Although the COVID-19 pandemic has now been down-graded, long COVID (LC) presents an ongoing risk of long-term disease for a significant percentage of the population, even after mild or no symptoms upon infection. LC post-viral effects have been associated with oxidative stress (OS), impacting canonical cell function. The aim of this study was to investigate the association of eight OS-related single nucleotide polymorphisms (SNPs) on LC susceptibility among patients with mild or no symptoms during SARS-CoV-2 infection, with emphasis on a clinically homogeneous population free from bias and overlap with other conditions. Blood samples were collected from 85 clinically confirmed LC patients and 96 unvaccinated controls (observational case control study) all with mild/asymptomatic infection, and analysed by targeted SNP genotyping in the GSTP1, SELENOS, CAT, SOD2, and EPHX1 OS-related genes. Τhe control individuals had been infected at least 6 months prior to enrollment and had not developed any symptoms related to long COVID. Our analysis revealed associations between SOD2 and EPHX1 polymorphisms and disease progression, with pre-existing thyroid disease and acute phase symptoms being significant aggravating factors. Machine Learning (ML) analysis produced a 10-factor predictive model for LC with a balanced accuracy over 0.74, released herein as an open-access LC risk rating webtool. Our findings suggest that individuals' genetic antioxidant capacity may plays an important role in long covid, fitting with current ideas of mitochondrial dysfunction and viral persistence. It is also shown how well diagnosed and bias free cohorts can reveal patterns often missed in self-reported cases and the potential for predictive tools that combine genetic and clinical data.

Abstract Background The association between diabetes mellitus and diabetic nephropathy with vascular and endothelial properties is well established. Purpose In this study, we compared the effect of combined treatment with dulaglutide and dapagliflozin versus DPP-4 inhibitors on endothelial glycocalyx, arterial stiffness, myocardial function and albuminuria in patients with type 2 diabetes mellitus and albuminuria. Methods A total of 60 patients with type 2 diabetes mellitus and albuminuria were randomized to combined dulaglutide and dapagliflozin treatment (n=30) or DPP-4 inhibitors (DPP-4is, n=30). We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (c) global left ventricular longitudinal strain (GLS) (d) urine albumin-to creatinine ratio (UACR). Results Twelve months post-treatment, the combination of dulaglutide and dapagliflozin showed a greater improvement in all indices compared to DPP-4is, despite a similar reduction in glycosylated hemoglobin. Specifically, dual therapy showed greater improvements vs DPP-4is in PBR (2,10±0,31 to 1,93±0,23 μm vs 2,11±0,31 to 2,08±0,28 μm, p<0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p<0,01), and in PWV (11,77±2,37 to 10,7±2,29 m/s vs 10,64±2,44 to 10,54±2,84 m/s, p<0,001), while only dual therapy showed improvement in cSBP (130,21±17,23 to 123,36±18,42 mmHg). Regarding GLS, both treatments were effective, but dual therapy showed a significantly higher percentage improvement compared to DPP-4is (18,19% vs 6,01%, respectively). Conclusions Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in vascular markers an albuminuria than DPP-4is in patients with type 2 diabetes mellitus and albuminuria. Early initiation of combined therapy as add-on to metformin should be considered in these patients.

Background: The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. Methods: Overall, 60 patients were randomized to combined dulaglutide and dapagliflozin treatment (n = 30) or DPP-4 inhibitors (DPP-4i, n = 30) (ClinicalTrials.gov: NCT06611904). We measured at baseline and 4 and 12 months post-treatment: (i) the perfused boundary region of the sublingual arterial microvessels, (ii) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (iii) global left ventricular longitudinal strain (GLS), and (iv) urine albumin-to-creatinine ratio (UACR). Results: After twelve months, dual therapy showed greater improvements vs. DPP-4i in PBR (2.10 ± 0.31 to 1.93 ± 0.23 μm vs. 2.11 ± 0.31 to 2.08 ± 0.28 μm, p < 0.001), UACR (326 ± 61 to 142 ± 47 mg/g vs. 345 ± 48 to 306 ± 60 mg/g, p < 0.01), and PWV (11.77 ± 2.37 to 10.7 ± 2.29 m/s vs. 10.64 ± 2.44 to 10.54 ± 2.84 m/s, p < 0.001), while only dual therapy showed improvement in cSBP (130.21 ± 17.23 to 123.36 ± 18.42 mmHg). These effects were independent of glycemic control. Both treatments improved GLS, but the effect of dual therapy was significantly higher compared to DPP-4i (18.19% vs. 6.01%, respectively). Conclusions: Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in arterial stiffness, endothelial function, myocardial function, and albuminuria than DPP-4is. Early initiation of combined therapy as an add-on to metformin should be considered in these patients.

IntroductionMigraine is a complex disorder with genetic and environmental inputs. Cumulative evidence implicates oxidative stress (OS) in migraine pathophysiology while genetic variability may influence an individuals' oxidative/antioxidant capacity. Aim of the current study was to investigate the impact of eight common OS-related genetic variants [rs4880 (SOD2), rs1001179 (CAT), rs1050450 (GPX1), rs1695 (GSTP1), rs1138272 (GSTP1), rs1799983 (NOS3), rs6721961 (NFE2L2), rs660339 (UCP2)] in migraine susceptibility and clinical features in a South-eastern European Caucasian population. MethodsGenomic DNA samples from 221 unrelated migraineurs and 265 headache-free controls were genotyped for the selected genetic variants using real-time PCR (melting curve analysis). ResultsAlthough allelic and genotypic frequency distribution analysis did not support an association between migraine susceptibility and the examined variants in the overall population, subgroup analysis indicated significant correlation between NOS3 rs1799983 and migraine susceptibility in males. Furthermore, significant associations of CAT rs1001179 and GPX1 rs1050450 with disease age-at-onset and migraine attack duration, respectively, were revealed. Lastly, variability in the CAT, GSTP1 and UCP2 genes were associated with sleep/weather changes, alcohol consumption and physical exercise, respectively, as migraine triggers. DiscussionHence, the current findings possibly indicate an association of OS-related genetic variants with migraine susceptibility and clinical features, further supporting the involvement of OS and genetic susceptibility in migraine.

BACKGROUND:Providing care for older adults has been associated with the presence of depressive symptoms among their informal caregivers. Numerous caregivers and older adults' characteristics have been mentioned as predictors of caregivers' depression. However, studies dealing with the impact of older adults' frailty status on caregivers' depression are scarce. This study was conducted to clarify the precise relationship between caregivers' depression, caregivers' burden, caregivers' characteristics and patients' characteristics, including frailty, among the variables that may have an impact on caregivers' depression.METHODS:In this cross-sectional study, patients and caregivers' characteristics were recorded for 311 patient-caregiver dyads, when the patient was admitted to the hospital. For the purpose of the study, a mediation analysis was used with patients and caregiver characteristics considered to be predictors, subjective caregivers' burden as the mediator, and caregivers' depression as the outcome variable.RESULTS:Only patients' frailty and caregivers' subjective burden had a direct effect on caregivers' depression. Moreover, caregivers' gender, patients' frailty status and comorbidity, duration of caregiving, and the relationship with the patient, had an indirect effect through caregivers' burden that acted as mediator. Regarding total effects, caregivers burden followed by patients' frailty status had the greater impact on caregivers' depression.CONCLUSIONS:By organising interventions to reduce caregivers' depression, patients' frailty status could be among the targets of those interventions considering that frailty might be delayed or reversed.

Migraine is a common primary headache disorder with both environmental and genetic inputs. Cumulative evidence indicates an association between vitamin D and headache. Unravelling the precise role of vitamin D and its receptor in the pathophysiology of migraine can eventually contribute to more efficient prevention and management of this headache disorder. The aim of the study was to investigate the relation of the three most studied VDR variants, i.e., FokI (rs2228570), TaqI (rs731236) and BsmI (rs1544410), with migraine susceptibility and distinct clinical phenotypes in a Southeastern European case-control population residing in Greece. DNA was extracted from 191 unrelated patients diagnosed with migraine and 265 headache-free controls and genotyped using real-time PCR (LightSNiP assays) followed by melting curve analysis. Genotype frequency distribution analysis of the TaqI and BsmI variants showed a statistically significant difference between migraine cases and controls. In addition, subgroup analyses revealed a significant association between all three studied VDR variants, particularly with a migraine without aura subtype. Therefore, the current study provides supporting evidence for a possible association of VDR variants with migraines, particularly migraine without aura susceptibility in Southeastern Europeans residing in Greece, further reinforcing the emerging role of vitamin D and its receptor in migraines.

Background: Diabetes burnout is a condition when a patient with diabetes feels tired from his/her disease and neglects it for a certain period or continuously. Objective: Diabetes burnout is frequent, and there is extended literature about psychosocial stress and its negative effects on health. Methods: A search for relevant studies was conducted using PubMed, Google Scholar and ResearchGate. A systematic review was conducted on the relevant articles after critical appraisal. Only publications in English were selected. The objective of this study was to evaluate the association between burnout syndrome and diabetes mellitus. Results: This article mainly focused on studies that evaluated the presence of burnout and diabetes mellitus effects. Diabetes can influence psychological health equally with somatic strength. Relatives can also express depression, guilt, fright, worry, rage, and burnout. Psychosocial job stress and extended working hours are linked with a higher possibility of myocardial infarction, diabetes mellitus, and hypertension. Conclusion: Diabetes burnout is a combination of emotions and practices, ranging from tiredness to indifference, linked with a distressing sense of hopelessness. Revealing this health condition is necessary so that preventive measures can be taken.

Aims/Introduction: Several reports indicate an increasing prevalence of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). Hyperglycemia and hypertension are the main risk factors for CKD development and progression. However, despite the achievement of recommended targets for blood glucose and blood pressure (BP), the residual risk of diabetic chronic kidney disease (DCKD) remains relatively high. The aim of this study is to examine dyslipidemia and other major risk factors to provide support for the prevention and treatment of DCKD. Materials and Methods: Participants are from the Redit-2-Diag study that examines 1759 subjects within a period of 6 months. DCKD severity is staged according to KDIGO criteria. Results: An increase in hemoglobin A1c (1 unit) and systolic blood pressure (1 mm Hg) increases the probability of being classified into a higher CKD stage by 14% and 26%, respectively. Moreover, an increase of triglycerides by 88.5 mg/dL increases the risk of classification to a worse CKD stage by 24%. Conclusions: Elevated triglycerides, systolic blood pressure, and poor glycemic control increase the risk of CKD in T2DM and should be addressed in the treatment strategies.

Coronavirus disease 2019 (COVID-19) has been proved as a multi-organ disease with deleterious effect on the cardiovascular system.1 COVID-19 infection has been associated with impaired subclinical markers of cardiovascular and endothelial function even in patients with mild severity of COVID-19.2 Furthermore, subclinical myocardial and vascular dysfunction during COVID-19 disease have been associated with worse outcomes and higher mortality risk.3 Carotid-femoral pulse wave velocity (PWVc-f) and central systolic blood pressure (SBPcentral) are reliable markers of aortic elastic properties and have been suggested as valuable prognostic markers for cardiovascular events.4 Glycocalyx damage, as assessed by perfused boundary region (PBR5–25) of sublingual microvessel, impaired artery flow-mediated dilatation (FMD) and coronary flow reserve (CFR) may represent early manifestations of endothelial dysfunction with prognostic value.5, 6 Left and right ventricular global longitudinal strain (GLS) and myocardial work indices permit early detection of subclinical myocardial deformation.7 In our previous study,8 COVID-19 patients displayed impaired endothelial function, aortic elasticity, CFR and myocardial deformation 4 months after COVID-19 infection compared to healthy controls with similar age, sex and risk factors. Additionally, we observed a 10-fold increase of malondialdehyde (MDA), an oxidative stress biomarker, suggesting that oxidative stress mediates cardiovascular damage.8 There are no studies to evaluate whether these changes are reversible in a longer-term follow-up. The aim of the present study is to examine markers of endothelial, vascular and myocardial function during a follow-up visit at 12 months after COVID-19 infection in order to clarify whether the changes observed at 4 months post-infection are reversible in the long term. In a prospective, observational study, we consecutively recruited 70 patients (62.85% male; mean age 54.53 years) who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at 4 and 12 months after a confirmed COVID-19 infection and 70 healthy individuals with similar clinical characteristics. In all participants, the medication remained unchanged during the study. A total of 24 patients (34.28%) were diagnosed with mild disease and were not subsequently hospitalized at any time of the course of the disease, whereas 23 (32.85%) patients were diagnosed to have moderate and 23 (32.85%) severe disease and thus were admitted to hospital. None of the examined patients required mechanical ventilation. Inclusion and exclusion criteria, study design and procedures have been previously described in detail.8 At 4 and 12 months we measured (a) PBR of the sublingual arterial microvessels (online supplementary Appendix S1), (b) PWV and SBPcentral, (c) FMD, (d) CFR, (e) LVGLS, RVGLS and right ventricular free wall strain (RVFWS), (f) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) (online supplementary Appendix S1), and (g) MDA as oxidative stress marker. ANOVA (factorial or for paired comparisons) was used for statistical analysis. Online supplementary Table S1 shows alterations in endothelial, vascular, and echocardiographic markers of myocardial function in COVID-19 patients at 4 and 12 months after the infection compared to the control group. The results regarding the effect of COVID-19 at 4 months after the infection have been already published.8 At 12-month follow-up, COVID-19 patients displayed an increase of PBR5–25 values compared to 4 months (p < 0.001). Likewise, FMD values were similar between 4 and 12 months (p = 0.198) and higher than those in controls (p < 0.001), suggesting persistence of endothelial damage. PWV and SBPcentral values remained similar between 4 and 12 months (p = 0.883 and p = 0.776, respectively) and were increased compared to controls (p = 0.057 and p = 0.003, respectively). Conversely, COVID-19 patients at 12 months presented higher CFR values than at 4 months (p = 0.002). However, CFR values remained decreased compared to controls (p = 0.003). At 12 months post-infection, LVGLS values in COVID-19 patients showed a borderline improvement compared to values at 4 months (p = 0.069), though again these remained impaired compared to controls (p = 0.003). Conversely, RVGLS, RVFWS and tricuspid annular plane systolic excursion in COVID-19 patients at 12 months were significantly improved compared to 4 months (p = 0.001, p < 0.001, and p = 0.002, respectively) and showed no significant difference compared to controls (p > 0.05 for all comparisons). At 4 and 12 months, 72.5% and 42.8% of the patients had abnormal (> −20%) LVGLS. The results regarding the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on myocardial work markers 4 months after the infection have not been published previously. COVID-19 patients at 4 months displayed higher myocardial wasted work and decreased myocardial efficiency compared to controls (p = 0.01 and p = 0.006, respectively). There was a modest improvement in GWW and GWE at 12 months, compared to 4 months in COVID-19 patients (p = 0.043 and p = 0.001, respectively); however, these markers remained impaired compared to controls (p > 0.05). At 12 months after COVID-19 infection, MDA levels were significantly decreased compared to 4 months (p < 0.001); however, these values remained higher than in controls (p = 0.002). Figure 1 shows the most important alterations in above markers in COVID-19 patients at 4 and 12 months after the infection compared to the control group. At 4 months, 37.87% of the patients had symptoms (fatigue, dyspnoea, cough and chest pain) but only 4.25% at 12 months. Our study supports that SARS-CoV-2 causes endothelial and cardiovascular dysfunction which are partially restored at 12 months after the infection. In our study, the values of right ventricular echocardiography markers in COVID-19 patients improved significantly at 1 year compared to their values at 4 months. Thus, right ventricular function markers in COVID-19 patients became in close range to those of controls with similar cardiovascular risk factors possibly due to complete resolution of lung lesions 1 year after the infection and thus resolution of myocardial stress caused by the preceding infection. In the current study, after 1 year of follow-up, the significant reduction in MDA levels and the subsequent improvement of cardiovascular markers suggest that oxidative stress mediates the cardiovascular derangements. However, oxidative stress remained nearly two-fold higher at 1 year compared to controls. Furthermore, COVID-19 patients at 12 months after infection presented greater values of PBR and similar values of PWV compared to 4 months and higher than controls indicating persistence of endothelial and vascular derangement 1 year after the infection. According to research data, increased arterial stiffness and endothelial glycocalyx damage have been associated with adverse cardiovascular events.4, 6 In conclusion, arterial stiffening, endothelial dysfunction and a persistently high oxidative burden may lead to a compromised cardiac performance as indicated by the impaired values of myocardial work and LVGLS in COVID-19 patients at 12 months compared to controls. To our knowledge, this is the first study to evaluate markers of endothelial and cardiovascular function as well as oxidative stress at 4 and 12 months after COVID-19 infection and to report that the alterations observed at 4 months post-infection are only partially reversed at 12 months. The present study has been supported by the Hellenic Cardiology Society. Conflict of interest: none declared. Appendix S1. Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND:During the last decades a considerable increase in biological and psychosocial approaches have occurred so as to enhance the study of prenatal period. This study aimed to investigate the validity and reliability of the Greek version of Pregnancy Outcome Questionnaire (POQ) in assessing pregnancy-related stress.MATERIAL AND METHODS:The study group consisted of 135 first-time expectant women with good knowledge of the Greek language, low-risk pregnancies and a gestational age of ≥24 weeks. Questionnaires containing the POQ scale questions in addition to other questions and scaleswere distributed in printed and digital format at private gynecological clinics. The collected data were analysed using the SPSS software.RESULTS:The POQ scale score showed satisfactory reliability (Cronbach's alpha = 0.8), while the factor analysis showed a major factor with an eigenvalue of 4.17 and an overall interpreted factor variance of 41%. The sample showed moderate intensity values on the scale. We observed that pregnancy-related characteristics affected the scale, while no significant correlations with demographic variables were recorded.CONCLUSION:The results of the reliability and factor analyses evaluating the scale structure indicated that the tool performed well in Greek, had a compact structure with satisfying reliability, and is suitable for use in the Greek pregnant population. However, additional research is warranted to investigate the effect of various additional factors on the scale.

Epidemiological data have consistently shown since the beginning of the pandemic that both the severity and the mortality of coronavirus disease (COVID-19) are higher in men than in women [1Alwani M. Yassin A. Al-Zoubi R.M. Aboumarzouk O.M. et al.Sex-based differences in severity and mortality in COVID-19.Rev. Med. Virol. 2021; 31e2223Crossref PubMed Scopus (20) Google Scholar, 2Prinellia F. Trevisan C. Noale M. et al.EPICOVID19 working group. Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis.Maturitas. 2022; https://doi.org/10.1016/j.maturitas.2021.11.015Abstract Full Text Full Text PDF Scopus (2) Google Scholar]. The Global Health 50/50 research initiative confirmed a greater mortality in men despite similar numbers of COVID-19 cases in both genders worldwide [[3]Global Health 5050. The sex, gender and COVID-19 project. https://globalhealth5050.org/the-sex-gender-and-covid-19-project/dataset/ Last accessed: 27 February 2, 2022.Google Scholar]. On the other hand, women appear to be at greater risk of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, the persistence of symptoms over a long period of time after infection, a condition known as long COVID, is more common in women than in men [1Alwani M. Yassin A. Al-Zoubi R.M. Aboumarzouk O.M. et al.Sex-based differences in severity and mortality in COVID-19.Rev. Med. Virol. 2021; 31e2223Crossref PubMed Scopus (20) Google Scholar, 4Rozenberg S. Vandromme J. Martin C. Are we equal in adversity? Does Covid-19 affect women and men differently?.Maturitas. 2020; 138: 62-68Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. Another interesting observation is that women are more likely to experience, or at least to report more frequently, side-effects after COVID-19 vaccination, including fever and pain at the site of injection [4Rozenberg S. Vandromme J. Martin C. Are we equal in adversity? Does Covid-19 affect women and men differently?.Maturitas. 2020; 138: 62-68Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. Moreover, it seems that the transient endothelial and inflammatory response after vaccination is larger in women, which may indicate greater protection in women [[6]Terentes-Printzios D. Gardikioti V. Solomou E. et al.The effect of mRNA vaccine against COVID-19 on endothelial function and arterial stiffness.Hypertens. Res. 2022; https://doi.org/10.1038/s41440-022-00876-6Crossref PubMed Scopus (4) Google Scholar]. The two genders of course have chromosomal differences, namely in one of our 23 pairs of chromosomes, XY for men and XX for women. This chromosomal variation results in different transcription and expression of some genes. Chromosomal variation is responsible for different gonads, testes and ovaries, which in turn secrete sex hormones, οestrogens and androgens, in different concentrations. However, differences between the two sexes are not only genetic or hormonal. In many societies, their lifestyle and social habits, such as smoking, diet, and alcohol consumption, can be quite different [[4]Rozenberg S. Vandromme J. Martin C. Are we equal in adversity? Does Covid-19 affect women and men differently?.Maturitas. 2020; 138: 62-68Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar]. Interestingly, the substantial divergence in various characteristics and functions between males and females is reflected in sex-specific differences in disease susceptibility and outcomes. Biological sex is ultimately associated with a difference in human life span, as women have a higher life expectancy [[5]Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. How do the above gender differences affect the clinical course of COVID-19? Overall lower life expectancy in men has already been ruled out as a major contributor to their increased mortality due to COVID-19 [4Rozenberg S. Vandromme J. Martin C. Are we equal in adversity? Does Covid-19 affect women and men differently?.Maturitas. 2020; 138: 62-68Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. However, patients with comorbidities, such as diabetes mellitus, hypertension and cardiovascular disease, have a higher risk of serious disease [[7]McGurnaghan S.J. Weir A. Bishop J. et al.Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.Lancet Diabetes Endocrinol. 2021; 9: 82-93Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar]. Indeed, men are more likely to present such comorbidities than women [1Alwani M. Yassin A. Al-Zoubi R.M. Aboumarzouk O.M. et al.Sex-based differences in severity and mortality in COVID-19.Rev. Med. Virol. 2021; 31e2223Crossref PubMed Scopus (20) Google Scholar, 4Rozenberg S. Vandromme J. Martin C. Are we equal in adversity? Does Covid-19 affect women and men differently?.Maturitas. 2020; 138: 62-68Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. Moreover, there are distinct gender differences in metabolism regulation, including insulin sensitivity and lipid metabolism [[8]Lagou V. Mägi R. Hottenga J.-J. et al.Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.Nat. Commun. 2021; 12: 1-18PubMed Google Scholar]. These differences are especially evident before menopause. Women also present lower risk of cardiovascular events compared with men of the same age, while this risk becomes somewhat similar after menopause. Oestrogens are generally thought to have a protective role in metabolism and the cardiovascular system [4Rozenberg S. Vandromme J. Martin C. Are we equal in adversity? Does Covid-19 affect women and men differently?.Maturitas. 2020; 138: 62-68Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 8Lagou V. Mägi R. Hottenga J.-J. et al.Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.Nat. Commun. 2021; 12: 1-18PubMed Google Scholar]. Hormonal differences between the two genders seem to significantly affect our response to stress, as well as the inflammatory processes that follow [[9]Manuel R.S.J. Liang Y. Sexual dimorphism in immunometabolism and autoimmunity: impact on personalized medicine.Autoimmun. Rev. 2021; 20102775Crossref PubMed Scopus (5) Google Scholar]. Furthermore, SARS-CoV-2 binding or proliferation is possibly affected at a cellular or molecular level, reflecting of both genetic and hormonal differences. For example, specific genes associated with the immune system, such as toll-like receptors TLR4, TLR7, TLR8, are located on chromosome X [[10]Schurz H. Salie M. Tromp G. Hoal E.G. Kinnear C.J. Möller M. The X chromosome and sex-specific effects in infectious disease susceptibility.Hum. Genomics. 2019; 13: 2Crossref PubMed Scopus (165) Google Scholar]. The gene encoding the major SARS-CoV-2 receptor (angiotensin-converting enzyme 2, ACE2) is also expressed on chromosome X, in regions that usually escape the inactivation of an X chromosome in XX cells [5Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 11Lan J. Ge J. Yu J. et al.Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.Nature. 2020; 581: 215-220Crossref PubMed Scopus (2673) Google Scholar]. In addition to ACE2, SARS-CoV-2 uses dipeptidyl peptidase-4 (DPP4) as a co-receptor. Experimental data, mainly from mice, have shown that exposure to oestrogens may reduce DPP4 activity [[5]Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. A recent large study from Sweden, including 14.685 women in total, provided evidence that among postmenopausal women with COVID-19, those taking oestrogen as hormone replacement therapy (HRT) were less than half as likely (55% reduced risk) to die from COVID-19 compared with those who did not receive such treatment [[12]Sund M. Fonseca-Rodríguez O. Josefsson A. Welen K. Fors Connolly A.M. Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden and death due to COVID-19: a cohort study.BMJ Open. 2022; 12e053032Crossref Scopus (3) Google Scholar]. These data highlight the role of hormonal differences between the two genders in the clinical course of COVID-19. Moreover, it is possible that drugs that increase oestrogen levels may reduce the severity of COVID-19 [[5]Bechmann N. Barthel A. Schedl A. et al.Sexual dimorphism in COVID-19: potential clinical and public health implications.Lancet Diabetes Endocrinol. 2022; 10: 221-230Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. Of course, this should be properly studied in randomized controlled trials. In conclusion, men and women present significant differences regarding COVID-19. These differences can be partly explained by known genetic, hormonal, physiological and other gender variations. Such differences between men and women should be considered in the treatment and follow-up of patients with COVID-19. Moreover, they are important for the formulation of public health policies. Stavroula A. Paschou wrote the initial draft. Theodora Psaltopoulou revised the manuscript. Panagiotis Halvatsiotis revised the manuscript. Athanasios Raptis revised the manuscript. Charalambos V. Vlachopoulos revised the manuscript. Meletios-Athanasios Dimopoulos revised the manuscript. All authors approved the final version of the manuscript. Authors received no funding from an external source for this editorial.

Background: stress hyperglycemia (SH) is a relatively frequent finding in pediatric patients. The purpose of this prospective observational study was to identify the prevalence of pediatric SH and its associated risk factors in Greece. Methods: A total of 1005 patients without diabetes who were admitted consecutively for acute illness in a Pediatric Emergency Department were included in the study. Medical history, anthropometric measurements, blood glucose levels, and the medication administered were recorded. A questionnaire was distributed to parents regarding medical and perinatal history and sociodemographic characteristics. Results: There were 72 cases of SH on admission (7.2%) and 39 (3.9%) during hospitalization. Mean age was 6.4 years; 50.3% were male. SH on admission was associated with oral corticosteroid therapy (21.1% vs. 4.7%, p < 0.001), inhaled corticosteroids (12.7% vs. 3%, p < 0.001), and inhaled β2-agonists (30.6% vs. 10.7%, p < 0.001). In-hospital hyperglycemia was associated with oral corticosteroids (adjusted OR = 3.32), inhaled corticosteroids (OR = 10.03) and inhaled β2-agonists (OR = 5.01). Children with asthma were 5.58 and 7.86 times more likely to present admission and in-hospital hyperglycemia, respectively. Conclusions: This is the first report of SH prevalence in pediatric patients in Greece. Asthma, corticosteroids, and β2-agonists significantly increase the risk of SH. No parental factors seem to predispose to SH.

Oxidative stress plays an important role in the pathogenesis of diabetes. We investigated oxidative stress and nitrite/nitrate concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDRs) of diabetic patients with normal oral glucose tolerance test (OGTT) results, 40 subjects with abnormal OGTT results (dysglycaemic) and 20 subjects with normal OGTT results (normoglycaemic). Malondialdehyde (MDA), protein carbonyls (PCs), nitrite/nitrate plasma levels, the perfused boundary region (PBR—Glycocheck) of the sublingual microvessels, a marker of glycocalyx integrity, coronary flow reserve (CFR) and left ventricular global longitudinal strain (GLS) were assessed at 0 and 120 min of the OGTT. Insulin sensitivity was evaluated using Matsuda and the insulin sensitivity index (ISI). In all subjects, there were no significant changes in MDA or PC after the OGTT (p > 0.05). Compared with normoglycaemic subjects, FDRs and dysglycaemic subjects had significantly decreased nitrite/nitrate levels (−3% vs. −24% vs. −30%, respectively), an increased PBR and reduced CFR and GLS at 120 min (p < 0.05). The percent reduction in nitrite/nitrate was associated with abnormal Matsuda and ISI results, reversely related with the percent increase in PBR (r = −0.60) and positively related with the percent decrease in CFR (r = 0.39) and GLS (r = 0.48) (p < 0.05). Insulin resistance is associated with reduced nitric oxide bioavailability and coronary and myocardial dysfunction in FDRs and dysglycaemic subjects.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with various medical and psychological adverse effects. Well-being in patients with T2DM is often compromised. The aim of the present study was to investigate clinicodemographic predictors of well-being in patients with T2DM with no known psychiatric history and explore the mediatory role of undiagnosed anxiety and depression. We recruited 175 outpatients with T2DM (54.3% males, aged 34-79 (mean 59.9) years) followed-up at the Diabetes Center of the General Hospital of Nikaia-Peiraeus in Athens. Patients included had no severe diabetes-related complications or known psychiatric history. Well-being was measured with the Mental Health Continuum Short-Form (MHC-SF), a novel 14-item tool measuring the emotional (EWB), social (SWB) and psychological (PWB) dimensions of well-being, as well as a total score of well-being (WBT). Hospital Anxiety and Depression Scale (HADS) was used for screening for undiagnosed anxiety (HADS-A) and depression (HADS-D). Patients' demographics, Body Mass Index (BMI), glycemic control (HbA1c), T2DM duration, comorbid hypertension or dyslipidemia and type of antidiabetic medication were investigated as predictors of well-being or its dimensions in stepwise linear regression models, also including or excluding HADS-A and HADS-D. Mediational effects of HADS-A and HADS-D were explored in structural equation models through path analyses. Results showed that 21.1% of participants had comorbid depression (HADS-D≥11) and 5.1% comorbid anxiety disorder (HADS-A≥11). In the models without HADS, higher WBT as well as EWB and PWB were significantly predicted by lower HbA1c (all p=0.001) and lower BMI (p=0.015, 0.019 and 0.030, respectively). After being included in the model, HADS-A and HADS-D significantly predicted WBT and every dimension of well-being, but the effects of HbA1c and BMI were no longer statistically significant. In path analyses, the indirect effects of HbA1c and BMI on well-being via HADS-D were statistically significant, while the direct and indirect effects via HADS-A were not. Therefore, the effects of HbA1c and BMI on EWB, PWB and WBT were completely mediated by HADS-D. Concludingly, this is the first study using MHC-SF to measure well-being in patients with T2DM. High levels of undiagnosed depression were recorded, in agreement with other studies. Depression was predicted by HbA1c and BMI and finally predicted well-being. Undiagnosed depression fully explained the effects of HbA1c and BMI on well-being. The interplay of glycemic control and positive mental health should be further investigated.

Vitamin D deficiency or insufficiency is common in obese people, with some studies suggesting that low vitamin D level might be an independent predictor of obesity. Thus, the purpose of the present randomized, double-blind, placebo-controlled study was to investigate the effect of oral spray vitamin D3 3000 IU supplementation along with personalized weight-loss diet on obesity markers in overweight and obese Caucasians with vitamin d deficiency or insufficiency. The impact of vitamin D receptor (VDR) and adrenergic receptors (ADRs) genetic variants on vitamin D levels and weight loss diet outcomes was also investigated. After signing informed consent, a total of 125 eligible volunteers were randomly assigned into vitamin D (vitamin D3 3000 IU/d oral spray supplementation, n = 76) or placebo (xylitol, water, mint, n = 49) group following a weight loss program (600 calories less than the total energy expenditure of each volunteer) for 3 months. Fat mass, BMI, REE and 25(OH)D serum level were monitored on baseline and each month. DNA samples were extracted from buccal swabs and genotyped for the rs2228570 (VDR), rs1544410 (VDR), rs731236 (VDR), rs1800544 (ADRA2A), rs1801252 (ADRB1), rs1042713 (ADRB2), and rs4994 (ADRB3) polymorphisms. Statistical analysis was performed using SPSS package (v.23). Between group comparisons revealed significant improvement in serum 25(OH)D level and greater reduction in weight, BMI and fat percentage in the vitamin D group compared to placebo group (p < 0.05). In the vitamin D group, carriers of the rs2228570 T allele tended to have greater vitamin D level improvement compared with the homozygous C allele (p = 0.067). Furthermore, heterozygous (CT) for the rs731236 tended to have lesser weight loss (p = 0.068) and for the rs1042713, a lower decline in fat percentage was observed for homozygous AA carriers compared to the heterozygous (p = 0.051). In the control group, differences in weight loss (p = 0.055) and BMI (p = 0.045) were observed between rs1544410 AA and GG homozygous. In conclusion, vitamin D oral spray supplementation seems to improve vitamin D status and decrease obesity markers during a weight-loss intervention in overweight/obese Caucasians with vitamin D deficiency or insufficiency. Also, the results of the present study indicate that VDR and ADRs genetic polymorphisms seem to influence vitamin D supplementation response and obesity markers.