Giacomo Zoppini

Background: Diabetic neuropathy manifests as symmetric distal and autonomic neuropathy, including cardiovagal dysfunction. Small-fiber involvement can occur, leading to neuropathic pain and dysautonomia. The diagnostic gold standard of these two conditions comprehends skin biopsy and cardiovascular autonomic reflex tests (CARTs), respectively. Non-invasive diagnostic tools, such as laser-evoked potentials (LEPs), show promise in detecting small-fiber damage, though correlations between LEP abnormalities and cardiovascular autonomic dysfunction remain poorly investigated. Methods: We retrospectively evaluated LEPs (from hands and feet stimulation) in 33 diabetic patients, comparing them to a cohort of 33 age-matched healthy subjects, to highlight any significant abnormalities in the diabetic cohort. We further analyzed the LEP results in T2DM cohort with clinical, laboratory variables and CARTs to explore potential correlations and to assess whether any association between LEPs and CARTs could be identified. Results: N2/P2 complex amplitude was significantly reduced in diabetic patients compared to healthy subjects, with greater involvement in the lower limbs. While no association between LEP abnormalities and abnormal CARTs was observed, LEP amplitude reductions were notably associated with elevated glycated hemoglobin levels and longer disease duration, which appeared to be the strongest predictor of LEP reduction. Conclusions: Our findings corroborated literature data regarding length-dependent LEP alterations detectable even in initial diabetic stages. The lack of correlation between LEP abnormalities and autonomic dysfunction may stem from the predominant involvement of C fibers in autonomic neuropathy, which are not adequately assessed by currently used LEPs.

Vitamin A is a fundamental micronutrient in the diet. In recent years, hypervitaminosis A has been described in subjects, mainly children, with renal dysfunction. The aim of the present study was to estimate the prevalence of hypervitaminosis A in adult patients affected by type 2 diabetes and to evaluate the associated factors. This cross-sectional observational study included 200 ambulatory patients affected by type 2 diabetes regularly attending the Diabetes Clinic of Verona (Italy). Eligible patients were consecutively enrolled. Vitamin A was measured by reverse phase high performance liquid chromatography with UV detection. The normal range of values for vitamin A concentrations was 1.04–2.79 μmol/L. All other laboratory parameters were measured by standard methods. A multivariate logistic regression model was applied to study the factors independently associated with the hypervitaminosis A. Hypervitaminosis A was detected in 29% of our cohort of patients. Its prevalence was significantly higher in patients with cardiovascular complications (CVD). Nevertheless, when patients with CVD were stratified according to renal function, the latter emerged as the main factor associated with hypervitaminosis A. The multivariate analysis confirmed that estimated glomerular filtration rate was an independent predictor of hypervitaminosis A (0.97 CI 95% 0.96–0.99, p = 0.008).The main alteration of vitamin A in ambulatory patients affected by type 2 diabetes is hypervitaminosis. Renal function is strongly associated with hypervitaminosis A.

Purpose: A sharp increase in diabetes-related mortality has been registered during the pandemic. Although immigrants are known to suffer from a higher prevalence of diabetes than host populations, data on diabetes-related mortality in pandemic years among immigrants are lacking. Methods: All deaths with any mention of diabetes (multiple causes of death-MCOD) among subjects aged 20–64 years were extracted from the Italian National Cause of Death Register in the years 2019–2021. Directly age-standardized mortality rates (2013 European standard population) were computed. Standardized mortality ratios (SMR) for different immigrant groups were estimated with expected numbers based on rates registered among Italian citizens. Results: Overall age-standardized mortality rates related to diabetes increased by 30% in 2020 compared to 2019, remaining high in 2021. Before the pandemic, large differences were observed across different immigrant groups; during the pandemic, the mortality disadvantage versus the native population widened among those already at increased risk. Among female immigrants, SMR in 2021 were 1.9 (95% Confidence Interval 1.1–2.8) in North Africans, 4.4 (2.5–6.3) in Sub-Saharan Africans and 2.8 (1.6–4.1) in South Asians. Conclusion: Surveillance based on MCOD is warranted to assess if the large differences in diabetes-related mortality observed across different populations living in Italy will reduce in the next years.

OBJECTIVE: α-tocopherol has a protective role against free radical-induced damage. The intestinal absorption of α-tocopherol is in part carried out by Nieman-Pick1-like1 protein, which is the target of ezetimibe, a drug used for the treatment of hypercholesterolemia. Ezetimibe is frequently prescribed to patients with type 2 diabetes in combination with statins. Therefore, the aim of the present study was to investigate the impact of ezetimibe treatment on the blood level of α-tocopherol. MATERIALS AND METHODS: Two hundred patients affected by type 2 diabetes, regularly attending the diabetes clinic, were recruited. All patients should not have received vitamin supplements in the six months preceding the study. α-tocopherol was measured by reverse-phase high-performance liquid chromatography with UV detection. Other laboratory parameters were determined by standard laboratory procedures. Patients were analyzed according to ezetimibe treatment. A linear multivariate regression analysis was used to estimate the factors associated with α-tocopherol level. RESULTS: The majority of patients were on ezetimibe/statin treatment. Patients taking ezetimibe showed a significantly lower α-tocopherol level, 29.9±5.7 vs. 32.9±7.0 μmol/L (p=0.006) compared to those not taking the drug. Ezetimibe was significantly and negatively associated with α-tocopherol level in the multivariate analysis (β standardized coefficient = -.217, p = .002). CONCLUSIONS: Treatment with ezetimibe can reduce α-tocopherol plasma levels by inhibiting the Niemann-Pick C1-like protein. Future studies are required to address the clinical implications of this finding. https://www.europeanreview.org/wp/wp-content/uploads/Graphical-Abstract-NEW-2-scaled.jpg.

Vitamin C is a fundamental antioxidant with important metabolic actions in several biological processes. Patients with type 2 diabetes (T2D) are exposed to oxidative stress as a consequence of an increased production of reactive oxygen species (ROS). The aims of the present study were to estimate the prevalence of vitamin C deficiency in ambulatory patients with T2D, to study the relationship between vitamin C levels and cardiovascular diseases and to correlate the consumption of fresh fruit and vegetables with vitamin C levels and the presence of cardiovascular diseases. Vitamin C levels, determined by high-performance liquid chromatography (HPLC), and consumption of fresh fruit and vegetables, assessed by a food frequency questionnaire, were measured in 200 outpatients with T2D. All other laboratory variables were measured by standard methods. The association between vitamin C and cardiovascular diseases was assessed by multivariable logistic regression analysis. Vitamin C deficiency was found in 12.2% of the subjects. Vitamin C levels and consumption of fresh fruit and vegetables were lower in subjects with cardiovascular diseases. Consumption of fresh fruit and vegetables was associated with higher levels of vitamin C. In the multivariable analysis, vitamin C was independently associated with cardiovascular diseases. In conclusion, our study suggests that vitamin C may have an inverse relationship with cardiovascular diseases. Intake of vitamin C from fresh fruit and vegetables could play a protective role.

Purpose: Diabetes is a growing health problem. The aim of this study was to capture time trends in mortality associated with diabetes. Methods: The mortality database of the Veneto region (Italy) includes both the underlying causes of death, and all the diseases mentioned in the death certificate. The annual percent change (APC) in age-standardized rates from 2008 to 2017 was computed by the Joinpoint Regression Program. Results: Overall 453,972 deaths (56,074 with mention of diabetes) were observed among subjects aged ≥ 40 years. Mortality rates declined for diabetes as the underlying cause of death and from diabetes-related circulatory diseases. The latter declined especially in females − 4.4 (CI 95% − 5.3/− 3.4), while in males the APC was − 2.8 (CI 95% − 4.0/− 1.6). Conclusion: We observed a significant reduction in mortality during the period 2008–2017 in diabetes either as underlying cause of death or when all mentions of diabetes in the death certificate were considered.