Diabetic nephropathy and retinopathy

Jawa, Ali; Kcomt, Juanita; Fonseca, Vivian

doi:10.1016/j.mcna.2004.04.012

Cited by 126 publications

(102 citation statements)

References 150 publications

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“…Hyperglycemia and abnormalities in lipid metabolism generate the formation of ROS. This activates ␤ 2 protein kinase C-␤, which increases the action of NAD(P)H oxidase, generating ROS (30). In addition, there is activation of the nuclear transcription factor B with the induction of inducible NOS and reduction of eNOS (31).…”

Section: Statisticsmentioning

confidence: 99%

Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes

et al. 2006

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OBJECTIVE -The purpose of this study was to determine the effect of 24 weeks of treatment with 45 mg/day pioglitazone on peripheral skin blood flow (SkBF) and skin nitric oxide (NO) production in vivo in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -This was a randomized, parallel, cross-over, double-blind, within-and between-subject study designed to compare vascular responses before and after treatment. We studied 12 subjects with type 2 diabetes (average age 58.6 Ϯ 30.8 years, HbA 1c 7.9 Ϯ 00.4%, BMI 31.3 Ϯ 1.2 kg/m 2 ). SkBF was measured using laser Doppler techniques in response to ischemia reperfusion and local skin warming, and NO production was assessed in vivo using an amperometric NO meter inserted directly into the skin. These measurements were performed before treatment and at 6 and 24 weeks.RESULTS -The SkBF response was not significantly improved after 24 weeks in either of the groups. NO production was significantly decreased in the pioglitazone-treated group in the basal condition (area under the curve 6.4 Ϯ 1.0 vs. 2.8 Ϯ 0.8, P Ͻ 0.01), after local heat stimulation at 40°C (12.9 Ϯ 2.2 vs. 5.7 Ϯ 1.7, P Ͻ 0.01), and after nociceptor stimulated flow with local heating at 44°C (36.4 Ϯ 6.3 vs. 16.6 Ϯ 3.4). Differences were not significant in the placebotreated group.CONCLUSIONS -Treatment of patients with type 2 diabetes with pioglitazone for 24 weeks reduced skin NO production, thus probably reducing nitrosative stress without a demonstrable effect on SkBF. Because nitrosative stress is considered to be a factor in the pathogenesis of neurovascular dysfunction, these findings warrant further investigation. Diabetes Care 29:869 -876, 2006W e have previously described both impaired peripheral vasoconstriction and vasodilatation in cutaneous vessels of people with diabetes, which strongly resembles the normal aging effects seen in peripheral vasculature (1). We have suggested both an endothelial and a neuronal component to these defects (2). The neuronal component is only activated at noxious temperatures (Ͼ40°C) or after tissue damage. Endothelial integrity is a major component under normal tissue demands for oxygenation after ischemia. Other investigators have also proposed the notion that there is specific damage to vascular endothelium and/or smooth muscle in diabetes, but localization of such a defect remains elusive.Insulin is a vasodilator hormone and facilitates endothelial release of nitric oxide (NO) and prostacyclin as well as upregulation of prostacyclin receptors on vascular smooth muscle (3). Resistance to the action of insulin could theoretically contribute to impaired neurovascular function. Jaap et al. (4) showed an endothelial or smooth muscle defect associated with insulin resistance that may precede the development of diabetes. We also showed that defective neurovascular function correlates with features of the metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and obesity (2). Diabetes is now recognized to be part of the metabolic syndrome an...

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Section: Statisticsmentioning

confidence: 99%

Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes

et al. 2006

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“…These results may reflect associated nephropathy, fatty liver disease, and suppression of cellular immunity, respectively. [26][27][28] Furthermore, diabetes is associated with death from injuries, which could be related to end-organ complications such as neuropathy and eye disease or to episodes of hypoglycemia. Associations observed between diabetes and deaths due to mental and neurologic diseases should be studied further, including disaggregation into more specific conditions and investigation of the possible link between diabetes and the onset of depression, 29 particularly since we found that among people with diabetes there was a substantial excess of deaths due to intentional self-harm.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific Death

2011

N Engl J Med

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“…These results may reflect associated nephropathy, fatty liver disease, and suppression of cellular immunity, respectively. [26][27][28] Furthermore, diabetes is associated with death from injuries, which could be related to endorgan complications such as neuropathy and eye disease or to episodes of hypoglycemia. Associations observed between diabetes and deaths due to mental and neurologic diseases should be studied further, including disaggregation into more specific conditions and investigation of the possible link between diabetes and the onset of depression, 29 particularly since we found that among people with diabetes there was a substantial excess of deaths due to intentional self-harm.…”

Section: Discussionmentioning

confidence: 99%