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Diabetologia Mar 2016The activity of the digestive tract is usually regulated to match its content: physiological stimuli in the gut induce modulatory reflexes that control digestive... (Review)
Review
The activity of the digestive tract is usually regulated to match its content: physiological stimuli in the gut induce modulatory reflexes that control digestive function so that digestion is normally not perceived. However, under certain circumstances, digestive stimuli may activate sensory afferents and give rise to conscious sensations. Both reflex and sensory signals are modulated by a balance of excitatory and inhibitory mechanisms. Patients with diabetes may develop a neuropathy affecting the control of gastric and/or intestinal motor function and the sensory innervation as well. During fasting the stomach is contracted and relaxes to accommodate a meal. After ingestion the stomach progressively recontracts and this contraction gently produces gastric emptying. Impairment of excitatory pathways affects the contraction of the stomach, which may result in delayed gastric emptying and vomiting of retained food. Conversely, alteration of the inhibitory neural pathways results in impaired relaxation of the stomach in response to a meal; in this case increased wall tension may produce early satiation, fullness and nausea. Diabetic neuropathy may distort the control of intestinal motility, which can lead to diverse symptoms such as diarrhoea, constipation, intestinal distension and abdominal pain. Neuropathy in diabetes may also affect the sensory nerves of the gut, and depending on which pathways are involved, perception may be increased or reduced. In summary, in patients with diabetic neuropathy, disorders of gut motor function are associated with sensory abnormalities, and the combination of impaired pathways determines the clinical consequences. This review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Hans Törnblom, DOI: 10.1007/s00125-015-3829-9 ) and a commentary by the Session Chair, Péter Kempler (DOI: 10.1007/s00125-015-3826-y ).
Topics: Autonomic Nervous System Diseases; Diabetic Neuropathies; Gastrointestinal Motility; Gastrointestinal Tract; Humans
PubMed: 26643877
DOI: 10.1007/s00125-015-3831-1 -
Biochimica Et Biophysica Acta.... Jun 2023Western lifestyle contributes to an overt increase in the prevalence of metabolic anomalies including diabetes mellitus (DM) and obesity. Prevalence of DM is rapidly... (Review)
Review
Western lifestyle contributes to an overt increase in the prevalence of metabolic anomalies including diabetes mellitus (DM) and obesity. Prevalence of DM is rapidly growing worldwide, affecting many individuals in both developing and developed countries. DM is correlated with the onset and development of complications with diabetic nephropathy (DN), diabetic cardiomyopathy (DC) and diabetic neuropathy being the most devastating pathological events. On the other hand, Nrf2 is a regulator for redox balance in cells and accounts for activation of antioxidant enzymes. Dysregulation of Nrf2 signaling has been shown in various human diseases such as DM. This review focuses on the role Nrf2 signaling in major diabetic complications and targeting Nrf2 for treatment of this disease. These three complications share similarities including the presence of oxidative stress, inflammation and fibrosis. Onset and development of fibrosis impairs organ function, while oxidative stress and inflammation can evoke damage to cells. Activation of Nrf2 signaling significantly dampens inflammation and oxidative damage, and is beneficial in retarding interstitial fibrosis in diabetic complications. SIRT1 and AMPK are among the predominant pathways to upregulate Nrf2 expression in the amelioration of DN, DC and diabetic neuropathy. Moreover, certain therapeutic agents such as resveratrol and curcumin, among others, have been employed in promoting Nrf2 expression to upregulate HO-1 and other antioxidant enzymes in the combat of oxidative stress in the face of DM.
Topics: Humans; Diabetic Nephropathies; NF-E2-Related Factor 2; Antioxidants; Diabetic Neuropathies; Diabetes Complications; Cardiomyopathies; Fibrosis; Inflammation; Diabetes Mellitus
PubMed: 37028606
DOI: 10.1016/j.bbadis.2023.166714 -
Presse Medicale (Paris, France : 1983) Jun 2024Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity... (Review)
Review
Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity disorders responsible for numbness, tingling, and loss of feeling are part and parcel of diabetic foot syndrome and require investigation in view of preventing trophic ulcers. To date, there exists no specific treatment for diabetic neuropathy possibly preventable by careful control of metabolic disorder. Effective management of diabetic patients would make it possible to limit the dramatic consequences of diabetic neuropathy while at the same time acting on other complications.
Topics: Humans; Diabetic Neuropathies; Diabetic Foot
PubMed: 38663725
DOI: 10.1016/j.lpm.2024.104236 -
Current Pain and Headache Reports Jun 2022Many Americans cope with painful diabetic neuropathy (DN) as a sequela of high rates of diabetes mellitus in the US population. Appropriate management of this complex,... (Review)
Review
PURPOSE OF REVIEW
Many Americans cope with painful diabetic neuropathy (DN) as a sequela of high rates of diabetes mellitus in the US population. Appropriate management of this complex, debilitating chronic pain condition requires thorough evaluation through a biopsychosocial framework. This review aims to synthesize findings from original research studies and analyze the psychological factors that influence the experience of, and treatments for, DN pain.
RECENT FINDINGS
Existing clinical literature suggests a wide breadth of psychological factors impacting DN pain. One research study detailed the demographic characteristics of DN patients most likely to have significant anxiety or depressive symptoms, and have emotional distress adversely impacting their response to therapies. A retrospective study demonstrated a correlation between patients' mindfulness-based stress reduction and improvement in DN pain severity. In addtion, a small-scale, randomized controlled pilot study supported cognitive-behavioral therapy as a superior intervention to conventional medical treatments in reducing DN patients' pain severity and pain interference, even when not accompanied by significant improvement in depressive symptoms. This review of investigations into psychological factors implicated in DN pain suggests that diagnosable mental health conditions as well as discrete, adverse thinking processes both exert significant influences on DN pain. This review further brings attention to the beneficial impact that psychotherapeutic modalities can have on DN pain.
Topics: Chronic Disease; Chronic Pain; Cognitive Behavioral Therapy; Diabetes Mellitus; Diabetic Neuropathies; Humans; Neuralgia; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 35380405
DOI: 10.1007/s11916-022-01040-y -
International Review of Neurobiology 2016The study of diabetic neuropathy has relied primarily on the use of streptozotocin-treated rat and mouse models of type 1 diabetes. This chapter will review the creation... (Review)
Review
The study of diabetic neuropathy has relied primarily on the use of streptozotocin-treated rat and mouse models of type 1 diabetes. This chapter will review the creation and use of other rodent models that have been developed in order to investigate the contribution of factors besides insulin deficiency to the development and progression of diabetic neuropathy as it occurs in obesity, type 1 or type 2 diabetes. Diabetic peripheral neuropathy is a complex disorder with multiple mechanisms contributing to its development and progression. Even though many animal models have been developed and investigated, no single model can mimic diabetic peripheral neuropathy as it occurs in humans. Nonetheless, animal models can play an important role in improving our understanding of the etiology of diabetic peripheral neuropathy and in performing preclinical screening of potential new treatments. To date treatments found to be effective for diabetic peripheral neuropathy in rodent models have failed in clinical trials. However, with the identification of new endpoints for the early detection of diabetic peripheral neuropathy and the understanding that a successful treatment may require a combination therapeutic approach there is hope that an effective treatment will be found.
Topics: Animals; Antibiotics, Antineoplastic; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Disease Models, Animal; Humans; Neural Conduction; Rodentia; Streptozocin
PubMed: 27133146
DOI: 10.1016/bs.irn.2016.03.002 -
Frontiers in Endocrinology 2024
Topics: Humans; Diabetic Neuropathies; Early Diagnosis; Drug Therapy, Combination
PubMed: 38868745
DOI: 10.3389/fendo.2024.1422734 -
Disease-a-month : DM Sep 2023The global rise of prediabetes and diabetes has spawned an epidemic of complications associated with these conditions. Neuropathy is the most common consequence, with...
The global rise of prediabetes and diabetes has spawned an epidemic of complications associated with these conditions. Neuropathy is the most common consequence, with distal symmetric polyneuropathy (DSP) being the most prevalent. Diabetic neuropathy (DN) is a debilitating consequence of diabetes mellitus resulting in the highest morbidity and death, besides imposing a substantial financial burden on the patient. Loss of sensory function commencing distally in the lower limbs, accompanied by discomfort and considerable morbidity, characterizes diabetic neuropathy. The clinical evaluation and therapeutic options for diabetic peripheral neuropathy are multifaceted. At least fifty percent of people with diabetes acquire diabetic neuropathy over time. Good glycemic control halts the evolution in individuals with Type 1 diabetes mellitus. These results have prompted fresh attempts to comprehend the origin and develop new guidelines for prevention and treatment. New recommendations have also been established for the treatment of painful DN using separate classes of medications, with an emphasis on avoiding the use of opioids. Although our comprehension of the intricacies of diabetic neuropathy has progressed significantly over the past decade, the unique processes driving the neuropathy in type 1 and type 2 diabetes remain unexplained. Currently, glycemic control and pain management are the only effective therapies. While glucose management significantly reduces neuropathy development in type 1 diabetics, the effect is considerably lower in type 2 diabetics. Evidence supports the use of anticonvulsants and antidepressants for diabetic peripheral neuropathy pain treatment. However, the absence of disease-modifying medications for diabetic DSP necessitates the identification of unrecognized modifiable risk factors. It is imperative to identify the 'missed' risk factors and targets, allowing comprehensive, individualized care for patients.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Risk Factors; Pain Management
PubMed: 37164794
DOI: 10.1016/j.disamonth.2023.101582 -
Annual Review of Medicine Jan 2024Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and... (Review)
Review
Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 38285516
DOI: 10.1146/annurev-med-043021-033114 -
International Review of Neurobiology 2016Multiple phase III clinical trials have failed to show disease-modifying benefits for diabetic sensorimotor polyneuropathy (DSP) and this may be due to the design of the... (Review)
Review
Multiple phase III clinical trials have failed to show disease-modifying benefits for diabetic sensorimotor polyneuropathy (DSP) and this may be due to the design of the clinical trials. The perfect clinical trial in DSP would enroll sufficiently large numbers of patients having early or minimal disease, as demonstrated by nerve conduction studies (NCS). These patients would be treated with an intervention given at an effective and well-tolerated dose for a sufficient duration of time to show change in the end points selected. For objective or surrogate measures such as NCS and for some small fiber measures, the duration needed to show positive change may be as brief as 6-12 months, but subsequently, trials lasting 5-8 years will be required to demonstrate clinical benefits.
Topics: Autonomic Nervous System; Clinical Trials as Topic; Diabetic Neuropathies; Disease Progression; Humans; Hypoglycemic Agents; Neural Conduction; Patient Selection
PubMed: 27133143
DOI: 10.1016/bs.irn.2016.02.011 -
Arquivos de Neuro-psiquiatria Aug 2022
Topics: Brazil; Cornea; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Humans; Microscopy, Confocal
PubMed: 36252583
DOI: 10.1055/s-0042-1756169