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


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.

1 Follower
13 Reads
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aims HbA1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress. Methods Tests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E4 (LTE4), 11-dehydro-thromboxane B2 (TXB2) and 8-iso-prostaglandin F2α (PGF2). Results HbA1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P = 0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r ≥ 0.84, P < 0.0001). Conclusion A FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation ( NCT00973492).
    Diabetes & Metabolism 09/2014; 40(4). DOI:10.1016/j.diabet.2014.01.004 · 3.27 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in Type 1 diabetes during hyperinsulinemic clamp. Sixteen patients (51 ± 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmol·L(-1)). Insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. Microvascular reactivity (MVR) was measured by laser Doppler flowmetry. Maximum perfusion and the velocity of perfusion increase during PORH were higher in hyperglycemia compared to baseline (47 ± 16 versus 40 ± 16 PU, P < 0.01, and 10.4 ± 16.5 versus 2.6 ± 1.5 PU·s(-1), P < 0.05, resp.). Time to the maximum perfusion during TH was shorter and velocity of perfusion increase during TH higher at hyperglycemia compared to isoglycemic phase (69 ± 15 versus 77 ± 16 s, P < 0.05, and 1.4 ± 0.8 versus 1.2 ± 0.7 PU·s(-1), P < 0.05, resp.). An inverse relationship was found between insulinemia and the time to maximum perfusion during PORH (r = -0.70, P = 0.007). Acute glycemia did not impair microvascular reactivity in this clamp study in Type 1 diabetic patients. Our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with Type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.
    Experimental Diabetes Research 01/2012; 2012:851487. DOI:10.1155/2012/851487 · 4.33 Impact Factor
  • Source
    • "Nitrosative stress can lead to reactions that alter protein structure thus generates some toxic metabolic derivatives such as peroxynitrite and nitrotyrosine, which can cause endothelial damages and furthermore, microvascular and macrovascular complications. By reducing postprandial excursions, it has been demonstrated that oxidative and nitrosative stress can be diminished [22] [23] [24] [25] [26] [27]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Isolated hyperglycemia is associated with atherosclerosis in individuals with type 2 diabetes, but the relationship between postchallenge glucose excursion and atherosclerosis is less clear. This study examines the relationships between postchallenge glucose spikes (PGS), carotid intima-media thickness (IMT), and traditional risk factors for atherosclerosis in individuals with type 2 diabetes. A total of 474 individuals with type 2 diabetes who were within the highest or lowest IMT distribution quartile were included. The Student's t-test, one-way analysis of variance (ANOVA), single variate and multivariate analyses were implemented to study the data. An additional healthy control group (n=896) was selected during routine health examination. They were Han nationality and unrelated to the diabetic patients. (1) Compared with subjects of healthy control group, the subjects with type 2 diabetes had significantly higher levels of body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure, triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), 120 min postchallenge glucose (PG120), hemoglobin A1c (HbA1c) and IMT (P < or = 0.01) and relatively lower levels of high density lipoprotein cholesterol (HDL-C) (P < or = 0.05). (2) According to the IMT which was measured by B-mode ultrasonography, the patients of type 2 diabetes could be divided into two subgroups: one was the subgroup of IMT > or = P(75) and another was the subgroup of IMT < or = P(25). Compared with subjects of IMT > or = P(25) subgroup, subjects being in the IMT > or = P(75) subgroup exhibited significantly increased age, WHR, diabetes duration, systolic blood pressure, total cholesterol, triglyceride, LDL-C, and significantly decreased HDL-C levels. And among all the plasma glucose variables, except for FPG and PG30, all the other variables (include PG60, PG120, PG180, PGS, HbA1C, under area curve of glucose) showed a significant increase in the IMT>/=P(75) subgroup. (3) A multivariate logistic regression analysis was performed to establish which were independently related with carotid IMT, and the results showed the PGS was identified as the strongest determinant of IMT from all the atherosclerosis risk factors. (4) PGS is significantly correlated to a variety of atherosclerosis risk factors. This study identified several important associations between PGS and known risk factors for atherosclerosis and suggested that PGS is independently related to carotid IMT. Wide postchallenge glucose excursions may contribute to the development of atherosclerosis in individuals with type 2 diabetes, independent of other risk factors.
    Atherosclerosis 11/2009; 210(1):302-6. DOI:10.1016/j.atherosclerosis.2009.11.015 · 3.99 Impact Factor
Show more

Similar Publications


13 Reads
Available from