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The dominant sensory phenotype in patients with diabetic polyneuropathy and neuropathic pain is a loss of function. This raises questions as to which mechanisms underlie pain generation in the face of potentially reduced afferent input. One potential mechanism is spinal disinhibition, whereby a loss of spinal inhibition leads to increased ascending nociceptive drive due to amplification of, or a failure to suppress, incoming signals from the periphery. We aimed to explore whether a putative biomarker of spinal disinhibition, impaired rate-dependent depression of the Hoffmann reflex, is associated with a mechanistically appropriate and distinct pain phenotype in patients with painful diabetic neuropathy. In this cross-sectional study, 93 patients with diabetic neuropathy underwent testing of Hoffmann reflex rate-dependent depression and detailed clinical and sensory phenotyping, including quantitative sensory testing. Compared to neuropathic patients without pain, patients with painful diabetic neuropathy had impaired Hoffmann reflex rate-dependent depression at 1, 2 and 3 Hz (P ≤ 0.001). Patients with painful diabetic neuropathy exhibited an overall loss of function profile on quantitative sensory testing. However, within the painful diabetic neuropathy group, cluster analysis showed evidence of greater spinal disinhibition associated with greater mechanical pain sensitivity, relative heat hyperalgesia and higher ratings of spontaneous burning pain. These findings support spinal disinhibition as an important centrally mediated pain amplification mechanism in painful diabetic neuropathy. Furthermore, our analysis indicates an association between spinal disinhibition and a distinct phenotype, arguably akin to hyperpathia, with combined loss and relative gain of function leading to increasing nociceptive drive.

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2-4 and 2-5 at 1 Hz, AUC = 0.84 (95%CI 0.76-0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

Introduction: Diabetes mellitus worsens the prognosis of SARS‐CoV‐2 infection, and vaccination has been the major tool for reducing the risk of hospitalisation, and mortality. The primary aim of this study was to evaluate the response to the SARS‐CoV‐2 vaccine in subjects with diabetes and controls. Differences between type 1 (T1D) and type 2 (T2D) diabetes and clinical determinants of vaccination response were also evaluated. Methods: 128 subjects with diabetes (60 with T1D and 62 with T2D) and 202 subjects acting as controls who completed a full vaccination cycle with two doses of mRNA vaccine were enroled. People with previous SARS‐CoV‐2 infection were excluded. Antibodies (Ab) directed against the spike protein of the SARS‐CoV‐2 were evaluated at one and 6 months after vaccination. Results: In the whole cohort, the Ab level was higher among women than in men (p = 0.011) and negatively correlated with age (rho = −0.155, p = 0.005). Subjects with diabetes showed decreased levels of Ab after one month compared to controls (1217[747–1887]BAU/mL vs. 1477[942–2556]BAU/mL, p = 0.002), even after correction for age and gender (p = 0.002). No difference was found between subjects with T1D and T2D. After 6 months, antibody levels significantly decreased in people with and without diabetes, with no differences between groups, although some subjects were lost at follow‐up. In subjects with diabetes, only a significant correlation was found between Ab level and renal function (rho 0.190, p = 0.042). Conclusions: Both T1D and T2D are associated with a reduced early response to vaccination. The serum concentration of Ab significantly reduced over time in both groups, highlighting the relevance of vaccination boosters independently of the presence of diabetes. [ABSTRACT FROM AUTHOR]

Antibodies (Abs) against intracellular epitopes of the tyrosine-phosphatase 2 (IA-2) are detected in type 1 diabetes. Abs directed against the IA-2(256-760) portion, with both intra- and extracellular epitopes, are present in people with latent autoimmune diabetes in adults (LADA) and in obese subjects with normal glucose tolerance (NGT). We aim to characterize distribution and clinical features of intra- and extra-cellular IA-2(256-760) immunoreactivities in people with LADA compared to obese people with NGT. The intracellular immunoreactivity represented by immune response against two intracellular IA-2 constructs (IA-2JM(601-630) and IA-2IC(605-979)) was analyzed and related to clinical and biochemical features in 101 people with LADA and in 20 NGT obese subjects, all testing positive for IA-2(256-760) Abs. IA-2 intracellular immunoreactivity showed a frequency of 40.6% in LADA while it was not detected among NGT obese (p<0.001). Amongst LADA, the presence of immunoreactivity against the IA-2 intracellular domains was associated with lower BMI, waist circumference, higher HDL cholesterol and lower triglycerides, lower prevalence of hypertension and higher prevalence of other autoimmune disorders. Immunoreactivity against IA-2 does not involve intracellular domains in the majority of LADA and in obese people with NGT. This study shows that there is heterogeneity in the IA-2 epitopes, associated with different clinical features. [ABSTRACT FROM AUTHOR]

Keywords: Covid-19 vaccine; Glycaemia; diabetes EN Covid-19 vaccine Glycaemia diabetes 1 3 3 07/08/22 20220701 NES 220701 Coronavirus (COVID-19) disease is usually characterised by poor prognosis in patients with diabetes implying that mitigation of the COVID-19 pandemic risk becomes a priority in patients with type 1 (T1D) or type 2 (T2D) diabetes.1 Despite that COVID-19 vaccination represents the most powerful tool to mitigate COVID-19 disease, multiple unresolved issues with regard to the efficacy and durability of COVID-19 vaccine in patients with diabetes still remain unsolved. However, this reduced effect of vaccine in patients with diabetes was minimised when they were vaccinated at the time of good glycaemic control.2 This topic rises as central in the vaccination efforts against SARS-Cov-2 in diabetes. Third dose of COVID-19 vaccine in diabetes: Relevance of good metabolic control to improve its efficacy. [Extracted from the article]

Background: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. Methods: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. Results: Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12–3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37–3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23–5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61–6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90–3.06, adjp = 0.10). Conclusions: Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions. [ABSTRACT FROM AUTHOR]

In patients with autoimmune diabetes no significant differences were observed in glucose control, expressed as time in range evaluated by continuous glucose monitoring comparing the 3 days after Sars-Cov2 vaccine with the 14 days preceding the vaccine. [ABSTRACT FROM AUTHOR]

Aims: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19.Methods: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders.Results: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59-3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42-9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18-8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13-0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12-0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16-0.93, p = 0.033) were found among cases.Conclusions: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes. [ABSTRACT FROM AUTHOR]