High glucose induces DNA damage in cultured human endothelial cells.

Lorenzi, Mara; Montisano, D F; Toledo, Silva; Barrieux, A

doi:10.1172/jci112295

Cited by 242 publications

(132 citation statements)

References 27 publications

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“…Dandona et al (24) have demonstrated in a clinical study with diabetic subjects and healthy volunteers that diabetes is associated with increased production of reactive oxygen species and greater oxidative damage to DNA. In an experimental study, high glucose itself was shown to induce DNA damage (25). Thus, it is possible that increased production of reactive oxygen species or high glucose itself contributes to DNA damage, which may lead to mutational changes in oncogenes and tumor suppressor genes, and thereby to the development of gastric cancer.…”

Section: Results -mentioning

confidence: 99%

Impact of Fasting Plasma Glucose Levels on Gastric Cancer Incidence in a General Japanese Population

et al. 2005

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MITSUO IIDA, MD 1 OBJECTIVE -Several studies have shown associations between diabetes and various types of cancer other than gastric cancer. The aim of this cohort study was to evaluate the impact of fasting plasma glucose (FPG) levels on gastric cancer occurrence. RESEARCH DESIGN AND METHODS -A total of 2,466Japanese subjects aged Ն40 years were stratified into three groups according to FPG tertiles (Ͻ5.3 mmol/l, low FPG; 5.3-5.8 mmol/l, modest FPG; Ͼ5.8 mmol/l, high FPG) and followed up prospectively for 9 years.RESULTS -During the follow-up, 66 subjects experienced gastric cancer. In men, the ageadjusted incidences were significantly higher in the modest-FPG (7.0 per 1,000 person-years, P Ͻ 0.05) and high-FPG (7.2, P Ͻ 0.05) groups than in the low-FPG group (2.2). In women, the high-FPG group also had a significantly higher age-adjusted incidence of gastric cancer compared with the low-FPG group (2.5 vs. 0.8, P Ͻ 0.05). The multivariate analysis with Cox's proportional hazards model revealed that the risks of gastric cancer in the modest-FPG (relative risk [RR] 2.3 [95% CI 1.1-5.0]) and high-FPG (3.1 [1.5-6.4]) groups were significantly higher than that in the low-FPG group, even after adjusting for other comprehensive risk factors, including Helicobacter pylori status, smoking, and dietary factors. However, this FPG-cancer association was observed only among H. pylori-seropositive subjects.CONCLUSIONS -Our findings suggest that a modest increase in FPG is a risk factor for gastric cancer and that hyperglycemia is a possible cofactor increasing the risk posed by Helicobacter pylori infection. Diabetes Care 28:789 -794, 2005T he Japanese population is characterized by a high morbidity from gastric cancer and a high prevalence of Helicobacter pylori infection, especially in middle-aged and elderly individuals (1).We have previously reported a significant relationship between infection with H. pylori and a subsequent occurrence of gastric cancer for men in a general Japanese population (2). However, only a small percentage of people with H. pylori infection develop gastric cancer, indicating that H. pylori cannot be the only etiologic factor of gastric cancer; other cofactors must affect the relationship between H. pylori infection and the development of gastric cancer.On the other hand, a possible association between diabetes and an increase in mortality from malignant neoplasm has been discussed for many years (3). Several prospective cohort studies have examined the associations between diabetes and total cancers (4 -7). Among them, three studies have demonstrated that diabetes is associated with an excess risk for all cancers (4 -6), while another study could not confirm a positive association between diabetes and total cancer (7). Several recent studies have shown associations between diabetes and cancer in the pancreas (8,9), liver (8,10), and large bowel (11,12). To our knowledge, none of the previous studies evaluated the impact of hyperglycemia on the development of gastric cancer.In the present invest...

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Section: Results -mentioning

confidence: 99%

Impact of Fasting Plasma Glucose Levels on Gastric Cancer Incidence in a General Japanese Population

et al. 2005

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“…In mesangial cells exposed to HG, the mixture of vascular factors changed to an antiangiogenic combination that has a negative effect on the growth and matrix of endothelial cells including disrupting their differentiation and ability to form capillary structures. In the diabetic patient glucose itself is toxic to endothelial cells, [45][46][47] but the antiangiogenic vascular growth factors secreted by mesangial cells may cause an additional disruptive effect causing endothelial injury and leading to glomerulopathy.…”

Section: Discussionmentioning

confidence: 99%

Vascular factors altered in glucose-treated mesangial cells and diabetic glomeruli. Changes in vascular factors impair endothelial cell growth and matrix

Singh

Gudehithlu

Pegoraro

et al. 2004

Laboratory Investigation

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We studied the effect of a high glucose (HG) environment on the vascular factors that are secreted by mesangial cells, and regulate endothelial growth and mesangial matrix deposition. To this effect, we measured the vascular factors in the glomeruli of streptozotocin-induced diabetic kidneys and in mesangial cells exposed to a HG concentration. We then transferred the media of mesangial cells previously exposed to high glucose to cultured endothelial cells to study the effects on endothelial growth, matrix formation, and in vitro capillary proliferation. In 1-week diabetic kidneys, glomerular vascular endothelial growth factor (VEGF) and angiopoietin-1 were inhibited by 38 and 57%, respectively, but angiopoietin-2 was increased by 318%. We found similar results in mesangial cells exposed to HG. There was a decrease of VEGF (50% by enzyme immunoassay, 27% by mRNA), decrease of angiopoietin-1 (65% by mRNA), and a much greater increase of angiopoietin-2 (280% by immunoassay, 523% by mRNA). Compared to controls, the media of mesangial cells previously exposed to HG impaired endothelial cell growth by 61%, increased extracellular matrix by 100%, and decreased capillary formation by 90%. We conclude that high ambient glucose alters the secretion of vascular factors elaborated by mesangial cells, resulting in an expansion of the endothelial cell matrix and disruption of capillary structure.

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“…18 High glucose induces DNA damage in cultured human endothelial cells. 19 Cellular adhesion molecules mediating homotypic and heterotypic cellular interactions have also been implicated in the various stages of tumor progression and metastasis. 20 Patients with noninsulindependent diabetes mellitus are characterized by insulin resistance, compensatory hyperinsulinemia, and increased growth factor production.…”

Section: Discussionmentioning

confidence: 99%

Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection

et al. 1998

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We evaluated the effect of diabetes mellitus on the prognosis of hepatocellular carcinoma after an elective hepatic resection. Of the 342 patients who underwent a hepatic resection between April 1985 and March 1995, 87 (25.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (36.0% vs. 22.5%, P ‫؍‬ .0239). The postoperative survival rate and the cancer-free survival rate were also better in patients without diabetes than in those with diabetes (P ‫؍‬ .0333, P ‫؍‬ .0149). The results of a multivariate analysis show diabetes mellitus to be an independent and prognostic indicator after a hepatic resection with hepatocellular carcinoma. According to the above findings, diabetes mellitus is thus considered to be a risk factor for prognosis after hepatic resection in patients with hepatocellular carcinoma. (HEPATOLOGY 1998;27:1567-1571.)The influence of diabetes mellitus on the outcome of elective surgical procedures remains controversial. [1][2][3][4] We previously reported that diabetic patients who underwent elective hepatic resections developed a higher incidence of postoperative morbidity, but not a shorter long-term survival. 5,6 Recently, Adami et al. 7 reported diabetes mellitus to be a risk factor for carcinogenesis in primary liver cancer based on a cohort study. However, little proof has been found regarding the effect of diabetes mellitus on the long-term outcome of patients with hepatcellular carcinoma after a hepatic resection. Therefore, the purpose of this study is to clarify the effect of diabetes mellitus on the long-term survival after a hepatic resection for hepatocellular carcinoma. PATIENTS AND METHODSBetween April 1985 and March 1995, 342 patients with hepatocellular carcinoma underwent a curative hepatic resection in the department of Surgery II, Kyushu University Hospital and affiliated hospitals. They ranged in age from 33 to 79 years (mean Ϯ SD, 59.7 Ϯ 8.3 years), and 275 (80.4%) were males. Liver cirrhosis was identified in 183 patients (53.5%). The methods of resection used included a trisegmentectomy in eight patients, a lobectomy in 84, a segmentectomy in 52, a subsegmentectomy in 64, and a partial hepatectomy consisting of less than a subsegmentectomy in 134. The follow-up period ranged from 34 to 4,036 days (median, 1,278 days; 25th percentile, 724 days; 75th percentile, 2,012 days).Of these patients, 87 (25.4%) were diagnosed with diabetes. The definition of diabetes mellitus was a fasting serum glucose above 7.8 mmol/L (140 mg/dL), abnormal results for a 75-g oral glucose tolerant test, or the need for insulin or an oral antihyperglycemic drug to control glucose levels. The preoperative control of diabetes mellitus was done either by diet alone or in combination with subcutaneous injections of insulin to maintain the fasting glucose below 8.3 mmol/L (150 mg/dL) and the 24-hour urinary glucose excretion below 10 g.The preoperative, intraoperative, and postoperative variables in the patients who underwent a hepatic resection with (HCC) were...

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High glucose induces DNA damage in cultured human endothelial cells.

Cited by 242 publications

References 27 publications

Impact of Fasting Plasma Glucose Levels on Gastric Cancer Incidence in a General Japanese Population

Impact of Fasting Plasma Glucose Levels on Gastric Cancer Incidence in a General Japanese Population

Vascular factors altered in glucose-treated mesangial cells and diabetic glomeruli. Changes in vascular factors impair endothelial cell growth and matrix

Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection

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