Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes

Marra, Giampiero; Cotroneo, P; Pitocco, Dario; Manto, Andrea; Leo, M. A. S. Di; Ruotolo, Valeria; Caputo, Salvatore; Giardina, Bruno; Ghirlanda, Giovanni; Santini, Stefano Angelo

doi:10.2337/diacare.25.2.370

Cited by 173 publications

(119 citation statements)

References 52 publications

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“…The results showed a significant decrease in TaS in children with T1DM, regardless of the duration of the disease and metabolic control. This observation is consistent with the findings of other researchers [48,49]. Decreased levels of TaS, which result from the depletion of endogenous antioxidants, confirm the presence of oxidative stress in children with T1DM.…”

Section: Intra-erythrocyte Antioxidant Enzymes and Tassupporting

confidence: 82%

“…The present study did not reveal any correlation between TaS levels and the age of patients, the duration of their disease, Hba 1c or BMI. Similar results were obtained by Marra et al [49]; however, apart from decreased levels of TaS in patients with T1DM, Valabhji et al [50] and Vantyghem et al [51] found a negative correlation between TaS and Hba 1c levels and duration of the disease, and no correlation with BMI and lipid profile. In the present study, TaS did not correlate with the components of the lipid profile.…”

Section: Intra-erythrocyte Antioxidant Enzymes and Tassupporting

confidence: 74%

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Trace Elements, Magnesium, and the Efficacy of Antioxidant Systems in Children with Type 1 Diabetes Mellitus and in Their Siblings

Salmonowicz¹,

Krzystek−Korpacka²,

Noczyńska³

2014

Adv Clin Exp Med

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Background. Magnesium (Mg), selinium (Se), zinc (Zn), manganese (Mn), and copper (cu) are involved in the mechanisms of antioxidant defense. Mn and cu, which participate in the generation of reactive oxygen species (ROS), also have pro-oxidative properties. Objectives. To evaluate the levels of Mg, Se, Zn, Mn, and cu, as well as the effectiveness of antioxidant defense mechanisms in children with Type 1Diabetes Mellitus (T1DM) and in their siblings. The preliminary findings were originally reported in 2009 at the 35 th annual conference of the International Society for Pediatric and adolescent Diabetes (ISPaD) in Ljubljana, Slovenia. Material and Methods. The study involved 87 children with T1DM, 2-19 years old, treated for T1DM for an average of 3.5 years. The sibling and control groups comprised 27 and 41 children, aged 4.5-16.5 years and 10.5-18 years respectively. The parameters named above were assessed in relation to metabolic compensation levels (Hb a1c ) and disease duration. Results. compared with the control group, T1DM children had lower plasma levels of Mg and Zn and higher levels of cu; the siblings had lower levels of Zn; T1DM children had lower copper/zinc superoxide dismutase (cuZnSOD) activity; and both T1DM children and their siblings had higher catalase (caT) activity and lower total antioxidant status (TaS) levels. Conclusions. There may be a correlation between impaired antioxidant status and Mg and Zn deficiency and increased cu levels in T1DM children. Oxidative stress in T1DM is accompanied by alterations in enzymatic activity and non-enzymatic mechanisms of antioxidant defense. The decreased TaS levels noted in T1DM patients may impair the effectiveness of non-enzymatic antioxidant systems. The increased caT activity and unimpaired selenium-dependent glutathione peroxidase (Se-GSHPx) activity point indirectly to enhanced ROS generation in T1DM children. The impaired antioxidant defense found in the siblings of T1DM patients may indicate that genetic factors play a role (Adv Clin Exp Med 2014, 23, 2, 259-268).

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Section: Intra-erythrocyte Antioxidant Enzymes and Tassupporting

confidence: 82%

Section: Intra-erythrocyte Antioxidant Enzymes and Tassupporting

confidence: 74%

Trace Elements, Magnesium, and the Efficacy of Antioxidant Systems in Children with Type 1 Diabetes Mellitus and in Their Siblings

Salmonowicz¹,

Krzystek−Korpacka²,

Noczyńska³

2014

Adv Clin Exp Med

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“…Both clinical and experimental studies have revealed that diabetes itself is associated with altered cardiac function independent of macro-=micro-vascular complications (1,2). One of the most prominent complications of diabetes is impaired ventricular contraction and relaxation, which serve as the hallmarks of diabetic cardiomyopathy (3).…”

Section: Introductionmentioning

confidence: 99%

Influence of Gender on Intrinsic Contractile Properties of Isolated Ventricular Myocytes from Calmodulin‐Induced Diabetic Transgenic Mice

Zhang

Duan

et al. 2003

Endocrine Research

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Diabetes mellitus impairs ventricular function, which itself may be disparately influenced by gender. This study compared the impact of gender on cardiac contractile response in ventricular myocytes from wild-type FVB and calmodulin-induced diabetic transgenic (OVE26) mice at young (2 month) and older (11 month) age. Mechanical and intracellular Ca 2þ properties of cardiac myocytes were evaluated using an IonOptix MyoCam 1 system. Diabetic mice of both genders exhibited significantly elevated blood glucose regardless of age. OVE26 myocytes displayed reduced peak shortening (PS) and maximal velocity of shortening=relengthening (AEdL=dt), and prolonged time-to-PS (TPS) and time-to-90% relengthening (TR 90 ), associated with higher resting intracellular Ca 2þ levels and attenuated Ca 2þ -induced intracellular Ca 2þ release compared with the FVB myocytes. Peak shortening and AEdL=dt were smaller in female FVB groups when compared to the age-matched male counterparts. However, these gender differences were ablated by the diabetic state. No significant gender-related differences in intracellular Ca 2þ handling were noted in either FVB or OVE26 myocytes, with the exception of overt gender differences in OVE26 mice when age was taken into account. Young female OVE26 mice exhibited better-preserved mechanical function while older female OVE26 mice displayed the worst mechanical function among all four OVE26 groups. In conclusion, our data confirmed impaired cardiac contractile function in diabetes, partially due to altered intracellular Ca 2þ handling, in both genders. Mechanical differences existed between genders but were ''cancelled off'' by diabetic state. Nevertheless, a ''female advantage'' in ventricular function may still persist in young female diabetic subjects.

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“…Oxidative damage is widely considered to be a cause of diabetic complications (7,8), and signs of oxidative damage are found in diabetic patients. Recent proposals (9) suggest that overproduction of reactive oxygen species (ROS) may be the initiating event leading to long-term development of diabetic complications.…”

mentioning

confidence: 99%

Catalase Protects Cardiomyocyte Function in Models of Type 1 and Type 2 Diabetes

et al. 2004

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Many diabetic patients suffer from a cardiomyopathy that cannot be explained by poor coronary perfusion. Reactive oxygen species (ROS) have been proposed to contribute to this cardiomyopathy. Consistent with this we found evidence for induction of the antioxidant genes for catalase in diabetic OVE26 hearts. To determine whether increased antioxidant protection could reduce diabetic cardiomyopathy, we assessed cardiac morphology and contractility, Ca 2؉ handling, malondialdehyde (MDA)-modified proteins, and ROS levels in individual cardiomyocytes isolated from control hearts, OVE26 diabetic hearts, and diabetic hearts overexpressing the antioxidant protein catalase. Diabetic hearts showed damaged mitochondria and myofibrils, reduced myocyte contractility, slowed intracellular Ca 2؉ decay, and increased MDA-modified proteins compared with control myocytes. Overexpressing catalase preserved normal cardiac morphology, prevented the contractile defects, and reduced MDA protein modification but did not reverse the slowed Ca 2؉ decay induced by diabetes. Additionally, high glucose promoted significantly increased generation of ROS in diabetic cardiomyocytes. Chronic overexpression of catalase or acute in vitro treatment with rotenone, an inhibitor of mitochondrial complex I, or thenoyltrifluoroacetone, an inhibitor of mitochondrial complex II, eliminated excess ROS production in diabetic cardiomyocytes. The structural damage to diabetic mitochondria and the efficacy of mitochondrial inhibitors in reducing ROS suggest that mitochondria are a source of oxidative damage in diabetic cardiomyocytes. We also found that catalase overexpression protected cardiomyocyte contractility in the agouti model of type 2 diabetes. These data show that both type 1 and type 2 diabetes induce damage at the level of individual myocytes, and that this damage occurs through mechanisms utilizing ROS.

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Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes

Cited by 173 publications

References 52 publications

Trace Elements, Magnesium, and the Efficacy of Antioxidant Systems in Children with Type 1 Diabetes Mellitus and in Their Siblings

Trace Elements, Magnesium, and the Efficacy of Antioxidant Systems in Children with Type 1 Diabetes Mellitus and in Their Siblings

Influence of Gender on Intrinsic Contractile Properties of Isolated Ventricular Myocytes from Calmodulin‐Induced Diabetic Transgenic Mice

Catalase Protects Cardiomyocyte Function in Models of Type 1 and Type 2 Diabetes

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