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Acta Diabetologica Nov 2021The first reports of a link between thiamine and diabetes date back to the 1940s. Some years later, a role for thiamine deficiency in diabetic neuropathy became evident,...
The first reports of a link between thiamine and diabetes date back to the 1940s. Some years later, a role for thiamine deficiency in diabetic neuropathy became evident, and some pilot studies evaluated the putative effects of thiamine supplementation. However, the administration of thiamine and its lipophilic derivative benfotiamine for the treatment of this complication gained consensus only at the end of the '90 s. The first evidence of the beneficial effects of thiamine on microvascular cells involved in diabetic complications dates to 1996: from then on, several papers based on in vitro and animal models have addressed the potential use of this vitamin in counteracting diabetic microangiopathy. A few pilot studies in humans reported beneficial effects of thiamine administration on diabetic nephropathy, but, despite all promising proofs-of-concept, the possible role of thiamine in counteracting development or progression of retinopathy has not been addressed until now. Thiamine is a water-soluble vitamin, rapidly expelled from the body, with no issues of over-dosage or accumulation; unfortunately, it is non-patentable, and neither industry nor independent donors are interested in investing in large-scale randomized controlled clinical trials to investigate its potential in diabetes and its complications. Consequently, science will not be able to disprove a promising hypothesis and, more importantly, diabetic people remain deprived of a possible way to ameliorate their condition.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Humans; Thiamine
PubMed: 34091762
DOI: 10.1007/s00592-021-01752-4 -
Journal of Diabetes Oct 2022Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse... (Review)
Review
Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate-activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.
Topics: Adenosine Monophosphate; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Hypoglycemic Agents; Metformin; Neuroprotective Agents; Pain; Protein Kinases; Vitamin B 12
PubMed: 36117320
DOI: 10.1111/1753-0407.13310 -
Singapore Medical Journal Feb 2016Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence... (Review)
Review
Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction.
Topics: Diabetic Neuropathies; Dietary Supplements; Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins
PubMed: 26892473
DOI: 10.11622/smedj.2016027 -
Current Diabetes Reports Jun 2015Distal symmetric polyneuropathy (DSPN), the most common form of diabetic neuropathy, has a complex pathophysiology and can be a major source of physical and psychologic... (Review)
Review
Distal symmetric polyneuropathy (DSPN), the most common form of diabetic neuropathy, has a complex pathophysiology and can be a major source of physical and psychologic disability. The management of DSPN can be frustrating for both patient and physician. This article provides a general overview of typical patient pathways in DSPN, and highlights variations in diagnosis, management, and referral patterns among different providers. DSPN is managed in several settings by primary care physicians (PCPs), specialists, and nurse practitioners. The initial clinical management of the patient is often dependent on the presenting complaint, the referral pattern of the provider, level of comfort of the PCP in managing diabetic complications, and geographic access to specialists. The primary treatment of DSPN focuses mainly on glycemic control and adjustment of modifiable risk factors, but other causes of neuropathy should also be investigated. Several pharmacologic agents are recommended by treatment guidelines, and as DSPN typically exists with comorbid conditions, a multimodal therapeutic approach should be considered. Barriers to effective management include failure to recognize DSPN, and misdiagnosis. Patient education also remains important. Referral patterns vary widely according to geographic location, access to services, provider preferences, and comfort in managing complex aspects of the disease. The variability in patient pathways affects patient education, satisfaction, and outcomes. Standardized screening tools, a multidisciplinary team approach, and treatment algorithms for diabetic neuropathy should improve future care. To improve patient outcomes, DSPN needs to be diagnosed sooner and interventions made before significant nerve damage occurs.
Topics: Diabetic Neuropathies; Disease Management; Humans; Polyneuropathies
PubMed: 25899758
DOI: 10.1007/s11892-015-0609-2 -
Biomedicine & Pharmacotherapy =... Apr 2024Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes that causes neuropathic pain and negatively affects the quality of life. The management of... (Review)
Review
Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes that causes neuropathic pain and negatively affects the quality of life. The management of PDN is far from satisfactory. At present, interventions are primarily focused on symptomatic treatment. Ion channel disorders are a major cause of PDN, and a complete understanding of their roles and mechanisms may provide better options for the clinical treatment of PDN. Therefore, this review summarizes the important role of ion channels in PDN and the current drug development targeting these ion channels.
Topics: Humans; Diabetic Neuropathies; Quality of Life; Neuralgia; Drug Development; Diabetes Mellitus
PubMed: 38490158
DOI: 10.1016/j.biopha.2024.116417 -
International Journal of Molecular... Apr 2023The two-hit model has been proposed to explain the effects of diabetes on mothers who are already in a putative subclinical damaged state and then undergo neuronal... (Review)
Review
The two-hit model has been proposed to explain the effects of diabetes on mothers who are already in a putative subclinical damaged state and then undergo neuronal damage during the delivery process. However, the anatomical and pathophysiological mechanisms are not well understood. Our overarching hypothesis in this review paper is that pregnant women who are diabetic have a damaged peripheral nervous system, constituting the "first hit" hypothesis. The delivery process itself-the "second hit"-can produce neurological damage to the mother. Women with diabetes mellitus (DM) are at risk for neurological damage during both hits, but the cumulative effects of both "hits" pose a greater risk of neurological damage and pathophysiological changes during delivery. In our analysis, we introduce the different steps of our concept paper. Subsequently, we describe each of the topics. First, we outline the mechanisms by which diabetes acts as a detrimental variable in neuropathy by focusing on the most common form of diabetic neuropathy, diabetic distal symmetrical polyneuropathy, also known as distal sensorimotor neuropathy. The possible role of macrosomia in causing diabetic neuropathy and obstetric neurological injury is discussed. Second, we describe how vaginal delivery can cause various obstetrical neurological syndromes and pathophysiological changes. Third, we highlight the risk of obstetric neuropathy and discuss anatomical sites at which lesions may occur, including lesions during delivery. Fourth, we characterize the pathophysiological pathways involved in the causation of diabetic neuropathy. Finally, we highlight diabetic damage to sensory vs. motor nerves, including how hyperglycemia causes different types of damage depending on the location of nerve cell bodies.
Topics: Pregnancy; Humans; Female; Diabetic Neuropathies; Hyperglycemia; Diabetes Mellitus
PubMed: 37047786
DOI: 10.3390/ijms24076812 -
International Journal of Molecular... Nov 2021Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat... (Review)
Review
Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12-C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Diabetic Neuropathies; Humans; Neoplasms; Plants, Medicinal; Triterpenes; Ursolic Acid
PubMed: 34830043
DOI: 10.3390/ijms222212162 -
Diabetes Research and Clinical Practice Dec 2023Up to 25% of people with diabetes develop painful diabetic neuropathy (PDN). The standard of care pharmacotherapies for PDN have limited efficacy with a considerable... (Review)
Review
Up to 25% of people with diabetes develop painful diabetic neuropathy (PDN). The standard of care pharmacotherapies for PDN have limited efficacy with a considerable side effect profile. Spinal cord stimulation (SCS) is a form of electrical neurostimulation that modulates neural function via electrodes implanted into the spinal epidural space. While low frequency SCS has been shown to be potentially effective for treating pain associated with neuropathies, it masks pain perception by inducing paresthesia. Compared to low frequency SCS, high frequency (10 kHz) SCS delivers paresthesia-free therapy. As was shown in a randomized controlled trial, SENZA-PDN (NCT03228420), 10 kHz SCS is safe and effective for the treatment of painful diabetic neuropathy. 10 kHz SCS offered a comprehensive treatment that improved pain levels, sleep, quality of life, and neurological function. These improvements correlated with a high degree of patient satisfaction. 10 kHz SCS provides a safe, durable and effective treatment for PDN with the unique potential to improve neurological function. In patients for whom durable, effective treatments have been limited thus far, the findings of the SENZA-PDN study are encouraging.
Topics: Humans; Diabetes Mellitus; Diabetic Neuropathies; Pain; Pain Management; Quality of Life; Spinal Cord Stimulation; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38245324
DOI: 10.1016/j.diabres.2023.110760 -
Indian Journal of Ophthalmology Nov 2021To determine the relationship between diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and their associated risk factors.
PURPOSE
To determine the relationship between diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and their associated risk factors.
METHODS
We conducted a cross-sectional analysis on 500 patients who attended the Endocrinology department at a quaternary health care center in Kerala between November 2017 and April 2018. Patients above the age of 30 years with type 2 diabetes mellitus (DM) were included. They underwent a detailed medical history, dilated fundus examination for DR, assessment and grading of DPN, and blood investigations. Among these, 49 randomly selected patients without DR had peripapillary retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) assessed by optical coherence tomogram. RNFL and GCIPL changes in different grades of neuropathy were evaluated.
RESULTS
Out of 500 patients, 303 (60.6%) were males and 197 (39.4%) were females. Prevalence of DR was 48% and DPN 71.8%. Risk factors for the development of DR included duration of DM >15 years, HbA1c (glycated hemoglobin) greater than 6.5%, serum creatinine more than 1.5 mg/dl, and the presence of DPN. There was a statistically significant association between DR and DPN. There was significant thinning of GCIPL in patients with moderate to severe neuropathy without DR.
CONCLUSION
There is a significant association between DR and DPN and their severities. There are early changes in inner retinal layers of diabetic patients without microvascular changes of DR. These neurodegenerative changes parallel DPN in the course of DM. Our study stresses the importance of multidisciplinary approach in the management of diabetes and its complications.
Topics: Adult; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Male; Tomography, Optical Coherence
PubMed: 34708808
DOI: 10.4103/ijo.IJO_1279_21 -
Nature Reviews. Neurology Mar 2017The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annually. The most common complication of diabetes is peripheral... (Review)
Review
The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annually. The most common complication of diabetes is peripheral neuropathy, which has a prevalence as high as 50% and is characterized by damage to neurons, Schwann cells and blood vessels within the nerve. The pathogenic mechanisms of diabetic neuropathy remain poorly understood, impeding the development of targeted therapies to treat nerve degeneration and its most disruptive consequences of sensory loss and neuropathic pain. Involvement of Schwann cells has long been proposed, and new research techniques are beginning to unravel a complex interplay between these cells, axons and microvessels that is compromised during the development of diabetic neuropathy. In this Review, we discuss the evolving concept of Schwannopathy as an integral factor in the pathogenesis of diabetic neuropathy, and how disruption of the interactions between Schwann cells, axons and microvessels contribute to the disease.
Topics: Axons; Diabetic Neuropathies; Humans; Microvessels; Schwann Cells
PubMed: 28134254
DOI: 10.1038/nrneurol.2016.201