Diabetic Nerve Research Articles

Evaluation of the Corneal Thickness and Endothelial Changes Following Uncomplicated Phacoemulsification in Diabetic and Non-Diabetic Patients by Pentacam and Specular Microscopy

Background: Diabetes mellitus (DM) is an important health problem that induces unrestful complications. It causes significant morbidity owing to specific microvascular complications such as diabetic retinopathy, diabetic cataract, diabetic keratopathy, and diabetic optic nerve diseases. Patients and Methods: This is a prospective, comparative case series study assessing the corneal endothelial status in 20 diabetics and 20 non diabetics before, after 1 day, 1 week and 1 month of uneventful phacoemulsification using phaco-chop technique. Central corneal thickness (CCT), as well as endothelial cell density (ECD), coefficient of variation (CV) and percentage of polymegathism or hexagonality were measured by specular microscopy. The corneal thickness at 0, 2 and 4 mm from center of the cornea and corneal volume at 3, 5 and 7 mm from the center of the cornea. Changes were compared between both groups using pentacam in the same follow up period. Results: Preoperative CCT was found to be significantly higher in diabetic than in non-diabetic group. ECD and CV were insignificantly higher in diabetics in contrast with the percentage of hexagonality, which was found to be insignificantly lower preoperatively. Diabetics showed insignificant higher loss in endothelial cell count as compared to non-diabetics. Furthermore, the diabetics showed a slower recovery trend in the endothelial healing response as evidenced by lower change in the CV%. Postoperative CCT measurements demonstrated no significant variations between groups evidenced by specular microscopy as well as changes in corneal thickness and volume evidenced by pentacam. Conclusion: The present study revealed no significant differences between preoperative and postoperative values neither in terms of mean ECD values, nor in corneal thickness and corneal volume between diabetic patients and nondiabetic patients undergoing phacoemulsification employing phaco-chop technique.

Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment

BackgroundCharcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. DesignRetrieval of surgical pathology midfoot specimens from Charcot patients (2012–2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (<half 40× hpf) periarticular bone fragments to resolution, we devised and applied a Charcot neuropathic arthropathy novel FEMASK-score (named after coauthors: Fanburg-Smith, Frauenhoffer, Flemming, Fritsche, Elfar, Murie, Aynardi, Stauch, Smith, King, and Klein): 0 (initial) = the observed intraneural arteriolosclerosis in all diabetic neuropathic patient specimens (not observed in other diabetic nerves); and finally scored with the most destruction observed: 1 = large bone fragments without host histiocytic response; 2 = mixed bone fragments with host histiocytic response; 3 = small minute bone spicules resorption to fibrosis. Eichenholtz stage and outcome were then compared. ResultsForty-eight cases of Charcot neuropathic arthropathy included 34 males and 14 females, mean age 60.3 and age range 28–83 years, with clinical diabetes mellitus (predominantly Type II) and longstanding neuropathy. Elevated HbA1C, Eichenholtz stage, American Society of Anesthesia score, and Charlson comorbidity index indicated initial clinical amputation. Pathologic specimens varied from fixation tissue to amputation. In addition to neurotraumatic, neurovascular and inflammatory findings, a distinctive intraneural hyalinized arteriolosclerosis was observed. FEMASK-scores: 1 = 10%, 2 = 58%, and 3 = 32%. Score comparisons were 98% accurate compared with Eichenholtz and 98% reproducible among pathologists. FEMASK 2 and 3 correlate with clinical need for amputation. ConclusionsOur novel Charcot neuropathic arthropathy FEMASK-score classification, derived from the largest cohort of diabetic neuropathic specimens, is reproducible, explains pathophysiologic progression of destructive phase of Charcot, correlates with Eichenholtz, and predicts progression to or clinical need for amputation. The unique intraneural vasculopathy observed contributes to Charcot neuropathic arthropathy etiology.

DNase I improves corneal epithelial and nerve regeneration in diabetic mice.

DNase I has been reported to improve diabetic wound healing through the clearance of neutrophils extracellular traps (NETs) caused by neutrophil aggregation. However, the function of DNase I on diabetic corneal wound healing remains unclear. Here, we investigated the effect and mechanism of topical DNase I application on diabetic mouse corneal epithelial and nerve regeneration. Corneal epithelial defects, inflammatory response, regeneration‐related signalling pathways, oxidative stress, corneal innervation and sensation were examined and compared between the diabetic and normal mice. The results confirmed firstly the increased NETs production during the delayed corneal epithelial wound healing of diabetic mice, which was significantly improved through either DNase I or Cl‐amidine administration. Mechanistically, DNase I improved inflammation resolution, reactivated epithelial regeneration‐related signalling pathways and attenuated the accumulation of reactive oxygen species (ROS). Moreover, DNase I application also promoted corneal nerve regeneration and restored the impaired corneal sensitivity in diabetic mice. Therefore, these results indicate that topical DNase I application promotes corneal epithelial wound healing and mechanical sensation restoration in diabetic mice, representing the potential therapeutic approach for diabetic keratopathy.

Studying the Effect of Adding Alpha Lipoic Acid to Gabapentin to Improve Nerve Conduction Velocity and Glycemic Control of Patients with Diabetic Neuropathy (Sample of Iraqi population)

Diabetic neuropathy (DN) is the most common chronic complication of diabetes mellitus. Hyperglycemia-induced oxidative stress induces programmed cell death of nerves, which contributes to the pathology of Diabetic neuropathy. Many clinical trials depend on supplement, in an attempt to improve neuropathy symptoms such as (pain &amp; tingling) and patient quality of life, one of them is alpha-lipoic acid (ALA). Alpha-lipoic acid is a potent anti-inflammatory and antioxidant with insulin-mimetic activity, it has been shown to improve clinical symptoms in experimental Diabetic neuropathy and protect peripheral nerves from ischemia, in addition to stimulate the nerve growth factor and promote fiber regeneration. This study is aimed to evaluate the effect of Alpha-lipoic acid supplement as adjuvant therapy to gabapentin in patients with diabetic neuropathy, which can reflect by the improvement in nerve conduction velocity (NCV) a test was conducted to assess the severity of iabetic neuropathy and clinical symptoms. A prospective randomized- open-label interventional study for 3 months include 33 DN patients, aged (18-69) years were divided into two groups; group A include 16 patients received gabapentin 300 mg once daily at night, and group B include 17 patients received gabapentin 300 mg once daily at night plus alpha-lipoic acid 600mg once daily. Pre and post 3 months of treatment, blood samples used to measure metabolic biomarkers (FBG, HbA1c), in addition to Nerve conduction velocity. The results showed that, the intervention group produced a highly significant change in HbA1c &amp; no significant change in FBG levels after 3months of Alpha-lipoic acid supplementation. Meanwhile, there is no significant change in HbA1c &amp; FBG levels in patients treated with gabapentin alone. Moreover, results showed highly significant improvement (P˂0.01) in Nerve conduction velocity for two groups at the end of the study. Addition of Alpha-lipoic acid to gabapentin in diabetic neuropathy patients result to improve the glycemic control &amp; Nerve conduction velocity. after three months of treatment.

The Effects of Different Quantities and Qualities of Protein Intake in People with Diabetes Mellitus.

The recommended amount and quality of protein in diets of diabetic patients are highly controversial. In order to provide evidence-based information, the Diabetes Nutrition Study Group (DNSG) used a grading procedure used for quality of evidence and strength of recommendations (GRADE). A protein intake of 10% to 20% of energy intake (E%) or about 0.8 to 1.3 g/kg body weight in people below 65 years of age, and 15% to 20% of E% in people above 65 years of age appeared safe in weight-stable conditions. There were no intervention studies addressing metabolic effects, mortality, or cardiovascular events over prolonged periods. Body weight is closely linked to metabolic control and high protein diets are often recommended. Weight-loss diets that include 23% to 32% of E% as protein for up to one year reduced blood pressure and body weight slightly but significantly more than lower protein diets, whereas blood lipids, fasting blood glucose, and HbA1c improved similarly with higher or lower protein intakes in participants with a glomerular filtration rate (GFR) >60 mL/min/1.73 m2. Patients with a GFR <60 mL/min/1.73 m2 did not show a faster decline of GFR or kidney function with protein intakes around 0.8 g/kg body weight as compared with lower intakes, thereby arguing against a restriction. The effects of protein intake on diabetic eye or nerve disease have not been reported. There are a number of studies that have compared different types of animal proteins (milk, chicken, beef, pork, and fish) or compared animal with plant protein in diabetic patients and have reported a greater reduction of serum cholesterol with plant protein. In summary, the suggested range of protein intake appears to be safe and can be adapted according to personal dietary preferences.

Protective effect inhibiting the expression of miR-181a on the diabetic corneal nerve in a mouse model

To investigate the protective effect of inhibiting miR-181a on diabetic corneal nerve in mice, we chose male C57BL/6 mice with streptozotocin (STZ) -induced diabetes as animal models. The expression of miR-181a in trigeminal ganglion tissue (TG) of diabetic mice was detected by real-time PCR. In vitro, we cultured mouse trigeminal ganglion neurons and measured the neuronal axon growth when treated under miR-181a antagomir and negative conditions (NTC). Immunofluorescence showed a significant increase in neuronal axon length in trigeminal ganglion cells treated with miR-181a antagomir. In animal models, we performed epithelial scraping and subconjunctival injection of the miR-181a antagomir and miRNA antagomir NTC to observe the corneal nerve repair by corneal nerve staining. miR-181a antagomir subconjunctival injection significantly increased the corneal epithelium healing of diabetic mice compared with that of the NTC group. Meanwhile, corneal nerve staining showed that the repair of corneal nerve endings was significantly promoted. As the targets of the 181a, ATG5 and BCL-2 were previously identified. The results of Western blot showed that the expression of autophagy associated protein ATG5 and LC3B-II and the expression of anti-apoptotic protein Bcl-2 were decreased in the high-glucose cell culture environment and the diabetic TG tissue. The expression of ATG5, LC3B-II and Bcl-2 were significantly increased after miR-181a antagomir treatment compared with negative control group. This study showed that inhibition of miR-181a expression in diabetic mice could increase ATG5-mediated autophagic activation, BCL-2-mediated inhibition of apoptosis, and promote the growth of trigeminal sensory neurons and the regeneration of corneal nerve fibers. It has a protective effect on diabetic corneal neuropathy.

The Role of Nuclear Factor Erythroid 2-Related Factors (Nrf2) in Diabetic Neuropathy: A Literature Review

Pain is one of the health problems that really common in the field of medicine. Complaints of pain themselves are subjective and can affect the quality of life of patients. Therefore, a good understanding is needed to be able to diagnose and treat pain comprehensively. Along with the changing lifestyle in the community, the prevalence of diabetes mellitus (DM) also increased. Diabetic peripheral nerve (DPN) is a complication that often occurs in people with DM. This complication is the biggest cause of morbidity and mortality in patients with DM. There are several pathways that are thought to have a significant effect on the incidence of diabetic neuropathy, such as the activation of the polyol pathway from the hexosamine pathway and protein kinase C (PKC), the accumulation of advanced glycation end products (AGEs) in diabetic nerves, excessive levels of glucose and fatty acids. The last few decades of research suggest that there are transcription factors that affect the incidence of diabetic neuropathy will be discussed in this article.

A Case Report of Functional Acupuncture for Treatment of Elderly Type 2 Diabetic Oculomotor Nerve Palsy

Objective: To introduce and analyze the method and effect of functional acupuncture in treating one case of elderly type 2 diabetic oculomotor nerve palsy. Methods: The main emphasis is on taking the functional position of the affected area, selecting the functional acupuncture area, and choosing the electroacupuncture stimulation dose. That is, the functional acupuncture method is the main acupuncture method during treatment, that is, the functional position is taken before the upper eyelid acupuncture, and the patient’s left upper eyelid Lift to above the functional position (maximum lifting position-eye open state), determine the muscle functional area around the eye (needle entry area) of the raised eyelid, and select acupoints in the corresponding functional area around the eye: Cuanzhu, Yuyao, Sizhu For Kong, Shenting, Tou Linqi and Ashi points, choose a needle with a model of 0.35 mm×40 mm, take a 0.3 to 1 inch flat puncture, and use an electroacupuncture to form a dense wave. Results: After 20 days of functional acupuncture, the symptoms of ptosis of the left eye of the patient improved significantly, and the limitation of movement of the left eye was significantly improved. Follow-up six months later, there was no recurrence, and the clinical effect was satisfactory. Conclusion: The essence of functional acupuncture improvement is to re-form a powerful neuromuscular effect in the muscles, destroy the paralysis and weakness of the targeted muscle groups, and rebuild the normal neuromuscular coupling mode. The goal of this balancing mechanism is to destroy abnormal muscle paralysis and The reflex pattern of muscle weakness reconstructs an orderly and normal neuromuscular reflex.

Corneal alteration and pathogenesis in diabetes mellitus.

The incidence of diabetes mellitus (DM) and its complications have increased considerably worldwide. Diabetic keratopathy is the major complication of the cornea characterized by delayed corneal wound healing, decreasing corneal epithelial sensitivity, and recurrent corneal ulcers. There is accumulating evidence that diabetic keratopathy is correlated with the hyperglycemic state. Different corneal components may produce different alterations under hyperglycemia. In addition, diabetic nerve alteration may become a novel biomarker of early-stage DM. Abnormalities of the corneal nerve plexus have been associated with diabetic inflammatory states. There is rapidly growing evidence based on investigations of diabetic corneal nerves through in vivo confocal microscopy. Understanding the molecular pathogenesis caused by hyperglycemia may assist in the identification of novel biomarkers, as well as therapeutic targets for early treatment. This review mainly summarizes recent findings on corneal alteration and pathogenesis in DM.

Correlation between risk factors for diabetic peripheral neuropathy and nerve conduction study parameters in children with type 1 diabetes mellitus attending Sudan childhood diabetes centre

Diabetic peripheral neuropathy (DPN) is the commonest microvascular complication of diabetes mellitus. Risk factors related to the development of DPN are mainly duration of diabetes, degree of glycaemic control, height of the patient and age at onset of diabetes mellitus. This study aimed to correlate between the risk factors for diabetic peripheral neuropathy (DPN) and lower limbs nerve conduction study (NCS) parameters in children with type 1 diabetes mellitus attending Sudan Childhood Diabetes Centre. This cross-sectional study recruited 50 patients with type 1diabetes, with mean disease duration of 4.9 ± 3.8 years attending Sudan Childhood Diabetes Centre. NCS parameters (latency, amplitude, and conduction velocity) of sural, common peroneal and posterior tibial nerves were measured bilaterally. Using Pearson correlation statistics, the study revealed significant negative correlation between the patient age and the motor velocities of tibial and common peroneal nerves. Furthermore, it proved significant negative correlation between the patient height and velocities of sural, tibial and common peroneal nerves. It also showed significant negative correlation between the age at onset of the disease and the motor velocities of the right tibial and right common peroneal nerves. Moreover, there was significant negative correlation between HbA1c and the motor velocities of both right and left tibial nerves. Duration of the disease did not show any correlation with NCS parameters. The study proved that most of the risk factors for diabetic peripheral neuropathy decrease significantly the conduction velocity especially of the motor lower limbs nerves in type 1 diabetic children.

Diabetic Neuropathy.

Diabetes mellitus is becoming increasingly common worldwide. As this occurs, there will be an increase in the prevalence of known comorbidities from this disorder of glucose metabolism. One of the most disabling adverse comorbidities is diabetic neuropathy. The most common neuropathic manifestation is distal symmetric polyneuropathy, which can lead to sensory disturbances, including diminished protective sense, making patients prone to foot injuries. However, focal, multifocal, and autonomic neuropathies are also common. Diabetic nerve pain and Charcot osteoarthropathy are advanced neuropathic conditions that portend a severe deterioration in quality of life. To combat these symptoms, along with glycemic control and establishment of health care systems to educate and support patients with the complexities of diabetes, there are pharmacologic remedies to ameliorate the neurologic symptoms. Several guidelines and review boards generally recommend the use of tricyclic antidepressants, serotonin/norepinephrine-reuptake inhibitors, α-2-delta ligands, and anticonvulsants as medications to improve painful diabetic neuropathy and quality of life.

Sonographic assessment of nerve blood flow in diabetic neuropathy.

To undertake sonographic assessment of nerve blood flow in people with Type 2 diabetes and correlate the findings with neuropathy severity scores and electrophysiological measurements. Median and tibial nerve ultrasound scans were undertaken in 75 people with diabetes and 30 aged-matched controls without diabetes, using a high-resolution linear probe at non-entrapment sites. Nerve blood flow was quantified using power Doppler techniques to obtain the vessel score and the maximum perfusion intensity. Neuropathy severity was assessed using a total neuropathy score. Diabetic nerves had higher rates of nerve blood flow detection (28%) compared to the control group (P < 0.0001). Significant correlations were found between nerve blood flow measurements and nerve size (P <0.001), reported sensory symptoms (P < 0.05) and neuropathy severity scores (P < 0.001). The cohort with diabetes had significantly larger median (8.5 ± 0.3 mm2 vs 7.2 ± 0.1 mm2 ; P < 0.05) and tibial nerves (18.0 ± 0.9 mm2 vs 12.8 ± 0.5 mm2 ; P < 0.05) compared with controls. Peripheral nerve hypervascularity is detectable by ultrasonography in moderate to severe diabetic neuropathy with prominent sensory dysfunction.

EFFECTS OF DIABETES MELLITUS ON VISCOELASTICITY OF ULTRASTRUCTURES OF PERIPHERAL NERVES: THREE-DIMENSIONAL FINITE ELEMENT ANALYSES

Diabetes mellitus induces a variety of neuropathies and causes various symptoms. Understanding how diabetes affects mechanical properties of nerves is useful for preventing complications of diabetes mellitus such as the carpal tunnel syndrome. In a previous study, a two-dimensional hyper-viscoelastic finite element model (FEM) of the ultra-structures of normal rat sciatic nerves was developed using an optical coherence tomography (OCT) microscope and in vitro parallel compression tests. The main goal of this study was to extend the FEM from two to three dimensions and use it to explore hyper-viscoelasticity of ultra-structures of sciatic nerves of diabetic rats. A modification of the compression testing system to enhance OCT cross-sectional images of the nerve samples was also conducted. The results showed that the instantaneous shear moduli of the perineurium, epineurium, and endoneurium of the diabetic rat were all greater than those of the normal rats. Due to high instantaneous shear moduli and low percentage of relaxation, the diabetic nerve is prone to damage when subjected to prolonged mechanical loads.

30-LB: Diabetes Complications Including Nephropathy, Neuropathy, and Retinopathy Can Now Be Studied in a New Spontaneous Autoimmune Diabetes Transgenic Model

We have developed a spontaneous humanized transgenic mouse model of autoimmune diabetes chronically develops diabetic complications. Our humanized mouse develop diabetic nephropathy. The basal glomerular membrane thickness was doubled in size at 4 months of age as shown by electron microscopy. The manifestation of glomerulopathy subsequently correlates with microalbuminuria. At 6 month, mice show advanced features of diabetic nephropathy like focal segmental/global glomerular sclerosis and focal tubular atrophy. The typical features of Kimmelstiel-Wilson are seen when severe chronic kidney disease develops. Our humanized mice develop diabetic retinopathy. We have noted a significant increase in acellular capillaries of the retina at the age of 6 months. Ocular tomography revealed a significant reduction in total retinal thickening. Fundoscopic retinal images revealed a classic vascular leakage as observed in humans. Our humanized mice also show diabetic neuropathy. We have observed an impaired sciatic and optic nerve conduction. Specifically, optic nerves at 6-months old diabetic mice showed an increased refractory period of the second compound action potential (CAP). This increase in the refractory period of CAP in the diabetic optic nerves is consistent with the reduced conduction velocity. However, a limb vasculopathy has not been observed so far. In our mouse model, the mouse MHC-II was replaced with human DQ8 in all antigen-presenting cells. The mouse also expresses human GAD65 in pancreatic beta cells. The diabetic phenotype of our mouse mimics the human disease progression. Importantly, our mouse model has a genetic background that compromises beta-cell neogenesis and/or regeneration (1). Our humanized mice model has the closest known phenotype to human diabetes and is most suitable for addressing physiopathology and treatment of diabetes complications. (U.S. Provisional Patent #62/713,827). Disclosure S. Imam: None. J.C. Jaume: None. Funding University of Toledo

OR28-4 Spontaneous Autoimmune Diabetes in Humanized Mice Carrying Human Type 1 Diabetes Susceptibility

An animal model of type 1 diabetes (T1D), in which human beta cell autoantigen(s) are presented to effector cells in the context of human Major Histocompatibility Complex (MHC) diabetes-susceptibility genes, would be highly desirable for studies of molecular mechanisms of disease and development of antigen-specific immune-therapies applicable to man. It would be especially advantageous to develop an animal model of human T1D that also exhibits the chronic complications of diabetes. Our new spontaneous mouse model of T1D wherein mouse MHC-II was replaced by human DQ8 in all antigen-presenting cells (APCs), and pancreatic Beta-cells were made to express human GAD65 autoantigen resembles most human characteristics of the disease. Our humanized transgenics have a genetic background providing for compromised Beta-cell neogenesis and/or regeneration. Immune cells attack Beta-cells, which in turn leads to a chronically progressive disease characterized by the development of anti-GAD65 antibodies. Flow cytometric analysis of pancreas (PN) and peri-pancreatic lymph nodes (PLN) revealed that CD4 and CD8 T cells build up in the PLN while mostly CD8 infiltrate intra-islet locations, which first causes glucose intolerance, and later on diabetes. Animals spontaneously show hyperglycemia of >250 mg/dl at approximately eight weeks of age. Without intervention, animals develop the classic complications observed in human diabetes (i.e., retinopathy, nephropathy, and neuropathy). To date, all complications of diabetes have been observed in our model (1). Our humanized transgenics develop diabetic retinopathy. Diabetic mice develop a significant increase of acellular capillaries in the retina as compared to non-diabetic controls as early as 6 months. Ocular tomography revealed that total retinal thickening was reduced in diabetic mice. Fundoscopic retinal images also revealed vascular leakage only in diabetic mice. Six-month-old diabetic mice also show advanced features of diabetic nephropathy like focal segmental/global glomerular sclerosis and focal tubular atrophy. Basal glomerular membrane doubles in size at three months as shown by electron microscopy as compared to non-diabetic controls. Moreover, our humanized mice also show diabetic neuropathy. Optic nerves of 6-month-old diabetic mice show an increase in the refractory period of the second compound action potential (CAP) as compared to non-diabetic mice (p < 0.05). This increase in the refractory period of CAP in the diabetic optic nerves is consistent with the reduced conduction velocity over non-diabetic controls. Conclusively, our humanized mice model is the closest one to human diabetes and is not just suitable for therapies to halt diabetes and its development but also to address the physiopathology and treatment of diabetes complications. 1) U.S. Provisional Patent #62/713,827 Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Myocardial Infarction-Related Transcripts (MIAT) Participate in Diabetic Optic Nerve Injury by Regulating Heart Shock Protein 5 (HSPA5) via Competitively Binding to MicroRNA-379.

BackgroundThe aim of this study was to explore the role of MIAT (myocardial infarction related transcripts) in diabetic optic neuropathy and its underlying mechanism.Material/MethodsQRT-PCR (quantitative real-time polymerase chain reaction) was performed to detect the mRNA levels of MIAT and HSPA5 (heart shock protein 5) in diabetic rat model and high-glucose cultured Müller cells. After the intracellular MIAT level was increased by lentivirus transfection, the proliferation, cell cycle, and apoptosis of Müller cells were measured using the CCK-8 (Cell Counting Kit-8) assay, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling) assay, respectively. Mechanisms underlying the MIAT-related apoptosis were explored by Western blot analysis. The binding condition of microRNA-379 to MIAT and HSPA5 was confirmed by luciferase reporter gene assay.ResultsBoth MIAT and HSPA5 levels were remarkably increased in high-glucose cultured Müller cells. After transfected with LV (lentivirus)-MIAT, Müller cells showed a decreased proliferation and an enhanced apoptosis with the increased expressions of pro-apoptotic proteins. However, no remarkable changes were observed in cell cycle. Further mechanistic studies found that MIAT regulated HSPA5 expression by directly binding to microRNA-379.ConclusionsMIAT was overexpressed in the diabetic optic nerve. MIAT overexpression remarkably promoted the apoptosis of Müller cells by adsorbing microRNA-379 and thus regulating HSPA5, which was a direct target of microRNA-379.

Consumer tradeoff of advertising claim versus efficacy information in direct-to-consumer prescription drug ads.

Consumers' decision making about prescription drugs may be influenced by more than thoughts about drug efficacy and the potential for side effects. Choices may be based on tradeoffs among multiple factors, for example, medical condition, risk severity, risk likelihood, product efficacy, and resources. Some information used in tradeoff choices might be derived from marketing efforts by drug manufacturers. How market claims, such as "#1 Prescribed" may affect this tradeoff is an area that has yet to be explored fully. Using conjoint analysis techniques, this research examined the tradeoff of market claim and efficacy information in direct-to-consumer (DTC) print advertising for prescription drugs. Two hundred fifteen adult participants with a self-reported diagnosis of diabetes were recruited through an online consumer panel. Participants were presented a series of choices. Each choice pair represented a prescription diabetic nerve pain drug with a different efficacy level and one of the two had a market claim of "#1 Prescribed". Participants indicated which drug they would prefer if they had to choose one. Results showed an advantage of #1 Prescribed. A drug without this claim needed at least 1.23% greater efficacy to be chosen over a drug with this claim. Study findings align with previous research which found that extrinsic cues can influence consumer product choice, which has implications for optimal medication use.

MiR-34c Participates in Diabetic Corneal Neuropathy Via Regulation of Autophagy.

To investigate the contribution and mechanism of miRNAs and autophagy in diabetic peripheral neuropathy. In this study, we used streptozotocin (STZ)-induced type I diabetes C57 mice as animal models, and we detected the expression of miR-34c and autophagic intensity in trigeminal ganglion (TG) tissue. The bioinformatics software was used to predict and analyze the potential targets of miR-34c. Primary trigeminal ganglion neurons were cultured in vitro to investigate the effect of miR-34c on axon growth and survival of TG cells. A corneal epithelial damage-healing model was established on the diabetic mice, then miR-34c antagomir was injected subconjunctivally. The condition of corneal epithelial healing was observed through sodium fluorescein staining, and the peripheral nerve degeneration of the cornea was evaluated by β-tublin corneal nerve staining. The expression of miR-34c was significantly increased in TG tissue of type I diabetic mice by real-time PCR. Western blot showed that autophagy-related proteins Atg4B and LC3-II were significantly down-regulated in diabetes TG compared with normal control. Trigeminal neuron immunofluorescence showed that the length of the trigeminal ganglion cell synapses was significantly increased after miR-34c antagomir treatment compared with normal cultures. Subconjunctival injection of miR-34c antagomir can significantly promote corneal epithelium healing of diabetic mice and appreciably promote the regeneration of corneal nerve. At the same time, it can significantly increase the expression of autophagy in TG tissue of type I diabetic mice. In this study , miR-34c was found to affect the growth of trigeminal sensory neurons and the repair of diabetic corneal nerve endings by acting directly on Atg4B.

Nerve conduction velocity is negatively associated with intima-media thickness and brachial-ankle pulse wave velocity in men with type 2 diabetes mellitus.

ObjectivePrevious studies suggest that the presence of diabetic peripheral polyneuropathy (DPN) is associated with atherosclerotic diseases; however, little is known about the relationship between diabetic nerve conduction velocity (NCV) versus arterial stiffness and atherosclerosis parameters.MethodsThe subjects in this study were 292 men with type 2 diabetes mellitus (T2DM). All subjects underwent NCV examination at median and tibial nerves as motor nerve (MCV) as well as median and sural nerves as sensory nerve (SCV). Brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) were evaluated as arterial stiffness and atherosclerosis parameters.ResultsPearson’s correlation coefficient showed that NCV at all sites negatively correlated with baPWV, maximal and mean IMT (IMT-Max and IMT-Mean), and plaque score (all p values p<0.01 at least). Multiple regression analyses adjusted for confounding factors such as age, duration of diabetes, body mass index, HbA1c, fasting C-peptide, systolic blood pressure, HDL-cholesterol, LDL-cholesterol and albuminuria showed that the association of NCV with IMT-Max, ITM-Mean, and plaque score remained significant (all p values p<0.05 at least) except that between SCV at median and IMT-Max. Moreover, SCV at median (forearm) and sural were significantly associated with baPWV (p = 0.023 and p = 0.027, respectively).ConclusionThe present study showed that DPN estimated by quantitative NCV is linearly associated with the deterioration of arterial stiffness and atherosclerosis parameters in T2DM independently of various diabetic and atherosclerotic factors.

Alteration of Sciatic Nerve Histology and Electrical Function After Compression and After Neurolysis in a Diabetic Rat Model.

Diabetic rats are more sensitive to nerve entrapment. This study was conducted to evaluate nerve function and histological changes in diabetic rats after nerve compression and subsequent decompression. A total of 35 Wistar rats were included. The experimental group was divided into diabetic sciatic nerve compression group (DSNC, n = 5) and diabetic sciatic nerve decompression group (DSND, n = 20). The DSNC model was created by wrapping a silicone tube circumferentially around the nerve for 4 weeks, and then the DSND group accepted nerve decompression and was followed up to 12 weeks. The DSND group was equally divided into DSND 3 weeks (DSND3), 6 weeks (DSND6), 9 weeks (DSND9), and 12 weeks (DSND12) groups. Five rats were taken as normoglycemic control group (CR, n = 5), and another 5 rats as diabetic control group (DM, n = 5). The mechanical hyperalgesia of rats was detected by Semmes-Weinstein nylon monofilaments (SWMs) and by motor nerve conduction velocity (MNCV). These 2 physiological indicators and histology of sciatic nerves were compared among different groups. The SWM measurements improved toward normal values after decompression. The SWM value was significantly lower (more normal) in the DSNC groups than in the DSND group (P < 0.05). The MNCV was 53.7 ± 0.8 m/s in the CR group, whereas it was 28.4 ± 1.0 m/s in the DSNC group (P < 0.001). Six weeks after decompression, the MNCV was significantly faster than that in the DSNC group (P < 0.001). Histological examination demonstrated chronic nerve compression, which responded toward normal after decompression, but with degree of myelination never recovering to normal. Chronic compression of the diabetic sciatic nerve has measureable negative effects on sciatic nerve motor nerve function, associated with a decline of touch/pressure threshold and degeneration of myelin sheath and axon. Nerve decompression surgery can reverse these effects and partially restore nerve function.