dinoprost and Hypoglycemia

Mild hypoglycemia is common in clinical practice. Severe hypoglycemia results in heat shock protein and associate co-chaperone changes. Whether mild prolonged hypoglycemia elicits a similar response with inflammatory and oxidative-stress responses compared with a severe hypoglycemic event is unclear; therefore, this pilot exploratory study was undertaken. We performed a case-control induced hypoglycemia clamp study, maintaining blood glucose at 2.8 mmol/L (50 mg/dL) for 1 h in 17 subjects (T2D (

Topics: Adult; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Dinoprost; Female; Heat-Shock Proteins; Heat-Shock Response; Humans; Hypoglycemia; Inflammation; Male; Middle Aged; Oxidative Stress; Protein Interaction Mapping; Proteins; Ubiquitin-Conjugating Enzymes

To compare the effects of either vildagliptin or glimepiride on glycemic variability, oxidative stress, and endothelial parameters in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone.. In this randomized, open-label, parallel study, 34 patients with T2DM being treated with metformin having an HbA1c of 7.0-10.0% were allocated into either the vildagliptin or glimepiride group. A mixed-meal tolerance test and 72-hour continuous glucose monitoring were conducted, and urinary 8-iso-prostaglandinF. Similar significant improvements in HbA1c level were shown in both vildagliptin (-0.8%) and glimepiride (-0.9%) groups after treatment (Ps<0.001). The mean amplitude of glycemic excursions (MAGE) and the mean of daily differences (MODD) were significantly decreased by vildagliptin (P = 0.044 and P = 0.031, respectively) but not by glimepiride. Glimepiride was significantly associated with a higher incidence of hypoglycemia than vildagliptin (P = 0.005). There were no significant differences in urinary 8-iso-PGF. Vildagliptin effectively improved glucose level with a significantly greater reduction in glycemic variability and hypoglycemia than glimepiride in patients with T2DM ongoing metformin therapy. The two drugs showed no significant differences in urinary 8-iso-PGF. NCT01404676.

Topics: Adamantane; Blood Glucose; Diabetes Mellitus, Type 2; Dinoprost; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Nitriles; Pyrrolidines; Sulfonylurea Compounds; Treatment Outcome; Vildagliptin

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

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

Oxidative stress plays a leading role in the progression of diabetic secondary complications, e.g., of cardio-vascular illnesses. Physical activity has been shown to delay and even prevent the progression of type 2 diabetes by improving the antioxidative capacity and thereby decreasing systemic oxidative stress. Peroxiredoxins (PRDX) are important antioxidative components that are highly abundant in erythrocytes. The present study examines the influence of glycemic control and physical fitness on oxidative stress and the peroxiredoxin system in the erythrocytes of non-insulin-dependent type 2 diabetic men ( N=22, years=61 ± 10) at rest. Oxidative stress was measured by immunohistochemical stainings for 8-iso-prostaglandin-F2α (8-Iso-PGF) and the overoxidized form of peroxiredoxins (PRDX-SO (2-3)). Peroxiredoxin isoforms PRDX1 and PRDX2 were also quantified immunohistochemically. Physical fitness was determined during the WHO-step test. Regression analyses showed a positive relationship between 8-Iso-PGF plotted against HbA (1c) (hyperbolic curve (y=a+b/x), R (2)=0.346, P=0.013), a positive relationship between 8-Iso-PGF plotted against fasting glucose (hyperbolic curve (y=a+b/x), R (2)=0.440, P=0.003), as well as positive relationships between PRDX2 plotted against VO (2 peak) (S-curve (y=e(a+b/x)), R(2)=0.259, P=0.018) and between PRDX2 plotted against the workload corresponding to the 4 mmol/l blood lactate concentration (hyperbolic curve (y=a+b/x), R(2)=0.203, P=0.041). Further significant relationships were not found.. Poor glycemic control may increase oxidative stress in the erythrocytes of type 2 diabetic men. Good physical fitness seems to be associated with increased peroxiredoxin contents. Therefore, it can be speculated that physical training can contribute to the improvement of the erythrocyte peroxiredoxin system to counteract free radicals in type 2 diabetic patients.

Topics: Aged; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dinoprost; Erythrocytes; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Lipid Peroxidation; Male; Middle Aged; Overweight; Oxidation-Reduction; Oxidative Stress; Peroxiredoxins; Physical Fitness

Topics: Cross-Sectional Studies; Diabetes Mellitus; Dinoprost; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Inflammation; Insulin; Models, Biological; Oxidative Stress; Research Design

The effect of glucose excursions on oxidative stress is an important topic in diabetes research. We investigated this relationship by analyzing markers of oxidative stress and glycemic data from a continuous glucose monitoring system (CGMS) in 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR), and 27 patients with newly diagnosed type 2 diabetes (T2DM). We compared the mean amplitude of glycemic excursion (MAGE), mean postprandial glucose excursion (MPPGE), and mean postprandial incremental area under the curve (IAUC) with plasma levels of oxidative stress markers 8-iso-PGF2α, 8-OH-dG, and protein carbonyl content in the study subjects. Patients with T2DM or IGR had significantly higher glucose excursions and plasma levels of oxidative stress markers compared to normal controls (P < 0.01 or 0.05). Multiple linear regression analyses showed significant relationships between MAGE and plasma 8-iso-PGF2α, and between MPPGE and plasma 8-OH-dG in patients with IGR or T2DM (P < 0.01 or 0.05). Furthermore, 2h-postprandial glucose level and IAUC were related to plasma protein carbonyl content in the study cohort including T2DM and IGR (P < 0.01). We demonstrate that glucose excursions in subjects with IGR and T2DM trigger the activation of oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Blood Glucose; Cohort Studies; Deoxyguanosine; Diabetes Complications; Diabetes Mellitus, Type 2; Dinoprost; Female; Glucose Intolerance; Humans; Hyperglycemia; Hypoglycemia; Male; Middle Aged; Monitoring, Ambulatory; Oxidative Stress; Postprandial Period; Protein Carbonylation

Fetal hypoglycaemia consequent on food withdrawal for 48 h in sheep in late pregnancy is accompanied by an increase in fetal PGE2 plasma concentrations and myometrial contractility. To assess the contribution of fetal hypoglycaemia and related cellular glucopenia in the increased production of fetal PGE2 we studied the effect of 48 h insulin infusion to the fetus. Fetal whole blood glucose was lowered from 19 +/- 2 to 9 +/- 1 mg.dl-1. This experimental regimen maintains glucose availability to those fetal cells in which insulin increases glucose uptake. Fetal umbilical venous and femoral arterial PGE2 concentrations and umbilical veno-arterial PGE2 difference were unchanged, but maternal uterine veno-arterial difference for PGFM increased during the insulin induced fetal hypoglycaemia. Myometrial activity was also unchanged. We conclude that the increased fetal PGE concentration previously reported during food withdrawal is due to a deficiency of glucose to specific insulin dependent cells within vascular beds served by the fetal cardiovascular system. In addition, the findings suggest a need for a supply of glucose of fetal origin for cells that are responsible for increased PGFM concentrations in the maternal uteroplacental circulation.

Topics: Adrenocorticotropic Hormone; Animals; Dinoprost; Dinoprostone; Female; Fetal Blood; Fetus; Gestational Age; Hydrocortisone; Hypoglycemia; Insulin; Maternal-Fetal Exchange; Pregnancy; Prostaglandins; Sheep