Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes

Aims/hypothesis 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 F2 alpha (PGF(2 alpha)) 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-PGF2 alpha excretion was calculated. Results Median [interquartile range (IQR)] urinary 15(S)-iso-PGF(2 alpha) 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 (r(2)=0.01), MAGE (0.08) or CONGA-1 ( 0.07) with 15(S)-8-iso-PGF(2 alpha) excretion, nor was an association revealed when corrected for HbA(1c), age, sex and smoking. Spearman correlation coefficients (r) between 15(S)-8-iso-PGF(2 alpha) excretion and MODD, MAGE and CONGA-1 were non-significant: -0.112, -0.381 and -0.177. Conclusions/interpretation We report that there is no relationship between glucose variability and urinary 15(S)-8-iso-PGF(2 alpha). We also confirm that patients with type 1 diabetes have higher levels of urinary 15(S)-8-iso-PGF(2 alpha) 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.