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Changes in oxidant-antioxidant status in young diabetic patients from clinical onset onwards.

Martín-Gallán P, Carrascosa A, Gussinyé M, Domínguez C - J. Cell. Mol. Med. (2007 Nov-Dec)

Bottom Line: Plasma levels of oxidizable lipids were significantly associated with lipid and protein oxidation products.Overall, plasma antioxidant capacity was significantly and consistently lower from clinical onset onwards.Consequently, tight lipid and glycometabolic control may have therapeutic potential by diminishing oxidative tissue-damaging effects of hyperglycaemia.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry and Molecular Biology Research Center, Autonomous University, Barcelona, Spain.

ABSTRACT
Oxidative stress has been implicated as a mechanism underlying hyperglycaemia-associated cellular damage and could play a role in the development of diabetes-related complications. This study aimed to evaluate the significance of changes in oxidant-antioxidant status in 176 child and adolescent diabetic patients at clinical onset, during disease progression and when early microvascular complications appeared. Indicative lipid and protein oxidation markers and antioxidant defence activity were measured in plasma and correlated with clinical data, diabetes duration, long-term glycometabolic control and serum lipids. Compared with their respective age-matched controls, diabetic patients had greater oxidative damage to lipids and proteins, demonstrated through the analysis of hydroperoxides, lipoperoxides and oxidation protein products, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma levels of oxidizable lipids were significantly associated with lipid and protein oxidation products. Overall, plasma antioxidant capacity was significantly and consistently lower from clinical onset onwards. These results suggest that insulin therapy in the first year improved metabolic and oxidant homeostasis and consequently hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation processes, which supports the concept of glucose toxicity and lipotoxicity being interrelated. The greatest increase in lipid and protein oxidative damage biomarkers in young diabetic patients with premature microangiopathy points to oxidative stress as a possible contributing mechanism of microvascular dysfunction. Consequently, tight lipid and glycometabolic control may have therapeutic potential by diminishing oxidative tissue-damaging effects of hyperglycaemia.

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Plasma Total Radicaltrapping Antioxidant Parameter (TRAP) values (A) and protein sulphydryl groups (B) in diabetic patients at disease onset [DO], during the first 20 years of disease evolution [four subgroups: <1.5, 1.5–5, 5–10, 10–20], in diabetic patients with complications [+DC] and in their respective controls; Filled circles: diabetic patients data; open circles: control data. Correlation between protein sulphydryl groups and HbA1c (C). Data are means ± SEM and were analysed for statistically-significant differences by analysis of variance (ANOVA); P values <0.05 (versus respective control participants) were considered significant and are shown above each subgroup in the graph. * P<0.05 diabetic patients with complications versus[10–20] subgroup of patients.
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fig04: Plasma Total Radicaltrapping Antioxidant Parameter (TRAP) values (A) and protein sulphydryl groups (B) in diabetic patients at disease onset [DO], during the first 20 years of disease evolution [four subgroups: <1.5, 1.5–5, 5–10, 10–20], in diabetic patients with complications [+DC] and in their respective controls; Filled circles: diabetic patients data; open circles: control data. Correlation between protein sulphydryl groups and HbA1c (C). Data are means ± SEM and were analysed for statistically-significant differences by analysis of variance (ANOVA); P values <0.05 (versus respective control participants) were considered significant and are shown above each subgroup in the graph. * P<0.05 diabetic patients with complications versus[10–20] subgroup of patients.

Mentions: Mean plasma TRAP values were significantly lower in diabetic patients throughout disease evolution (Fig. 4A) with the greatest statistical differences being at [DO], after which there appeared to be a progressive 10-year partial recovery period with a sharp decline thereafter. Plasma TRAP values were significantly lower in samples of diabetic patients with complications compared with the values of the [10–20D] subgroup of patients with the same diabetes evolution time. Plasma thiol, a parameter of non-oxidation of protein-SH groups, was significantly lower in all diabetic patients, with the exception of subgroup [<1.5D], than in age-matched controls; the decrease was constant in all groups, although the more marked loss of SH groups occurred in patients at [DO] (Fig. 4B). A significant inverse association was observed between thiols and HbA1c (Fig. 4C). Concentrations of the liposoluble antioxidant (-tocopherol were similar in diabetic patients and controls. However, (-tocopherol levels corrected by total lipids were significantly decreased during the first 5 years of disease evolution and in +DC group (Table 1). Values of oxidative stress parameters expressed by diabetic patient subgroups and those of their respective controls are shown in Table 2. Biochemical and molecular oxidative damage biomarkers and antioxidant activities in plasma were not affected by age or pubertal stage in either controls or diabetic patients (Tables 3A, 3B and 4). Table 4 specifically presents the data of diabetic patients according to age and sex and shows there were no differences between males and females at the ages studied.


Changes in oxidant-antioxidant status in young diabetic patients from clinical onset onwards.

Martín-Gallán P, Carrascosa A, Gussinyé M, Domínguez C - J. Cell. Mol. Med. (2007 Nov-Dec)

Plasma Total Radicaltrapping Antioxidant Parameter (TRAP) values (A) and protein sulphydryl groups (B) in diabetic patients at disease onset [DO], during the first 20 years of disease evolution [four subgroups: <1.5, 1.5–5, 5–10, 10–20], in diabetic patients with complications [+DC] and in their respective controls; Filled circles: diabetic patients data; open circles: control data. Correlation between protein sulphydryl groups and HbA1c (C). Data are means ± SEM and were analysed for statistically-significant differences by analysis of variance (ANOVA); P values <0.05 (versus respective control participants) were considered significant and are shown above each subgroup in the graph. * P<0.05 diabetic patients with complications versus[10–20] subgroup of patients.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4401297&req=5

fig04: Plasma Total Radicaltrapping Antioxidant Parameter (TRAP) values (A) and protein sulphydryl groups (B) in diabetic patients at disease onset [DO], during the first 20 years of disease evolution [four subgroups: <1.5, 1.5–5, 5–10, 10–20], in diabetic patients with complications [+DC] and in their respective controls; Filled circles: diabetic patients data; open circles: control data. Correlation between protein sulphydryl groups and HbA1c (C). Data are means ± SEM and were analysed for statistically-significant differences by analysis of variance (ANOVA); P values <0.05 (versus respective control participants) were considered significant and are shown above each subgroup in the graph. * P<0.05 diabetic patients with complications versus[10–20] subgroup of patients.
Mentions: Mean plasma TRAP values were significantly lower in diabetic patients throughout disease evolution (Fig. 4A) with the greatest statistical differences being at [DO], after which there appeared to be a progressive 10-year partial recovery period with a sharp decline thereafter. Plasma TRAP values were significantly lower in samples of diabetic patients with complications compared with the values of the [10–20D] subgroup of patients with the same diabetes evolution time. Plasma thiol, a parameter of non-oxidation of protein-SH groups, was significantly lower in all diabetic patients, with the exception of subgroup [<1.5D], than in age-matched controls; the decrease was constant in all groups, although the more marked loss of SH groups occurred in patients at [DO] (Fig. 4B). A significant inverse association was observed between thiols and HbA1c (Fig. 4C). Concentrations of the liposoluble antioxidant (-tocopherol were similar in diabetic patients and controls. However, (-tocopherol levels corrected by total lipids were significantly decreased during the first 5 years of disease evolution and in +DC group (Table 1). Values of oxidative stress parameters expressed by diabetic patient subgroups and those of their respective controls are shown in Table 2. Biochemical and molecular oxidative damage biomarkers and antioxidant activities in plasma were not affected by age or pubertal stage in either controls or diabetic patients (Tables 3A, 3B and 4). Table 4 specifically presents the data of diabetic patients according to age and sex and shows there were no differences between males and females at the ages studied.

Bottom Line: Plasma levels of oxidizable lipids were significantly associated with lipid and protein oxidation products.Overall, plasma antioxidant capacity was significantly and consistently lower from clinical onset onwards.Consequently, tight lipid and glycometabolic control may have therapeutic potential by diminishing oxidative tissue-damaging effects of hyperglycaemia.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry and Molecular Biology Research Center, Autonomous University, Barcelona, Spain.

ABSTRACT
Oxidative stress has been implicated as a mechanism underlying hyperglycaemia-associated cellular damage and could play a role in the development of diabetes-related complications. This study aimed to evaluate the significance of changes in oxidant-antioxidant status in 176 child and adolescent diabetic patients at clinical onset, during disease progression and when early microvascular complications appeared. Indicative lipid and protein oxidation markers and antioxidant defence activity were measured in plasma and correlated with clinical data, diabetes duration, long-term glycometabolic control and serum lipids. Compared with their respective age-matched controls, diabetic patients had greater oxidative damage to lipids and proteins, demonstrated through the analysis of hydroperoxides, lipoperoxides and oxidation protein products, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma levels of oxidizable lipids were significantly associated with lipid and protein oxidation products. Overall, plasma antioxidant capacity was significantly and consistently lower from clinical onset onwards. These results suggest that insulin therapy in the first year improved metabolic and oxidant homeostasis and consequently hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation processes, which supports the concept of glucose toxicity and lipotoxicity being interrelated. The greatest increase in lipid and protein oxidative damage biomarkers in young diabetic patients with premature microangiopathy points to oxidative stress as a possible contributing mechanism of microvascular dysfunction. Consequently, tight lipid and glycometabolic control may have therapeutic potential by diminishing oxidative tissue-damaging effects of hyperglycaemia.

Show MeSH
Related in: MedlinePlus