title: Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes.
abstract: OBJECTIVE
  Glucose fluctuations may help predict diabetic complications. We evaluated the relation between glucose variability and oxidative stress in patients with type 1 diabetes.
  
  
  METHODS
  Continuous glucose monitors were inserted subcutaneously in 25 patients. During the measurement, patients collected two 24 h urine samples, while 24 healthy controls collected one 24 h urine sample for determination of 15(S)-8-iso-prostaglandin F2alpha(PGF2alpha) using HPLC tandem mass spectrometry. Mean of the daily differences (MODD), mean amplitude of glycaemic excursions (MAGE) and continuous overlapping net glycaemic action calculated with n hour time-intervals (CONGA-n) were calculated as markers for glucose variability and correlation with 15(S)-8-iso-PGF2alpha excretion was calculated.
  
  
  RESULTS
  Median [interquartile range (IQR)] urinary 15(S)-8-iso-PGF2alpha was higher in patients than healthy controls: 161 (140-217) pg/mg creatinine vs 118 (101-146) pg/mg creatinine (p = 0.001). Median (IQR) MODD was 3.7 (3.2-5.0) mmol/l, MAGE 7.6 (6.4-9.0) mmol/l and CONGA-1 2.3 (2.1-2.8) mmol/l. Univariate regression did not reveal an association for MODD (r2 = 0.01), MAGE (0.08) or CONGA-1 (0.07) with 15(S)-8-iso-PGF2alpha excretion, nor was an association revealed when corrected for HbA1c, age, sex and smoking. Spearman correlation coefficients (r) between 15(S)-8-iso-PGF2alpha excretion and MODD, MAGE and CONGA-1 were non-significant: -0.112, -0.381 and -0.177.
  
  
  CONCLUSIONS
  We report that there is no relationship between glucose variability and urinary 15(S)-8-iso-PGF2alpha. We also confirm that patients with type 1 diabetes have higher levels of urinary 15(S)-8-iso-PGF2alpha than healthy controls, suggesting that in addition to glucose variability, other factors favouring oxidative stress may exist. We did not see a relation between high glucose variability and elevated levels of oxidative stress in patients with type 1 diabetes.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. i.m.wentholt@amc.uva.nl
authors.forename: I M E
authors.initials: IM
authors.lastname: Wentholt
authors.forename: W
authors.initials: W
authors.lastname: Kulik
authors.forename: R P J
authors.initials: RP
authors.lastname: Michels
authors.forename: J B L
authors.initials: JB
authors.lastname: Hoekstra
authors.forename: J H
authors.initials: JH
authors.lastname: DeVries
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018384:Oxidative Stress; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost