Recognizing and treating diabetic autonomic neuropathy.

Vinik, Aaron I.; Erbaş, Tomris

doi:10.3949/ccjm.68.11.928

Cited by 164 publications

(118 citation statements)

References 55 publications

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“…Diabetic autonomic neuropathy (DAN) is among the least recognized and understood complications of diabetes despite its significant negative impact on survival and quality of life in people with diabetes (1,2). DAN can involve the entire autonomic nervous system (ANS).…”

Section: Introductionmentioning

confidence: 99%

New insights in diabetic autonomic neuropathy in children and adolescents

Verrotti

Loiacono

Mohn

et al. 2009

European Journal of Endocrinology

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Diabetic autonomic neuropathy (DAN) represents a major complication of diabetes mellitus but there is considerable uncertainty about its incidence, prevalence, pathogenesis, diagnosis, and prognosis. There are conflicting opinions about the pathogenesis of DAN: the 'classical hypothesis' has been supplemented by some new insights. Clinical symptoms of autonomic neuropathy do not generally occur until long after the onset of diabetes. DAN seems to be detectable even in asymptomatic children and adolescents with diabetes and is associated with the most serious consequences, such as cardiovascular dysfunction. Because of its association with a variety of adverse outcomes, including cardiovascular deaths, cardiovascular autonomic neuropathy is the most clinically important and well-studied form of DAN. No form of therapy in DAN has been identified that provides unequivocal, safe, and effective stabilization or reversal of the condition, just a near normal control of blood glucose in the early years after the onset of diabetes that may delay the development of clinically significant nerve impairment. This article reviews recent developments in knowledge of epidemiology, pathogenesis, clinical symptoms, diagnosis, and therapy of DAN.

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Section: Introductionmentioning

confidence: 99%

New insights in diabetic autonomic neuropathy in children and adolescents

Verrotti

Loiacono

Mohn

et al. 2009

European Journal of Endocrinology

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“…Estimated care costs exceed $150 billion annually (1,2). The nerve dysfunction as a consequence of diabetes is debilitating and can lead to lifethreatening autonomic neuropathy, cardiac diseases, and CNS atrophy (3,4). Dying back of distal peripheral nerve fibers because of glucose toxicity and the ensuing spinal sensitization are thought to be the underlying causes of pain (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes

Inceoglu

Wagner

Yang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The nerve damage occurring as a consequence of glucose toxicity in diabetes leads to neuropathic pain, among other problems. This pain dramatically reduces the quality of life in afflicted patients. The progressive damage to the peripheral nervous system is irreversible although strict control of hyperglycemia may prevent further damage. Current treatments include tricyclic antidepressants, anticonvulsants, and opioids, depending on the severity of the pain state. However, available therapeutics have drawbacks, arguing for the need to better understand the pathophysiology of neuropathic pain and develop novel treatments. Here we demonstrate that stabilization of a class of bioactive lipids, epoxygenated fatty acids (EpFAs), greatly reduces allodynia in rats caused by streptozocin-induced type I diabetes. Inhibitors of the soluble epoxide hydrolase (sEHI) elevated and stabilized the levels of plasma and spinal EpFAs, respectively, and generated dose-dependent antiallodynic effects more potently and efficaciously than gabapentin. In acute experiments, positive modulation of EpFAs did not display differences in insulin sensitivity, glucose tolerance, or insulin secretion, indicating the efficacy of sEHIs are not related to the glycemic status. Quantitative metabolomic analysis of a panel of 26 bioactive lipids demonstrated that sEHI-mediated antiallodynic effects coincided with a selective elevation of the levels of EpFAs in the plasma, and a decrease in degradation products coincided with the dihydroxy fatty acids in the spinal cord. Overall, these results argue that further efforts in understanding the spectrum of effects of EpFAs will yield novel opportunities in treating neuropathic pain.analgesic drug | soluble epoxide hydrolase inhibitor | cytochrome P450 | glucose homeostasis | motor depressant

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“…The reported prevalence of DAN varies widely depending on cohort studies and methods of assessment. DAN frequently coexists with peripheral neuropathies and other diabetic complications, but may be isolated 6,7 . Treatment of diabetic autonomic neuropathy can be difficult; it is therefore desirable to prevent this complication or once established, slow disease progression [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%