The co-existence of peripheral and vestibular neuropathy in diabetes: a cross-sectional study.

PURPOSE: Diabetic neuropathy can lead to decreased peripheral sensation and motor neuron dysfunction associated with impaired postural control and risk of falling. However, the relationship between decreased peripheral sensation and impaired vestibular function in diabetes mellitus is poorly investigated. Therefore, the aim of this study was to investigate the relationship between peripheral and autonomic measurements of diabetic neuropathy and measurements of vestibular function. METHODS: A total of 114 participants with type 1 diabetes (n = 52), type 2 diabetes (n = 51) and controls (n = 11) were included. Vestibular function was evaluated by video head impulse testing. Peripheral neuropathy was assessed by quantitative sensory testing and nerve conduction. Autonomic neuropathy using the COMPASS 31 questionnaire. Data were analyzed according to data type and distribution. RESULTS: Measurements of vestibular function did not differ between participants with type 1 diabetes, type 2 diabetes or controls (all p-values above 0.05). Subgrouping of participants according to the involvement of large-, small- or autonomic nerves did not change this outcome. Correlation analyses showed a significant difference between COMPASS 31 and right lateral gain value (ρ = 0.23, p = 0.02,), while no other significant correlations were found. CONCLUSION: Diabetic neuropathy does not appear to impair vestibular function in diabetes, by means of the VOR. CLINICAL TRIALS: NCT05389566, May 25th, 2022.

The stability of perception threshold tracking for long session evaluation of Aß- and Aδ-fiber function.

INTRODUCTION/AIMS: Research has proven that epidermal and transcutaneous stimulation can identify the function of Aß and Aδ fibers (i.e., in diabetes) individually using different electrodes. In this study we aimed to determine the stability of perception thresholds when using such electrodes. METHODS: Twenty healthy volunteers participated in this study. The perception threshold of Aß fibers (patch electrode) and Aδ fibers (pin electrode) was estimated 30 times during a period of 60 minutes. A threshold was established every other minute, alternating between the two electrodes. The stimulus duration was 1 millisecond and the interstimulus interval was 1.5 to 2.5 seconds. Linear regressions of the perception threshold as a function of time were performed. The slopes were used as an estimate of habituation and were compared between the electrodes. RESULTS: The slope was significantly larger when assessed by the pin electrode (median: 0.020 [0.009 to 0.030] mA/trial) than when assessed by the patch electrode (median: 0.005 [0.001 to 0.018] mA/trial) (P = .017, paired t test). During the session, total increases in perception threshold of approximately 55% and 1% were seen for the pin and patch electrodes, respectively. DISCUSSION: The two fiber types assessed showed significant perception threshold increases. The higher slope of the pin electrode indicated that the Aδ fibers were more prone to habituation than the Aß fibers, and that habituation should be considered during prolonged experiments. This assessment is valuable for future research on nerve fiber function using the technique for long session experiments.

Optimizing examination time and diagnostic performance of the histamine-induced axon-reflex flare response in diabetes.

INTRODUCTION/AIMS: The axon-reflex flare response is a reliable method for functional assessment of small fibers in diabetic peripheral neuropathy (DPN), but broad adoption is limited by the time requirement. The aims of this study were to (1) assess diagnostic performance and optimize time required for assessing the histamine-induced flare response and (2) associate with established parameters. METHODS: A total of 60 participants with type 1 diabetes with (n = 33) or without (n = 27) DPN participated. The participants underwent quantitative sensory testing (QST), corneal confocal microscopy (CCM), and flare intensity and area size assessments by laser-Doppler imaging (FLPI) following an epidermal skin-prick application of histamine. The flare parameters were evaluated each minute for 15 min, and the diagnostic performance compared to QST and CCM were assessed using area under the curve (AUC). Minimum time-requirements until differentiation and to achieve results comparable with a full examination were assessed. RESULTS: Flare area size had better diagnostic performance compared with CCM (AUC 0.88 vs. 0.77, p < 0.01) and QST (AUC 0.91 vs. 0.81, p = 0.02) than mean flare intensity, and could distinguish people with and without DPN after 4 min compared to after 6 min (both p < 0.01). Flare area size achieved a diagnostic performance comparable to a full examination after 6 and 7 min (CCM and QST respectively, p > 0.05), while mean flare intensity achieved it after 5 and 8 min (CCM and QST respectively, p > 0.05). DISCUSSION: The flare area size can be evaluated 6-7 min after histamine-application, which increases diagnostic performance compared to mean flare intensity.

The Danish-American Research Exchange (DARE): a cross-sectional study of a binational research education program.

BACKGROUND: Most medical educational programs emphasize clinical observation or clinical skill acquisition, fewer focus upon research. The Danish-American Research Exchange (DARE) program, sponsored by the Lundbeck Foundation, is unique in that the medical student initiates biomedical research collaboration between Danish and US medical institutions. To achieve this, Danish medical students (DARE students) conduct binational mentored research projects while based in the United States for 10 months. In addition, DARE students are introduced to interdisciplinary thinking about how to develop ultra-low-cost healthcare interventions through the '$10 Challenge'. METHODS: We conducted a cross-sectional study of DARE alumni over five consecutive years (2015-2020, n = 24). Research metrics included completion of a research project, primary authorship, and co-authorship of publications. The number of publications, prior to and after the DARE program were enumerated. For the first four cohorts, graduation from medical school and acceptance or intention to enter a joint MD-PhD program also were assessed. Two focus groups were conducted using constructivist grounded theory. Discussions were transcribed, redacted, and coded using Dedoose software. RESULTS: DARE Medical students were 31.2 years (range 24-35), the majority were women (67%;16/24). The majority (17/24;71%) completed a first author publication in a peer-reviewed journal with a median of 3.9 per DARE alumnus. DARE alumnus reported increased proficiency in biostatistics, epidemiology, coding and public speaking as well as stronger research qualities in creativity, critical thinking, comfort in approaching scientist in both the US and Denmark (p < 0.001 for all). Qualitative key themes included: increased confidence, a deepening of research inquiry and linkage to a research network. CONCLUSIONS: Preliminarily, this study suggests that medical students can initiate binational collaboration in medicine. Benefits include research productivity, intention to pursue academic medical careers, as well as positive impacts on motivation. This medical student-initiated research model lays the groundwork for using this model across other country pairs to promote binational collaboration.

Gastrointestinal function in diabetes is affected regardless of asymptomatic appearance.

BACKGROUND: Gastrointestinal dysmotility may exist without concomitant symptoms. We hypothesize that asymptomatic individuals with diabetes have altered gastrointestinal function associated with age, cardiac vagal tone and glycaemic control. METHODS: One hundred fifty-four asymptomatic participants (61 with type 1 diabetes (T1D), 70 type 2 diabetes (T2D) and 23 healthy volunteers (HV)) underwent wireless motility capsule investigation. Transit times, motility indices and pH were retrieved. Age, cardiac vagal tone, glucose and haemoglobin A1c levels were collected. RESULTS: In T1D, prolongation of colonic (p = 0.03) and whole-gut transit times (p = 0.04) were shown. Transpyloric pH rise was decreased in T1D (p = 0.001) and T2D (p = 0.007) and was associated with cardiac vagal tone (p = 0.03) or glucose (p = 0.04) and haemoglobin A1c (p = 0.005). Ileocaecal pH fall was decreased in T2D (p < 0.001). CONCLUSIONS: Gastrointestinal function was altered in asymptomatic individuals with diabetes. These findings call for further investigations of gastrointestinal function in order to identify risk factors or even predictors for diabetic enteropathy, particularly when glycaemic control is impaired.

Incidence, hospitalization and mortality and their changes over time in people with a first ever diabetic foot ulcer.

AIMS: A diabetic foot ulcer (DFU) is a severe condition associated with morbidity and mortality. Population-based studies are rare and limited by access to reliable data. Without this data, efforts in primary prevention cannot be evaluated. Therefore, we examined the incidence and changes over time for the first DFU in people with diabetes. We also examined hospitalization and all-cause mortality and their changes over time. METHODS: From the UK primary care CPRD GOLD database (2007-2017), we identified 129,624 people with diabetes by a prescription for insulin or a non-insulin anti-diabetic drug. DFUs were identified using Read codes and expressed as incidence rates (IRs). Changes over time were described using Poisson and logistic regression and expressed as incidence rate ratios (IRRs) and odds ratios (ORs) respectively. RESULTS: The mean IR of first registered DFUs was 2.5 [95% CI: 2.1-2.9] per 1000 person-years for people with type 2 diabetes and 1.6 [1.3-1.9] per 1000 person-years for people with type 1. The IRs declined for people with type 2 diabetes (IRR per year: 0.97 [0.96-0.99]), while no changes were observed for people with type 1 diabetes (IRR per year: 0.96 [0.89-1.04]). Average hospitalization and 1-year mortality risk for people with type 2 diabetes were 8.2% [SD: 4.7] and 11.7% [SD: 2.2] respectively. Both declined over time (OR: 0.89 [0.84, 0.94] and 0.94 [0.89, 0.99]). CONCLUSION: The decline in all IRs, hospitalizations and mortality in people with type 2 diabetes suggests that prevention and care of the first DFU has improved for this group in primary care in the UK.

Diabetic Peripheral Neuropathy.

Diabetic painless and painful peripheral neuropathy remains the most frequent complication of diabetes mellitus, but the pathophysiology remains undescribed, there are no robust clinical endpoints and no efficient treatment exists. This hampers good clinical practice, fruitful clinical research and successful pharmacological trials, necessary for the development of early detection, prevention and treatment. This chapter supplies an update on background and treatment of diabetic peripheral neuropathy. Goals and perspectives for future clinical and scientific approaches are also described.

Increased levels of inflammatory factors are associated with severity of polyneuropathy in type 1 diabetes.

OBJECTIVE: Distal symmetrical polyneuropathy (DSPN) is a severe common long-term complication of type 1 diabetes caused by impaired sensory-motor nerve function. As chronic low-grade inflammation may be involved in the pathogenesis of DSPN, we investigated the circulating levels of inflammatory markers in individuals with type 1 diabetes with and without DSPN. Furthermore, we determined to what extent these factors correlated with different peripheral sensory nerve functions. DESIGN: Cross-sectional study. PATIENTS: The study included 103 individuals with type 1 diabetes with (n = 50) and without DSPN (n = 53) as well as a cohort of healthy controls (n = 21). MEASUREMENTS: Circulating levels of various inflammatory markers (cytokines, chemokines and soluble adhesion molecules) were determined in serum samples by Luminex multiplexing technology. Peripheral sensory nerve testing, for example vibration, tactile and thermal perception, was assessed by standardized procedures. RESULTS: The cytokines IL-1α, IL-4, IL-12p70, IL-13, IL-17A and TNF-α; the chemokine MCP-1; and the adhesion molecule E-selectin were significantly increased in individuals with type 1 diabetes with DSPN compared to those without DSPN (P < .001). These observations were independent of age, sex, BMI, disease duration and blood pressure. Additionally, higher serum concentrations of cytokines and chemokines were associated with higher vibration and tactile perception thresholds, but not with heat tolerance threshold. CONCLUSIONS: Individuals with type 1 diabetes and concomitant DSPN display higher serum levels of several inflammatory markers. These findings support that systemic low-grade inflammation may play a role in the pathogenesis of DSPN.

Circulating Inflammatory Markers Are Inversely Associated with Heart Rate Variability Measures in Type 1 Diabetes.

INTRODUCTION: A neuroimmune communication exists, and compelling evidence suggests that diabetic neuropathy and systemic inflammation are linked. Our aims were (1) to investigate biomarkers of the ongoing inflammation processes including cytokines, adhesion molecules, and chemokines and (2) to associate the findings with cardiovascular autonomic neuropathy in type 1 diabetes by measuring heart rate variability and cardiac vagal tone. MATERIALS AND METHODS: We included 104 adults with type 1 diabetes. Heart rate variability, time domain, and frequency domains were calculated from a 24-hour Holter electrocardiogram, while cardiac vagal tone was determined from a 5-minute electrocardiogram. Cytokines (interleukin- (IL-) 1α, IL-4, IL-12p70, IL-13, IL-17, and tumor necrosis factor- (TNF-) α), adhesion molecules (E-selectin, P-selectin, and intercellular adhesion molecule- (ICAM-) 1), and chemokines (chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4, and C-X-C motif chemokine (CXCL)10) were assessed using a Luminex multiplexing technology. Associations between concentrations of inflammatory biomarkers and continuous variables of heart rate variability and cardiac vagal tone were estimated using multivariable linear regression adjusting for age, sex, disease duration, and smoking. RESULTS: Participants with the presence of cardiovascular autonomic neuropathy had higher systemic levels of IL-1α, IL-4, CCL2, and E-selectin than those without cardiovascular autonomic neuropathy. IL-1α, IL-4, IL-12, TNF-α, and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p > 0.01). Discussion. Our results show that several pro- and anti-inflammatory factors, believed to be involved in the progression of diabetic polyneuropathy, are associated with cardiovascular autonomic neuropathy, suggesting that these factors may also contribute to the pathogenesis of cardiovascular autonomic neuropathy. Our findings emphasize the importance of the neuroimmune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.

Diffusion tensor imaging MR neurography for the detection of polyneuropathy in type 1 diabetes.

PURPOSE: To evaluate if diffusion tensor imaging MR neurography (DTI-MRN) can detect lesions of peripheral nerves in patients with type 1 diabetes. MATERIALS AND METHODS: Eleven type 1 diabetic patients with polyneuropathy (DPN), 10 type 1 diabetic patients without polyneuropathy (nDPN), and 10 healthy controls (HC) were investigated with a 3T MRI scanner. Clinical examinations, nerve-conduction studies, and vibratory-perception thresholds determined the presence of DPN. DTI-MRN (voxel size: 1.4 × 1.4 × 3 mm3 ; b-values: 0, 800 s/mm2 ) covered proximal (sciatic nerve) and distal regions of the lower extremity (tibial nerve). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated and compared to T2 -relaxometry and proton-spin density obtained from a multiecho turbo spin echo (TSE) sequence. Furthermore, we evaluated DTI reproducibility, repeatability, and diagnostic accuracy. RESULTS: DTI-MRN could accurately discriminate between DPN, nDPN, and HC. The proximal FA was lowest in DPN (DPN 0.37 ± 0.06; nDPN 0.47 ± 0.03; HC 0.49 ± 0.06; P < 0.01). In addition, distal FA was lowest in DPN (DPN 0.31 ± 0.05; nDPN 0.41 ± 0.07; HC 0.43 ± 0.08; P < 0.01). Likewise, proximal ADC was highest in DPN (DPN 1.69 ± 0.25 × 10-3 mm2 /s; nDPN 1.50 ± 0.06 × 10-3 mm2 /s; HC 1.42 ± 0.12 × 10-3 mm2 /s; P < 0.01) as was distal ADC (DPN 1.87 ± 0.45 × 10-3 mm2 /s; nDPN 1.59 ± 0.19 × 10-3 mm2 /s; HC 1.57 ± 0.26 × 10-3 mm2 /s; P = 0.09). The combined interclass-correlation (ICC) coefficient of DTI reproducibility and repeatability was high in the sciatic nerve (ICC: FA = 0.86; ADC = 0.85) and the tibial nerve (ICC: FA = 0.78; ADC = 0.66). T2 -relaxometry and proton-spin-density did not enable detection of neuropathy. CONCLUSION: DTI-MRN accurately detects DPN by lower nerve FA and higher ADC. These alterations are likely to reflect proximal and distal nerve fiber pathology. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:1125-1134.

Magnetic resonance neurography and diffusion tensor imaging of the peripheral nerves in patients with Charcot-Marie-Tooth Type 1A.

INTRODUCTION: Investigation of peripheral neuropathies by magnetic resonance neurography (MRN) may provide increased diagnostic accuracy when performed in combination with diffusion tensor imaging (DTI). This study seeks to evaluate DTI in the detection of neuropathic abnormalities in Charcot-Marie-Tooth type 1A (CMT1A). METHODS: MRI of the sciatic and tibial nerves, including MRN and DTI, was prospectively performed in 15 CMT1A patients and 30 healthy controls (HCs). The following MRI parameters were evaluated and correlated with clinical and neurophysiological findings: T2-relaxation time, proton spin density (PD) and DTI (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]). RESULTS: DTI showed lower FA and higher ADC in CMT1A compared with HCs. T2 relaxation time showed no difference; however, PD of the sciatic nerve was higher in CMT1A. There were some close associations between neuropathy severity and MRN-DTI, with the closest correlation between FA and nerve conduction velocity in the sciatic nerve (r = 0.76, P < 0.01). DISCUSSION: MRN-DTI evaluation of sciatic and tibial nerves improves the detection of nerve abnormalities in patients with CMT1A. Muscle Nerve 56: E78-E84, 2017.

The impact of "modern telecommunication" in palliative care--the views of the professionals.

BACKGROUND: Specialized palliative care teams are typically based in larger hospitals, from where home visits, telephone consultations, and support are given directly to patients and relatives, but also to professionals working on the frontline. One of the challenges is the long distances to the patients' homes. Modern telecommunication may help overcome this, but little is known about the perceived advantages and barriers to palliative care. This study analyzed the views on modern telecommunication from specialized palliative care professionals' perspective. MATERIALS AND METHODS: This descriptive study is based on four semistructured group interviews where 17 health professionals from three different palliative care teams in the Central Denmark Region were interviewed from November 2009 to March 2010. RESULTS: We found that face-to-face communication is essential. The participants perceived a potentially added communicative value in visual telecommunication but would never let it replace face-to-face communication. Ethical and practical concerns were expressed on the implementation of "modern telecommunication" and in particular strong reservations against permanent telemonitoring in the patient's home. CONCLUSIONS: Our study underlines the necessity of face-to-face contact in optimal palliative care and that home visits were favored. The participants were generally positive toward telecommunication, although reservations and prerequisites were voiced.

Rectal sensitivity correlated with gastrointestinal-mediated glucose disposal, but not the incretin effect.

OBJECTIVE: The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes. DESIGN AND METHODS: For a cross-sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal-mediated glucose disposal (GIGD). RESULTS: Sixty-five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p = .005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = -0.204, p = .106), but an association was found with GIGD (rho -0.341, p = .005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes. CONCLUSIONS: Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes. PREVIOUSLY PUBLISHED: Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658-P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658-P. https://doi.org/10.2337/db23-1658-P.

Health literacy and cognitive function in people with diabetic foot ulcer with focus on knowledge, attitude, and practice in relation to foot self-care.

Introduction: Preventative foot self-care is vital for avoiding diabetic foot ulcer episodes and lowering the risk of amputations. Yet, it demands high levels of health literacy and cognitive function. Objective: To investigate health literacy and cognitive function in persons presenting with a diabetic foot ulcer. Methods: Participants with type 2 diabetes were recruited from the tertiary foot clinic at Steno Diabetes Center North Denmark. The European Health Literacy Survey Questionnaire and Addenbrooke's Cognitive Examination were applied. A semi-structured interview guide was developed to evaluate foot self-care knowledge, attitude, and practice. The qualitative data were analyzed with a deductive approach based on a qualitative thematic analysis model. Subsequently, an integrated analysis of the quantitative and qualitative results was conducted. Results: The participants (n = 12) had a mean age of 62.6 ± 8.4 years, and 11 were males. The mean diabetes duration was 15.9 ± 8.9 years. Eight participants had a recurrent diabetic foot ulcer. The health literacy level was sufficient in nine participants, and cognitive function was normal in five participants. Three different profiles related to foot self-care (proactive, active, or passive, respectively) were constructed by the final integrated analysis: a proactive profile refers to taking preventative action in concordance with knowledge and attitude, an active profile to taking action in response to a situation, but challenged by conflicting levels of knowledge and attitude, and a passive profile to not taking action. Conclusion: The study suggests that people presenting with a diabetic foot ulcer have different foot self-care profiles based on person-specific health literacy, cognitive function, and knowledge, attitude, and practice element characteristics, highlighting the need for individualized education and intervention strategy instead of a one-size-fits-all approach.

Alterations in Functional Connectivity of Thalamus and Primary Somatosensory Cortex in Painful and Painless Diabetic Peripheral Neuropathy.

OBJECTIVE: In this study we aimed to investigate the functional connectivity of brain regions involved in sensory processing in diabetes with and without painful and painless diabetic peripheral neuropathy (DPN) and the association with peripheral nerve function and pain intensity. RESEARCH DESIGN AND METHODS: In this cross-sectional study we used resting-state functional MRI (fMRI) to investigate functional brain connectivity of 19 individuals with type 1 diabetes and painful DPN, 19 with type 1 diabetes and painless DPN, 18 with type 1 diabetes without DPN, and 20 healthy control subjects. Seed-based connectivity analyses were performed for thalamus, postcentral gyrus, and insula, and the connectivity z scores were correlated with peripheral nerve function measurements and pain scores. RESULTS: Overall, compared with those with painful DPN and healthy control subjects, subjects with type 1 diabetes without DPN showed hyperconnectivity between thalamus and motor areas and between postcentral gyrus and motor areas (all P ≤ 0.029). Poorer peripheral nerve functions and higher pain scores were associated with lower connectivity of the thalamus and postcentral gyrus (all P ≤ 0.043). No connectivity differences were found in insula (all P ≥ 0.071). CONCLUSIONS: Higher functional connectivity of thalamus and postcentral gyrus appeared only in diabetes without neuropathic complications. Thalamic/postcentral gyral connectivity measures demonstrated an association with peripheral nerve functions. Based on thalamic connectivity, it was possible to group the phenotypes of type 1 diabetes with painful/painless DPN and type 1 diabetes without DPN. The results of the current study support that fMRI can be used for phenotyping, and with validation, it may contribute to early detection and prevention of neuropathic complications.

The PanGut-study: Evoked potentials following rectal balloon distention, a way of evaluating diabetic autonomic neuropathy in the gut?

AIM: There is a lack of methods for investigating the autonomic nerves of the gastrointestinal tract. Our aim was to explore a novel test measuring visceral sensory evoked potentials (EPs) in response to rapid balloon distention in the rectum and compare it to established tests for diabetic neuropathy. METHOD: Participants with longstanding type 2 diabetes, newly onset, untreated diabetes <1 year, and matched controls, were included. Tests included cardiovascular reflex tests, orthostatic blood pressure, electrical skin conductance assessment, sural nerve testing and monofilament test. The rectal balloon distention pressure at earliest sensation and threshold of unpleasantness were identified and used to elicit mechanical EPs. RESULTS: The pressure at earliest sensation was higher in people with diabetes, 0.038 (0.012) bar vs. controls 0.030 (0.009) bar, p = 0.002, and in people with signs of peripheral neuropathy, 0.045 (0.014) bar, p < 0.01. Clinical correlations between EP amplitude and latency, and other tests were found. CONCLUSIONS: Rectal hyposensitivity was associated with both longstanding and early diabetes, indicating enteric sensory dysfunction already in early stages of diabetes. Correlation analyses may indicate that central afferent processing is affected in parallel with peripheral neuronal function.

The co-existence of sensory and autonomic neuropathy in type 1 diabetes with and without pain.

AIMS: To investigate the co-existence of diabetic peripheral neuropathy (DPN), painful diabetic peripheral neuropathy (PDPN), and cardiac autonomic neuropathy (CAN) and to establish a model to predict CAN based on peripheral measurements. METHODS: Eighty participants (20 type 1 diabetes (T1DM) + PDPN, 20 T1DM + DPN, 20 T1DM-DPN (without DPN), and 20 healthy controls (HC)) underwent quantitative sensory testing, cardiac autonomic reflex tests (CARTs), and conventional nerve conduction. CAN was defined as ≥ 2 abnormal CARTs. After the initial analysis, the participants with diabetes were re-grouped based on the presence or absence of small (SFN) and large fibre neuropathy (LFN), respectively. A prediction model for CAN was made using logistic regression with backward elimination. RESULTS: CAN was most prevalent in T1DM + PDPN (50%), followed by T1DM + DPN (25%) and T1DM-DPN and HC (0%). The differences in prevalence of CAN between T1DM + PDPN and T1DM-DPN/HC were significant (p < 0.001). When re-grouping, 58% had CAN in the SFN group and 55% in the LFN group, while no participants without either SFN or LFN had CAN. The prediction model had a sensitivity of 64%, a specificity of 67%, a positive predictive value of 30%, and a negative predictive value of 90%. CONCLUSION: This study suggests that CAN predominantly co-exists with concomitant DPN.

The Composite Autonomic Symptom Score 31 Questionnaire: A Sensitive Test to Detect Risk for Autonomic Neuropathy.

Background and Aims: Autonomic neuropathy is a common but often neglected complication of diabetes, prediabetes, and even in individuals with an elevated risk of diabetes. The Composite Autonomic Symptom Score (COMPASS) 31 is a validated and easy-to-use questionnaire regarding autonomic symptoms. We aimed to use a digitally, Norwegian version of the COMPASS 31 in people with different durations of diabetes and healthy controls to consider feasibility and to investigate if scores could discriminate between positive and negative outcomes for established tests for diabetic neuropathy, including cardiovascular autonomic neuropathy (CAN) and a novel method of examining the gastrointestinal visceral sensitivity. Method: We included 21 participants with longstanding type 2 diabetes, 15 with early type 2 diabetes, and 30 matched controls. The mean age for all groups was 69 years. Participants were phenotyped by cardiovascular autonomic reflex tests, electrical skin conductance, sural nerve electrophysiology, and the monofilament test. As a proxy for gastrointestinal visceral and autonomic nerve function, evoked potentials were measured following rapid rectal balloon distention. Results: Participants with longstanding diabetes scored a median (IQR) of 14.9 (10.8-28.7) points, early diabetes of 7.3 (1.6-15.2), and matched controls of 8.6 (4.1-21.6), p = 0.04. Women and men scored 14.4 (5.5-28.7) and 7.8 (3.6-14.6) points, respectively, p = 0.01. Participants with definite or borderline CAN scored 14.3 (10.4-31.9) points, compared to participants with no CAN, 8.3 (3.2-21.5), p = 0.04. Lowering the diagnostic cut-off from 16 to 10 points increased the sensitivity from 0.33 to 0.83, with a decreased specificity from 0.68 to 0.55. Conclusion: We successfully used COMPASS 31 in Norwegian. Thus, following the guidelines, we suggest clinical implementation for the assessment of autonomic neuropathy. Participants with longstanding diabetes had an increased likelihood of symptoms and signs of autonomic neuropathy. For screening purposes, the sensitivity was improved by lowering the cut-off to 10 points, with a lower score nearly excluding the diagnosis.

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.

ABSTRACT: 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.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.