Article

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

Department of Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Diabetologia (Impact Factor: 6.67). 02/2008; 51(1):183-90. DOI: 10.1007/s00125-007-0842-6
Source: PubMed

ABSTRACT

Glucose fluctuations may help predict diabetic complications. We evaluated the relation between glucose variability and oxidative stress in patients with type 1 diabetes.
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.
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.
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.

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    • "This correlation was stronger than that observed with PPG (r = 0.55, p = 0.09), suggesting that GV amplifies the effects of PPG spikes on oxidative stress. These results were consistent with another204,208,230). In a group of T1DM patients, higher levels of urinary 15(S)-8-isoPGF 2α were observed compared to healthy controls, but GV (MAGE, CONGA, and MODD) was not associated with oxidative stress levels (230). "
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    ABSTRACT: The primary therapeutic target for diabetes management is the achievement of good glycemic control, of which glycated hemoglobin (HbA1c) remains the standard clinical marker. However, glycemic variability (GV; the amplitude, frequency, and duration of glycemic fluctuations around mean blood glucose) is an emerging target for blood glucose control. A growing body of evidence supports GV as an independent risk factor for diabetes complications. Several techniques have been developed to assess and quantify intraday and interday GV. Additionally, GV can be influenced by several nutritional factors, including carbohydrate quality, quantity; and distribution; protein intake; and fiber intake. These factors have important implications for clinical nutrition practice and for optimizing blood glucose control for diabetes management. This review discusses the available evidence for GV as a marker of glycemic control and risk factor for diabetes complications. GV quantification techniques and the influence of nutritional considerations for diabetes management are also discussed. Expected final online publication date for the Annual Review of Nutrition Volume 35 is July 17, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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    • "In contrast, in T2D patients a positive correlation between blood glucose variability and reactive oxygen species (ROS) production has been evidenced, and ROS remain major determinants of vascular complications [8]. However, this correlation has yet to be confirmed in T1D [9]. "
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    • "It is also not quite clear how increased glycemic variability could induce diabetic complications. Oxidative stress was suggested as a possible common mechanism of the endothelial impairment induced by increased glycemic variability [12] [13] [14] [15] [16]. Endothelial dysfunction, a first event in the process of vascular impairment, can be induced by increased oxidative stress. "
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