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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 -
Frontiers in Bioscience (Landmark... Feb 2022Diabetes Mellitus is a highly prevalent disease in Mexico and in the world, among whose complications is diabetic neuropathy. DN is a group of disorders that present... (Review)
Review
Diabetes Mellitus is a highly prevalent disease in Mexico and in the world, among whose complications is diabetic neuropathy. DN is a group of disorders that present signs and/or symptoms of peripheral nerve dysfunction and have different clinical manifestations in both peripheral neuropathy and autonomic neuropathy. As a part of the mechanisms by which DN develops, oxidative stress and inflammation have been described. Cocoa is a plant origin product which includes around 300 components and through different studies, it has been suggested that cocoa has different mechanisms of action through which exerts its beneficial effects on health. It has been proposed that cocoa has hypoglycemic, lipid-lowering, antioxidant and anti-inflammatory effects, and thus, potentially have a beneficial direct or indirect effect on diabetic neuropathy. Specially in preclinical studies, the anti-inflammatory and anti-nociceptive effect of cocoa has been evaluated through different mechanisms of action. However, most of the studies presented concerning this complication, are or preclinical studies, so there is still a great area of opportunity regarding the use of cocoa on diabetic neuropathy.
Topics: Anti-Inflammatory Agents; Cacao; Chocolate; Diabetes Mellitus; Diabetic Neuropathies; Humans; Hypoglycemic Agents
PubMed: 35227000
DOI: 10.31083/j.fbl2702057 -
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 -
Cardiovascular Diabetology Sep 2022Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention,...
BACKGROUND
Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events.
METHODS
This retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts.
RESULTS
Both gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37-1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27-1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27-1.47), stroke (HR: 1.31, 95% CI 1.2-1.43), myocardial infarction (HR: 1.25, 95% CI 1.14-1.38) and heart failure (HR: 1.14, 95% CI 1.07-1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31-1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22-1.49), myocardial infarction (HR: 1.29, 95% CI 1.13-1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04-1.59), stroke (HR: 1.26, 95% CI 1.12-1.42), and heart failure (HR: 1.2, 95% CI 1.11-1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease.
CONCLUSION
In patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.
Topics: Amines; Analgesics; Cardiovascular Diseases; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Gabapentin; Heart Disease Risk Factors; Heart Failure; Humans; Myocardial Infarction; Pain; Peripheral Vascular Diseases; Pregabalin; Pulmonary Embolism; Retrospective Studies; Risk Factors; Stroke; gamma-Aminobutyric Acid
PubMed: 36050764
DOI: 10.1186/s12933-022-01610-9 -
Clinical Therapeutics Sep 2021Diagnosing early diabetic peripheral neuropathy remains a challenge due to deficiencies in currently advocated end points. The cornea is densely innervated with small... (Review)
Review
PURPOSE
Diagnosing early diabetic peripheral neuropathy remains a challenge due to deficiencies in currently advocated end points. The cornea is densely innervated with small sensory fibers, which are structurally and functionally comparable to intraepidermal nerve fibers. Corneal confocal microscopy is a method for rapid, noninvasive scanning of the living cornea with high resolution and magnification.
METHODS
This narrative review presents the framework for the development of biomarkers and the literature on the use and adoption of corneal confocal microscopy as an objective, diagnostic biomarker in experimental and clinical studies of diabetic peripheral neuropathy. A search was performed on PubMed and Google Scholar based on the terms "corneal confocal microscopy," "diabetic neuropathy," "corneal sensitivity," and "clinical trials."
FINDINGS
A substantial body of evidence underpins the thesis that corneal nerve loss predicts incident neuropathy and progresses with the severity of diabetic peripheral neuropathy. Corneal confocal microscopy also identifies early corneal nerve regeneration, strongly arguing for its inclusion as a surrogate end point in clinical trials of disease-modifying therapies.
IMPLICATIONS
There are sufficient diagnostic and prospective validation studies to fulfill the US Food and Drug Administration criteria for a biomarker to support the inclusion of corneal confocal microscopy as a primary end point in clinical trials of disease-modifying therapies in diabetic neuropathy.
Topics: Biomarkers; Cornea; Diabetes Mellitus; Diabetic Neuropathies; Humans; Microscopy, Confocal; Nerve Fibers
PubMed: 33965237
DOI: 10.1016/j.clinthera.2021.04.003 -
Current Problems in Cardiology Aug 2023Microvascular complications of diabetes seem to be clustered and put patients at higher risk of developing cardiovascular disease (CVD). This was a questionnaire-based... (Review)
Review
Microvascular complications of diabetes seem to be clustered and put patients at higher risk of developing cardiovascular disease (CVD). This was a questionnaire-based study designed to screen for the presence of diabetic peripheral neuropathy (DPN), defined as the score in the Michigan Neuropathy Screening Instrument (MNSI) above 2, and to evaluate its association with other complication of diabetes, including CVD. There were 184 patients included into the study. The prevalence of DPN in the study group was 37.5%. The regression model analysis revealed that the presence of DPN was significantly associated with the presence of diabetic kidney disease (DKD) (P = 0.0034;) and patient's age (P < 0.0001). Thirty-four patients (49.3%) with MNSI score >2 were diagnosed with CVD in comparison to 24 (20.1%) subjects with MNSI score ≤ 2 (P = 0.00006). In case of having one diabetes complication diagnosed, it is important to screen for others, including macrovascular ones.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Cardiovascular Diseases
PubMed: 36967071
DOI: 10.1016/j.cpcardiol.2023.101726 -
Antioxidants & Redox Signaling Jan 2022Diabetes is a major source of neuropathy and neuropathic pain that is set to continue growing in prevalence. Diabetic peripheral neuropathy (DPN) and pain associated...
Diabetes is a major source of neuropathy and neuropathic pain that is set to continue growing in prevalence. Diabetic peripheral neuropathy (DPN) and pain associated with diabetes are not adequately managed by current treatment regimens. Perhaps the greatest difficulty in treating DPN is the complex pathophysiology, which involves aspects of metabolic disruption and neurotrophic deficits, along with neuroimmune interactions. There is, therefore, an urgent need to pursue novel therapeutic options targeting the key cellular and molecular players. To that end, cellular targeting becomes an increasingly compelling drug delivery option as our knowledge of neuroimmune interactions continues to mount. These nanomedicine-based approaches afford a potentially unparalleled specificity and longevity of drug targeting, using novel or established compounds, all while minimizing off-target effects. The DPN therapeutics directly targeted at the nervous system make up the bulk of currently available treatment options. However, there are significant opportunities based on the targeting of non-neuronal cells and neuroimmune interactions in DPN. Nanomedicine-based agents represent an exciting opportunity for the treatment of DPN with the goals of improving the efficacy and safety profile of analgesia, as well as restoring peripheral neuroregenerative capacity. 36, 122-143.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Nanomedicine; Neuralgia; Neuroimmunomodulation; Pain Management
PubMed: 34416821
DOI: 10.1089/ars.2021.0123 -
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 -
Frontiers in Endocrinology 2020Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV...
Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes. Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE). The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction ( = 0.03), abnormal SNAP ( = 0.04) and incidents of definite CAN ( = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN ( = 0.03), abnormal SNAP ( = 0.01), and SNCV ( = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV ( = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN ( < 0.02) and HRV ( < .03) in fully adjusted models. No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.
Topics: Adolescent; Adult; Blood Glucose Self-Monitoring; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Male; Risk Factors; Young Adult
PubMed: 33071962
DOI: 10.3389/fendo.2020.00644 -
Metabolism: Clinical and Experimental May 2024Diabetic peripheral neuropathy (DPN) is a complication of diabetes with a high rate of disability. However, current clinical treatments for DPN are suboptimal.... (Review)
Review
Diabetic peripheral neuropathy (DPN) is a complication of diabetes with a high rate of disability. However, current clinical treatments for DPN are suboptimal. Non-coding RNAs (ncRNAs) are a type of RNAs that are not translated into proteins. NcRNAs perform functions that regulate epigenetic modifications, transcriptional or post-transcriptional regulators of proteins, and thus participate in the physiological and pathological processes of the body. NcRNAs play a role in the progress of DPN by affecting the processes of inflammation, oxidative stress, cellular autophagy or apoptosis. Therefore, ncRNAs treatment is regarded as a promising therapeutic approach for DPN. In addition, since some ncRNAs present stably in the blood of DPN patients, they are considered as potential biomarkers that contribute to early clinical diagnosis. In this paper, we review the studies on the role of ncRNAs in DPN in the last decade, and discuss the mechanisms of ncRNAs, aiming to provide a reference for the future research on the treatment and early diagnosis of DPN.
Topics: Humans; Diabetic Neuropathies; RNA, Untranslated; RNA; Biomarkers; Diabetes Mellitus
PubMed: 38462040
DOI: 10.1016/j.metabol.2024.155833