Oxidative stress in families of type 1 diabetic patients

Matteucci, Elena; Cinapri, V; Quilici, S; Forotti, G; Giampietro, Ottavio

doi:10.1016/s0168-8227(00)81050-5

Cited by 31 publications

(42 citation statements)

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“…A familial predisposition to oxidative stress is reported in Type I diabetic patients [16]. An association has been found between the genetic polymorphism of paraoxonase enzyme and oxidative DNA damage in patients with Type II diabetes mellitus and in control subjects [17].…”

Section: Discussionmentioning

confidence: 93%

Urinary excretion of 8-oxo-7, 8-dihydro-2′-deoxyguanosine as a predictor of the development of diabetic nephropathy

et al. 2002

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Aims/hypothesis. The increased oxidative stress in diabetes is known to contribute to the progression of diabetes and its complications. We have reported a significant relation between the content of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a product of oxidative DNA damage in urine or leukocytes and the severity of diabetic nephropathy and retinopathy [1]. We investigated whether 8-oxodG in urine or leukocytes is associated with the progression of diabetic nephropathy. Methods. We measured urinary 8-oxodG contents at entry and carried out a prospective longitudinal study to assess the progression of nephropathy over 5 years.Results. There was a significant progression of diabetic nephropathy in the patients with higher excretion of 8-oxodG in urine compared with the patients with moderate or lower excretion of 8-oxodG. There was no significant association between the leukocyte 8-oxodG contents and the development of nephropathy. The multivariate logistic regression analysis suggests that the urinary 8-oxodG was the strongest predictor of nephropathy among several known risk factors. Conclusion/interpretation. This study provides evidence that increased oxidative stress has a primary role in the pathogenesis of diabetic nephropathy. A local enhancement of oxidative stress in diabetic kidney might explain the possible linkage between the increased urinary excretion of 8-oxodG and the development of nephropathy. 8-oxodG in urine is a useful clinical marker to predict the development of diabetic nephropathy in diabetic patients. Oxidative stress is one of the important mediators of vascular complications in diabetes including nephropathy. The hyperglycaemia-induced generation of reactive oxygen species (ROS) is linked by three pathological pathways to diabetic complications: activation of protein kinase C (PKC), the formation of advanced glycation end products (AGE), and sorbitol accumulation [4,5]. Normalising mitochondrial ROS production was reported to block these hyperglycaemia-mediated signalling pathways.8-oxodG is a product of oxidative DNA damage following specific enzymatic cleavage after ROSinduced 8-hydroxylation of the guanine base in mitochondrial and nuclear DNA [6]. 8-oxodG is known to be a sensitive marker of oxidative DNA damage and of the total systemic oxidative stress in vivo [7]. SevThe link between hyperglycaemia and the complications of diabetes is still not clear. Increased oxidative stress in diabetes might contribute to the pathogenesis of diabetic complications, including nephropathy [2,

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Section: Discussionmentioning

confidence: 93%

Urinary excretion of 8-oxo-7, 8-dihydro-2′-deoxyguanosine as a predictor of the development of diabetic nephropathy

et al. 2002

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“…Experimental diabetes can be induced in rodents by alloxan or streptozotocin by generating ROS [15,16]. Markers of oxidative stress were reported to be abnormal in nondiabetic relatives of type 1 diabetic patients, suggesting that oxidative stress preceded the onset of type 1 diabetes [17]. Therefore, there was a possibility that a certain genetic predisposition vulnerable to ROS might play a role in the development of type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Association Study of Human MTH1 Gene Polymorphisms with Type 1 Diabetes Mellitus

et al. 2004

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Abstract. Reactive oxygen species are considered to play a role in the development of diabetes mellitus and its complications. Human MTH1 (mutT homologue 1) has 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase activity, which repairs oxidized forms of dGTP. This enzyme is known to have a thermolabile Met83 variant. We examined whether Val83Met polymorphism of human MTH1 gene is associated with type 1 diabetes mellitus. We recruited 156 type 1 diabetic patients (59 males and 97 females). The polymorphism was analyzed by restriction fragment length polymorphism analysis with Nsi I. The Met/Met genotype at codon 83 was very rare in both control and patient groups. Val/Met genotype tended to be more frequent in the whole type 1 diabetic patients than in controls. When subjects were divided into subgroups according to gender, there were no differences in the genotype and allele frequencies between patients and controls in males. On the other hand, in female type 1 diabetic patients, the Val/Met genotype was more frequent than in female controls (corrected P = 0.102). The Met allele was significantly more frequent in female type 1 diabetic patients than in female controls (corrected P = 0.022). Our results suggested that the Met allele at codon 83 of MTH1 gene might be involved in the development of type 1 diabetes mellitus in the Japanese female population.

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“…We concluded that anthropometric and anamnestic data on child and family yield more accurate estimates of risk profile: fat distribution seems relevant for metabolic and cardiovascular disorders. Since our initial investigations on type 1 diabetes families, we found that first degree relatives' BMI tended to be higher when compared with healthy control subjects who had no first-degree relative with type 1 diabetes, although the difference did not always reach statistical significance (Matteucci & Giampietro, 2000a;Matteucci et al 2004aMatteucci et al , 2004bMatteucci et al 2006). In recent years, on the contrary, the difference in BMI between unaffected siblings of type 1 diabetic probands and healthy control subjects has reached the statistical significance ( Figure 1, .…”

Section: Body Weight In Type 1 Diabetes Familiesmentioning

confidence: 91%

“…Since 2000 we documented metabolic perturbations in nondiabetic relatives: parents differed from age-matched control subjects in the higher plasma concentrations of glucose and Lipoprotein (a); their fibrinogen was borderline but did not reach any statistical significance; in turn, siblings of type 1 diabetes patients differed from age-matched control subjects in the higher levels of Lipoprotein (a) (Matteucci et al, 2000a). In the same study, we investigated the redox status and antioxidant defences in these families.…”

Section: Biochemical Phenotype and Redox Balance In Type 1 Diabetes Rmentioning

confidence: 99%

“…We presented first evidence that markers of lipoprotein metabolism (Lipoprotein (a)), oxidative stress (plasma and erythrocyte malodialdehyde), and cellular fragility (haemolysis) are abnormal in non diabetic relatives of type 1 diabetics supporting the view that familial elements even precede diabetes. It seemed reasonable that the same biologic markers considered major predictors of cardiovascular disease could also trace familial susceptibility to type 1 diabetes, just as they have been associated with the development of type 2 diabetes (Matteucci et al, 2000a). Based on the finding of elevated circulating markers of lipid peroxidation and increased cellular fragility, we decided to complete and integrate our investigation with further biochemical measurements of possible first-chain initiating or stimulating factors in order to evaluate, in the same families, the contribution of extracellular antioxidants to the increased oxidative stress.…”

Section: Biochemical Phenotype and Redox Balance In Type 1 Diabetes Rmentioning

confidence: 99%

See 1 more Smart Citation

The Enlarging List of Phenotypic Characteristics That Might Allow the Clinical Identification of Families at Risk for Type 1 Diabetes

Matteucci¹,

Giampietro²

2011

Type 1 Diabetes - Complications, Pathogenesis, and Alternative Treatments

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Oxidative stress in families of type 1 diabetic patients

Cited by 31 publications

References 0 publications

Urinary excretion of 8-oxo-7, 8-dihydro-2′-deoxyguanosine as a predictor of the development of diabetic nephropathy

Urinary excretion of 8-oxo-7, 8-dihydro-2′-deoxyguanosine as a predictor of the development of diabetic nephropathy

Association Study of Human MTH1 Gene Polymorphisms with Type 1 Diabetes Mellitus

The Enlarging List of Phenotypic Characteristics That Might Allow the Clinical Identification of Families at Risk for Type 1 Diabetes

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