of glucose and polyols (myo-inositol, sorbitol, and fructose) in 50 patients who had type 2 diabetes without nephropathy and 20 healthy subjects.
Results: In the diabetic patients with poor glycemic control, urinary sorbitol levels were significantly increased and urinary myo-inositol excretion was approximately 6.5-fold higher than in healthy controls (33.0+/-6.5 vs 221.7+/-45.9 mg/day, mean+/-SE, P<0.01). During strict glycemic control, some patients (Group A) showed simultaneous disappearance of glucosuria and normalization of the urinary excretion of myo-inositol (<50 mg/day) and, while others (Group B) showed delayed normalization of urinary myo-inositol excretion. Group B showed significantly higher urinary myo-inositol, sorbitol, and fructose excretion than Group A at the time of disappearance of glucosuria. These findings suggest that patients in Group B may have increased polyol pathway activity.
Conclusion: Even though short-term strict glycemic regulations were established in long-standing hyperglycemic diabetic patients, to normalize the once-exaggerated polyol pathway activities, it was essential to maintain glucosuria-free conditions for some period. Quantitation of urinary polyols using GC/MS appears to be a clinically useful method for assessing polyol pathway activity.