Diabetic Distal Sensorimotor Polyneuropathy Research Articles

Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes

ObjectiveThe objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. MethodsIn 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. ResultsRF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

ODP186 Difficulties in diagnosing MODY: clinical case

Abstract Background MODY is one of the monogenic forms of diabetes mellitus, which includes 14 subtypes with different course and clinical picture. Final clinical diagnosis involves a molecular genetic study and is a key factor in successful treatment. Clinical case. Patient P., 33 years old, complained of aggravation of the condition after and during the dialysis procedure: general weakness, blood pressure rose to 220 mmHg, after the procedure a drop to 110-120 mmHg, lack of effect from hypertensive drugs, headaches. In 2004, type 1 diabetes mellitus was diagnosed based on complaints of polydipsia, polyuria, and fasting glycemia up to 9 mmol/l. Basic bolus insulin therapy was prescribed. Patient noted a frequent development of hypoglycemic conditions and independently canceled insulin therapy. For a long time the patient went without hypoglycemic therapy. In 2016, baseline insulin therapy was prescribed again, which resulted with frequent episodes of hypoglycemia resuming. In 2019, a diagnosis of MODY type 3 was made without medical and genetic counseling. Due to the high level of C-peptide 3057.1 pmol /L (160-1100), Repaglinide 0.5 mg was prescribed to be taken 3 times a day. Against the background of this treatment, compensation and stabilization of the condition has been observed. Family history: the mother has diabetes mellitus since the age of 22, manifested during pregnancy; receives Glibenclamide with a positive effect. Since 2011, diabetic distal sensorimotor polyneuropathy of the upper and lower extremities, diabetic foot syndrome, neuropathic form have been identified. Ulcerative defect of the I degree. Long-term non-healing trophic ulcer of the right foot for 6 years. In 2016, chronic kidney disease C5 A3 was detected. At the moment, the patient is on program dialysis. Complications of nephropathy were verified – secondary hyperparathyroidism, osteoporosis, moderate nephrogenic anemia, symptomatic nephrogenic arterial hypertension of grade 3, risk 4. In 2018, proliferative diabetic retinopathy of both eyes was detected. Total recurrent hemophthalmos of the right eye, subtotal hemophthalmos of the left eye. In 2021, autonomic neuropathy, gastrointestinal form and autonomic cardiovascular form were verified. The patient underwent a molecular genetic study for the identification of pathogenic mutations in the HNF1A gene, however, according to the study, mutations in the HNF1A gene were not detected. Thus, the diagnosis of MODY type 3 has not been confirmed. It is necessary to conduct a further diagnostic search for the type of MODY in order to make a final diagnosis. Conclusion This clinical case demonstrates the importance of a personalized approach to each patient, as well as conducting a molecular genetic study to make a final clinical diagnosis and prescribe timely pathogenetic therapy. Presentation: No date and time listed

A Waves in Diabetic Neuropathy: Pathophysiology and Neurographic Images.

To evaluate the presence of A waves in diabetic neuropathy, we designed a retrospective observational study recruiting patients with type II diabetes and chronic diabetic distal sensorimotor polyneuropathy. We recruited 238 patients of both sexes aged between 41 and 89 years. Neurography was undertaken on two bilateral upper (median and ulnar) and lower (peroneal and tibial) limb nerves. As controls, we considered that neurographs performed bilaterally on the same nerves of 40 healthy subjects. In addition to neurographic changes typical of chronic distal sensorimotor neuropathy, patients had a 32.77% incidence of A waves, mostly found in the tibial (16.38%) and peroneal (8.8%) nerves. Among controls, A waves were found only in the tibial nerve of a single subject (2.5%). Chi-square test with Yates correction to compare the two percentages (32.77% of patients and 2.5% of healthy subjects): 13.98, P = 0.0002, highly significant. We postulate that demyelination may be the site of backfiring or slowing of nerve conduction velocity, explaining the appearance of A waves in their different varieties. Implementing the search for A waves in routine neurographic examination can be a useful option for the diagnosis of neuropathy and the prediction of possible latent neuropathic processes.

Validation of a simple disease-specific, quality-of-life measure for diabetic polyneuropathy: CAPPRI.

We studied the performance of a 15-item, health-related quality-of-life polyneuropathy scale in the clinic setting in patients with diabetic distal sensorimotor polyneuropathy (DSPN). Patients with DSPN from 11 academic sites completed a total of 231 Chronic Acquired Polyneuropathy Patient-Reported Index (CAPPRI) scales during their clinic visits. Conventional and modern psychometric analyses were performed on the completed forms. Conventional and modern analyses generally indicated excellent psychometric properties of the CAPPRI in patients with DSPN. For example, the CAPPRI demonstrated unidimensionality and performed like an interval-level scale. Attributes of the CAPPRI for DSPN include ease of use and interpretation; unidimensionality, allowing scores to be summed; adequate coverage of disease severity; and the scale's ability to address relevant life domains. Furthermore, the CAPPRI is free and in the public domain. The CAPPRI may assist the clinician and patient with DSPN in estimating disease-specific quality of life, especially in terms of pain, sleep, psychological well-being, and everyday function. The CAPPRI may be most useful in the everyday clinical setting but merits further study in this setting, as well as the clinical trial setting.

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study.

Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n=80), with and without symptoms of neuropathy, were investigated. Patient-determined neuropathy was based on 15-item self-administered questionnaire (Michigan Neuropathy Screening Instrument) developed to assess distal symmetrical peripheral neuropathy in diabetes. Patients who scored ≥4, or reported inability to sense their feet during walking or to distinguish hot from cold water while bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin, hexosyl- and lactosylceramide species, and amino acids were measured and analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24- and C26-ceramide were higher in patients with neuropathy than those without neuropathy. Cysteine was higher in patients with neuropathy. No differences in other sphingolipids or amino acids were detected. The covariate-adjusted Odds Ratios of positive patient-reported neuropathy was associated with increased levels of deoxy-C24-, and deoxy-C24:1-ceramide; C22-, C24-, and C26-ceramide; and cysteine. Plasma deoxy-ceramide and ceramide species may have potential diagnostic and prognostic significance in diabetic neuropathy.

Cocarnit in the treatment of diabetic polyneuropathy

Study the effect of cocarnit on the peripheral nerve functions in patients with diabetic distal sensorimotor polyneuropathy (DDSP). Thirty patients with DDSP, aged from 27 to 65 years, mean 55.3±10.8 years, with diabetes mellitus duration from 2 to 20 years (mean 8.0±5.8 years) received cocarnit as monotherapy in dose of 2 ml daily during 9 days. The intensity and character of pain were assessed with PainDetect, ТSS and NSS inquirers, quality-of-life was measured with the Russian version of EuroQol-5D questionnarie. The state of the neuromotor apparatus was studied using stimulation electromyography with the analysis of conduction along motor fibers of peripheral nerves and evoked sympathetic skin responses (ESSR). After treatment, there was the improvement of scores on PainDetect by 44.3% (p<0.05), NSS by 41.9% (p<0.05) and ТСС by 103.9% (p<0.05). An increase in the impulse conduction velocity, M- and S-response amplitudes and normalization of ESSR parameters were observed. In the first turn, the improvement was related to damaged nerves. Cocarnit is an effective drug in the treatment of patients with DDSP.

Alpha-lipoic acid modifies circulating angiogenic factors in patients with type 2 diabetes mellitus

AimsIn recent years interest has been focused on angiogenesis as a process involved in coronary artery disease (CAD) and diabetic distal sensorimotor polyneuropathy (DSPN). Recent studies have demonstrated the possible angiogenesis-modulating potential of alpha-lipoic acid (ALA) for DSPN and CAD. The aim of our study was to investigate the influence of ALA on serum angiogenic factors in patients with DM-2 (type 2 diabetes) with CAD and DSPN. MethodsSixty patients with type 2 DM (T2DM) and CAD and 25 non-diabetic subjects were studied. Thirty patients with T2DM, CAD and DSPN were given 600mg of ALA a day for 90 days. VEGF, bFGF, MCP-1, angiogenin, IL-12 and IL-10 concentrations in the sera were measured by flow cytometry. ResultsALA significantly increased VEGF, bFGF and IL-10 and decreased MCP-1 serum concentrations in patients with T2DM and CAD and DSPN. VEGF and IL-10 serum levels, both before and after ALA-treatment, were higher in this group than in T2DM and CAD patients, while circulating bFGF was higher and MCP-1 serum level lower in patients with T2DM and CAD and DSPN only in the post-ALA-treatment, compared to the T2DM and CAD group. ConclusionsALA may influence angiogenesis in type 2 diabetic patients through an effect on some circulating factors including VEGF, bFGF, MCP-1 and IL-10.

Association of Subclinical Inflammation With Polyneuropathy in the Older Population

OBJECTIVEInflammatory processes have been implicated in the pathogenesis of diabetic distal sensorimotor polyneuropathy (DSPN), but their possible relationship has not been assessed at the population level.RESEARCH DESIGN AND METHODSWe determined serum concentrations of mediators of subclinical inflammation among 1,047 participants 61–82 years of age from the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (Germany). Logistic and linear regression models were fitted to assess associations between immune mediators (log-transformed) and the presence of clinical DSPN (dichotomous variable) or Michigan Neuropathy Screening Instrument (MNSI) examination score (continuous variable), respectively.RESULTSSerum concentrations of the anti-inflammatory interleukin (IL)-1 receptor antagonist (IL-1RA) were positively associated with the presence of DSPN and higher MNSI scores in age-adjusted and sex-adjusted analyses, whereas IL-6, IL-18, and soluble intercellular adhesion molecule-1 were positively associated with only MNSI scores. No associations were observed for adiponectin, C-reactive protein, or tumor necrosis factor-α. Associations for IL-1RA and IL-6 with the MNSI score remained statistically significant after additional adjustment for waist circumference, height, hypertension, cholesterol, smoking, alcohol intake, physical activity, history of myocardial infarction or stroke, presence of neurological conditions, and use of nonsteroidal anti-inflammatory drugs.CONCLUSIONSWe conclude that DSPN is linked to proinflammatory and anti-inflammatory, possibly compensatory, processes in the older general population. Future studies should clarify the temporal sequence and causality of these associations.

Two-Stage Community-Based Screening Model for Estimating Prevalence of Diabetic Polyneuropathy (KCIS No. 6)

The aim of this study was to apply a calibrated two-stage community-based design to estimate the prevalence of diabetic distal sensorimotor polyneuropathy (DPN) in Taiwan. Type 2 diabetics were identified from a population-based screening program in Keelung, Taiwan. Administration of the Neurological Symptom Score (NSS) questionnaire identified 210 DPN-positive cases of the 587 diabetic subjects tested. The accuracy of this NSS screening was tested with sensitive electrophysiological DPN diagnosis. A smaller validation study was also conducted to estimate the sensitivity and specificity of the NSS questionnaire. In the validation study, the overall prevalence rate for DPN among type 2 diabetics was 26.79%. The sensitivity, specificity, positive predictive value and negative predictive values were 73.33, 30.49, 24.72 and 75.76%, respectively. The estimates of sensitivity, specificity and positive predictive values were 75.00, 33.33 and 42.86% for old cases of diabetes, and 72.22, 29.69 and 22.41% for newly diagnosed cases. The range of prevalence rate in the main study was adjusted to 28.46–36.30% after calibration for sensitivity and specificity with the validation study data. A two-stage community-based screening model with calibration of prevalence rate was developed and enabled a cost-effective DPN prevalence rate estimate in a study with a large number of subjects.