Treatment Of Diabetic Autonomic Neuropathy Research Articles

Антиоксидантные эффекты альфа-липоевой кислоты и перспектива ее применения в терапии диабетической автономной невропатии

Антиоксидантные эффекты альфа-липоевой кислоты и перспектива ее применения в терапии диабетической автономной невропатии

Treatment of Diabetic Autonomic Neuropathy in Older Adults with Diabetes Mellitus.

To review the epidemiology, pathophysiology, screening and diagnosis, and optimal treatment of diabetic autonomic neuropathy (DAN) and its implications in older adults. A search of PubMed using the Mesh terms "diabetes," "type 1," "insulin-dependent," "T1DM," and "diabetic autonomic neuropathy" was performed to find relevant primary literature. Additional search terms "epidemiology," "geriatric," and "risk" were employed. All English-language articles from 2005 to 2015 appearing in these searches were reviewed for relevance. Related articles suggested in the PubMed search and clinical guidelines from the American Diabetes Association and the American Association of Clinical Endocrinologists were reviewed. These uncovered further resources for risk stratification, pathophysiology, diagnosis, and treatment of DAN. DAN is highly prevalent in the diabetes population and increases the risk of morbidity and mortality in older adults, yet, often goes undiagnosed and untreated. Treatment of DAN is complex in the older adult because of poor tolerability of many pharmacologic treatment options; therefore, great care must be taken when selecting therapy as to avoid unwanted adverse effects. With increasing life-expectancy of patients with diabetes mellitus, awareness of DAN and its implications to older adults is needed in primary care. Consistent screening and appropriate treatment of DAN in older adults with diabetes mellitus is essential in helping to maintain functional status and avoid adverse events.

Does Hyperbaric Oxygen Therapy Have a Role in Diabetic Autonomic Neuropathy ?

Objectives: To determine if hyperbaric oxygen therapy could benefit patients with diabetic autonomic neuropathy treated at our hospital. Methods: Thirty-one consecutive patients, who were treated at Princess Haya Hospital and Prince Hahim Bin Abdullah II hospital from January 2012 to April 2014, were included. Four tests of autonomic function were carried out on all patients before and after treatment in the hyperbaric recompression chamber. Data analyzed using Statistical Package for the Social Sciences version 17 and stata version 10. Results: Twenty male and eleven female patients were included, with a mean age of 53.6 years. About 84% had Type II diabetes. Seventy-one percent of patients were found to have greater than or equal to three abnormal tests prior to treatment, and the risk of autonomic neuropathy was found to be independent of patients' sex, age, type or duration of diabetes. A statistically significant improvement was found in all tests after hyperbaric oxygen therapy. The improvement in parasympathetic function was found to be more likely affected by the number of sessions than sympathetic function (P value 0.001 and 0.07, respectively) Conclusion: Hyperbaric oxygen therapy is a promising technology in the treatment of diabetic autonomic neuropathy. Further research which includes a control group is needed.

Erythropoietin and its carbamylated derivative prevent the development of experimental diabetic autonomic neuropathy in STZ-induced diabetic NOD-SCID mice

Autonomic neuropathy is a significant diabetic complication resulting in increased morbidity and mortality. Studies of autopsied diabetic patients and several rodent models demonstrate that the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in prevertebral ganglia is the occurrence of synaptic pathology resulting in distinctive dystrophic neurites (“neuritic dystrophy”). Our prior studies show that neuritic dystrophy is reversed by exogenous IGF-I administration without altering the metabolic severity of diabetes, i.e. functioning as a neurotrophic substance. The description of erythropoietin (EPO) synergy with IGF-I function and the recent discovery of EPO's multifaceted neuroprotective role suggested it might substitute for IGF-I in treatment of diabetic autonomic neuropathy. Our current studies demonstrate EPO receptor (EPO-R) mRNA in a cDNA set prepared from NGF-maintained rat sympathetic neuron cultures which decreased with NGF deprivation, a result which demonstrates clearly that sympathetic neurons express EPO-R, a result confirmed by immunohistochemistry. Treatment of STZ-diabetic NOD-SCID mice have demonstrated a dramatic preventative effect of EPO and carbamylated EPO (CEPO, which is neuroprotective but not hematopoietic) on the development of neuritic dystrophy. Neither EPO nor CEPO had a demonstrable effect on the metabolic severity of diabetes. Our results coupled with reported salutary effects of EPO on postural hypotension in a few clinical studies of EPO-treated anemic diabetic and non-diabetic patients may reflect a primary neurotrophic effect of EPO on the sympathetic autonomic nervous system, rather than a primary hematopoietic effect. These findings may represent a major clinical advance since EPO has been widely and safely used in anemic patients due to a variety of clinical conditions.

Neuropatía autonómica en la diabetes mellitus

We analyse the different studies conducted on the prevalence, aetiopathology, clinical symptoms and treatment of diabetic autonomic neuropathy (AN), together with its involvement in the mortality of patients. AN can affect any part of the nervous system to varying degrees and at different moments in time, and its prevalence is significant in any of the stages of diabetes. The aetiopathogenesis of AN results from a multifactorial process involving metabolic disorders triggered by the activation of the polyolic pathway, microangiopathy and alterations affecting the synthesis of essential fatty acids due to hyperglycemia, which is made worse by a deficient regeneration of nerve tissue. Any of the systems innervated by the autonomous nervous system can be affected; the initial symptoms are insidious and of little cause for concern until the more advanced stages of the disease. The chief dysfunctions affect the cardiovascular, digestive, genitourinary and thermoregulatory systems. How AN courses in time varies from patient to patient and depends on the glycemic control that is carried out. Its presence is a factor that increases the mortality rate in diabetic patients. The prevalence of AN is notable, and the symptoms of autonomic dysfunction are usually under-diagnosed owing to its variability, lack of specificity and the wide range of symptoms. It is important to recognise this entity because of its effects on increasing morbidity and mortality, although they can be reduced by means of a strict glycemic control and specific treatment.

α-Lipoic acid treatment prevents the diabetes-induced attenuation of the afferent limb of the baroreceptor reflex in rats

Autonomic neuropathies, common complications of prolonged diabetes, may result from diabetes-induced increased oxidative stress. Recently, we found that the afferent component of the baroreceptor reflex is attenuated in streptozotocin-induced diabetic rats. This study sought to determine the influence of the anti-oxidant, α-lipoic acid on the diabetes-induced deficits of the afferent limb of the baroreceptor reflex and on plasma malondialdehyde (a measure of lipid peroxidation). The number of c-Fos-ir neurons in the nucleus tractus solitarius in response to phenylephrine-induced baroreceptor activation was used as an index of the integrity of the afferent limb of the baroreceptor reflex. Groups of streptozotocin-induced diabetic and non-diabetic control rats, maintained from 8 to 16 weeks, were treated with α-lipoic acid (100 mg kg −1 IP, 5×/week), or vehicle for the last 4 weeks prior to the experimental procedure. Vehicle-treated diabetic rats had elevated plasma malondialdehyde levels when compared to non-diabetic rats. α-Lipoic acid-treated diabetic rats had plasma malondialdehyde levels similar to those seen in non-diabetic rats and less than those of vehicle-treated diabetic rats at both the 8- and 16-week time points. α-Lipoic acid treatment did not affect the baseline (absence of baroreceptor activation) presence of c-Fos-ir in the nucleus tractus solitarius. In response to phenylephrine and regardless of treatment, the diabetic and control rats displayed increases in blood pressure and reflex bradycardia. As previously reported, phenylephrine-induced baroreceptor activation resulted in significantly fewer c-Fos-ir neurons in the nucleus tractus solitarius (commissural and caudal subpostremal regions) of diabetic rats when compared to non-diabetic rats at both 8- and 16-week time points. Four weeks of α-lipoic acid treatment reversed the diabetes-induced decrement in the numbers of c-Fos-ir neurons in the nucleus tractus solitarius in response to baroreceptor activation. α-Lipoic acid-treated diabetic rats showed the same phenylephrine-induced c-Fos response in the nucleus tractus solitarius as those of α-lipoic-acid- and vehicle-treated control rats at both 8- and 16-week time points. These data suggest that diabetes-induced oxidative stress plays a role in diabetes-induced baroreceptor dysfunction and that the α-lipoic acid may have a beneficial effect in treatment of diabetic autonomic neuropathy.

The Efficacy Of Hyperbaric Oxygen Theraphy For The Treatment Of Diabetic Autonomic Neuropathy

Objective: The aim of the present study was to examine the efficacy of hyperbaric oxygen therapy for the treatment of diabetic autonomic neuropathy. Research Design and Methods: We conducted a study of 20 consecutive eligible patients with diabetic autonomic neuropathy. All patients had been stabilized in terms of their glycemic control for 3 months before the study. The mean age of patients was 61.7±8.2 years, the mean diabetes duration 13.8±7.9 years. For the identification of autonomic diabetic neuropathy, non-invasive testing of cardiocirculatory functions were performed. All patients underwent electromyelography to obtain sympathic cutaneous responses by stimulating two different extremities. Results: There was a significant difference in autonomic neuropathy tests after hyperbaric oxygen therapy (p>0.001). Before hyperbaric oxygen therapy, mean valsalva ratio was 1.1±0.1, mean heart rate variation with inspiration was 10.4±2.4 beats/min, mean heart rate response to stand up was 1.0±0.04, mean systolic blood pressure response to stand up was 33.4±2.9mmHg. After hyperbaric oxygen therapy, mean valsalva ratio was 1.2±0.1, mean heart rate variation with inspiration was 15.9±2.2 beats/min, mean heart rate response to stand up was 1.0±0.03, mean systolic blood pressure response to stand up was 14.1±6.6mmHg. There was a significant differences in symphatic cutaneous responses that were obtained by stimulation of different region during electromyelography procedure. Conclusion: After hyperbaric oxygen therapy, the autonomic neuropathy tests and electromyelographic findings were significiantly improved. We supposed that hyperbaric oxygen therapy was an effective therapeutic modality for the treatment of diabetic autonomic neuropathy

Diagnosis and treatment of diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) is associated with a markedly reduced quality of life and poor prognosis. The manifestations of DAN cause multiple symptoms and involve the 1) cardiovascular system: resting tachycardia, reduced heart rate variability and circadian rhythm of heart rate and blood pressure, painless myocardial ischemia/infarction, orthostatic hypotension, exercise intolerance, perioperative instability, sudden death; 2) respiratory system: reduced ventilatory drive to hypercapnia/hypoxemia, sleep apnea; 3) gastrointestinal tract: esophageal motor dysfunction, diabetic gastroparesis, gallbladder atony, diabetic enteropathy, colonic hypomotility, anorectal dysfunction; and 4) genitourinary tract: diabetic cystopathy, erectile dysfunction. Treatment is based on four cornerstones: 1) causal treatment aimed at near-normoglycemia; 2) treatment based on pathogenetic mechanisms; 3) symptomatic treatment; and 4) avoidance of risk factors and complications. Pharmacologic treatment of symptomatic DAN may be difficult, due to limited efficacy and frequent adverse reactions. First-line treatments include midodrine for orthostatic hypotension, prokinetic drugs for gastroparesis, broad-spectrum antibiotics for diabetic diarrhea, and sildenafil for erectile dysfunction. Prior to an adequate symptomatic treatment a thorough risk-benefit estimate, aimed at maintaining the patient's quality of life, is required.