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Diabetes Research and Clinical Practice Dec 2023The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal... (Review)
Review
The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal symmetrical polyneuropathy (DSPN) and the autonomic neuropathies are the most frequently seen forms of diabetic neuropathy. The 2017 American Diabetes Association classification system for the neuropathies of diabetes are in general use. Treatment challenges remain and the need for revised recommendations and further discussion of management of severely painful DSPN that does not fully respond to conventional medical management is clear, especially in light of the recent opioid crisis in the USA.
Topics: Humans; Autonomic Nervous System; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Pain; Polyneuropathies
PubMed: 38245328
DOI: 10.1016/j.diabres.2023.110758 -
Diabetes Research and Clinical Practice Dec 2023This article summarizes the latest epidemiology of diabetic autonomic neuropathy (DAN), and provides a brief overview on epidemiology, current outcomes measures for... (Review)
Review
This article summarizes the latest epidemiology of diabetic autonomic neuropathy (DAN), and provides a brief overview on epidemiology, current outcomes measures for screening and diagnosis in research and clinical settings, the latest evidence on effective management, and novel perspectives on the impacts of social determinants of health in development and management of DAN. Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy, are by far the most studied. However, emerging data highlight the impact of other forms of autonomic neuropathies such as gastrointestinal and urogenital autonomic neuropathies, on healthcare and patients' reported outcomes [1].
Topics: Humans; Diabetic Neuropathies
PubMed: 38245325
DOI: 10.1016/j.diabres.2023.110762 -
Diabetes & Metabolism Journal Jul 2021Diabetic peripheral neuropathy (DPN) is one of the most serious complications of type 2 diabetes mellitus (T2DM). DPN increases the risk of ulcers, foot infections, and...
BACKGROUND
Diabetic peripheral neuropathy (DPN) is one of the most serious complications of type 2 diabetes mellitus (T2DM). DPN increases the risk of ulcers, foot infections, and noninvasive amputations, ultimately leading to long-term disability.
METHODS
Seven hundred patients with T2DM were investigated from 2013 to 2017 in the Sanlin community by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 681 patients (19 missing) were investigated using a questionnaire, physical examination, biochemical index test, and follow-up Toronto clinical scoring system (TCSS) test. Patients with a TCSS score ≥6 points were diagnosed with DPN. After removing missing values, 612 patients were divided into groups in a 3:1 ratio for external validation. Using different Lasso analyses (misclassification error, mean squared error, -2log-likelihood, and area under curve) and a logistic regression analysis of the training set, models A, B, C, and D were established. The receiver operating characteristic (ROC) curve, calibration plot, dynamic component analysis (DCA) measurements, net classification improvement (NRI) and integrated discrimination improvement (IDI) were used to validate discrimination and clinical practicality of the model.
RESULTS
Through data analysis, model A (containing four factors), model B (containing five factors), model C (containing seven factors), and model D (containing seven factors) were built. After calibration, ROC curve, DCA, NRI and IDI, models C and D exhibited better accuracy and greater predictive power.
CONCLUSION
Four prediction models were established to assist with the early screening of DPN in patients with T2DM. The influencing factors in model C and D are more important factors for patients with T2DM diagnosed with DPN.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; ROC Curve; Risk Factors
PubMed: 34352988
DOI: 10.4093/dmj.2020.0100 -
International Journal of Molecular... May 2021Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients' quality of life. DN could be present... (Review)
Review
Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients' quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of "metabolic memory" in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.
Topics: Animals; Diabetic Neuropathies; Epigenesis, Genetic; Epigenomics; Genetic Predisposition to Disease; Humans; Inflammation; Peripheral Nervous System
PubMed: 34063061
DOI: 10.3390/ijms22094887 -
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 2023Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality...
BACKGROUND
Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality have left the causality of this relationship uncertain.
METHODS
Univariate Mendelian randomization (MR), multivariate MR and linkage disequilibrium score (LDSC) regression analysis were utilized to assess the causal link between SUA and DN. Summary-level data for SUA were drawn from the CKDGen consortium, comprising 288,648 individuals, while DN data were obtained from the FinnGen consortium, with 2,843 cases and 271,817 controls. Causal effects were estimated primarily using inverse variance weighted (IVW) analysis, supplemented by four validation methods, with additional sensitivity analyses to evaluate pleiotropy, heterogeneity, and result robustness.
RESULTS
The LDSC analysis revealed a significant genetic correlation between SUA and DN (genetic correlation = 0.293, P = 2.60 × 10). The primary methodology IVW indicated that each increase of 1 mg/dL in SUA would increase DN risk by 17% (OR = 1.17, 95% CI 1.02-1.34, P = 0.02), while no causal relationship was found in reverse analysis (OR = 1.00, 95% CI 0.98~1.01, = 0.97). Multivariate MR further identified that the partial effect of SUA on DN may be mediated by physical activity, low density lipoprotein cholesterol (LDL-C), insulin resistance (IR), and alcohol use.
CONCLUSION
The study establishes a causal link between elevated SUA levels and an increased risk of DN, with no evidence for a reverse association. This underscores the need for a comprehensive strategy in DN management, integrating urate-lowering interventions with modulations of the aforementioned mediators.
Topics: Humans; Diabetic Neuropathies; Mendelian Randomization Analysis; Uric Acid; Alcohol Drinking; Cholesterol, LDL; Diabetes Mellitus
PubMed: 38034019
DOI: 10.3389/fendo.2023.1277984 -
Diabetes Research and Clinical Practice Dec 2023Diabetic neuropathy is a common complication of diabetes that affects up to 50% of patients during the course of the disease; 20-30% of the patients also develop...
Diabetic neuropathy is a common complication of diabetes that affects up to 50% of patients during the course of the disease; 20-30% of the patients also develop neuropathic pain. The mechanisms underlying neuropathy are not known in detail, but both metabolic and vascular factors may contribute to the development of neuropathy. The development of the most common type of neuropathy is insidious, often starting distally in the toes and feet and gradually ascending up the leg and later also involving fingers and hands. The symptoms are mainly sensory with either sensory loss or positive symptoms with different types of paresthesia or painful sensations. In more advanced cases motor dysfunction may occur, causing gait disturbances and falls. The diagnosis of neuropathy is based on history and a careful examination, which includes a sensory examination of both large and small sensory nerve fiber function, as well as an examination of motor function and deep tendon reflexes of the lower limbs. Attention needs to be paid to the feet including examination of the skin, joints, and vascular supply. Nerve conduction studies are rarely needed to make a diagnosis of neuropathy. In patients with clear motor deficit or with an asymmetrical presentation, additional electrophysiological examination may be necessary. Early detection of diabetic neuropathy is important to avoid further irreversible injury to the peripheral nerves.
Topics: Humans; Diabetic Neuropathies; Neural Conduction; Peripheral Nerves; Neuralgia; Hand; Diabetes Mellitus
PubMed: 38245319
DOI: 10.1016/j.diabres.2023.110753 -
Frontiers in Endocrinology 2022
Topics: Humans; Diabetic Neuropathies; Risk Factors; Diabetes Mellitus, Type 2
PubMed: 36601016
DOI: 10.3389/fendo.2022.1110928 -
Diabetologia May 2020Frustratingly, disease-modifying treatments for diabetic neuropathy remain elusive. Glycaemic control has a robust effect on preventing neuropathy in individuals with... (Review)
Review
Frustratingly, disease-modifying treatments for diabetic neuropathy remain elusive. Glycaemic control has a robust effect on preventing neuropathy in individuals with type 1 but not in those with type 2 diabetes, which constitute the vast majority of patients. Encouragingly, recent evidence points to new metabolic risk factors and mechanisms, and thus also at novel disease-modifying strategies, which are desperately needed. Obesity has emerged as the second most important metabolic risk factor for neuropathy (diabetes being the first) from consensus findings of seven observational studies in populations across the world. Moreover, dyslipidaemia and altered sphingolipid metabolism are emergent novel mechanisms of nerve injury that may lead to new targeted therapies. Clinical history and examination remain critical components of an accurate diagnosis of neuropathy. However, skin biopsies and corneal confocal microscopy are promising newer tests that have been used as outcome measures in research studies but have not yet demonstrated clear clinical utility. Given the emergence of obesity as a neuropathy risk factor, exercise and weight loss are potential interventions to treat and/or prevent neuropathy, although evidence supporting exercise currently outweighs data supporting weight loss. Furthermore, a consensus has emerged advocating tricyclic antidepressants, serotonin-noradrenaline (norepinephrine) reuptake inhibitors and gabapentinoids for treating neuropathic pain. Out-of-pocket costs should be considered when prescribing these medications since their efficacy and tolerability are similar. Finally, the downsides of opioid treatment for chronic, non-cancer pain are becoming increasingly evident. Despite these data, current clinical practice frequently initiates and continues opioid prescriptions for patients with neuropathic pain before prescribing guideline-recommended treatments.
Topics: Analgesics, Opioid; Animals; Diabetic Neuropathies; Dyslipidemias; Humans; Obesity; Sphingolipids
PubMed: 31974731
DOI: 10.1007/s00125-020-05085-9 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Apr 2022Diabetic neuropathy is a common diabetic complication.The application of metabolomics in the research on diabetic neuropathy is beneficial for us to understand the...
Diabetic neuropathy is a common diabetic complication.The application of metabolomics in the research on diabetic neuropathy is beneficial for us to understand the pathophysiological processes and overall metabolic disturbance of the nervous system under the condition of hyperglycemia,decipher the pathogenesis of diabetic neuropathy,and mine the potential biomarkers for clinical diagnosis and treatment.Long-term hyperglycemia may lead to disorders in multiple pathways,such as tricarboxylic acid circle,amino acid metabolism,and lipid metabolism.These metabolic changes are closely associated with the injuries of the peripheral and central nervous system.In the paper,we reviewed the metabolomics-based studies about diabetic neuropathy in the last five years.
Topics: Biomarkers; Diabetes Mellitus; Diabetic Neuropathies; Humans; Hyperglycemia; Metabolomics
PubMed: 35538768
DOI: 10.3881/j.issn.1000-503X.13040