Diabetic Nerve Research Articles

Novel Biomarker for Demyelination in Diabetic Distal Symmetric Polyneuropathy: A Prospective Study (P11-8.006)

<h3>Objective:</h3> To develop a new strategy to identify acquired demyelination in diabetic distal symmetric polyneuropathy (DSP). <h3>Background:</h3> Motor nerve conduction velocity (CV) slowing in diabetic DSP exceeds what is expected from pure axonal loss and can be attributed to additional acquired demyelination. <h3>Design/Methods:</h3> We prospectively studied CV and urine secretory phospholipase A2 (sPLA2) activity in 90 diabetic DSP patients divided into 2 groups A and B with and without at least one motor nerve with CV slowing in the demyelination range by AAN criteria. sPLA2 activity was tested in 46 healthy controls. In parallel, we studied CV in these diabetic patients using a regression analysis that we developed and validated from data from 114 CIDP patients. <h3>Results:</h3> Mean urine sPLA2 activity was significantly higher in diabetic groups compared to healthy controls, (942.9 ± 977.97 vs. 591.6 ± 390.15, pmol/min/ml p &lt; 0.05), and was significantly higher in group A compared to B, (1328.3 ± 1274.21 vs. 673.8 ± 576.93 pmol/min/ml, p = 0.0014). The number of patients with elevated sPLA2 activity and have more than 2 motor nerves with CV slowing in the AAN or regression analysis ranges was significantly higher in patients of group A compared to group B (35.1% vs. 5.7%, p = 0.0005). Furthermore, 13.5% in diabetic DSP group A and no patient in diabetic DSP group B fulfilled an additional criteria of more than one motor nerve with CV slowing in the demyelinating range with the corresponding F response in the demyelinating range by AAN criteria. <h3>Conclusions:</h3> To the best of our knowledge, the present study is the first to use a combination of regression analysis of electrodiagnostic data and a urine biological marker of inflammation to identify a subgroup of diabetic DSP with significant contribution of acquired demyelination and neuroinflammation in diabetic nerve injury. <b>Disclosure:</b> Mr. Jaffry has nothing to disclose. Miss Shaikh has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Mandava has nothing to disclose. Mr. Trivedi has nothing to disclose. Mr. Ors has nothing to disclose. Ms. Faiz has nothing to disclose. Dr. Patel has nothing to disclose. Ankit Pahwa has nothing to disclose. Hongxin Chen has nothing to disclose. Timothy Cunningham has received intellectual property interests from a discovery or technology relating to health care. Dr. Sander has received personal compensation for serving as an employee of Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Law firm. Dr. Souayah has received publishing royalties from a publication relating to health care.

Methods for evaluation of corneal nerve fibres in diabetes mellitus by in vivo confocal microscopy: a scoping review protocol

IntroductionGlobally, 422 million people have diabetes. Late complications of diabetes are blindness, kidney failure, heart attack, stroke and lower limb amputation. The prevalence of diabetic peripheral neuropathy and diabetic retinopathy...

Dry eye disease in diabetics versus non-diabetics: Associating dry eye severity with diabetic retinopathy and corneal nerve sensitivity.

To compare the prevalence of dry eye disease (DED) and assess corneal nerve sensitivity (CNS) in diabetic and non-diabetic patients. To study the association of severity of DED in patients with diabetic retinopathy (DR) and CNS in DED. A cross-sectional prospective comparative study was conducted on 400 patients attending the ophthalmology OPD. The patients above 18 years of age were divided into two groups-diabetic (T2DM) and non-diabetic. All patients were subjectively assessed for DED based on Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire and objectively, using Schirmer's II test and Tear Film Break-Up Time (TBUT). Visual acuity assessment, anterior segment, and posterior segment evaluation were done. Considering the SPEED score, Schirmer II values, TBUT values, and Dry Eye Work Shop (DEWS) II diagnostic criteria, mild DED was seen in 23% diabetic and 22.25% non-diabetic groups, moderate DED in 45.75% diabetic and 9.75% non-diabetic groups, and severe DED in 2% diabetic and 1.75% non-diabetic groups. Moderate DED was more common within all grades of DR. CNS was reduced more in diabetic group and also in patients with higher degree of DED. Prevalence of DED is more in the patients with T2DM. CNS was reduced more in patients with T2DM and in patients with moderate DED. Our study also correlated that severity of DR affects the severity of DED.

Effect of Surgical Release of Entrapped Peripheral Nerves in Sensorimotor Diabetic Neuropathy on Pain and Sensory Dysfunction—Study Protocol of a Prospective, Controlled Clinical Trial

Nerve entrapment has been hypothesized to contribute to the multicausal etiology of axonopathy in sensorimotor diabetic neuropathy. Targeted surgical decompression reduces external strain on the affected nerve and, therefore, may alleviate symptoms, including pain and sensory dysfunction. However, its therapeutic value in this cohort remains unclear. Quantifying the treatment effect of targeted lower extremity nerve decompression in patients with preexisting painful sensorimotor diabetic neuropathy and nerve entrapment on pain intensity, sensory function, motor function, and neural signal conduction. This prospective, controlled trial studies 40 patients suffering from bilateral therapy-refractory, painful (n = 20, visual analogue scale, VAS ≥ 5) or painless (n = 20, VAS = 0) sensorimotor diabetic neuropathy with clinical and/or radiologic signs of focal lower extremity nerve compression who underwent unilateral surgical nerve decompression of the common peroneal and the tibial nerve. Tissue biopsies will be analyzed to explore perineural tissue remodeling in correlation with intraoperatively measured nerve compression pressure. Effect size on symptoms including pain intensity, light touch threshold, static and moving two-point discrimination, target muscle force, and nerve conduction velocity will be quantified 3, 6, and 12 months postoperatively, and compared (1) to the preoperative values and (2) to the contralateral lower extremity that continues non-operative management. Targeted surgical release may alleviate mechanical strain on entrapped lower extremity nerves and thereby potentially improve pain and sensory dysfunction in a subset of patients suffering from diabetic neuropathy. This trial aims to shed light on these patients that potentially benefit from screening for lower extremity nerve entrapment, as typical symptoms of entrapment might be erroneously attributed to neuropathy only, thereby preventing adequate treatment.

Schwann cells contribute to demyelinating diabetic neuropathy and nerve terminal structures in white adipose tissue

Peripheral neuropathy, which can include axonal degeneration and/or demyelination, impacts adipose tissues with obesity, diabetes, and aging. However, the presence of demyelinating neuropathy had not yet been explored in adipose. Both demyelinating neuropathies and axonopathies implicate Schwann cells (SCs), a glial support cell that myelinates axons and contributes to nerve regeneration after injury. We performed a comprehensive assessment of SCs and myelination patterns of subcutaneous white adipose tissue (scWAT) nerves, and changes across altered energy balance states. We found that mouse scWAT contains both myelinated and unmyelinated nerves and is populated by SCs, including SCs that were associated with synaptic vesicle-containing nerve terminals. BTBR ob/ob mice, a model of diabetic peripheral neuropathy, exhibited small fiber demyelinating neuropathy and alterations in SC marker gene expression in adipose that were similar to obese human adipose. These data indicate that adipose SCs regulate the plasticity of tissue nerves and become dysregulated in diabetes.

Deficient deposition of new myelin impairs adult optic nerve function in a murine model of diabetes.

Visual impairment in diabetes is a growing public health concern. Apart from the well-defined diabetic retinopathy, disturbed optic nerve function, which is dependent on the myelin sheath, has recently been recognized as an early feature of visual impairment in diabetes. However, the underlying cellular mechanisms remain unclear. Using a streptozotocin-induced diabetic mouse model, we observed a myelin deficiency along with a disturbed composition of oligodendroglial lineage cells in diabetic optic nerve. We found that new myelin deposition, a continuous process that lasts throughout adulthood, was diminished during pathogenesis. Genetically dampening newly generated myelin by conditionally deleting olig2 in oligodendrocyte precursor cells within this short time window extensively delayed the signal transmission of the adult optic nerve. In addition, clemastine, an antimuscarinic compound that enhances myelination, significantly restored oligodendroglia, and promoted the functional recovery of the optic nerve in diabetic mice. Together, our results point to the role of new myelin deposition in optic neuropathy under diabetic insult and provide a promising therapeutic target for restoring visual function.

RAGE activation in macrophages and development of experimental diabetic polyneuropathy

It is suggested that activation of receptor for advanced glycation end products (RAGE) induces proinflammatory response in diabetic nerve tissues. Macrophage infiltration is invoked in the pathogenesis of diabetic polyneuropathy (DPN), while the association between macrophage and RAGE activation and the downstream effects of macrophages remain to be fully clarified in DPN. This study explored the role of RAGE in the pathogenesis of DPN through the modified macrophages. Infiltrating proinflammatory macrophages impaired insulin sensitivity, atrophied the neurons in dorsal root ganglion, and slowed retrograde axonal transport (RAT) in the sciatic nerve of type 1 diabetic mice. RAGE-null mice showed an increase in the population of antiinflammatory macrophages, accompanied by intact insulin sensitivity, normalized ganglion cells, and RAT. BM transplantation from RAGE-null mice to diabetic mice protected the peripheral nerve deficits, suggesting that RAGE is a major determinant for the polarity of macrophages in DPN. In vitro coculture analyses revealed proinflammatory macrophage-elicited insulin resistance in the primary neuronal cells isolated from dorsal root ganglia. Applying time-lapse recording disclosed a direct impact of proinflammatory macrophage and insulin resistance on the RAT deficits in primary neuronal cultures. These results provide a potentially novel insight into the development of RAGE-related DPN.

Painful Diabetic Nerve Damage Common in Spine Practices

Painful Diabetic Nerve Damage Common in Spine Practices

Comparative co-expression analysis of RNA-Seq transcriptome revealing key genes, miRNA and transcription factor in distinct metabolic pathways in diabetic nerve, eye, and kidney disease.

Diabetes and its related complications are associated with long term damage and failure of various organ systems. The microvascular complications of diabetes considered in this study are diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. The aim is to identify the weighted co-expressed and differentially expressed genes (DEGs), major pathways, and their miRNA, transcription factors (TFs) and drugs interacting in all the three conditions. The primary goal is to identify vital DEGs in all the three conditions. The overlapped five genes (AKT1, NFKB1, MAPK3, PDPK1, and TNF) from the DEGs and the co-expressed genes were defined as key genes, which differentially expressed in all the three cases. Then the protein-protein interaction network and gene set linkage analysis (GSLA) of key genes was performed. GSLA, gene ontology, and pathway enrichment analysis of the key genes elucidates nine major pathways in diabetes. Subsequently, we constructed the miRNA-gene and transcription factor-gene regulatory network of the five gene of interest in the nine major pathways were studied. hsa-mir-34a-5p, a major miRNA that interacted with all the five genes. RELA, FOXO3, PDX1, and SREBF1 were the TFs interacting with the major five gene of interest. Finally, drug-gene interaction network elucidates five potential drugs to treat the genes of interest. This research reveals biomarker genes, miRNA, TFs, and therapeutic drugs in the key signaling pathways, which may help us, understand the processes of all three secondary microvascular problems and aid in disease detection and management.

Perception threshold tracking: validating a novel method for assessing function of large and small sensory nerve fibers in diabetic peripheral neuropathy with and without pain.

It remains unknown why some people with diabetes develop painful neuropathies while others experience no pain. This study aimed to validate a novel method for assessing the function of small sensory nerves in diabetes to further elucidate this phenomenon. The function of large and small nerves was assessed using a novel perception threshold tracking technique in 3 well-characterized groups (n = 60) with type 1 diabetes, namely, (1) painful diabetic peripheral neuropathy (T1DM + PDPN), (2) painless diabetic peripheral neuropathy (T1DM + DPN), and (3) no neuropathy (T1DM - DPN), and healthy controls (n = 20). Electrical currents with different shapes, duration, and intensities were applied by 2 different skin electrodes activating large and small fibers, respectively. The minimal current needed to activate the fibers were analyzed as the rheobase of the stimulus-response function. Nerve fiber selectivity was measured by accommodation properties of stimulated nerves. The rheobase of both fiber types were highest for T1DM + PDPN, followed by T1DM + DPN, T1DM - DPN, and healthy controls, indicating that the nerve properties are specific in individuals with diabetes and pain. There was an overall significant difference between the groups ( P < 0.01). The accommodation properties of stimulated fibers were different between the 2 electrodes ( P < 0.05) apart from in the group with T1DM + PDPN, where both electrodes stimulated nerves displaying properties similar to large fibers. Perception threshold tracking reveals differences in large and small nerve fiber function between the groups with and without diabetes, DPN, and pain. This indicates that the methods have potential applications in screening DPN and explore further the features differentiating painful from nonpainful DPN.

The receptor for advanced glycation end products and its ligands' expression in OVE26 diabetic sciatic nerve during the development of length-dependent neuropathy.

Type 1 diabetes (T1D) may affect the peripheral nervous system and alter the expression of proteins contributing to inflammation and cellular cytoskeleton dysfunction, in most cases leading to the development of diabetic length-dependent neuropathy (DLDN). In the present study, we performed immunohistochemistry (IHC) to probe the expression of the receptor for advanced glycation end products (RAGE); its key ligands, high-mobility group box 1 (HMGB1), S100 calcium-binding protein B (S100B), and carboxymethyl-lysine (CML - advanced glycation end products (AGE)); and its cytoplasmic tail-binding partner, diaphanous related formin 1 (DIAPH1) and associated molecules, beta-actin (ACTB) and profilin 1 (PFN1) proteins in sciatic nerves harvested from seven-month old FVB/OVE26 mice with genetically-mediated T1D. We found that the amount of RAGE, HMGB1, and S100B proteins was elevated in diabetic vs the non-diabetic groups, while the amount of DIAPH1, ACTB, as well as PFN1 proteins did not differ between these groups. Moreover, our data revealed linear dependence between RAGE and HMGB1 proteins. Interaction criss-cross of selected sets of proteins in the sciatic nerve revealed that there were connected in a singular network. Our results indicate that T1D may alter expression patterns of RAGE axis proteins and thus contribute to DLDN.

Beneficial Effects of lncRNA-UC.360+ shRNA on Diabetic Cardiac Sympathetic Damage via NLRP3 Inflammasome-Induced Pyroptosis in Stellate Ganglion.

Hyperglycemia is one of the common symptoms of diabetes, and it produces excessive reactive oxygen species (ROS). This study investigated whether the long noncoding RNA (lncRNA) UC.360+ is involved in diabetic cardiac autonomic neuropathy (DCAN) mediated by NLRP3 inflammasome-induced pyroptosis in the stellate ganglion (SG). Using a rat type 2 diabetes model, we found that lncRNA UC.360+ short hairpin RNA (shRNA) ameliorated the dyslipidaemia of type 2 diabetic rats and reduced serum adrenaline and ROS production in SG under hyperglycemia. In addition, UC.360+ shRNA also reduced the expression of nuclear factor kappa-B (NF-κB), NLRP3, ASC, caspase-1, interleukin-1β (IL-1β), and IL-18 in the SG of diabetic rats and inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Therefore, lncRNA-UC.360+ shRNA may modulate the NLRP3 inflammasome/inflammatory pathway in the SG, which in turn alleviates diabetic heart sympathetic nerve damage.

25-LB: Peripheral Neuropathy and Associated Factors in Patients with Type 2 Diabetes Mellitus in Vietnam—A Cross-Sectional Study

Peripheral neuropathy and associated factors in patients with type 2 diabetes mellitus in Vietnam: A cross-sectional study Diabetes peripheral neuropathy (DPN) is the most common complication associated with diabetes mellitus. We aimed to establish the characteristic and associated factors of DPN in Vietnam. In total, 140 patients with type 2 diabetes mellitus (T2DM) were screened and enrolled consecutively over a six month period at the endocrinology department in 103 Military hospital. Questionnaires, demographic details, clinical examination, and blood tests were used to collect data from all patients. DPN was evaluated using diabetes neuropathy symptom score and nerve conduction study. Potential factors related to DPN were explored including body mass index, years with disease (&amp;lt;10 vs. ≥10 years) , glycemic control (HbA1C &amp;lt;7.5% vs. ≥ 7.5%) , glomerular filtration rate (GFR) , lipid profile. The prevalence of DPN was 43.5% (61/140) in the number of patients with T2DM. The main manifestation of peripheral nerve damage in subject is numbness 54,1%, decreased rough touch 52,56%. The majority of patients did not have movement disorders 95.08% and normal sense of deep sensation 93,4%. The percentage of patients with a burning sensation, reduction in raw tactile and movement disorders was higher in the group with duration of disease over 10 years (n=23) , compared to the group less than 10 years (n=38) (p &amp;lt;0.05) . The neurotransmitter index in the group of patients with HbA1C ≥ 7.5% (n=17) was significantly different compared to the group with HbA1C &amp;lt; 7.5% (n=44) (p &amp;lt; 0.05) . The group with GFR &amp;lt;70 ml/ph/1.73m2 (n=12) showed the significant change in nerve conduction parameters compared to the group with GFR ≥ 70 ml/ph/1.73m2 (n=49) (p &amp;lt; 0.05) . DPN is highly frequent among patients with T2DM in Vietnam. Associated factors to DPN included duration of disease, HbA1C level and GFR index. The good glycemic control and early clinical manifestation as well as evaluating the kidney function would play an important role in this problem. Disclosure N. T. T. Trang: None. T. Fong: None. T. D. Do: None.

Painful Diabetic Nerve Damage Common in Spine Practices

Painful Diabetic Nerve Damage Common in Spine Practices

Association of serum vitamin d level with diabetic polyneuropathy in rural population of central India

To evaluate association of serum Vitamin D level and development of polyneuropathy. This was a case -control study and the study was conducted on an outpatient basis. Fifty-five subjects were recruited from the Medicine OPD of UPUMS Saifai. All subjects had type-2 diabetes (male and female, 40-60 years old). The Michigan Neuropathy Screening Instrument (15-point questionnaire) was used to identify patients with neuropathy (score &gt; 7/15). 20 patients did not have neuropathy and were designated the control group. 35 patients did have neuropathy (“study group”) and these patients underwent a detailed quantitative neuropathy evaluation by a neurologist using the 46-point Michigan Diabetic Neuropathy Scale (MDNS) and nerve conduction studies. We measured the serum 25-hydroxyvitamin D concentrations with liquid chromatography-tandem mass spectrometry (LC/MS) chromatography in all patients. These values were compared between the control and study group, and were correlated with the detailed neuropathy score in the study group. Patients with diabetic polyneuropathy had a lower mean serum 25- hydroxyvitamin D level (16. 41 ng/ml with the SD of: 2.026) in comparison to the controls (38.76 ng/ml with the SD of 5.483).

P127. EFFECT OF LOWER EXTREMITY NERVE DECOMPRESSION IN PATIENTS WITH PAINFUL DIABETIC NEUROPATHY ON NARCOTIC USE AND ULCERATION RATES: A 10-YEAR FOLLOW-UP FROM THE PROSPECTIVE, CONTROLLED, RANDOMIZED, DOUBLE BLINDED, DNND I AND DNND II TRIALS

PURPOSE: 10% of over 80 million American patients suffering from painful Diabetic Peripheral Neuropathy (DPN) rely on narcotics for pain relief. We present the 10-year follow-up from the Diabetic Neuropathy Nerve Decompression (DNND) I & II trials to determine the effect of nerve decompression on narcotic reliance and foot ulceration. METHODS: The DNND I study, a prospective, randomized, patient and rater-blinded, observation group plus same-patient sham surgery-controlled trial with 5-year follow-up, evaluated the effect of nerve decompression on pain. The DNND II study consisted of 10 year follow ups on the same cohort. Narcotic requirements were calculated in Milligrams Morphine Equivalents per day (MME/day) through standardized conversions and podiatric foot exams recorded ulcerations. RESULTS: Of 2987 screened patients, 138 were enrolled in DNND I - 92 randomized to surgery and 46 to controls. 24 surgical and 12 control patients who participated in all visits were included for analysis. Compared to baseline, at 12 months, surgical and control groups did not experience significant changes in MME/day requirements, but the surgical group experienced a significant reduction of -2.8 (p=0.004) at 56 months, and -23.3 (p=0.0001) at 10 years while controls experienced no change (p=0.96). Compared to control patients, surgical patients had similar mean MME/day requirements at 0 months (p=0.98) and 12 months (p=0.78), but lower requirements at 56 months (p=0.003) and 10 years (p=0.006). Prevalence of foot ulceration was similar between groups at 10 years (p=0.67). CONCLUSION: Nerve decompression provides long-term analgesic and decreased reliance on narcotics in DPN patients.

Blockage of MLKL prevents myelin damage in experimental diabetic neuropathy

SignificanceDiabetic neuropathy is a commonly occurring complication of diabetes that affects hundreds of millions of patients worldwide. Patients suffering from diabetic neuropathy experience abnormal sensations and have damage in their peripheral nerve axons as well as myelin, a tightly packed Schwann cell sheath that wraps around axons to provide insulation and increases electrical conductivity along the nerve fibers. The molecular events underlying myelin damage in diabetic neuropathy are largely unknown, and there is no efficacious treatment for the disease. The current study, using a diabetic mouse model and human patient nerve samples, uncovered a molecular mechanism underlying myelin sheath damage in diabetic neuropathy and provides a potential treatment strategy for the disease.

Altered Circulating microRNAs in Patients with Diabetic Neuropathy and Corneal Nerve Loss: A Pilot Study.

An alteration in circulating miRNAs may have important diagnostic and therapeutic relevance in diabetic neuropathy. Patients with type 2 diabetes mellitus (T2DM) underwent an assessment of neuropathic symptoms using Douleur Neuropathique 4 (DN4), the vibration perception threshold (VPT) using a Neurothesiometer, sudomotor function using the Sudoscan, corneal nerve morphology using corneal confocal microscopy (CCM) and circulating miRNAs using high-throughput miRNA expression profiling. Patients with T2DM, with (n = 9) and without (n = 7) significant corneal nerve loss were comparable in age, gender, diabetes duration, BMI, HbA1c, eGFR, blood pressure, and lipid profile. The VPT was significantly higher (p < 0.05), and electrochemical skin conductance (p < 0.05), corneal nerve fiber density (p = 0.001), corneal nerve branch density (p = 0.013), and corneal nerve fiber length (p < 0.001) were significantly lower in T2DM patients with corneal nerve loss compared to those without corneal nerve loss. Following a q-PCR-based analysis of total plasma microRNAs, we found that miR-92b-3p (p = 0.008) was significantly downregulated, while miR-22-3p (p = 0.0001) was significantly upregulated in T2DM patients with corneal nerve loss. A network analysis revealed that these miRNAs regulate axonal guidance and neuroinflammation genes. These data support the need for more extensive studies to better understand the role of dysregulated miRNAs’ in diabetic neuropathy.

Isolation and Characterization of Primary Retinal Microglia From the Human Post-mortem Eyes for Future Studies of Ocular Diseases.

Microglia, the primary resident immunocytes in the retina, continuously function as immune system supervisors in sustaining intraocular homeostasis. Microglia relate to many diseases, such as diabetic retinopathy, glaucoma, and optic nerve injury. To further investigate their morphology and functions in vitro, a reliable culture procedure of primary human retinal microglia is necessary. However, the culture condition of microglia from the adult retina is unclear. Researchers created several protocols, but most of them were carried out on rodents and newborns. This study describes a protocol to isolate and characterize human primary retinal microglia from human post-mortem eyes. The whole procedure started with removing the retinal vessels, mechanical separation and enzymatic dissociation, filtration, and centrifugation. Then, we cultured the cell suspensions on a T-75 flask for 18 days and then shook retinal microglia from other retinal cells. We found numerous retinal microglia grow and attach to Müller cells 10 days after seeding and increase rapidly on days 14–18. Iba1 and P2RY12 were used to qualify microglia through immunofluorescence. Moreover, CD11b and P2RY12 were positive in flow cytometry, which helps to discriminate microglia from other cells and macrophages. We also observed a robust response of retinal microglia in lipopolysaccharide (LPS) treatment with proinflammatory cytokines. In conclusion, this study provides an effective way to isolate and culture retinal microglia from adult human eyes, which may be critical for future functional investigations.

Type 1 Diabetes Mellitus and Peripheral Nerve Injury Occurring After PD-1 Treatment: A Case Report and Analysis

Objective: To raise the clinicians’ awareness of the rare adverse event of Immune Checkpoint Inhibitor (ICPis)-associated diabetes mellitus and peripheral nerve injury. Methods: We report a case of ICPis-associated diabetes and peripheral nerve injury caused by treatment with pablizumab in a 60-year-old male with lung cancer. Results: We describe a 60-year-old male who presented with “three more and one less” diabetic symptoms and severe numbness in the extremities after treatment with pabrolizumab. Based on the patient’s clinical symptoms, ancillary tests and corresponding follow-up findings, the patient was finally diagnosed with ICPis-associated type 1 diabetes and ICPis-associated peripheral nerve injury. The patient had poor compliance and was not given insulin glucose-lowering therapy at the beginning of the disease, and now the pancreatic islet function was severely impaired, the glycemic control was poor, and the numbness of the extremities did not improve significantly, which seriously affected the quality of life of the patient. Conclusion: ICPis-related diabetes mellitus and peripheral nerve injury is a relatively rare immune-related adverse reaction, which progresses rapidly and is more harmful, and therefore, should be taken seriously by doctors and patients in clinical work.