Painful Diabetic Peripheral Neuropathy Research Articles

478-P: Brain Volume Changes after Long-Term Opioid Treatment in Painful Diabetic Peripheral Neuropathy

Aim: Opioid medications are commonly used to treat Painful-Diabetic Peripheral Neuropathy (Painful-DPN). However, opioids are associated with significant adverse effects, including prescription opioid use disorder which has reached epidemic proportions in the United States. There is an urgent need to determine the effect of long-term opioid treatment (>6-months) on cerebral structure in Painful-DPN. Methods: A total of 56 participants with Painful-DPN were recruited (17 on long-term opioid treatment [O+] and 39 not on opioid treatment [O-]). Participants underwent detailed clinical and neurophysiological assessments and cerebral imaging (3T, Phillips Medical Systems, Holland). Brain morphometric analysis was performed using Freesurfer. Results: O+ participants were prescribed: codeine (n=3, 18%), tramadol (n=5, 29%), morphine modified release (n=1, 6%), buprenorphine (n=1, 6%), and combination treatment (n=5, 29%). O+ participants had a longer duration of diabetes, greater HbA1c, higher pain severity and higher scores on Hospital Anxiety and Depression scales compared to the O- group. Participants in the O+ group had a greater mean caudate volume (O+ 3.5mL ± 0.4; O- 3.2 ± 0.4mL, p=0.034); mean insula volume (O+ 6.3 ± 0.8; O- 5.9 ± 0.6, p=0.049) and mean insular vertices (O+ 3,286 ± 411; O- 3055 ± 282, p=0.018). Conclusion: This is the first study to examine the impact of long-term opioid use on cerebral structure in Painful-DPN. Our findings suggest that chronic opioid use may alter affective/attentional pain processing (insular cortex) and brain regions associated with binge/intoxication (caudate nucleus). These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure in Painful-DPN. Clearer clinical utility will come from future longitudinal modelling of the prognostic characteristics of opioid use disorder from the neuroimaging features identified in this study. Disclosure G.P.Sloan: None. K.Teh: None. P.Shillo: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH & Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter & Gamble, Novo Nordisk, Berlin-Chemie AG. D.Selvarajah: None. I.D.Wilkinson: None. Funding European Foundation for the Study of Diabetes; Novartis Knowledge Exchange Support Fund (X/162218); Efficacy and Mechanism Evaluation Programme (NIHR129921); Medical Research Council/National Institute for Health Research Partnership

103-OR: LX9211, an Orally-Administered, Non-opioid, AAK1 Inhibitor for Painful Diabetic Peripheral Neuropathy—Results from a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study

Diabetic peripheral neuropathy (DPN) is a common complication in individuals with diabetes with high morbidity and mortality. Painful DPN impacts quality of life and is very challenging to treat. The efficacy and safety of LX9211, a potent, non-opioid inhibitor of a novel target, AP2-associated protein kinase 1 (AAK1) was evaluated in a Phase 2 randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical study (RELIEF-DPN 1). The baseline characteristics [mean (SD)] of 319 adults were age 62.2 (9.94) years, A1C 7.7 (1.28) %, BMI 32.07 (4.45) kg/m2, and average daily pain score (ADPS) after placebo run-in period 6.55 (1.089). Patients were randomized to either placebo, LX9211 100 mg/10 mg (100 mg Day 1, 10 mg thereafter-Low Dose arm), or LX9211 200 mg/20 mg (200 mg Day 1, 20 mg thereafter-High Dose arm) for 6 weeks followed by 5-week safety follow-up period. At Week 6, LX9211 was associated with significant improvement in Neuropathic Pain Symptom Inventory (NPSI) total score (Low Dose: -5.18, p=0.064; High Dose: -7.22, p=0.008), burning pain (Low Dose: -1.40; p<0.001; High Dose: -0.89, p=0.017), pain interference on sleep (Low Dose: -0.96, p=0.005; High Dose: -1.04, p=0.002) and Patient Global Impression of Change score (Low Dose: -0.35, p=0.031; High Dose: -0.15, p=0.351) compared to placebo while achieving the primary endpoint (change from placebo in ADPS) in the low dose arm. LX9211 was safe (no treatment-related SAEs or deaths) and did not affect key cardiometabolic parameters (body weight, blood pressure, glucose control, cholesterol levels). RELIEF-DPN 1 demonstrated significant improvements in validated neuropathic pain instruments and in other patient reported outcomes suggesting that LX9211 is a promising, opioid independent new avenue to treat people with painful DPN. Confirmation of these positive results are planned in future Phase 3 trials. Disclosure R.Busui: Board Member; American Diabetes Association, Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Novo Nordisk, Roche Diagnostics, Procter & Gamble, Research Support; Novo Nordisk, Medtronic, National Institutes of Health. A.Patel: Other Relationship; Lexicon Pharmaceuticals, Inc. C.N.Sang: Consultant; Arena Pharmaceuticals, Inc., Covance, SOLVD, Other Relationship; Kolon, Research Support; AbbVie Inc., Merck & Co., Inc., Tonix, Lexicon Pharmaceuticals, Inc., Vivozon, Helixmith. C.B.Granowitz: None. P.L.Banks: Employee; Lexicon Pharmaceuticals, Inc. P.Pierce: Employee; Lexicon Pharmaceuticals, Inc. F.W.Sun: Employee; Lexicon Pharmaceuticals, Inc. S.Gopinathan: Employee; Lexicon Pharmaceuticals, Inc. Funding Lexicon Pharmaceuticals, Inc.

Painful Diabetic Peripheral Neuropathy: Practical Guidance and Challenges for Clinical Management.

Painful diabetic peripheral neuropathy (PDPN) is present in nearly a quarter of people with diabetes. It is estimated to affect over 100 million people worldwide. PDPN is associated with impaired daily functioning, depression, sleep disturbance, financial instability, and a decreased quality of life. Despite its high prevalence and significant health burden, it remains an underdiagnosed and undertreated condition. PDPN is a complex pain phenomenon with the experience of pain associated with and exacerbated by poor sleep and low mood. A holistic approach to patient-centred care alongside the pharmacological therapy is required to maximise benefit. A key treatment challenge is managing patient expectation, as a good outcome from treatment is defined as a reduction in pain of 30-50%, with a complete pain-free outcome being rare. The future for the treatment of PDPN holds promise, despite a 20-year void in the licensing of new analgesic agents for neuropathic pain. There are over 50 new molecular entities reaching clinical development and several demonstrating benefit in early-stage clinical trials. We review the current approaches to its diagnosis, the tools, and questionnaires available to clinicians, international guidance on PDPN management, and existing pharmacological and non-pharmacological treatment options. We synthesise evidence and the guidance from the American Association of Clinical Endocrinology, American Academy of Neurology, American Diabetes Association, Diabetes Canada, German Diabetes Association, and the International Diabetes Federation into a practical guide to the treatment of PDPN and highlight the need for future research into mechanistic-based treatments in order to prioritise the development of personalised medicine.

ID: 205108 Long-Term Evaluation of SCS in Patients With Painful Diabetic Peripheral Neuropathy: 8- to 10-Year Prospective Cohort Study

Painful diabetic peripheral neuropathy (PDPN) is defined as ‘pain caused by lesions of the somatosensory system, attributed to diabetes’, and is reported to develop in 10-20% of patients suffering from diabetes mellitus. Conservative pharmacological treatment alone often offers little pain relief and is frequently poorly tolerated. Therefore, better treatment options are a necessity. The first use of spinal cord stimulation (SCS) for PDPN dates from 1996. High-quality studies followed, showing SCS to be up to 8 times more effective in terms of pain relief than best medical treatment at that time. Because most studies only evaluated short-term efficacy of SCS, long-term efficacy remains yet unclear. The aim of this study is to evaluate the long-term effects of spinal cord stimulation (SCS) in patients with painful diabetic polyneuropathy (PDPN).

ID: 200950 Differential Targeted Multiplexed, High-Frequency and Conventional Spinal Cord Stimulation Reduce Streptozotocin induced Mechanical Hypersensitivity

Treatment of painful diabetic peripheral neuropathy (PDPN) patients remains a major challenge, as most pharmacological options still are unsuccessful. For these patients, spinal cord stimulation (SCS) can be a last resort treatment option. Although SCS often provides effective pain relief, a substantial number of PDPN patients do not respond to the treatment. Novel stimulation paradigms such as Differential Targeted Multiplexed (DTM) SCS are suggested to further improve the efficacy of SCS on pain relief and increase responder rates. DTM-SCS is a combination of more than one electrical field delivered with signals at different stimulation parameters (1). The aim of this study was to investigate the effects of DTM-SCS on pain relief in an animal model for PDPN and compare this to Sham-SCS, conventional (Con-) SCS and High frequency (HF-) SCS.

P38: Dual Field Pulsed Electromagnetic Therapy: A Non-Opioid Means of Reducing Pain in Diabetic Peripheral Neuropathy - Report of the RELIEF Trial

P38: Dual Field Pulsed Electromagnetic Therapy: A Non-Opioid Means of Reducing Pain in Diabetic Peripheral Neuropathy - Report of the RELIEF Trial

ID: 211861 Painful DPN and SCS: Using the Product Surveillance Registry (PSR) to Collect Real World Evidence

Painful Diabetic Peripheral Neuropathy (DPN) is the most common neuropathic syndrome seen in persons with diabetes and is accompanied by pain in the feet and lower legs by the typical ‘glove and stocking’ pattern of distribution. Patients can experience a variety of symptoms, including prickling or tingling, burning, shooting, or stabbing pain or unusual sensations, which can interfere with sleep and quality of Life (QoL) leading to reduced activity levels, depression and social isolation1. Literature has demonstrated that conventional Spinal Cord Stimulation (SCS) is an effective treatment for painful DPN of the lower extremities, showing significant benefits of pain relief and improved QoL2,3,4. New stimulation paradigms may offer additional options for DPN patients. The purpose of this study is collecting real-world data on pain, QoL, stimulation paradigms, sleep, and activity.

ID: 215433 The History of Spinal Cord Stimulation to Treat Painful Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is the most common neuropathic syndrome seen in patients with diabetes. Roughly 30% of the diabetes patient population1 experience painful DPN symptoms including bilateral stabbing or burning pain in addition to numbness in the feet and lower legs. Traditionally painful DPN symptoms have been treated with conventional medical management (CMM) including glycemic control, general risk factor management, as well as pharmaceutical agents. These treatment approaches are often unsuccessful in the long-term1. Spinal cord stimulation (SCS) has been demonstrated as an effective treatment for painful DPN of the lower extremities with multiple publications dating back to 1996 showing benefits of SCS for pain relief and improved Quality of Life (QoL) in DPN patients (Figure 1)2-18.

ID: 217111 Use of High Frequency Spinal Cord Stimulation to Treat Monoclonal Antibody Induced Neuropathy: Case Report

The use of spinal cord stimulators (SCS) in the treatment of painful diabetic peripheral neuropathy is well-described in medical literature1,2. However, the efficacy of SCS to treat other peripheral neuropathic pain states is not well described. In this case study, we report the use of a high frequency SCS system to treat monoclonal antibody-induced peripheral neuropathy.

ID: 211765 Multiple RCTs of SCS Show Consistent Outcomes in the Treatment of Painful Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is the most common neuropathic syndrome seen in patients with diabetes. DPN symptoms include stabbing or burning pain eventually progressing to numbness in the lower extremities resulting in loss of protective sensation. Traditionally, pain associated with DPN has been treated with gabapentin/pregabalin, tri-cycling antidepressants, and serotonin-norepinephrine reuptake inhibitors1. These treatment approaches are often unsuccessful in the long-term, with many DPN patients abandoning initial prescription analgesics within months1. Spinal Cord Stimulation (SCS) has been examined in 3 randomized controlled trials (RCTs)2,3,4 comparing SCS to conventional treatments.

ID: 209351 Real-World Outcomes in Patients Using SCS for Treatment of Painful Diabetic Peripheral Neuropathy (DPN)

Incidence of type-2 diabetes mellitus is a disorder that has been increasing on a global scale. Within this patient population, there exists a substantial segment that experience Diabetic Peripheral Neuropathy (DPN). Consequently, a growing proportion of this sub-population (thought to occur in up to ∼26%) will likely experience painful DPN.1 Recent advances in Spinal Cord Stimulation (SCS) devices (e.g., waveform options, programming capabilities, hardware designs etc.) has fueled interest in re-assessing various indications for which SCS might be beneficial. In this regard, we sought to examine outcomes for the use of SCS in treatment pain associated with DPN as part of two ongoing real-world studies.

Diabetic neuropathy: Pathogenesis and evolving principles of management

The global rise of prediabetes and diabetes has spawned an epidemic of complications associated with these conditions. Neuropathy is the most common consequence, with distal symmetric polyneuropathy (DSP) being the most prevalent. Diabetic neuropathy (DN) is a debilitating consequence of diabetes mellitus resulting in the highest morbidity and death, besides imposing a substantial financial burden on the patient. Loss of sensory function commencing distally in the lower limbs, accompanied by discomfort and considerable morbidity, characterizes diabetic neuropathy. The clinical evaluation and therapeutic options for diabetic peripheral neuropathy are multifaceted. At least fifty percent of people with diabetes acquire diabetic neuropathy over time. Good glycemic control halts the evolution in individuals with Type 1 diabetes mellitus. These results have prompted fresh attempts to comprehend the origin and develop new guidelines for prevention and treatment. New recommendations have also been established for the treatment of painful DN using separate classes of medications, with an emphasis on avoiding the use of opioids. Although our comprehension of the intricacies of diabetic neuropathy has progressed significantly over the past decade, the unique processes driving the neuropathy in type 1 and type 2 diabetes remain unexplained. Currently, glycemic control and pain management are the only effective therapies. While glucose management significantly reduces neuropathy development in type 1 diabetics, the effect is considerably lower in type 2 diabetics. Evidence supports the use of anticonvulsants and antidepressants for diabetic peripheral neuropathy pain treatment. However, the absence of disease-modifying medications for diabetic DSP necessitates the identification of unrecognized modifiable risk factors. It is imperative to identify the ‘missed’ risk factors and targets, allowing comprehensive, individualized care for patients.

Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies.

Neuropathic pain is a frequent feature of diabetic peripheral neuropathy (DPN) and small fiber neuropathy (SFN). Resolving the genetic architecture of these painful neuropathies will lead to better disease management strategies, counselling and intervention. Our aims were to profile ten sodium channel genes (SCG) expressed in a nociceptive pathway in painful and painless DPN and painful and painless SFN patients, and to provide a perspective for clinicians who assess patients with painful peripheral neuropathy. Between June 2014 and September 2016, 1125 patients with painful-DPN (n = 237), painless-DPN (n = 309), painful-SFN (n = 547) and painless-SFN (n = 32), recruited in four different centers, were analyzed for SCN3A, SCN7A-SCN11A and SCN1B-SCN4B variants by single molecule Molecular inversion probes-Next Generation Sequence. Patients were grouped based on phenotype and the presence of SCG variants. Screening of SCN3A, SCN7A-SCN11A, and SCN1B-SCN4B revealed 125 different (potential) pathogenic variants in 194 patients (17.2%, n = 194/1125). A potential pathogenic variant was present in 18.1% (n = 142/784) of painful neuropathy patients vs. 15.2% (n = 52/341) of painless neuropathy patients (17.3% (n = 41/237) for painful-DPN patients, 14.9% (n = 46/309) for painless-DPN patients, 18.5% (n = 101/547) for painful-SFN patients, and 18.8% (n = 6/32) for painless-SFN patients). Of the variants detected, 70% were in SCN7A, SCN9A, SCN10A and SCN11A. The frequency of SCN9A and SCN11A variants was the highest in painful-SFN patients, SCN7A variants in painful-DPN patients, and SCN10A variants in painless-DPN patients. Our findings suggest that rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification should aid in a better understanding of the genetic variability in patients with painful and painless neuropathy, and may lead to better risk stratification and the development of more targeted and personalized pain treatments.

Prevalence and Predictive Factors of Painful Diabetic Peripheral Neuropathy in The Department of Endocrinology and Metabolic Diseases of The Uhc Ibn Rochd In Casablanca: About 623 cases

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Treatment of Painful Diabetic Neuropathy Using Frequency Rhythmic Electro Magnetic Neural Stimulation (FREMS); Effectiveness in Daily Practice.

Painful diabetic peripheral neuropathy (PDPN) is common and difficult to treat with limited treatment options. We assessed the efficacy of frequency rhythmic electromagnetic neural stimulation (FREMS) in patients with PDPN. An uncontrolled prospective survey of patients with PDPN and pain despite at least two lines of pharmacotherapy. The primary outcome, 50% reduction in pain scores at 1 and/or 3 months post FREMS. FREMS was applied to both legs below the knees using 4 sets of electrodes per leg; the treatment consisted of 10 sessions of 35 min applications given over 14 days. FREMS was repeated every 4 months and patients were followed up for 12 months. Pain was assessed using the neuropathic pain symptom inventory (NPSI) and quality of life (QOL) by the EQ-5D. Out of 336 subjects, 248 patients met the inclusion criteria (56% men), average age and diabetes duration were 65 and 12.6 years respectively. FREMS was associated with a median decrease NPSI of 31% at M1 (range -100;+93%), and a median decrease of -37.5% at M3 (range -100;+250%). The 50% reduction in pain was reached in 80/248 (32.3%) and 87/248 (35.1%) after M1 and M3 respectively. The change in NPSI was accompanied by a decrease in self reported use of opiates of >50%. FREMS treatment was associated with a significant reduction in pain severity over a three months period in patients who did not have adequate response to pharmacotherapy. Randomised (sham)-controlled trials examining the role of FREMS as a treatment for PDPN in non-responders to pharmacotherapy are needed.

Effect of novel Matrix Rhythm Therapy (MaRhyThe®) on neuropathic pain and maximum plantar pressure distribution among type 2 diabetes mellitus patients with peripheral neuropathy

BackgroundThere is a need for a non-pharmacological approach to reduce pain and plantar pressure in diabetic peripheral neuropathy (DPN). Matrix Rhythm Therapy (MaRhyThe®) is a therapeutic modality that works on the principle of physiologic rhythmic oscillations of the body cells. This study aimed to evaluate the effect of MaRhyThe® on neuropathic pain and maximum plantar pressure distribution among type 2 diabetes mellitus patients with peripheral neuropathy.Materials and methodsA total of 33 participants with DPN were recruited for the study based on inclusion criteria. Maximum plantar pressure was recorded using Win-Track 11K005, and the pain score was obtained using a visual analogue scale. Ten sessions of MaRhyThe® were given to all the participants. Outcome measures were evaluated at the baseline and after 10th session. Paired t-test was performed to analyze the changes in outcome measures.ResultsParticipants of DPN were recruited with the average age of 64 ± 9 years, and an average duration of diabetes was 14 ± 9 years were included. Results of the present study found significant improvement in neuropathic pain and plantar pressure in post intervention assessment. (p < 0.05)ConclusionIn the present study, we found that MaRhyThe® is effective in reducing neuropathic pain and maximum plantar pressure in type 2 diabetes mellitus with peripheral neuropathy.

Cognitive function in individuals with and without painful and painless diabetic polyneuropathy-A cross-sectional study in type 1 diabetes.

Previous studies suggest that cognitive impairment is more prevalent in individuals with painful and painless diabetic peripheral neuropathy (DPN). However, the current evidence is not well described. This study investigated cognitive function in adults with type 1 diabetes mellitus (T1DM) and the association to painful/painless DPN and clinical parameters. This cross-sectional, observational, case-control study included 58 participants with T1DM, sub-grouped into 20 participants with T1DM and painful DPN, 19 participants with T1DM and painless DPN, 19 participants with T1DM without DPN, and 20 healthy controls were included. The groups were matched for sex and age. The participants performed Addenbrooke's examination III (ACE-III), which assesses attention, memory, verbal fluency, language and visuospatial skills. Working memory was evaluated using an N-back task. Cognitive scores were compared between the groups and correlated to age, diabetes duration, HbA1c and nerve conduction measurements. Compared to healthy controls, T1DM participants showed lower total ACE-III (p = .028), memory (p = .013) and language scores (p = .028), together with longer reaction times in the N-back task (p = .041). Subgroup analyses demonstrated lower memory scores in those with painless DPN compared with healthy controls (p = .013). No differences were observed between the three T1DM subgroups. Cognitive scores and clinical parameters were not associated. This study supports the notion of cognitive alterations in T1DM and indicates that cognitive function is altered in T1DM regardless of underlying neuropathic complications. The memory domain appears altered in T1DM, particularly in those with painless DPN. Further studies are needed to verify the findings.

Human IAPP is a contributor to painful diabetic peripheral neuropathy.

Peripheral neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). We investigated whether human islet amyloid polypeptide (hIAPP), which forms pathogenic aggregates that damage pancreatic islet β cells in T2DM, is involved in T2DM-associated peripheral neuropathy. In vitro, hIAPP incubation with sensory neurons reduced neurite outgrowth and increased levels of mitochondrial reactive oxygen species. hIAPP-transgenic mice, which have elevated plasma hIAPP levels without hyperglycemia, developed peripheral neuropathy as evidenced by pain-associated behavior and reduced intraepidermal nerve fiber (IENF) density. Similarly, hIAPP Ob/Ob mice, which have hyperglycemia in combination with elevated plasma hIAPP levels, had signs of neuropathy, although more aggravated. In wild-type mice, intraplantar and intravenous hIAPP injections induced long-lasting allodynia and decreased IENF density. Non-aggregating murine IAPP, mutated hIAPP (pramlintide), or hIAPP with pharmacologically inhibited aggregation did not induce these effects. T2DM patients had reduced IENF density and more hIAPP oligomers in the skin compared with non-T2DM controls. Thus, we provide evidence that hIAPP aggregation is neurotoxic and mediates peripheral neuropathy in mice. The increased abundance of hIAPP aggregates in the skin of T2DM patients supports the notion that hIAPP is a potential contributor to T2DM neuropathy in humans.

Treatment of DPN with 8% topical capsaicin without the use of a topical anesthetic

PURPOSEA qualitative study was done to look at the use of 8% topical capsaicin without the use of a topical anesthetic prior to treatment of DPN. In the PI it is indicated to anesthetize the affected area with topical lidocaine prior to the treatment for painful diabetic peripheral neuropathy of the feet. Many patients with diabetic peripheral neuropathy have significant numbness in their feet and limited feeling and there may not be a need for a topical anesthetic prior to application of the topical system. Applying a topical anesthetic can be time consuming to allow it to take full effect and may not be necessary. For the purposes of this study the clinics ethics committee was consulted, and approval was granted. METHODSIs topical anesthetic necessary before the procedure for the treatment of painful diabetic peripheral neuropathy with 8% topical capsaicin? 15 patient charts were reviewed at random that had received treatment with administered 8% topical capsaicin patches for their diabetic peripheral neuropathy. No topical anesthetic was used prior to the procedure. The patient was monitored throughout the procedure and ice was offered to place over the top of the patch, if needed for administration site pain. RESULTSMost patient's that did not have a topical anesthetic prior to their procedure of 8% topical capsaicin for the treatment of painful diabetic peripheral neuropathy, tolerated the procedure well without any significant increased pain or the need for interventions, such as ice. CONCLUSIONTopical anesthetic can be time consuming and cumbersome. In many patients with severe diabetic peripheral neuropathy that has resulted in significant paresthesia, a topical anesthetic is not necessary due to the patient's limited feeling in the feet. This results in a more streamline process with less time for the patient to be in the office.

Multi-omics analysis revealed the role of CYP1A2 in the induction of mechanical allodynia in type 1 diabetes.

Background: Mechanical allodynia (MA) is one of the leading clinical symptoms of painful diabetic peripheral neuropathy (PDPN), which is a primary reason for non-traumatic amputations, foot ulceration, and gait abnormalities in patients with diabetes. However, the pathogenic mechanisms of MA have not yet been fully elucidated, and there is no effective treatment. This study aims to study the potential pathogenetic mechanisms of MA and to provide targets for the therapy of MA. Methods: A single intraperitoneal injection of streptozotocin induced type 1 diabetes in rat models. Subsequently, rats were divided into the control group, the diabetic group without MA, and the diabetic group with MA based on weekly behavioral assays. The differentially expressed lipids in the sciatic nerve of each group were detected using untargeted lipidomics, and the differentially expressed genes in the sciatic nerve of each group were detected by transcriptomics. The pathogenesis of MA was predicted using integrated analysis and validated by immunofluorescence staining and transmission electron microscopy. Results: Untargeted lipidomics revealed the accumulation of a more severe lipid in MA rats. Transcriptomics results suggested that differentially expressed genes in MA rats were primarily related to lipid droplets and myelin sheath. Integrated analysis results indicated that the downregulation of Cytochrome P450 1A2 (CYP1A2) expression was closely linked to lipid metabolism disorders. Immunofluorescence staining demonstrated that down-regulation of CYP1A2 expression occurred in MA rats. Transmission electron microscopy results showed that more severe lipid droplet accumulation and myelin sheath degeneration occurred in MA rats. Conclusion: Our findings imply that the downregulation of CYP1A2 expression leads to disorders of lipid metabolism and further leads to lipid droplet accumulation and myelin sheath degeneration, which might ultimately lead to the development of MA. Therefore, our study contributes to promoting the understanding of the molecular mechanisms of MA and providing potential targets for the clinical treatment of MA.