Related Experiment Video
Updated: Jun 12, 2026

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)
Published on: January 7, 2018
Elevated Serum Sorbitol and not Fructose in Type 2 Diabetic Patients
Gregory M Preston1, Roberto A Calle
1Pfizer Global Research and Development, Groton, CT 06340 USA.
Abstract:
Reductions in fasting serum fructose or erythrocyte sorbitol have been proposed as markers for early proof of mechanism in clinical development of aldose reductase (AR) inhibitors. However fructose is significantly impacted by meals and evaluation of erythrocyte sorbitol poses technical challenges. To more accurately assess the performance of these markers in biological samples, a gas chromatography-mass spectrometry assay was modified and validated. Serum was collected on three consecutive days from 13 healthy volunteers (HV) and 14 patients with type 2 diabetes mellitus (T2DM), and assayed for sorbitol and fructose using this assay. Serum fructose and sorbitol were relatively constant across the three days. Fasting fructose levels were comparable between the two groups (T2DM: 1.48 +/- 0.49 mg/L; HV: 1.39 +/- 0.38 mg/L, mean +/- standard deviation, P = 0.61), but fasting sorbitol levels were significantly higher in diabetics (T2DM: 0.280 +/- 0.163 mg/L; HV: 0.164 +/- 0.044 mg/L, P = 0.02). Feeding resulted in a 5-6 fold increase in serum fructose levels, but only a 5%-10% increase in sorbitol. Only sorbitol remained significantly elevated pre- and post feeding in T2DM patients relative to HV. These data suggest that serum sorbitol may be a robust proof of mechanism biomarker and facilitate dose selection for clinical development of AR inhibitors.
Related Concept Videos
Type II Diabetes Mellitus III: Clinical Manifestations and Diagnosis
Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Diabetes Mellitus: Type 2 and Gestational
Diabetic Neuropathy
Hyperglycemia
Type II Diabetes II: Pathophysiology
