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International Immunopharmacology Feb 2024Diabetic neuropathy (DN) is a serious microvascular complication and a major cause of morbidity and mortality in diabetes mellitus. It is characterized by...
BACKGROUND
Diabetic neuropathy (DN) is a serious microvascular complication and a major cause of morbidity and mortality in diabetes mellitus. It is characterized by neurodegeneration of terminal sensory nerve fibers with subsequent pain, loss of sensation, and paresthesia, thus compromising the quality of life of diabetic patients. It is considered the leading cause of non-traumatic amputations worldwide, reflecting the insufficiency of current therapies. Pramipexole (PPX) is a dopamine receptor agonist used for the treatment of Parkinson's disease. The current study aims to investigate the potential neuroprotective effect of PPX in an experimental model of DN.
METHODS
Sprague Dawley rats were randomly assigned into five groups: normal control, Normal + PPX (1 mg/kg) group, STZ control, STZ + PPX (0.25 and 1 mg/kg/day for eight weeks). The neuroprotective effect of PPX in rats was evaluated in terms of sciatic nerve histological alterations, oxidative stress, and protein expression of TLR4/MyD88/IRAK-1/TRAF-6/NF-κB axis and downstream inflammatory mediators.
RESULTS
PPX administration ameliorated histopathological signs of neuronal inflammation and apoptosis. Additionally, PPX attenuated STZ-induced sciatic nerve oxidative stress and downregulated neural tissue expression of TLR4, MyD88, IRAK-1, TRAF-6, NF-κB and downstream mediators (TNF-α, IL-1β and ICAM-1).
CONCLUSION
Collectively, the current study sheds light on PPX as a potential protective medication to alleviate neuropathy progression in diabetic patients. PPX neuroprotective effect can be attributed to modulating TLR4/ MyD88/IRAK-1/TRAF-6/ NF-κB axis signaling in nerve tissues with subsequent attenuation of oxidative stress and inflammation.
Topics: Animals; Humans; Rats; Adaptor Proteins, Signal Transducing; Diabetic Neuropathies; Inflammation; Inflammation Mediators; Myeloid Differentiation Factor 88; Neuroprotective Agents; NF-kappa B; Oxidative Stress; Pramipexole; Quality of Life; Rats, Sprague-Dawley; Toll-Like Receptor 4
PubMed: 38199193
DOI: 10.1016/j.intimp.2024.111514 -
Endocrine Research Jan 2024Diabetes mellitus is a multifactorial metabolic disease, of which type 2 diabetes (T2D) is one of the most common. The complications of diabetes are far more harmful... (Review)
Review
Diabetes mellitus is a multifactorial metabolic disease, of which type 2 diabetes (T2D) is one of the most common. The complications of diabetes are far more harmful than diabetes itself. Type 2 diabetes complications include diabetic nephropathy (DN), diabetic heart disease, diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR) . Many animal models have been developed to study the pathogenesis of T2D and discover an effective strategy to treat its consequences. In this sense, it is crucial to choose the right animal model for the corresponding diabetic complication. This paper summarizes and classifies the animal modeling approaches to T2D complications and provides a comprehensive review of their advantages and disadvantages. It is hopeful that this paper will provide theoretical support for animal trials of diabetic complications.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Foot; Diabetic Nephropathies; Diabetic Neuropathies; Models, Animal; Risk Factors
PubMed: 37950485
DOI: 10.1080/07435800.2023.2278049 -
Emergency Medicine Clinics of North... May 2024Diabetic foot infection (DFI) is among the most common diabetic complications requiring hospitalization. Prompt emergency department diagnosis and evidence-based... (Review)
Review
Diabetic foot infection (DFI) is among the most common diabetic complications requiring hospitalization. Prompt emergency department diagnosis and evidence-based management can prevent eventual amputation and associated disability and mortality. Underlying neuropathy, arterial occlusion, immune dysfunction, and hyperglycemia-associated dehydration and ketoacidosis can all contribute to severity and conspire to make DFI diagnosis and management difficult. Serious complications include osteomyelitis, necrotizing infection, and sepsis. Practice guidelines are designed to assist frontline providers with correct diagnosis, categorization, and treatment decisions. Management generally includes a careful lower extremity examination and plain x-ray, obtaining appropriate tissue cultures, and evidence-based antibiotic selection tailored to severity.
Topics: Humans; Diabetic Foot; Communicable Diseases; Osteomyelitis; Anti-Bacterial Agents; Diabetes Mellitus
PubMed: 38641391
DOI: 10.1016/j.emc.2024.01.003 -
Acta Pharmacologica Sinica Dec 2023Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are...
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic β-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle, is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg·d, i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either β-Arrestin2 or β-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKβ/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.
Topics: Animals; Mice; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Indole Alkaloids; Monoterpenes; Receptors, G-Protein-Coupled; Sciatic Nerve; Signal Transduction; Vincamine
PubMed: 37580494
DOI: 10.1038/s41401-023-01135-1 -
Journal of Diabetes Science and... Jan 2024Spinal cord stimulation (SCS) technology has been recently approved by the US Food and Drug Administration (FDA) for painful diabetic neuropathy (PDN). The treatment... (Review)
Review
Spinal cord stimulation (SCS) technology has been recently approved by the US Food and Drug Administration (FDA) for painful diabetic neuropathy (PDN). The treatment involves surgical implantation of electrodes and a power source that delivers electrical current to the spinal cord. This treatment decreases the perception of pain in many chronic pain conditions, such as PDN. The number of patients with PDN treated with SCS and the amount of data describing their outcomes is expected to increase given four factors: (1) the large number of patients with this diagnosis, (2) the poor results that have been obtained for pain relief with pharmacotherapy and noninvasive non-pharmacotherapy, (3) the results to date with investigational SCS technology, and (4) the recent FDA approval of systems that deliver this treatment. Whereas traditional SCS replaces pain with paresthesias, a new form of SCS, called high-frequency 10-kHz SCS, first used for pain in 2015, can relieve PDN pain without causing paresthesias, although not all patients experience pain relief by SCS. This article describes (1) an overview of SCS technology, (2) the use of SCS for diseases other than diabetes, (3) the use of SCS for PDN, (4) a comparison of high-frequency 10-kHz and traditional SCS for PDN, (5) other SCS technology for PDN, (6) deployment of SCS systems, (7) barriers to the use of SCS for PDN, (8) risks of SCS technology, (9) current recommendations for using SCS for PDN, and (10) future developments in SCS.
Topics: Humans; Diabetic Neuropathies; Spinal Cord Stimulation; Paresthesia; Pain Measurement; Pain; Diabetes Mellitus
PubMed: 36384312
DOI: 10.1177/19322968221133795 -
Diabetes/metabolism Research and Reviews Mar 2024Diabetes mellitus is associated with a wide range of neuropathies, vasculopathies, and immunopathies, resulting in many complications. More than 30% of diabetic patients... (Review)
Review
Diabetes mellitus is associated with a wide range of neuropathies, vasculopathies, and immunopathies, resulting in many complications. More than 30% of diabetic patients risk developing diabetic foot ulcers (DFUs). Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play essential roles in various biological functions in the hyperglycaemic environment that determines the development of DFU. Ulceration results in tissue breakdown and skin barrier scavenging, thereby facilitating bacterial infection and biofilm formation. Many bacteria contribute to diabetic foot infection (DFI), including Staphylococcus aureus (S. aureus) et al. A heterogeneous group of "ncRNAs," termed small RNAs (sRNAs), powerfully regulates biofilm formation and DFI healing. Multidisciplinary foot care interventions have been identified for nonhealing ulcers. With an appreciation of the link between disease processes and ncRNAs, a novel therapeutic model of bioactive materials loaded with ncRNAs has been developed to prevent and manage diabetic foot complications.
Topics: Humans; Diabetic Foot; Staphylococcus aureus; Bacterial Infections; Foot; Wound Healing; Diabetes Mellitus
PubMed: 37839046
DOI: 10.1002/dmrr.3740 -
Environmental Science and Pollution... Aug 2023Cucurbita pepo (C. pepo) is cultivated and used traditionally as vegetable as well as medicine in different parts of the world. The aim of current study was to...
BACKGROUND
Cucurbita pepo (C. pepo) is cultivated and used traditionally as vegetable as well as medicine in different parts of the world. The aim of current study was to investigate the potential of C. pepo in attenuation of diabetic neuropathy via using streptozotocin (STZ)-induced diabetes model in male wistar rats.
MATERIALS AND METHODS
Diabetic neuropathy was induced by administration of STZ; 65 mg/kg, i.p. and Nicotinamide (NAD; 230 mg/kg i.p.) and assessed by measuring thermal hyperalgesia, mechanical hyperalgesia and motor nerve conduction velocity (MNCV) in experimental animals. Treatment with different doses of (100, 200 and 400 mg/kg, p.o.) petroleum ether extract of C. pepo (CPE) and hydroethanolic extract of C. pepo (CHE) was started from the 60 day of STZ/NAD administration and continued upto 90 day.
RESULTS
CPE and CHE significantly attenuated the behavioural changes including hyperalgesia, allodynia and MNCV linked to diabetic neuropathy. Moreover, the oxidative stress and level of TNF-α, TGF-β and IL-1β was found to be significantly attenuated in experimental animals.
CONCLUSION
Thus C. pepo might ameliorate the progression of diabetic neuropathy via modulation of chronic hyperglycemia and therefore and have therapeutic potential for treatment of diabetic neuropathic pain.
Topics: Rats; Male; Animals; Diabetic Neuropathies; Cucurbita; Hyperalgesia; Diabetes Mellitus, Experimental; NAD; Oxidative Stress; Rats, Wistar; Inflammation
PubMed: 37400700
DOI: 10.1007/s11356-023-28339-6 -
Middle East African Journal of... 2022The purpose of the study was to evaluate the corneal sensitivity and its quadrature variability in patients with diabetic neuropathy (DN) diagnosed with electromyography...
PURPOSE
The purpose of the study was to evaluate the corneal sensitivity and its quadrature variability in patients with diabetic neuropathy (DN) diagnosed with electromyography and to compare these results with age- and sex-matched healthy individuals.
METHODS
The left eyes of 32 patients who applied for refraction or fundus examination and had a diagnosis of DN by electromyography in their medical history were included in this study. Corneal sensitivity was evaluated using the Cochet-Bonnet esthesiometer (Luneau, Paris) in five zones: central, nasal, superior, temporal, and inferior. The measurements of the patients were compared with the measurements of 32 age- and sex-matched healthy volunteers. Furthermore, the measurements of five corneal zones were compared with each other, and the level of correlation was investigated in each group.
RESULTS
The central corneal sensitivity values were measured as 4.12 ± 1.04 (mm) and 5.92 ± 0.14 (mm) ( < 0.001). While the sensitivity values at the superior, inferior, nasal, and temporal quadrants were detected as 5.85 ± 0.21, 5.85 ± 0.26, 5.94 ± 0.13, 5.93 ± 0.13, and 5.92 ± 0.14 (mm) in the control group, it was measured as 3.67 ± 0.66, 3.67 ± 0.62, 3.67 ± 0.62, and 3.89 ± 0.73 (mm) in the DN group, respectively. The corneal sensitivity values were all found to be significantly lower in the DN group ( < 0.001 for all parameters) at all quadrants as well as the central cornea. Furthermore, a moderate positive correlation between all five zones in the control group and a very strong positive correlation in the DN group were found in terms of the corneal quadrature sensitivity.
CONCLUSION
The current study revealed a significant reduction in corneal sensitivity in patients with DN. In both the control group and DN group, all corneal zones showed positive correlations which show the consistency of the measurement in different quadratures. Evaluating corneal sensitivity with a Cochet-Bonnet esthesiometer might serve as a useful screening tool in detecting neuropathy development. By taking the necessary precautions, further damage can be prevented.
Topics: Humans; Cornea; Diabetes Mellitus; Diabetic Neuropathies; Microscopy, Confocal; Refraction, Ocular; Vision Tests
PubMed: 38162562
DOI: 10.4103/meajo.meajo_111_23 -
Frontiers in Endocrinology 2024We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2...
BACKGROUND
We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM).
METHODS
A 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019.
RESULTS
In 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13-1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72-1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019.
CONCLUSION
Suboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups.
Topics: Humans; Diabetic Neuropathies; Male; Female; Diabetes Mellitus, Type 2; Middle Aged; Aged; Glycemic Control; Glycated Hemoglobin; Follow-Up Studies; Age Factors; Blood Glucose; Adult; Incidence; Risk Factors
PubMed: 38694945
DOI: 10.3389/fendo.2024.1377923 -
Journal of Diabetes Science and... Jan 2024Painful diabetic neuropathy is a common vexing problem for people with diabetes and a costly problem for society. The pathophysiology is not well understood, and no safe... (Review)
Review
Painful diabetic neuropathy is a common vexing problem for people with diabetes and a costly problem for society. The pathophysiology is not well understood, and no safe and effective mechanistically-based treatment has been identified. Poor glycemic control is a risk factor for painful diabetic neuropathy. Excessive intraneuronal glucose in people with diabetes can be shunted away from physiological glycolysis into multiple pathological pathways associated with neuropathy and pain. The first three treatments that are traditionally offered consist of risk factor reduction, lifestyle modifications, and pharmacological therapy, which includes only three drugs that are approved for this indication by the United States Food and Drug Administration. All of these traditional treatments are often inadequate for relieving neuropathic pain, and thus, new approaches are needed. Modern devices based on neuromodulation technology, which act directly on the nervous system, have been recently cleared by the United States Food and Drug Administration for painful diabetic neuropathy and offer promise as next-in-line therapy when traditional therapies fail.
Topics: Humans; Diabetic Neuropathies; Pain; Hyperglycemia; Diabetes Mellitus
PubMed: 36305521
DOI: 10.1177/19322968221132252