dinoprost and Diabetes-Mellitus--Type-1

Topics: Blood Glucose; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dinoprost; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Oxidative Stress

This report describes, at least in part, the role of prostaglandin and cyclic nucleotide metabolism in the etiology of the vascular disease associated with diabetes mellitus. Alterations in this metabolism seem associated with induction of platelet aggregation leads to microthromboses leads to microangiopathy sequences that are subtle but inexorable over a long period of time. Prostaglandins are generally elevated in blood from patients having frank signs of diabetic retinopathy when compared with nondiabetic subjects. Prostaglandin concentration remained elevated in diabetic retinopathy patients receiving indomethacin. We formed, therefore, the working hypothesis--yet to be fully tested either in patients or animal models with and without indomethacin treatment--that the increased prostacyclin (synthesized by endothelial microsomes) and cyclic-AMP production, both of which favor prevention of platelet aggregation, accompany the increased concentration of one or more of the prostaglandin E and F compounds. Concurrently, there may be an accompanying reduction of thromboxane A2 (synthesized by platelet microsomes) and cyclic-GMP (both of which favor platelet aggregation) production in the diabetic patients. The elevated prostaglandin in the diabetic patients not receiving indomethacin could possibly be directed toward slowing but not preventing the progression of the complex disease process in diabetes.

Topics: Alprostadil; Aspirin; Blood Platelets; Calcimycin; Collagen; Cyclic AMP; Cyclic GMP; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dinoprost; Dinoprostone; Humans; Indomethacin; Models, Biological; Platelet Aggregation; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2

To investigate the effect of initial insulin dosage on blood glucose (BG) dynamics, β-cell protection, and oxidative stress in type 1 diabetes mellitus.. Sixty newly diagnosed type 1 diabetes mellitus patients were randomly assigned to continuous subcutaneous insulin infusions of 0.6 ± 0.2 IU/kg/d (group 1), 1.0 ± 0.2 IU/kg/d (group 2), or 1.4 ± 0.2 IU/kg/d (group 3) for 3 wk. BG was monitored continuously for the first 10 d and the last 2 d of wk 2 and 3. A total of 24-hour urinary 8-iso-PGF2α was assayed on days 8, 9, and 10. The occurrence and duration of the honeymoon period were recorded. Fasting C-peptide and glycosylated hemoglobin (HbA1c) were assayed after 1, 6, and 12 months of insulin treatment.. BG decreased to the target range by the end of wk 3 (group 1), wk 2 (group 2), or wk 1 (group 3). The actual insulin dosage over the 3 wk, frequency of hypoglycemia on wk 1 and 2, and median BG at the end of wk 1 differed significantly, but not 8-iso-PGF2α and the honeymoon period in the three groups. No severe hypoglycemia event was observed in any patient, but there was significant difference in the first occurrence of hypoglycemia.. Differences in initial insulin dosage produced different BG dynamics in wk 1, equivalent BG dynamics on wk 2 and 3, but had no influence on short- and long-term BG control and honeymoon phase. The wide range of initial insulin dosage could be chosen if guided by BG monitoring.

Topics: Biomarkers; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Dinoprost; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin Secretion; Insulin-Secreting Cells; Male; Monitoring, Ambulatory; Oxidative Stress

The impact of excess weight on cardiovascular disease risk in type 1 diabetes patients is unclear.. This study examined associations of BMI and body composition with cardiovascular risk factors in youth followed prospectively for 18 months.. The sample includes youth with type 1 diabetes (N = 136, baseline age = 12.3 ± 2.5y, glycated hemoglobin = 8.1 ± 1.1%) participating in an 18-month behavioral nutrition intervention trial. BMI, body composition (by dual energy x-ray absorptiometry), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C); triglycerides (TG), c-reactive protein (CRP), 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), adiponectin and systolic and diastolic blood pressure (SBP and DBP, respectively) were assessed at clinic visits every 6 months. Random effects regression models for repeated measures estimated associations of time-varying BMI and body composition with time-varying cardiovascular risk factors, adjusted for treatment assignment and covariates.. There was no intervention effect on cardiovascular risk factors. Percent body fat was positively associated with TG, LDL-C, CRP, SBP and DBP, while trunk fat mass and trunk %fat were associated positively with TG, LDL-C, CRP, SBP and DBP, and inversely with HDL-C. Higher BMI was associated with greater TG, CRP, SBP and DBP and lower HDL-C. BMI and body composition indicators were unrelated to 8-iso-PGF2α and adiponectin.. Excess adiposity is associated with increased cardiovascular risk factors in this sample of youth with type 1 diabetes. Non-significant associations with adiponectin and 8-iso-PGF2α suggest potential differences from the general population in the role of adiposity in cardiovascular health.

Topics: Absorptiometry, Photon; Adiposity; Adolescent; Biomarkers; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 1; Dinoprost; Female; Glycated Hemoglobin; Humans; Lipids; Male; Obesity; Prospective Studies; Risk Factors

To test the effect of normoglycemia and glucagon-like peptide-1 (GLP-1), alone or in combination, on the possible normalization of endothelial function in type 1 diabetes.. Fifteen people with type 1 diabetes participated in three experiments: reaching and maintaining normoglycemia for 4h; reaching and maintaining hyperglycemia plus GLP-1 infusion for 4h; and reaching and maintaining normoglycemia for 4h with simultaneous infusion of GLP-1.. Both normoglycemia and GLP-1 infusion restored endothelial function and decreased and plasma 8-iso prostaglandin F2α levels. However, only the combination of normoglycemia and GLP-1 was able to normalize endothelial function.. This study confirms that long-lasting hyperglycemia in type 1 diabetes induces a permanent alteration which contributes to maintaining endothelial dysfunction even when glycemia is normalized, and that in the presence of normoglycemia, GLP-1 can contribute to normalizing endothelial function.

Topics: Adult; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 1; Dinoprost; Endothelium, Vascular; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Infusions, Parenteral; Male; Oxidative Stress; Vascular Diseases; Young Adult

Hypoglycemia produces thrombosis activation, but little attention has been paid to the effects of hyperglycemia following recovery from hypoglycemia on thrombosis activation.. In both twenty-two healthy subjects and twenty-one matched persons with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or hyperglycemia for another 2 h. After this, normal glycemia was maintained for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. In both controls and people with diabetes, the recovery with normo-glycemia was accompanied by a significant improvement of Von Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1 (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2α (8-iso-PGF2α) (p < 0.01 vs hypoglycemia for all the parameters), all directly affected by hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the contrary, the recovery with hyperglycemia after hypoglycemia worsens all these parameters (p < 0.01 vs normoglycemia for all the parameters), an effect persisting even after the additional 6 h of normo-glycemia. The effect of hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting that hyperglycemia following hypoglycemia may activate thrombosis through the oxidative stress production.. This study shows that, in type 1 diabetes as well as in controls, the way in which recovery from hypoglycemia takes place could play an important role in favoring the activation of thrombosis and oxidative stress, widely recognized cardiovascular risk factors.

Topics: Adult; Antithrombin III; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprost; Endothelium, Vascular; Female; Healthy Volunteers; Humans; Hyperglycemia; Hypoglycemia; Male; Oxidative Stress; P-Selectin; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Protein Precursors; Prothrombin; Thrombosis; von Willebrand Factor; Young Adult

It has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested.. 15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured.. After 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia.. This study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprost; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inflammation; Inflammation Mediators; Infusions, Parenteral; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Oxidative Stress; Reperfusion Injury; Time Factors; Treatment Outcome; Tyrosine; Vasodilation; Young Adult

Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients.. Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed.. Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2)  < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups.. Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.

Topics: Adult; Biomarkers; Blood Glucose; Brachial Artery; Diabetes Mellitus, Type 1; Dinoprost; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Oxidative Stress; Pilot Projects; Treatment Outcome; Vasodilation

Type 1 diabetes is associated with increased platelet reactivity. We investigated whether α-lipoic acid (ALA) has any effect on platelet reactivity in these patients.. We randomly assigned 51 type 1 diabetic patients to ALA (600 mg once daily) or placebo for 5 weeks. Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression. C-reactive protein (CRP) and 8-iso-prostaglandin F2α serum levels also were measured.. Baseline variables were similar in the two groups. After treatment, closure time was longer (P = 0.006) and CD62P platelet expression was lower, both before (P = 0.002) and after (P = 0.009) ADP stimulation in the ALA group compared with the placebo group. CRP and 8-iso-prostaglandin F2α levels showed no differences between the two groups.. Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients, independently of antioxidant or anti-inflammatory effects.

Topics: Adult; Antioxidants; Blood Platelets; C-Reactive Protein; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Male; Middle Aged; P-Selectin; Platelet Membrane Glycoprotein IIb; Thioctic Acid

Much evidence has suggested that oxidative stress (OS) may play a role in the pathogenesis of diabetic complications. However, the relationship between hyperglycemia and OS is inconsistent in diabetic clinical studies. The aim of this study was to evaluate the effect of normalization of blood glucose levels on urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) excretion at the onset of type 1 diabetes. We studied 14 type 1 diabetic patients (50% males; mean age, 24.3 +/- 4.9 years) and 14 control subjects matched by age and body mass index. A 24-hour urine collection was performed to determine 8-epi-PGF(2alpha) as an integrated index of OS production at baseline, before starting insulin therapy, and 16 weeks later. Insulin treatment induced a significant reduction in glycosylated hemoglobin (HbA(1c)) (from 11.5% to 5.4% P =.0001), triglycerides (from 1.0 to 0.8 mmol/L, P =.002), and an increase in high-density lipoprotein (HDL)-cholesterol levels (from 1.1 to 1.5 nmol/L, P =.01) at week 16. This improvement in metabolic control was associated with a statistically significant reduction in 8-epi-PGF(2alpha) values (from 92.0 +/- 41.5 to 66.9 +/- 28.9 pg/mg urinary reatinine excretion, P =.015), although compared with the control group, 8-epi-PGF(2alpha) values remained higher in diabetic patients (66.9 +/- 28.9 v 39.1 +/- 13.8 pg/mg creatinine, P =.004). Enhanced OS is present in early clinical phases of type 1 diabetes, and the amelioration in metabolic control is associated with improvement in this pathogenic pathway.

Topics: Adult; Autoantibodies; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprost; F2-Isoprostanes; Female; Glycated Hemoglobin; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Hypoglycemic Agents; Insulin; Lipids; Male

To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A2 biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F2-isoprostane formation in this setting.. A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM (1 year, group B). Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 were measured in all patients and in age- and gender-matched controls. Circulating interleukin-6 (IL-6), tumor necrosis factor-alpha, and C-reactive protein were also determined as markers of the inflammatory response. Fifteen of the 23 children in group A were reexamined after 12 months. Compared with either controls or group B, diabetic children in group A showed significantly higher levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, IL-6, tumor necrosis factor-alpha, and C-reactive protein. Statistically significant correlations between IL-6 and both 8-iso-PGF2alpha (r=0.63, P<0.001) and 11-dehydro-TXB2 (r=0.51, P<0.01) were observed. The 15 patients reexamined after 1 year showed a significant reduction in lipid peroxidation and platelet activation (P<0.02 and P<0.001, respectively), consistent with reduced levels of IL-6 and tumor necrosis factor-alpha.. These results demonstrate that enhanced lipid peroxidation and platelet activation represent early events in T1DM that are possibly related to an acute inflammatory response. These noninvasive indexes may help in further examining T1DM pathophysiology and monitoring pharmacological interventions to interfere with disease development and progression.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Dinoprost; Disease Progression; F2-Isoprostanes; Female; Follow-Up Studies; Humans; Inflammation; Insulin; Interleukin-6; Lipid Peroxidation; Male; Oxidative Stress; Platelet Activation; Reference Values; Thromboxane A2; Thromboxane B2; Time; Tumor Necrosis Factor-alpha

Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid (GLA) on serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capsules (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. After administration of 4 capsules daily the DGLA levels increased and PGE2 levels decreased significantly (p less than 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE2 and PGF2 alpha levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Dinoprost; Dinoprostone; Double-Blind Method; Fatty Acids; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Oenothera biennis; Plant Oils; Prostaglandins

To evaluate serum concentration of 8-isoprostane, nitrotyrosine (NT), and total antioxidant capacity (TAC) in pregnant women with diabetes mellitus (DM) considering preconception planning and method of diabetes correction in 11-14 and 30-34 weeks.. The study included 130 women: T1DM (n = 40), T2DM (n = 35), gestational diabetes (GDM, n = 40) and the control group (n = 15). The serum concentrations of NT, 8-isoprostane, and TAC were measured by ELISA methods.. Elevated 8-isoprostane levels were observed in all patients with DM, but this biomarker's maximum values have been seen in T1DM and T2DM on insulin groups. A similar tendency was observed for the concentration of NT in both the 1st and 3rd trimesters. TAC levels showed a statistically relevant decrease in all DM groups compared to the control. The correlation analysis showed a direct correlation between HbA1c and serum 8-isoprostane levels in the 1st (r = .27) and 3rd (r = .3) pregnancy trimesters as well as inverse correlation with TAC level (r = -.48). Direct (NT, 8-isoprostane) and inverse correlations (TAC) were fixated for this biomarker concentration and preeclampsia rates.. DM in pregnancy is related to oxidative stress activation, which might lead to the development of adverse perinatal outcomes.

Topics: Adult; Antioxidants; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dinoprost; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Russia; Tyrosine

Few studies assessing the relationship between oxidative stress and glycemic variability in children with type 1 diabetes mellitus (T1DM) are available, and most of them reported no significant results.. To assess the relationship between glucose control, glycemic variability, and oxidative stress as measured by urinary excretion of 8-iso-prostanglandin F2-alpha (8-iso-PGF2α) in children with T1DM.. A cross-sectional study including 25 children with T1DM. Participants were evaluated during five days in two different situations: 1st phase during a summer camp, and 2nd phase in their everyday life at home. The following data were collected in each study phase:. - Six capillary blood glucose measurements per day. Mean blood glucose (MBG) levels and glucose variability parameters, including standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE), were calculated. - Capillary HbA1c level. - 24-h urine sample to measure 8-iso-PGF2α.. There were no statistically significant differences in urinary 8-iso-PGF2α levels (142±37 vs. 172±61pg/mg creatinine) and glucose control and glycemic variability parameters between both phases. In the 2nd phase, statistically significant correlations were found between urinary 8-iso-PGF2α and HbA1c levels (r=0.53), MBG (r=0.72), standard deviation (r=0.49), and MAGE (r=0.42). No significant correlations between glucose control, glycemic variability and urinary 8-iso-PGF2α excretion were found in the 1st phase.. A significant correlation was found between glycemic variability and HbA1c level and urinary 8-iso-PGF2α excretion in a group of children with T1DM during their daily lives. Additional studies are needed to confirm this finding and to explore its long-term impact on health.

Topics: Adolescent; Biomarkers; Blood Glucose; Child; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Male; Oxidative Stress; Seasons

Serum carotenoids are commonly used as biomarkers of fruit and vegetable (F/V) intake in the general population. Although hyperglycemia induces oxidative stress, it is unknown whether this pathway is associated with lower serum carotenoid concentrations in individuals with type 1 diabetes. Consequently, the utility of serum carotenoids as markers of F/V intake in individuals with type 1 diabetes is unclear.. The study objectives were: 1) to investigate the relationship of glycemic control, oxidative stress, dietary carotenoid and F/V intake with serum carotenoid concentrations in youth with type 1 diabetes and 2) to determine whether glycemic control or oxidative stress moderates the association of carotenoid and F/V intake with serum carotenoids.. The study participants were youth with type 1 diabetes (n=136; age range: 8 to 16.9 years; diabetes duration ≥1 year; glycated hemoglobin: 5.8% to 11.9%) enrolled in a nutrition intervention trial from 2010 to 2013 at a tertiary diabetes center in Boston, MA.. Serum carotenoids (total carotenoids and α-carotene, β-carotene, lycopene, β-cryptoxanthin, and lutein+zeaxanthin).. Regression analyses were used to estimate the association of glycemic control, oxidative stress, F/V and carotenoid intake with serum carotenoids, as well as the role of glycemic control and oxidative stress in moderating diet-serum carotenoid associations.. Greater F/V intake (β=0.35, P<0.001) and carotenoid intake (β=0.28, P<0.01) were associated with higher total serum carotenoids, and no moderation by glycemic control or oxidative stress was observed. Greater hyperglycemia, as indicated by lower 1,5-anhydroglucitol (β=0.27, P<0.01), was related to lower serum carotenoids; however, glycated hemoglobin was not associated with serum carotenoids. 8-Iso-prostaglandin F2α was not associated with glycemic control or serum carotenoids.. Findings support the validity of serum carotenoids as markers of F/V and carotenoid intake in youth with type 1 diabetes.

Topics: Adolescent; Biomarkers; Boston; Carotenoids; Child; Deoxyglucose; Diabetes Mellitus, Type 1; Diet Records; Dinoprost; Female; Fruit; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Oxidative Stress; Regression Analysis; Vegetables

Type 1 diabetes is an insulin deficiency-based chronic disease. It leads to the development of hyperglycaemia, which plays a key role in the initiation and progression of tissue damage in patients with diabetes. This mostly results from oxidative stress, whose increased severity is observed in this group of patients. Increased levels of 8-isoprostanes are seen in many inflammatory diseases, including asthma, COPD and cystic fibrosis. These diseases demonstrated the usefulness of the exhaled breath condensate (EBC) for extracting material for markers of oxidative stress, including 8-isoprostanes. The purpose of this study was to assess the severity of oxidative stress measured with 8-isoprostane concentrations in the exhaled breath condensate in healthy subjects and in patients with type 1 diabetes with and without vascular complications.. 33 patients assigned to the control group, type 1 diabetes without complications group and type 1 diabetes group with advanced complications were included in the study. Retinopathy, nephropathy or neuropathy have been reported as a criterion distinguishing between complicated and uncomplicated diabetes. EBC was obtained for each subject. 8-isoprostane concentrations were determined in serum and EBC by ELISA.. Mean (± SD) blood levels of 8-isoprostane in patients with type 1 diabetes mellitus without complications and those with type 1 diabetes with advanced complications were significantly higher compared to the control group (178.17 [135.73] vs. 183.34 [200.41] vs. 47.13 [25.20] pg/ml; p < 0.05). The mean (± SD) concentration of 8-isoprostane in EBC was lower in diabetic patients with type 1 diabetes with advanced complications than in patients with type 1 diabetes without advanced complications and in the control group (8.32 [4.60] vs. 19.13 [22.35] vs. 28.17 [35.11] pg/ml; p < 0.05). Measurement of 8-isoprostanes in the EBC in patients with type 1 diabetes does not appear to be a good diagnostic tool for monitoring the activity of oxidative stress in these patients.

Topics: Adult; Biomarkers; Breath Tests; Diabetes Mellitus, Type 1; Dinoprost; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Reference Values; Young Adult

Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.

Topics: Adult; Albuminuria; Aspirin; Blood Glucose; Cross-Sectional Studies; Cyclooxygenase 1; Diabetes Mellitus, Type 1; Dinoprost; Epoprostenol; Female; Humans; Male; Matched-Pair Analysis; Microvessels; Middle Aged; Oxidative Stress; Platelet Activation; Platelet Aggregation Inhibitors; Sex Factors; Thromboxane A2

The aim of this study is to determine the relationship between oxidative stress marker (8-iso-prostaglandine F2α) and glycemic indices computed from daily glucose monitoring data in children with type 1 diabetes mellitus (T1DM).. Thirty-one children and adolescents with T1DM (median age 12.2 years) and healthy subjects (median age 11.7 years) were enrolled into the study. Anthropometric data were recorded for the entire group before the study. In addition, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c were recorded in T1DM subjects. T1DM subjects performed self-monitoring of blood glucose (SMBG) for a month (at least four times a day) for calculating glycemic indices. Twenty-four-hour urine 8-iso-prostoglandine F2α levels were studied at the end of the study period in the both groups.. Median diabetes duration was 5 years, hemoglobin A1c (HbA1c) was 7.3%. Standard deviation (SD) of the blood glucose (BG) was determined as 85 mg/dL. Median urinary 8-iso-prostoglandine F2α was found to be significantly higher than that of the healthy subjects (2808.9 and 298 pg/mg creatinine, p<0.001, respectively). There was no correlation between urinary 8-iso-prostoglandine F2α and age, anthropometric data, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA1c, or SD of BG in T1DM groups.. This study showed that, 8-iso-prostoglandine F2α that is an oxidative stress marker, is significantly higher in T1DM than that of healthy subjects while, no significant relation between glycemic indices and urinary 8-iso-prostoglandine F2α levels were demonstrated. Further studies are needed to assess other factors, and the relationship between glucose fluctuations and oxidative stress markers.

Topics: Adolescent; Blood Glucose; Blood Glucose Self-Monitoring; Case-Control Studies; Child; Diabetes Mellitus, Type 1; Dinoprost; Female; Follow-Up Studies; Glycated Hemoglobin; Glycemic Index; Humans; Male; Oxidative Stress; Prognosis

Previous studies on the association between glucose fluctuations and oxidative stress in diabetes mellitus were all conducted in adults, and most study participants had type 2 diabetes mellitus.. The study objective was to examine the association of glucose fluctuation and oxidative stress in children with type 1 diabetes mellitus (T1DM) across different phases.. This was a case-control study.. The setting was the Beijing Children's Hospital (2010-2013).. Children treated for T1DM were divided into three study groups, including group A (newly diagnosed cases in the acute metabolic disturbance phase), group B (the honeymoon phase), and group C (the long-standing phase). Healthy control children were matched to the T1DM patients by age and sex.. There were no interventions.. The 24-hour urinary free 8-iso-prostaglandin F2α to creatinine (8-iso-PGF2α/Cr) ratio indicated oxidative stress. Glucose fluctuation parameters (GFPs) included mean blood glucose levels, standard deviation of daily blood glucose levels, mean amplitude of glucose excursions, and incremental area under the curve for postprandial glucose.. In each study group, 8-iso-PGF2α/Cr and all GFPs in children with T1DM were significantly higher than those in normal controls. 8-iso-PGF2α/Cr was significantly correlated with all GFPs in all three T1DM groups. A stronger association with 8-iso-PGF2α/Cr for mean amplitude of glucose excursions than for glycated hemoglobin was observed in both the acute metabolic disturbance and long-standing phases of T1DM.. Glucose fluctuations were positively associated with oxidative stress in T1DM patients in different phases. Glucose fluctuations may have a stronger effect than sustained chronic hyperglycemia on triggering oxidative stress, but coexisting high levels of blood glucose may be required.

Topics: Adolescent; Blood Glucose; Case-Control Studies; Child; Child, Preschool; Creatinine; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Male; Oxidative Stress; Postprandial Period

To assess glycemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp.. Cross-sectional study that included 54 children and adolescents with T1DM aged 7-16, attending a 7 day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano® glucose meter were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-hour urine sample collected at the end of the camp in 14 children.. The Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39 pg/mg creatinine. The Spearman correlation coefficients between markers of glycemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycemic variability and urinary 8-iso-PGF2α.. High glycemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycemic variability in children with T1DM.

Topics: Adolescent; Blood Glucose; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Male; Oxidative Stress; Seasons

Oxidative stress and inflammatory reactions are known to hold an important role in the etiopathogeny and persistence of acute or chronic clinical entities. Isoprostanes--a group of prostaglandin-like compounds, active products of arachidonic acid--have proved to be representative biomarkers of lipid peroxidation. The aim of this study was to determine the activity of serum 8-iso-prostaglandin F2alpha, (8iPGF2alpha), as an in vivo oxidative stress marker, in paediatric patients with diabetes mellitus type 1 (DM1) and in a control group. The main goals of this study were the following: establishing a possible correlation between the activity of 8iPGF2alpha and the presence of an autoimmune disease associated with DM1 and identifying a possible correlation between 8iPGF2alpha, the value of glycosylated hemoglobin (HbA1c) and the pancreatic autoimmune markers GAD65, IA2, IA in the group of patients with DM1 and other associated autoimmune diseases.. Fifty-one children and adolescents (31 males) aged 11.65 +/- 4.1 years with DM1 were enrolled in the study. Twenty-seven healthy children, age- and gender-matched, were enrolled as controls. Patients and controls underwent the 8iPGFzalpha assessment through an ELISA serum method.. The mean 8iPGF2alpha value was 2090.6 +/- 3536.5 in the DM1 patient group and 509.9 +/- 493.5 in controls (p = 0.03). The mean 8iPGF2alpha value was 2178.19 +/- 4017.05 in patients with DM1 who did not suffer from other associated autoimmune diseases (n = 38) vs. 1834.95 +/- 1504.73 in patients with DM1 and other associated autoimmune diseases (n = 13) (p = 0.76). The correlation between the 8iPGF2alpha and the HbA1c values was determined by obtaining a correlation coefficient r = 0.38 and p = 0.0057. No correlation was observed between GAD65 and 8iPGF2alpha (r = 0.3; p = 0.29), IA2 and 8iPGF2alpha (r = -0.02; p = 0.92), IAA and 8iPGF2alpha (r = 0.4; p = 0.12).. Oxidative stress reactions are more intense in patients with diabetes mellitus type 1 than in healthy patients. Similar results were obtained in patients associating other autoimmune diseases. 8iPGF2alpha can be an ideal marker for determining oxidative reactions in vivo.

Topics: Adolescent; Autoimmunity; Biomarkers; Case-Control Studies; Child; Diabetes Mellitus, Type 1; Dinoprost; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Male; Oxidative Stress

Brahma-related gene 1 (Brg1) is a key gene in inducing the expression of important endogenous antioxidant enzymes, including heme oxygenase-1 (HO-1) which is central to cardioprotection, while cardiac HO-1 expression is reduced in diabetes. It is unknown whether or not cardiac Brg1 expression is reduced in diabetes. We hypothesize that cardiac Brg1 expression is reduced in diabetes which can be restored by antioxidant treatment with N-acetylcysteine (NAC). Control (C) and streptozotocin-induced diabetic (D) rats were treated with NAC in drinking water or placebo for 4 weeks. Plasma and cardiac free15-F2t-isoprostane in diabetic rats were increased, accompanied with increased plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6), while cardiac Brg1, p-STAT3 and HO-1 protein expression levels were significantly decreased. Left ventricle weight/body weight ratio was higher, while the peak velocities of early (E) and late (A) flow ratio was lower in diabetic than in C rats. NAC normalized tissue and plasma levels of 15-F2t-isoprostane, significantly increased cardiac Brg1, HO-1 and p-STAT3 protein expression levels and reduced TNF-alpha and IL-6, resulting in improved cardiac function. In conclusion, myocardial Brg1 is reduced in diabetes and enhancement of cardiac Brg1 expression may represent a novel mechanism whereby NAC confers cardioprotection.

Topics: Acetylcysteine; Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dinoprost; DNA Helicases; Free Radical Scavengers; Heart; Heme Oxygenase-1; Interleukin-6; Isoprostanes; Myocardium; Nuclear Proteins; Phosphorylation; Rats; STAT3 Transcription Factor; Transcription Factors; Tumor Necrosis Factor-alpha

Although oxidative stress (OxS) is thought to contribute to atherosclerosis and coronary artery disease (CAD), little is known about the variability in an individual's ability to respond to OxS. Therefore, we assessed potential indices of response to OxS and evaluated whether they modify the association between OxS and CAD.. We evaluated plasma α- and γ-tocopherol per unit cholesterol (potential response markers); urinary 15-isoprostane F2t per milligram creatinine (isoprostane [IsoP], a potential stress marker); and the α-tocopherol-to-IsoP ratio (as a measure of response to stress), measured three times during 20 years of follow-up, in relation to CAD incidence in a cohort with childhood-onset type 1 diabetes (n = 658; mean age at baseline, 28 years; duration of diabetes, 19 years). Participants with three samples (blood and either 24-h or overnight urine) available before the onset of CAD or the end of follow-up (n = 356) were selected for study.. In multivariable mixed models, α-tocopherol over time was inversely associated with CAD (β = -0.27; P = 0.02), whereas a direct association was observed for IsoP (β = 0.0008; P = 0.06). Moreover, the α-tocopherol-to-IsoP ratio was strongly and inversely related to CAD incidence (β = -0.72; P = 0.003), whereas in a separate model including α-tocopherol and IsoP, both biomarkers maintained statistical significance. No association was observed for γ-tocopherol (β = -0.22; P = 0.54).. These data suggest that a greater potential capability (α-tocopherol) to respond to OxS (urinary IsoP) relates to CAD incidence.

Topics: Adult; alpha-Tocopherol; Biomarkers; Coronary Artery Disease; Creatinine; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Incidence; Isoprostanes; Male; Oxidative Stress; Young Adult

Large body of evidences accumulated in clinical and epidemiological studies indicate that hearts of diabetic subjects are more sensitive to ischemia reperfusion injury (IRI), which results in a higher rate of mortality at post-operation than that of non-diabetes. However, experimental results are equivocal and point to either increased or decreased susceptibility of the diabetic hearts to IRI, especially at the early stage of the disease. The present study was designed to test the hypothesis that the duration/severity of the indexed ischemia is a major determinant of the vulnerability to myocardial IRI at early stage of diabetes.. Four weeks streptozotocin (STZ)-induced diabetic (D) and non-diabetic (C) Sprague-Dawley rats were randomly assigned to receive 30 or 45 min of left anterior descending artery ligation followed by 2 or 3 hours of reperfusion, respectively. Cardiac function was recorded by using Pressure-Volume (PV) conduction system. Myocardial infarct size was determined with triphenyltetrazolium chloride staining. Plasma Creatine kinase-MB (CK-MB), Lactate dehydrogenase (LDH) release, myocardial nitric oxide(NO) content and nitrotyrosine formation, 15-F(2t)-Isoprostane and plasma superoxide dismutase (SOD) were measured with colorimetric assays. Cardiomyocyte apoptosis was assessed by TUNEL staining. Myocardial TNFα, Caspase-3, STAT3, Akt, and GSK-3β were determined by Western blotting.. Prolongation of ischemia but not reperfusion from 30 min to 45 min significantly increased infarct size in D compared to C rats (P < 0.05), accompanied with significantly increased plasma CK-MB (P < 0.05). Prolongation of the duration of either ischemia or reperfusion significantly increased plasma LDH release and myocardial 15-F(2t)-Isoprostane and reduced plasma SOD activity, with concomitant reduction of myocardial NO and increase of nitrotyrosine formation in D relative to C (P < 0.05). Prolongation of ischemia and reperfusion significantly reduced left ventricular ejection fraction and increased the peak rate of pressure, accompanied with increased end systolic pressure in D relative to C rats (P < 0.05) but reduced phosphorylations of myocardial STAT3 at site Ser727 and Akt at site Ser473 as well as GSK-3β at Ser 9 (P < 0.05).. Diabetic hearts, even at early stage of the disease are more sensitive to IRI, and this increased severity of post-ischemic myocardial injury depends more on the duration of ischemia than that of reperfusion.

Topics: Animals; Biomarkers; Caspase 3; Creatine Kinase, BB Form; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dinoprost; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; L-Lactate Dehydrogenase; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Nitric Oxide; Oxidative Stress; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Severity of Illness Index; STAT3 Transcription Factor; Stroke Volume; Superoxide Dismutase; Time Factors; Tumor Necrosis Factor-alpha; Tyrosine; Ventricular Function, Left; Ventricular Pressure

Studies have shown that complications in type 1 diabetes mellitus (T1DM) in children are mainly due to oxidative stress (OS). Lipid peroxidation is the main marker of OS and iso-prostaglandin is a reliable biomarker of lipid peroxidation in type 2 diabetes mellitus (T2DM). However, there have been few studies on OS in T1DM children with hyperglycemia and glucose fluctuations.. We prospectively enrolled 23 newly diagnosed T1DM patients and 23 age and sex matched healthy controls in Beijing Children's Hospital from May 2010 to January 2011. They were treated with continuous subcutaneous insulin injection (CSII) and monitored by continuous glucose monitoring system (CGMS). Twenty-four-hour urine samples were collected to measure the concentration of 8-iso prostaglandin F2a (8-isoPGF2α). Samples taken from diabetic children were collected at days 8 to 10 after insulin treatment. Intraday glucose fluctuations were assessed by mean amplitude of glucose excursions (MAGE), largest amplitude of glycemic excursions (LAGE), standard deviation of blood glucose (SDBG) and number of glycemic excursions (NGE). The correlations between glucose parameters and the index of oxidative stress were analyzed.. Urine 8-isoPGF2α in the T1DM group was higher than that in the control group ((967.70±412.68) ng vs. (675.23±354.59) ng, P = 0.019). There was a correlation between urine 8-isoPGF2a level and MAGE (r = 0.321, P = 0.039), a significant correlation between low-density lipoprotein and urine 8-isoPGF2a level (r = 0.419, P = 0.03). There was no significant correlation between urine 8-isoPGF2α level and blood pressure, glycosylated hemoglobin (HbA1c), fasting C-peptide or other lipid indices.. A correlation between urine 8-isoPGF2a levels and MAGE and low-density lipoprotein was found in children newly diagnosed with T1DM.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Insulin; Lipoproteins, LDL; Male; Oxidative Stress

Oxidative stress has been implicated in the pathogenesis of diabetes mellitus (DM). Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin-F(2α) (8-epi-PGF2α), and total protein carbonyls were measured to assess whether DM is associated with altered salivary redox homeostasis.. A total of 215 patients with diabetes and 481 healthy controls were recruited from the Department of Endocrinology at the Jewish General Hospital in Montreal. Levels of oxidative biomarkers were assayed using enzyme-linked immunosorbent assay (ELISA) in whole unstimulated saliva. Associations of the redox data with exposure to insulin, metformin and dietary control were assessed by logistic regression analyses.. We observed (i) significantly higher mean levels of 8-OHdG and protein carbonyls in whole unstimulated saliva of patients with diabetes compared to controls, (ii) higher mean levels of protein carbonyls in type 1 diabetes as well as higher mean levels of 8-OHdG and protein carbonyls in type 2 diabetes compared to controls, (iii) elevated levels of protein carbonyls in diet-controlled patients and in patients with diabetes on insulin and metformin, (iv) elevated levels of 8-OHdG in patients on metformin, and (v) significant associations between subjects with DM and salivary 8-OHdG and protein carbonyls.. DM is associated with increased oxidative modification of salivary DNA and proteins. Salivary redox homeostasis is perturbed in DM and may inform on the presence of the disease and efficacy of therapeutic interventions.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Age Factors; Biomarkers; Deoxyguanosine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet, Diabetic; Dinoprost; DNA Damage; Homeostasis; Humans; Hypoglycemic Agents; Insulin; Lipid Peroxidation; Metformin; Oxidation-Reduction; Oxidative Stress; Protein Carbonylation; Saliva; Salivary Proteins and Peptides; Sex Factors

We examined whether type of diabetes and/or insulin treatment can modulate the impact of sustained hyperglycaemia and glycaemic variability as activators of oxidative stress.. This was an observational study in 139 patients with diabetes, 48 with type 1, 60 with type 2 treated by oral hypoglycaemic agents (OHAs) alone and 31 with type 2 treated with insulin plus OHAs. In addition, two groups of ten patients with type 2 diabetes were investigated either before and after introducing insulin treatment (add-on insulin group) or before and after add-on OHA therapy to metformin (add-on OHA group). Oxidative stress was estimated from 24 h urinary excretion rates of 8-isoprostaglandin F2alpha (8-iso-PGF2alpha). HbA(1c) was assessed and mean amplitude of glycaemic excursions (MAGE) was estimated by continuous monitoring.. The 24 h excretion rate of 8-iso-PGF2alpha (median [range] picomoles per millimole of creatinine) was much higher (p < 0.0001) in type 2 diabetes patients treated with OHAs alone (112 [26-329]) than in the type 1 diabetes group (65 [29-193]) and the type 2 diabetes group treated with insulin (69 [30-198]). It was associated with HbA(1c) (F = 12.9, p = 0.0008) and MAGE (F = 7.7, p = 0.008) in non-insulin-treated, but not in insulin-treated patients. A significant reduction in 24 h excretion rate of 8-iso-PGF2alpha from 126 (47-248) to 62 (35-111] pmol/mmol of creatinine was observed in the add-on insulin group (p = 0.005) but not in the add-on OHA group.. In type 1 and type 2 diabetes, insulin exerts an inhibitory effect on oxidative stress, a metabolic disorder that is significantly activated by sustained hyperglycaemia and glucose variability in non-insulin-treated type 2 diabetes.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dinoprost; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Oxidative Stress

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.

Topics: Adult; Blood Glucose; Case-Control Studies; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Male; Middle Aged; Models, Biological; Oxidative Stress; Sex Factors; Time Factors; Treatment Outcome

Diabetic cardiomyopathy has been documented as an underlying cause of heart failure in diabetic patients. Although oxidative stress has been implicated in diabetic cardiomyopathy, much of the current evidence lacks specificity. Furthermore, studies investigating antioxidant protection with vitamin E in this unique cardiac phenomenon have yet to be performed. In the present study, we sought to determine whether vitamin E supplementation can confer cardioprotective effects against diabetic cardiomyopathy in relation to specific and quantitative markers of myocardial oxidative stress.. Diabetes was induced in rats by a single injection of streptozotocin. Animals were fed either a basal diet or a diet enriched with 2000 IU of vitamin E per kilogram beginning immediately after induction of diabetes and continued for 8 weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) hemodynamic analysis. Myocardial oxidative stress was assessed by measuring the formation of 8-iso-prostaglandin F2alpha and oxidized glutathione. In the unsupplemented streptozotocin-diabetic rats, LV systolic pressure, rate of pressure increase (+dP/dt), and rate of pressure decay (-dP/dt) were depressed, whereas LV end-diastolic pressure was increased, indicating reduced LV contractility and slowing of LV relaxation. These hemodynamic alterations were accompanied by increased myocardial formation of 8-iso-prostaglandin F2alpha and oxidized glutathione. Vitamin E supplementation improved LV function and significantly attenuated myocardial 8-iso-prostaglandin F2alpha and oxidized glutathione accumulation in streptozotocin-diabetic rats.. These findings demonstrate the usefulness of vitamin E supplementation during the early phases of type I diabetes for the prophylaxis of cardiomyopathy and subsequent heart failure.

Topics: Animals; Cardiomyopathies; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dietary Supplements; Dinoprost; Glutathione; Heart Failure; Immunoenzyme Techniques; Male; Myocardium; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Treatment Outcome; Vitamin E; Vitamins

Hyperglycemia has been linked to increased oxidative stress, a resultant endothelial cell dysfunction, and, ultimately, apoptosis. Heme oxygenases (HO-1/HO-2) and the products of their activity, biliverdin/bilirubin and carbon monoxide (CO), play a physiological role in the vascular system. The effects of heme-mediated HO-1 induction, CO, and biliverdin on urinary 8-epi-isoprostane PGF(2alpha) and endothelial cell sloughing were examined in an animal model of streptozotocin (STZ)-induced diabetes. Hyperglycemia itself did not affect HO-1 and HO-2 protein levels, but caused a net decrease in HO activity. Weekly heme administration induced HO-1 protein, as demonstrated by immunohistochemistry and Western blot analyses. Administration of biliverdin or the CO donor, CORM-3, decreased urinary 8-epi-isoprostane PGF(2alpha), P < 0.5 compared to diabetes. Hyperglycemia increased endothelial cell sloughing; 8.2 +/- 0.8 cells/ml blood in control rats vs. 48 +/- 4.8 cells/ml blood in diabetic rats (P < 0.05). Heme administration significantly increased endothelial cell sloughing in diabetic rats (98 +/- 8.1 cells/ml blood, P < 0.0007) whereas biliverdin modestly decreased endothelial cell sloughing (26 +/- 3.5 cells/ml blood, P < 0.003). Administration of CORM-3 to diabetic rats resulted in a significant decrease in endothelial cell sloughing to 21.3 +/- 2.3 (P < 0.001). Administration of SnMP to CORM-3 diabetic rats only partially reversed the protective effects of CORM-3 on endothelial cell sloughing from 21.3 +/- 2.3 to 29 +/- 2.1 cells/ml, thus confirming a direct protective of CO, in addition to the ability of CORM-3 to induce HO-1 protein. These results demonstrate that exogenously administered CO or bilirubin can prevent endothelial cell sloughing in diabetic rats, likely via a decrease in oxidative stress, and thus represents a novel approach to prophylactic vascular protection in diabetes.

Topics: Animals; Biliverdine; Carbon Monoxide; Cell Aggregation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dinoprost; Endothelial Cells; Endothelium, Vascular; Heme; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Organometallic Compounds; Protective Agents; Rats

The objective of this study was to establish if diabetes in the presence of polyneuropathy (PN) and/or cardiovascular autonomic neuropathy (CAN) is associated with alterations in the amounts of 8-epi-PGF2alpha (IP) and its metabolites including 2, 3-dinor-8-epi-PGF2alpha (dinor-IP) and 2, 3-dinor-5, 6 dihydro-8-epi-PGF2alpha (dinor-dihydro-IP) in urine. Mass spectrometric separation showed that excretion of IP was similar in the PN + /CAN- and PN+/CAN+ groups but higher than in the PN-/CAN- group (n = 103, 22 and 60, respectively; P < 0.05). By contrast, excretion of dinor-IP or dinor-dihydro-IP were similar in the PN-/CAN- and PN+/CAN- groups but higher than in PN+/CAN+ group. Correlations were obtained between IP and dinor-IP or dinor-dihydro-IP (r = 0.30; P < 0.001 and r = 0.31; P < 0.001, respectively). A significant association was also observed between dinor-IP and dinor-dihydro-IP (r = 0.48; P < 0.001). In conclusion, these biomarkers should prove useful in studies evaluating the impact of therapeutic drugs or antioxidant interventions aimed at delaying the onset of diabetic complications.

Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Oxidation-Reduction; Polyneuropathies

Markers of oxidative stress were studied in plasma and urine of prepubertal patients with type 1 diabetes mellitus (DM1) with less than 5 years of disease (n = 27). The results were compared to healthy, age- and sex-matched control children (n = 27). Oxidative stress parameters evaluated included advanced oxidation protein products (AOPP), total peroxyl radical-trapping antioxidant parameter (TRAP), and F2-isoprostanes (8-epi-prostaglandin-F2: 8-isoPGF2alpha). No statistically significant differences were found for any of the oxidative stress markers assessed between patients with DM1 and controls. In addition, weight, height, and routine metabolic tests, including creatininemia and cholesterol levels, were similar between the groups. The lack of significant differences between healthy controls and patients with DM1 suggests that treatment is able to counteract the increase in free radical production.

Topics: Antioxidants; Biomarkers; Child; Child, Preschool; Diabetes Mellitus, Type 1; Dinoprost; Female; Free Radicals; Glycation End Products, Advanced; Humans; Insulin; Male; Oxidation-Reduction; Oxidative Stress; Peroxides

The present study was performed to determine whether increased lipid peroxidation, as assessed from malondialdehyde (MDA) excretion, is associated with deterioration in peripheral nerve function in early type 1 diabetes mellitus. These parameters were measured annually for 3 years in 36 patients who entered the study less than 2 years after the diagnosis of diabetes. Malondialdehyde excretion was 1.51 +/- 0.20 micromol/g creatinine in the controls, and 2.43 +/- 0.21, 2.39 +/- 0.22, and 1.93 +/- 0.21 micromol/g creatinine at the first, second, and third evaluations, respectively (P < .005). The increased MDA was seen only in the female participants. Malondialdehyde excretion was increased in those with high vs low hemoglobin Alc across all years (P < .05). Malondialdehyde excretion correlated negatively with sudomotor function below the waist. The mean sweat production from the 3 evaluations correlated with mean MDA excretion across all years in the proximal leg (r = -0.42, P < .005) and distal leg (r = -0.40, P < .01). Below the waist, sweating correlated with MDA (r = -0.40, P < .01) as did total sweat (r = -0.38, P < .01). The response amplitudes of the peroneal nerves correlated negatively with MDA excretion (for the mean values at the second 2 evaluations, P < .005, r = -0.45). Tests of sensory function correlated inconsistently with MDA excretion. In summary, lipid peroxidation, as assessed from malondialdehyde excretion, is associated with sudomotor dysfunction in early diabetes.

Topics: Adolescent; Adult; Child; Diabetes Mellitus, Type 1; Dinoprost; Female; Glycated Hemoglobin; Heart Rate; Humans; Lipid Peroxidation; Longitudinal Studies; Male; Malondialdehyde; Neural Conduction; Nitrates; Norepinephrine; Peripheral Nervous System; Regression Analysis; Renin; Sweating; Vanilmandelic Acid

To assess the antioxidant/non-antioxidant effects of a hydroxytyrosol (HT)-rich phenolic extract from olive mill wastewaters administered with a breakfast.. Five type I diabetic patients received 25 mg of HT the first day and 12.5 mg/day the following 3 days. Blood sampling was carried out at T(0) (baseline) and T(4d) just before the breakfast + HT administration and at time points 1, 2, 3 and 4 h after T(0). Urines (24-h) were collected from T(0) to T(4d). Baseline HbA1c was generally inferior to 10%, glycemia was within the range 6-24 mmol/l, whereas total cholesterol, HDL-chol and triglycerides were normal.. The major finding was the 46% decrease in the serum TXB(2) production after blood clotting at T(4d). Plasma vitamin A, E, beta-carotene were not changed. Vitamin C tended to increase (P = 0.075). Plasma antioxidant capacity was enhanced at T(0)+1 h only, whereas its main determinants (albumin, bilirubin, uric acid) were not modified. Urinary 8-isoPGF(2alpha) levels were highly variable and were not affected significantly by HT administration.. The major effect of HT accounts for an antiaggregating platelet action, leading to a possible prevention of thrombotic and microthrombotic processes.

Topics: Adult; Aged; Antioxidants; Diabetes Mellitus, Type 1; Dinoprost; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Olive Oil; Phenylethyl Alcohol; Plant Oils; Platelet Aggregation; Thromboxane B2; Time Factors; Waste Disposal, Fluid; Waste Products

The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood.. Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects.. The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements.. These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.

Topics: Adult; Albuminuria; C-Reactive Protein; Cytokines; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dinoprost; Female; Humans; Hypertension; Inflammation; Lipids; Male; Reference Values; Regression Analysis

Oxidative stress and transforming growth factor-beta 1 (TGF-beta1) are associated with diabetic complications, and smoking is a risk factor.. This study aimed (i) to compare urinary 8-epi-PGF2alpha and plasma and urinary TGF-beta1 levels obtained in heavy smokers with Type 1 diabetes with those observed in age-matched non-smoker patients with Type 1 diabetes and controls, and (ii) to investigate the effects of smoking cessation (SC) on the above-mentioned parameters in patients with Type 1 diabetes.. Compared with control subjects (n = 12), non-smoker diabetic patients (n = 12) presented higher values of urinary 8-epi-PGF2alpha (74.2 +/- 29.6 vs. 29.6 +/- 11.1 pg/mg urinary creatinine, P = 0.01), plasma TGF-beta1 (7.7 +/- 4.7 vs. 3.6 +/- 1.7 ng/ml, P = 0.001) and urinary TGF-beta1 (15.3 +/- 6.3 vs. 8.1 +/- 4.4 ng/mg urinary creatinine, P = 0.02). Compared with non-smoker diabetic patients, smoker diabetic patients (n = 16) showed higher levels of urinary 8-epi-PGF2alpha (107.8 +/- 40.2 vs. 74.2 +/- 29.6 pg/mg urinary creatinine, P = 0.0001), plasma TGF-beta1 (12.6 +/- 4.9 vs. 7.7 +/- 4.7 ng/ml, P = 0.001) and urinary TGF-beta1 (27.5 +/- 16.0 vs. 15.3 +/- 6.3 ng/mg urinary creatinine, P = 0.01). Smoker patients were included in a smoking cessation programme. In the 10 patients that gave up smoking there was a reduction of urinary 8-epi-PGF2alpha (basal: 110.47 +/- 47.0 vs. week 12: 73.2 +/- 25.6; P < 0.001), plasma TGF-beta1 (basal: 11.2 +/- 5.9 vs. week 12: 4.89 +/- 2.25; P < 0.01) and urinary TGF-beta1 (basal: 18.12 +/- 9.27 vs. week 12: 10.32 +/- 2.0; P < 0.01) levels.. In patients with Type 1 diabetes, smoking increased oxidative stress, evaluated by lipid peroxidation, and TGF-beta1 production. Smoking cessation decreased these parameters, providing additional support to encourage diabetic patients to give up smoking.

Topics: Adult; Cotinine; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Humans; Immunoassay; Male; Smoking; Smoking Cessation; Transforming Growth Factor beta; Transforming Growth Factor beta1; Vasoconstrictor Agents

The purpose of this study was to analyze biochemical measures of oxidative stress and assess their relationship to insulin requirements early in type 1 diabetes. Thirty-seven patients enrolled in a 3-yr longitudinal study of the effects of oxidative stress on the early natural history of this disorder. We measured plasma nitrite and nitrate (collectively NOx), nitrotyrosine, and 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)). Plasma NOx was 34.0 +/- 4.9 micro mol/liter in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 micro mol/liter in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine was 13.3 +/- 2.0 micro mol/liter in controls and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 micro mol/liter in the diabetic patients (P < 0.01). 8-Iso-PGF(2alpha) was higher in the poorly controlled than in the well controlled patients. NOx correlated with insulin dose at the first (P < 0.05), second (P < 0.025), and third (P < 0.05) evaluations. 8-Iso-PGF(2alpha) correlated with insulin dose at the first (P < 0.01) and third (P < 0.0025) evaluations. Systemic measures of oxidative stress correlate with insulin requirements in early type 1 diabetes. These results suggest that oxidative stress is taking place in the pancreas and damaging the beta-cell.

Topics: Adolescent; Adult; Child; Diabetes Mellitus, Type 1; Dinoprost; F2-Isoprostanes; Female; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans; Longitudinal Studies; Male; Nitrates; Nitrites; Oxidative Stress; Tyrosine

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO(x)) were 34.0 +/- 4.9 micro mol/l in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine (NTY) was 13.3 +/- 2.0 micro mol/l in the control subjects and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 in the diabetic patients (P < 0.01). Uric acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor nerve conduction velocity for the median, ulnar, and peroneal nerves was decreased in patients with high versus low NTY (mean Z score -0.522 +/- 0.25 versus 0.273 +/- 0.22; P < 0.025). Patients with high NO(x) had decreased sweating, and those with suppressed uric acid had decreased autonomic function. In conclusion, nitrosative stress in early diabetes is associated with suppressed uric acid and deterioration in peripheral nerve function.

Topics: Adolescent; Adult; Autonomic Nervous System; Child; Diabetes Mellitus, Type 1; Dinoprost; F2-Isoprostanes; Female; Heart Conduction System; Humans; Male; Motor Neurons; Neural Conduction; Nitrates; Nitrites; Peripheral Nerves; Peroxynitrous Acid; Reference Values; Sweating; Time Factors; Tyrosine; Uric Acid

To test the hypothesis that type 1 diabetes is associated with increased oxidative stress and/or antioxidant status by investigating concentrations of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) in urine and plasma and malondialdehyde (MDA) in plasma as indicators of lipid peroxidation in vivo, and antioxidant status in diabetic subjects compared with healthy control subjects.. Thirty-eight subjects with type 1 diabetes mellitus and 41 healthy age- and sex-matched control subjects were included in the study. Blood and urine samples were obtained and analysed for 8-iso-PGF2alpha with a newly developed radioimmunoassay, as well as for MDA, total antioxidant capacity (TAOC) and serum tocopherol levels.. None of the variables of lipid peroxidation showed any significant difference between the two groups. Similarly, there were no significant correlations between the levels of 8-iso-PGF2alpha or MDA, and degree of glycemic control (HbA1c). Total antioxidant capacity in plasma was 16% lower amongst the subjects with type 1 diabetes than in the control group (P < 0.0005). Lipid corrected levels of alpha-tocopherol in serum were significantly increased in type 1 diabetic subjects (P < 0.05), as were gamma-tocopherol levels (P < 0.005).. In spite of lower total antioxidant defence, our results do not support the oxidative stress hypothesis for type 1 diabetes mellitus. The higher tocopherol levels suggest that no vitamin E supplementation is necessary for subjects with type 1 diabetes mellitus.

Topics: Adult; Case-Control Studies; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Radioimmunoassay; Tocopherols; Vitamin E

The role of nitric oxide (NO) and free radicals in the development of microvascular disease in type 1 diabetes remains unclear. We have measured NO and isoprostane (a stable marker of in vivo lipid peroxidation) production in 13 type 1 diabetic subjects with normal urinary albumin excretion and 13 healthy volunteers. Whole-body NO synthesis was quantified by measuring the urinary excretion of 15N-nitrate after the intravenous administration of L-[15N]2-arginine. The urinary excretion of the major urinary metabolite of 15-F2t-isoprostane (8-iso-prostaglandin-F2alpha), 2,3-dinor-5,6-dihydro-F2t-IsoP, was quantified as a marker of in vivo lipid peroxidation. Whole-body NO synthesis was significantly higher in diabetic subjects compared with control subjects (342 vs. 216 nmol 15N-nitrate/mmol creatinine [95% CI of the difference 45-207], P = 0.005). This increase was not explained by a difference in renal function between the 2 groups. There was no difference in 2,3-dinor-5,6-dihydro-F2t-IsoP excretion between diabetic subjects and control subjects (44.8+/-7.8 vs. 41.4+/-10.0 ng/mmol creatinine, mean +/- 95% CI). However, there was an inverse correlation between NO synthesis and free radical activity in subjects with diabetes (r = -0.62, P = 0.012) that was not observed in control subjects (r = 0.37, P = 0.107). We conclude that whole-body NO synthesis is higher in type 1 diabetic subjects with normal urinary albumin excretion than in control subjects. The inverse correlation between isoprostane production and NO synthesis in diabetic subjects is consistent with the hypothesis that NO is being inactivated by reactive oxygen species.

Topics: Adult; Albuminuria; Creatinine; Diabetes Mellitus, Type 1; Dinoprost; Female; Humans; Male; Middle Aged; Nitrates; Nitric Oxide; Reactive Oxygen Species; Reference Values; Sex Characteristics

The recently discovered arachidonic acid derivatives, isoprostanes, are increased in pathological conditions associated with oxidative stress, such as diabetes. No role has yet been described for isoprostanes during the development of diabetic nephropathy. Cell culture in high ambient glucose has been used as a model in elucidating cellular mechanisms underlying diabetic nephropathy. Among the growth factors involved in the effect of high glucose, transforming growth factor-beta (TGF-beta) has been described as playing a key role in the development of nephropathy.. Streptozotocin-induced diabetic rats were supplemented in their diet with the antioxidant vitamin E (1000 U/kg diet). Blood and urine samples were taken to determine renal function and isoprostane concentration, as determined by gas chromatography/mass spectrometry. Glomerular mesangial and endothelial cells were cultured in high ambient glucose to determine the synthesis of isoprostanes and the role of isoprostanes in high glucose-induced synthesis of TGF-beta.. Streptozotocin-induced diabetic rats had marked increases in plasma levels and urinary excretion rates of F(2)-isoprostanes. Dietary supplementation with vitamin E normalized (plasma) and reduced (urine) isoprostane levels and, surprisingly, improved proteinuria and blood urea nitrogen (BUN) levels. High ambient glucose increased F(2)-isoprostane synthesis in glomerular endothelial and mesangial cells in culture. Incubation of glomerular cells with F(2)-isoprostanes stimulated the production of TGF-beta.. Increased F(2)-isoprostane synthesis during diabetes appears to be responsible in part for the increase in renal TGF-beta, a well-known mediator of diabetic nephropathy.

Topics: Animals; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dinoprost; Endothelium; F2-Isoprostanes; Glomerular Mesangium; Glucose; Kidney Glomerulus; Male; Mice; Mice, Inbred Strains; Proteinuria; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta

Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation.. Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion.. We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

Topics: Adult; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Platelet Activation; Thromboxane B2; Vitamin E

Platelet prostaglandin (PG) E and plasma PGF2 alpha concentrations were measured by radioimmunoassay methods and compared in non-pregnant and pregnant, normal and diabetic subjects. The blood samples were obtained in the follicular phase in the non-pregnant women and in the third trimester and after delivery in the pregnant women. The immunoreactive platelet PGE (IRPGE) levels were significantly higher in the pregnant diabetic women than in the normal non-pregnant and pregnant women and diabetic non-pregnant women. The immunoreactive plasma PGF2 alpha (IRPGF2 alpha) concentrations were significantly higher in the non-pregnant diabetic women than in the normal non-pregnant and pregnant women. During pregnancy, the plasma IRPGF2 alpha were further increased significantly in the diabetic subjects compared to the non-pregnant diabetics. Both the platelet IRPGE and plasma IRPGF2 alpha concentrations were higher in the pregnant diabetic subjects with retinopathy than in those without retinopathy. These findings suggest that pregnancy and diabetes influence the synthesis of PGE and PGF2 alpha in the platelets and plasma, respectively. The increased production of these prostaglandins are possible exacerbating factors of diabetic retinopathy during pregnancy.

Topics: Adult; Blood Platelets; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dinoprost; Female; Humans; Postpartum Period; Pregnancy; Pregnancy in Diabetics; Pregnancy Trimester, Third; Prostaglandins E; Puerperal Disorders; Reference Values