PMID- 20520742
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1177-2719 (Electronic)
IS  - 1177-2719 (Linking)
VI  - 5
DP  - 2010 May 4
TI  - Elevated Serum Sorbitol and not Fructose in Type 2 Diabetic Patients.
PG  - 33-8
AB  - 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.
FAU - Preston, Gregory M
AU  - Preston GM
AD  - Pfizer Global Research and Development, Groton, CT 06340 USA. Email: 
      gregory.m.preston@pfizer.com.
FAU - Calle, Roberto A
AU  - Calle RA
LA  - eng
PT  - Journal Article
DEP - 20100504
PL  - United States
TA  - Biomark Insights
JT  - Biomarker insights
JID - 101288638
PMC - PMC2879225
OTO - NOTNLM
OT  - diabetic complications
OT  - fructose
OT  - polyol pathway
OT  - sorbitol
EDAT- 2010/06/04 06:00
MHDA- 2010/06/04 06:01
PMCR- 2010/05/04
CRDT- 2010/06/04 06:00
PHST- 2010/06/04 06:00 [entrez]
PHST- 2010/06/04 06:00 [pubmed]
PHST- 2010/06/04 06:01 [medline]
PHST- 2010/05/04 00:00 [pmc-release]
AID - bmi-2010-033 [pii]
AID - 10.4137/bmi.s4530 [doi]
PST - epublish
SO  - Biomark Insights. 2010 May 4;5:33-8. doi: 10.4137/bmi.s4530.