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Annals of Palliative Medicine Mar 2023Painful diabetic peripheral neuropathy (DPN) affects approximately 6-34% of all patients with diabetes. DPN-induced pain reduces the quality of life and makes daily... (Review)
Review
BACKGROUND AND OBJECTIVE
Painful diabetic peripheral neuropathy (DPN) affects approximately 6-34% of all patients with diabetes. DPN-induced pain reduces the quality of life and makes daily activities difficult. Distal symmetric polyneuropathy (DSPN) is the most common type of DPN. Here we review the pathophysiology, diagnosis, and treatment of DPN.
METHODS
A MEDLINE database (PubMed) search was conducted for English-language articles dealing with the effect of DPN that were published until April 1, 2022. To identify potentially relevant articles, the following key search phrases were combined: 'diabetes mellitus', 'diabetes', 'neuropathy', 'polyneuropathy', 'diabetic neuropathies', 'peripheral neuropathy', 'diabetic polyneuropathy', 'pathophysiology', 'diagnosis', and 'treatment'.
KEY CONTENT AND FINDINGS
In a biopsy study of the sural nerve, damage to C and Aδ fibers were seen in patients who had recent onset of pain in their feet consisting of tingling, burning, and prickling, followed by initial demyelination/remyelination of large fibers. DPN is characterized by a pattern of distal-to-proximal axonal loss with symptoms. Hyperglycemia and dyslipidemia are the primary causes of DPN in patients with type 1 and 2 diabetes, respectively. The pattern of pain from DPN is described as "glove and stocking". DPN-induced pain is described as burning, electric, sharp, and dull aching with various pain intensities. DPN is a diagnosis of exclusion; diagnosis is made with a thorough medical history, physical examination, and clinical testing to rule out other causes of pain. Anticonvulsants (pregabalin and gabapentin), antidepressants (duloxetine, venlafaxine, and amitriptyline), opioids (tramadol, tapentadol, and oxycodone), and topical capsaicin are commonly administered to treat DPN. The combination of two or three of these pharmacological agents better resolves pain at lower doses and with fewer side effects.
CONCLUSIONS
Clinicians should have sufficient knowledge of DPN to ensure its accurate diagnosis and appropriate treatment. This review provides clinicians with the necessary knowledge of the pathophysiology, diagnosis, and treatment of painful DPN.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 1; Quality of Life; Diabetes Mellitus, Type 2; Pain
PubMed: 36786097
DOI: 10.21037/apm-22-693 -
Current Diabetes Reports Aug 2019Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain,... (Review)
Review
PURPOSE OF REVIEW
Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain, foot ulcers, and lower limb amputation. This review summarizes the epidemiology, risk factors, and management of diabetic peripheral neuropathy and related lower extremity complications.
RECENT FINDINGS
The prevalence of peripheral neuropathy is estimated to be between 6 and 51% among adults with diabetes depending on age, duration of diabetes, glucose control, and type 1 versus type 2 diabetes. The clinical manifestations are variable, ranging from asymptomatic to painful neuropathic symptoms. Because of the risk of foot ulcer (25%) and amputation associated with diabetic peripheral neuropathy, aggressive screening and treatment in the form of glycemic control, regular foot exams, and pain management are important. There is an emerging focus on lifestyle interventions including weight loss and physical activity as well. The American Diabetes Association has issued multiple recommendation statements pertaining to diabetic neuropathies and the care of the diabetic foot. Given that approximately 50% of adults with diabetes will be affected by peripheral neuropathy in their lifetime, more diligent screening and management are important to reduce the complications and health care burden associated with the disease.
Topics: Amputation, Surgical; Cost of Illness; Diabetic Foot; Diabetic Neuropathies; Humans; Lower Extremity; Mass Screening; Risk Factors
PubMed: 31456118
DOI: 10.1007/s11892-019-1212-8 -
The Journal of Clinical Investigation Feb 2021The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include... (Review)
Review
The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include motor, secretory, sensory, storage, and excretory functions. Disorders of the nervous system affecting gastrointestinal tract function manifest primarily as abnormalities in motor (rather than secretory) functions. Common gastrointestinal symptoms in neurologic disorders include sialorrhea, dysphagia, gastroparesis, intestinal pseudo-obstruction, constipation, diarrhea, and fecal incontinence. Diseases of the entire neural axis ranging from the cerebral hemispheres to the peripheral autonomic nerves can result in gastrointestinal motility disorders. The most common neurologic diseases affecting gastrointestinal function are stroke, parkinsonism, multiple sclerosis, and diabetic neuropathy. Diagnosis involves identification of the neurologic disease and its distribution, and documentation of segmental gut dysfunction, typically using noninvasive imaging, transit measurements, or intraluminal measurements of pressure activity and coordination of motility. Apart from treatment of the underlying neurologic disease, management focuses on restoration of normal hydration and nutrition and pharmacologic treatment of the gut neuromuscular disorder.
Topics: Diabetic Neuropathies; Enteric Nervous System; Gastrointestinal Diseases; Gastrointestinal Motility; Humans
PubMed: 33586685
DOI: 10.1172/JCI143771 -
Neuron Mar 2017Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a... (Review)
Review
Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our understanding of DN pathogenesis are paving the way for critical mechanism-based therapy development.
Topics: Animals; Axons; Diabetic Neuropathies; Energy Metabolism; Humans; Models, Neurological; Neuralgia; Peripheral Nervous System; Schwann Cells
PubMed: 28334605
DOI: 10.1016/j.neuron.2017.02.005 -
Current Neurology and Neuroscience... Aug 2014Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a... (Review)
Review
Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na(+)/K(+)-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality.
Topics: Diabetic Neuropathies; Humans
PubMed: 24954624
DOI: 10.1007/s11910-014-0473-5 -
Clinical Therapeutics May 2022Neuropathy is one of the most important complications of diabetes. According to recent advances, vitamin D deficiency might play a role in the development and... (Review)
Review
PURPOSE
Neuropathy is one of the most important complications of diabetes. According to recent advances, vitamin D deficiency might play a role in the development and progression of diabetic neuropathy. Moreover, therapeutic vitamin D supplementation has the potential to improve this condition. The aim of the present review was to summarize new data available in this area.
METHODS
The PubMed database was searched for articles written in English and published through September 2021, using combinations of the following key words: vitamin D, diabetes, diabetes mellitus, diabetic neuropathy, polyneuropathy, peripheral neuropathy, cardiac autonomic neuropathy, supplementation, and therapy.
FINDINGS
A number of studies have suggested that vitamin D deficiency can play a significant role in the development of peripheral neuropathy, diabetic foot ulcers, as well as cardiovascular autonomic neuropathy in patients with type 2 diabetes. Vitamin D supplementation might serve as an effective adjuvant therapy for neuropathic pain and may slow or stop the progression of neural damage.
IMPLICATIONS
Vitamin D therapy for diabetic complications could be a reliable option; however, further studies are needed to confirm this notion.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 35428527
DOI: 10.1016/j.clinthera.2022.03.012 -
JPMA. the Journal of the Pakistan... Jul 2023Diabetic foot ulcer disease is the combination of vasculopathy, neuropathy and infection. It is important to identify the main aetiology and to treat it for optimal... (Review)
Review
Diabetic foot ulcer disease is the combination of vasculopathy, neuropathy and infection. It is important to identify the main aetiology and to treat it for optimal ulcer healing so that limb amputation may be prevented. A literature review spanning five years (2018-2021) was performed to assess the current understanding of these aetiologies and management options for their treatment. Peripheral artery disease is prevalent in patients with diabetes. Before performing any amputations, whether minor or major, vascular supply in these patients needs to be evaluated and, if needed, improved. Diabetic neuropathy is a long-term complication of uncontrolled diabetes. Patients' education is very important with respect to selfcare and prevention of foot complications arising out of minor trauma in diabetic population. Better foot care and regular use of off-loading shoe wear can prevent neuropathic diabetic foot ulcers. Infection in diabetic patients is mostly polymicrobial and it can present as superficial or deep infections. Early diagnosis, use of broad-spectrum antibiotics, and aggressive debridement, when needed, is advocated to prevent foot amputation. Contemporary treatment armamentarium provides many options for treating diabetic foot ulcers. Nevertheless, one must exhaust all preventive strategies to avoid ulcers in the first place. Once an ulcer has developed, it should be managed aggressively with appropriate soft tissue and, if required, with bony procedures. The current narrative review was planned to explore the current understanding about the main aetiologies of diabetic foot ulcers and about the available treatment options.
Topics: Humans; Diabetic Foot; Diabetic Neuropathies; Foot; Risk Factors; Amputation, Surgical; Diabetes Mellitus
PubMed: 37469062
DOI: 10.47391/JPMA.6634 -
International Journal of Molecular... Aug 2021Diabetic neuropathy, a major complication of diabetes mellitus, refers to a collection of clinically diverse disorders affecting the nervous system that may present with... (Review)
Review
Diabetic neuropathy, a major complication of diabetes mellitus, refers to a collection of clinically diverse disorders affecting the nervous system that may present with pain. Although the number of patients suffering from severe neuropathy is increasing, no optimal treatment method has been developed yet. Acupuncture is well known for its ability to reduce various kinds of pain, and a number of studies have also reported its effect on diabetes mellitus; however, its effect and underlying mechanism against diabetic neuropathy are not yet clearly understood. In this review, ten and five studies performed in humans and animals, respectively, were analyzed. All studies reported that acupuncture significantly relieved diabetic neuropathy. ST36, BL13, BL20, SP6, and SP9 were the most widely used acupoints. Five studies used electro-acupuncture, whereas other studies used manual acupuncture. Furthermore, the effect of acupuncture was shown to be mediated through the various molecules present in the peripheral nerves and spinal cord, such as P65, GPR78, and TRPV1. Five studies reported side effects, such as swelling, numbness, and nausea, but none were reported to be serious. Based on these results, we suggest that acupuncture should be considered as a treatment option for diabetic neuropathy.
Topics: Acupuncture Analgesia; Acupuncture Points; Animals; Diabetic Neuropathies; Endoplasmic Reticulum Chaperone BiP; Humans
PubMed: 34445280
DOI: 10.3390/ijms22168575 -
Indian Journal of Ophthalmology Nov 2021To evaluate the presence of nephropathy and neuropathy in patients with diabetic retinopathy (DR) and to correlate the severity of DR to that of diabetic nephropathy and...
PURPOSE
To evaluate the presence of nephropathy and neuropathy in patients with diabetic retinopathy (DR) and to correlate the severity of DR to that of diabetic nephropathy and diabetic neuropathy.
METHODS
This prospective noninterventional hospital-based study included 57 consecutive cases of DR of either sex, presenting to the eye OPD between January 2019 and November 2020 with minimum 5-year duration of Type 1 and 2 DM. Complete ophthalmic examination was done and DR was classified according to early treatment diabetic retinopathy study classification. Severity of diabetic nephropathy was based on urine albumin creatinine ratio and estimated glomerular filtration rate. Severity of diabetic neuropathy was based on nerve conduction velocity.
RESULTS
The study was conducted on 57 patients of whom patients 45 were males and 12 were females. Mild nonproliferative diabetic retinopathy was present in 22 patients, moderate in 14 patients, severe in 18 patients, and proliferative diabetic retinopathy in 3 patients. In our study, group 30 patients of DR presented without clinically significant macular edema (CSME) and 27 patients presented with CSME. The distribution of severity of DR according to CSME was observed to be statistically significant (P<<0.05). The association of severity of DR with severity of diabetic nephropathy was observed to be statistically significant (P<<0.05). The association of severity of DR with that of diabetic neuropathy was inconclusive.
CONCLUSION
The association of severity of DR with severity of diabetic nephropathy and diabetic neuropathy can be used as a marker for future chronic kidney diseases progression and also to prognosticate neurological outcomes in diabetic patients.
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Macular Edema; Male; Prospective Studies; Risk Factors
PubMed: 34708806
DOI: 10.4103/ijo.IJO_1237_21 -
Frontiers in Endocrinology 2021The incidence of both type 1 and type 2 diabetes is increasing worldwide. Diabetic peripheral neuropathy (DPN) is among the most distressing and costly of all the... (Review)
Review
The incidence of both type 1 and type 2 diabetes is increasing worldwide. Diabetic peripheral neuropathy (DPN) is among the most distressing and costly of all the chronic complications of diabetes and is a cause of significant disability and poor quality of life. This incurs a significant burden on health care costs and society, especially as these young people enter their peak working and earning capacity at the time when diabetes-related complications most often first occur. DPN is often asymptomatic during the early stages; however, once symptoms and overt deficits have developed, it cannot be reversed. Therefore, early diagnosis and timely intervention are essential to prevent the development and progression of diabetic neuropathy. The diagnosis of DPN, the determination of the global prevalence, and incidence rates of DPN remain challenging. The opinions vary about the effectiveness of the expansion of screenings to enable early diagnosis and treatment initiation before disease onset and progression. Although research has evolved over the years, DPN still represents an enormous burden for clinicians and health systems worldwide due to its difficult diagnosis, high costs related to treatment, and the multidisciplinary approach required for effective management. Therefore, there is an unmet need for reliable surrogate biomarkers to monitor the onset and progression of early neuropathic changes in DPN and facilitate drug discovery. In this review paper, the aim was to assess the currently available tests for DPN's sensitivity and performance.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Early Diagnosis; Humans; Mass Screening
PubMed: 34122344
DOI: 10.3389/fendo.2021.671257