Oxidative stress and antioxidant status in patients with late-onset gestational diabetes mellitus

The relationship between late-onset gestational diabetes mellitus [GDM] and oxidative stress is not well known, and the importance of the oxidant/antioxidant equilibrium in the clinical evolution and its complications require elucidation. The aim of the study was to evaluate the relationships between maternal levels of markers of oxidative stress in women with late-onset GDM that, potentially, may have considerable clinical implications in the pathogenesis and/or the evolution of GDM. Pregnant women (n = 78; 53 with GDM, 25 controls), between the 24th and 29th week of gestation, were enrolled. Both groups were analysed for demographic data, perinatal and obstetrics outcomes together with the levels of the marker’s oxidative stress and antioxidant status. Control versus patient results in the univariate analysis were the following: pre-gestational body mass index [BMI] 23.31 ± 4.2 vs. 27.13 ± 4.6 kg/m² (P = 0.001); weeks at delivery 39.2 ± 3.05 vs. 38.9 ± 1.8 (P = 0.09); Caesarean delivery 12.5 vs. 43% (P = 0.004); macrosomia 4 vs. 9.4% (P = 0.6); lipoperoxides [LPO] 2.06 ± 1.00 vs. 3.14 ± 1.55 μmol/mg (P = 0.001); catalase 3.23 ± 1.41 vs. 2.52 ± 1.3 nmol/min/ml (P = 0.03); superoxide dismutase [SOD] 0.11 ± 0.04 vs. 0.08 ± 0.01 U/ml (P = 0.0003); glutathione peroxidase [GPX] 0.03 ± 0.006 vs. 0.025 ± 0.006 nmol/min/ml (P = 0.01); glutathione reductase [GSH] 0.004 ± 0.002 vs. 0.004 ± 0.004 nmol/min/ml (P = 0.9)]; and glutathione transferase [GST] 0.0025 ± 0.0012 vs. 0.0027 ± 0.00017 nmol/min/ml (P = 0.7). Multivariate analysis showed catalase might have a protective effect against GDM development and LPO seems to be a risk factor for the disease. These data suggest an increase in oxidative stress and a decrease in antioxidative defence in women with late-onset GDM and, as such, may have considerable clinical implications in the pathogenesis and/or the course of the pregnancy in these patients.     

Infections in diabetes mellitus and hyperglycemia

Infections in diabetes mellitus are relatively more common and serious. Diabetic patients run the risk of acute metabolic decompensation during infections, and conversely patients with metabolic decompensation are at higher risk of certain invasive infections. Tight glycemic control is of paramount importance during acute infected or high stress state. Infections in diabetic patients result in extended hospital stays and additional financial burden. Given the risks of not alleviating the metabolic dysregulation and the benefits of decent glycemic control, it is necessary that besides antimicrobial therapy, equal emphasis be placed on intensified glycemic control.     

Oxidative stress and antioxidant status in type 1 diabetes mellitus

OBJECTIVES: 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. DESIGN AND 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. RESULTS: 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). CONCLUSIONS: 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.     

Preservation of the antioxidant status in chemically-induced diabetes mellitus by melatonin

Oxidant stress is believed to be enhanced in patients with diabetes mellitus, which may lead to endothelial dysfunction and the development of atherosclerosis. In diabetes, hyperglycemia drives non-enzymatic glycation and oxidation of proteins and lipids which enhances the formation of advanced glycation end products (AGEs), which may be involved in the pathogenesis of diabetic vascular disease. The macrovascular complications of diabetes seem to be due to enhanced cellular oxidant stress by the interaction of AGEs with their receptor. It would be worthwhile to devise methods to reduce this oxidant stress. In alloxan-induced diabetic rats lipid peroxidation products were increased, while levels of nitric oxide glutathione peroxidase and superoxide dismutase were reduced. Melatonin restored these biochemical abnormalities to normalcy independent of hyperglycemia. This model can be used to study the role of oxidant stress in the development of macrovascular complications in diabetes mellitus.     

Impaired deformability of erythrocytes and neutrophils in children with newly diagnosed insulin-dependent diabetes mellitus

Aims/hypothesis. Abnormal rheological properties of erythrocytes, leucocytes and plasma may have a role in the development of diabetic microangiopathy. We hypothesized that changed haemorrheological variables may already be found in children with onset diabetes. Methods. Erythrocyte deformation (rheoscope), neutrophil deformation (micropipette), erythrocyte aggregation, blood and plasma viscosity were measured in 15 children with insulin-dependent diabetes mellitus before initiation of insulin treatment and 4 to 6 weeks later, 15 diabetic children treated with insulin for 5 to 8 years, 15 healthy children and 15 healthy adults. Results. At a low shear stress of 0.6 Pa, erythrocyte deformation was decreased in the diabetic children before (–28 %), after 4 to 6 weeks (–22 %) and after 5 to 8 years (–17 %) of insulin treatment compared with healthy children. More active neutrophils were counted in the untreated diabetic children (9 ± 6 %) than in healthy children (3 ± 2 %). Deformability of passive neutrophils was greatly decreased in the children with onset diabetes and moderately reduced in the diabetic children who were treated with insulin. Neutrophil deformation (r = –0.52) and erythrocyte deformation at 0.6 Pa (r = –0.62) were inversely related to haemoglobin A1 c. Haematocrit and blood viscosity were increased in the untreated children and in the children treated with insulin for 5 to 8 years. Plasma viscosity and erythrocyte aggregation were similar in the three groups of children. Conclusion/interpretation. Decreased erythrocyte deformation at low shear force, increased count of active neutrophils and impaired deformability of passive neutrophils may increase the risk for acute cerebro-vascular complications in children with uncontrolled insulin-dependent diabetes mellitus. [Diabetologia (1999) 42: 865–869] Received: 17 November 1998 and in final revised form: 2 February 1999     

Oxidative stress and antioxidant status in elderly diabetes mellitus and glucose intolerance patients

Increased oxidative stress and impaired anti-oxidant defense have been suggested as contributory factors for initiation and progression of complications in diabetes mellitus. Aging itself has been shown to be along with increased oxidative stress and lower anti-oxidant defense. We aimed at investigating oxidative stress and anti-oxidant enzymes in 61 elderly subjects. Fifteen healthy individuals (group 1, mean age 72.2 +/- 5.13), 13 glucose intolerant patients (group 2, mean age 71.7 +/- 4.9), 19 patients with type 2 diabetes mellitus (T2DM) without any complication (group 3, mean age 70.0 +/- 6.0), and 14 patients with T2DM with at least one complication (group 4, mean age 69.8 +/- 4.7) were included in the study. Whilst plasma levels for malondialdehyde (MDAP) and erythrocyte malondialdehyde (MDAE) were measured as markers of oxidative stress, activity of erythrocyte superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) were taken as markers of oxidative defense system. MDAP level was significantly elevated in group 4 (P = 0.001). MDAE was elevated in patients with T2DM, particularly in group 4, however, the difference between the groups was of borderline significance (P = 0.07). Whilst CAT was elevated in groups 3 and 4 compared to control subjects (P = 0.025 and 0.002, respectively), no difference was found for SOD between the groups. GSH-Px activity was found to be increased in groups 2, 3 and 4, it did not reach statistical significance (P = 0.106). There were significant correlations between CAT and MDAE (P < 0.0001, r = 0.056) and MDAP (P = 0.016, r = 0.306). These results suggest that there was an increased oxidative stress in elderly diabetics, however, this is not due to reduced erythrocyte antioxidant defense potential but, rather, increased free radical production possibly due to hyperglycemia.     

Morphofunctional changes in the erythrocytes in diabetes mellitus

The paper is concerned with some data on change in the ultrastructure and ultrahistochemistry of erythrocytes in 85 patients with diabetes mellitus. Correlation between change of erythrocytic homeostasis and an extent of metabolic derangements and vascular symptoms is substantiated. Some mechanisms of pathogenesis of diabetic angiopathies have been unraveled, principles of their prevention and therapy are substantiated.     

Effect of Dapagliflozin on renal protection in patients with uncontrolled type 2 diabetes mellitus

<正>Objective To observe the effect of Dapagliflozin on renal protection in patients with type 2 diabetes mellitus(T2DM) with poor glycemic control.Methods Ninety hospitalized T2DM patients who had never used sodiumglucose co-transporter 2 (SGLT2) inhibitors with poor     

Flexibility of erythrocytes in juvenile diabetes mellitus

Summary The rheological properties of erythrocytes of 47 diabetic children and adolescents were studied. Deformability of red cells of 32 patients under poor metabolic control was markedly decreased while the deformability of red cells of patients (15 individuals) under good control was normal. This diminished flexibility of erythrocytes of patients under poor control can be explained partly by an increased concentration of free fatty acids in plasma. Moreover we found a decreased fluidity of the intracellular hemoglobin caused possibly by a decreased concentration of 2, 3-diphosphoglycerate in the cells.Supported by Deutsche Forschungsgemeinschaft     

长期高血糖对继发磺脲类药物失效患者胰岛β细胞功能的影响

目的　探讨长期高血糖对继发磺酰脲类药物 (SU )失效的 2型糖尿病 (T2DM )患者胰岛β细胞功能的影响。 　方法　继发SU失效的T2DM患者 51例 ,血糖控制前后均行标准馒头餐和精氨酸兴奋试验 ,血糖控制后另行格列苯脲试验。观察葡萄糖刺激的胰岛素反应 (IRG)、校正的胰岛 β细胞分泌功能指数 (MBCI)、精氨酸刺激的急性胰岛素反应 (AIRARG)。　结果　血糖控制前后AIRARG、IRG、MBCI的差异无显著意义。血糖控制前 ,格列苯脲有效组AIRARG 较失效组高 (P <0 0 5) ,IRG、MBCI两组间的差异无显著意义 ;血糖控制后 ,格列苯脲有效组AIRARG、IRG、MBCI均较失效组显著升高 (均P <0 0 5)。格列苯脲有效组血糖控制后IRG、MBCI均较控制前升高 (均P <0 0 5) ,而AIRARG在血糖控制前后的差异无显著意义。格列苯脲失效组血糖控制前后AIRARG、IRG、MBCI的差异无显著意义。　结论　长期高血糖损害胰岛β细胞功能 ,部分患者血糖控制后可使 β细胞功能部分恢复     

Effect of insulin resistance and hyperglycemia on proinsulin release in a primate model of diabetes mellitus.

An elevated plasma proinsulin (PI) to immunoreactive insulin (IRI) ratio occurs in relatives of patients with insulin-dependent diabetes mellitus and in subjects with non-insulin-dependent diabetes mellitus. To determine whether this alteration is the result of B-cell dysfunction and/or insulin resistance, we infused nicotinic acid for 3 weeks to produce insulin resistance in five adolescent male baboons before and after the administration of streptozocin (200 mg/kg). We measured basal PI and IRI levels and the acute incremental PI (APIR) and IRI (AIRIR) responses to iv arginine. The quantity of IRI comprised of PI was calculated in the basal state (PI/IRI) and following arginine injection (APIR/AIRIR). Streptozocin administration did not change the fasting plasma glucose (FPG) compared to that in the normal animals (4.7 +/- 0.3 vs. 4.3 +/- 0.2 mM) but raised the PI/IRI (16.4 +/- 3.4 vs. 5.9 +/- 1.7%) and APIR/AIRIR (7.1 +/- 1.0 vs. 2.8 +/- 1.0%) due to a concurrent reduction in IRI and increase in PI concentrations. The induction of experimental insulin resistance with nicotinic acid in the normal animals had no effect on the FPG (4.4 +/- 0.2 mM) but in the streptozocin treated animals, fasting hyperglycemia (8.3 +/- 1.7 mM) developed. Neither the basal PI/IRI (10.2 +/- 2.2%) or the APIR/AIRIR (2.3 +/- 0.6%) increased in the insulin-resistant streptozocin animals thus being no different to that of normal control animals before or during experimental insulin resistance. We conclude that disproportionate proinsulinemia is a manifestation of B-cell damage from streptozocin which is not exacerbated by insulin resistance or hyperglycemia.     

Effect of diabetes mellitus on outcomes of hyperglycemia in a mixed medical surgical intensive care unit

Background:

Intensive insulin therapy and degree of glycemic control in critically ill patients remains controversial, particularly in patients with diabetes mellitus. We hypothesized that diabetic patients who achieved tight glucose control with continuous insulin therapy would have less morbidity and lower mortality than diabetic patients with uncontrolled blood glucose.

Method:

A retrospective chart review was performed on 395 intensive care unit (ICU) patients that included 235 diabetic patients. All patients received an intravenous insulin protocol targeted to a blood glucose (BG) level of 80–140mg/dl. Outcomes were compared between (a) nondiabetic and diabetic patients, (b) diabetic patients with controlled BG levels (80–140mg/dl) versus uncontrolled levels (>140 mg/dl), and (c) diabetic survivors and nonsurvivors.

Results:

Diabetic patients had a shorter ICU stay compared to nondiabetic patients (10 ± 0.7 vs 13 ± 1.1, p = .01). The mean BG of the diabetic patients was 25% higher on average in the uncontrolled group than in the controlled (166 ± 26 vs 130 ± 9.4 mg/dl, p < .01). There was no difference in ICU and hospital length of stay (LOS) between diabetic patients who were well controlled compared to those who were uncontrolled. Diabetic nonsurvivors had a significantly higher incidence of hypoglycemia (BG <60 mg/dl) compared to diabetic survivors.

Conclusion:

The results showed that a diagnosis of diabetes was not an independent predictor of mortality, and that diabetic patients who were uncontrolled did not have worse outcomes. Diabetic nonsurvivors were associated with a greater amount of hypoglycemic episodes, suggesting these patients may benefit from a more lenient blood glucose protocol.     

Effect of thyroxine on methemoglobin content and the activity of antioxidant enzymes of human erythrocytes in vitro

A study was made of the effect of thyroxine in vitro on the activity of antioxidant enzymes: superoxide dismutase (SOD) and catalase, and on the methemoglobin content in the erythrocytes of 23 healthy persons aged 17-25. Erythrocyte incubation was performed in different media: in their own plasma, a weak solution of NaOH, tris-HCl buffer solution (pH 7.4) with thyroxine in the physiological concentration and without it. The enzyme activity was compared in the native and incubated erythrocytes. After the incubation of erythrocytes with thyroxine in their own plasma the SOD and catalase activity showed a statistically significant rise, and the methemoglobin content decreased. This effect was undetectable in the incubation of erythrocytes with thyroxine in tris-buffer solution. Direct incubation of SOD with thyroxine isolated from the erythrocytes did not cause any changes in enzyme activity. Probably the interaction of thyroxine with erythrocyte membrane components is important for the implementation of the hormonal effect. Some unidentified factors contained in the blood plasma may play a role in the SOD activation. The authors discuss thyroxine ab to cause rapid regulation of the activity antioxidant enzymes.     

Changing environment of hyperglycemia in pregnancy: Gestational diabetes and diabetes mellitus in pregnancy

The diagnosis and treatment of gestational diabetes mellitus (GDM) have been in a state of flux since the World Health Organization accepted and endorsed the International Diabetes and Pregnancy Study Group's diagnostic pathway and criteria in 2013. These new diagnostic criteria identify an increasing number of women at risk of hyperglycemia in pregnancy (HGiP). Maternal hyperglycemia represents a significant risk to the mother and fetus, in both the short and long term. Controversially, metformin use for the treatment of GDM is increasing in Australia. This article identifies the multiple and varied presentations of HGiP, of which GDM is the most commonly encountered. The degree of maternal hyperglycemia experienced affects the outcomes for both the mother and neonate, and specific diagnosis determines the appropriate treatment for the pregnancy. Given the increasing incidence of women with dysglycemia and those developing HGiP, this is an important area for research and clinical attention for all health professionals.     

Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus

The metabolism of glutathione and activities of its related enzymes were studied in erythrocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM). A decrease in the levels of the reduced form of glutathione and an increase in the levels of glutathione disulfide were found in erythrocytes of diabetics. To elucidate these changes in the levels of glutathione, synthetic and degradative processes were studied. The activity of gamma-glutamylcysteine synthetase was significantly lower in diabetics than in normal controls. The activity of glutathione synthetase of each group was the same. The rate of outward transport of glutathione disulfide in diabetics decreased to approximately 70% of that of normal controls. The activity of glutathione reductase decreased in diabetics. These data suggest that the decrease in the levels of reduced form of glutathione in erythrocytes of diabetics is brought about by impaired glutathione synthesis and that the increase in the levels of glutathione disulfide is brought about by the decreased transport activity of glutathione disulfide through the erythrocyte membrane together with a decrease in the activity of glutathione reductase. These data also suggest that the impairment of glutathione metabolism weakens the defense mechanism against oxidative stress in erythrocytes of diabetics.     

Lung function in children with diabetes mellitus

A cross-sectional study design was undertaken to assess pulmonary function in children with insulin-dependent diabetes mellitus (IDDM), and to establish if there is any relationship with diabetic factors and complications. Thirty-eight children (10 +/- 1.8 years) with IDDM and without clinical or radiological evidence of lung involvement, and 41 healthy age-matched reference subjects, underwent a pulmonary function study. Thirteen (34%) of 38 subjects with IDDM were studied at the onset of their disease. Adjusted values expressed as SD score of forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and the transfer factor for carbon monoxide (TLCO) were found to be significantly lower than in controls (-0.54 +/- 0.87 vs. 0.40 +/- 1.10, P = 0.0008; -0.11 +/- 0.96 vs. 0.52 +/- 1.07, P = 0.01; -1.60 +/- 1.07 vs. -0.57 +/- 1.28, P = 0.001, respectively). These differences also existed in the group investigated at onset of diabetes. Residual volume (RV) and RV/total lung capacity ratio (RV/TLC) were significantly higher in the whole group of patients with IDDM than in controls (-0.20 +/- 0.83 vs. -0.80 +/- 0.88, P = 0.003; and 26 +/- 6.2 vs. 21 +/- 5.0, P = 0.0002, respectively). Seventeen patients (45%) had abnormal pulmonary function (SD score, less than -1.64): 16 subjects had reduced TLCO, 4 had reduced FVC, and in 3 of the 17, both functional indices were abnormal. There was no significant relationship between pulmonary function indices and diabetic factors or complications. The only significant association was between abnormal TLCO and females (P = 0.03), suggesting that sex may be a predisposing factor for the development of pulmonary complications. This study supports the view that the lung is functionally involved in children with IDDM early on in the course of the disease.