Does Iodine Influence the Metabolism of Glucose?

Thyroid function and glucose status are linked; experimental, clinical, and epidemiological studies have shown this. Iodine is a vital trace element that is inextricably linked to thyroid hormone synthesis. The latter is also associated with glucose metabolism and diabetes. Recently, some-but not all-studies have shown that iodine is linked to glucose metabolism, glucose intolerance, impaired fasting glucose, prediabetes, diabetes mellitus, or gestational diabetes. In this concise review, we review these studies, focusing on iodine and glucose metabolism and prediabetic conditions or type 2 diabetes mellitus. The potential beneficial effect of iodine on glucose metabolism may be attributed to its antioxidant properties.

Psychological and Social Aspects of Vaccination Hesitancy-Implications for Travel Medicine in the Aftermath of the COVID-19 Crisis: A Narrative Review.

Vaccines are an important tool of preventive medicine. Although organized vaccination programs have saved large populations from serious infectious diseases, there is a considerable part of the population who oppose vaccinations. In particular, anti-vaccination perceptions, among travelers to countries with endemic diseases, are a major public health concern. Although hesitancy towards vaccinations is not a novel phenomenon, it came back to the forefront during the fight against the COVID-19 pandemic. This review explores the etiology of anti-vaccination beliefs among travelers and draws conclusions about their impact on public health and society in general. For this purpose, a purposeful search for data on the causative factors of vaccine hesitancy and their impact on people's health was conducted. A descriptive analysis of the findings and conclusions regarding possible implications in health policy and clinical practice are presented. A fear of side effects, lack of credence in the necessity of vaccines, and mistrust of medical authorities are important causative factors. Their interplay shapes hesitancy towards vaccines. However, anti-vaccination beliefs can also be an aspect of a more general unconventional stance of life. Health care professionals and organizations must be ready to tackle vaccine hesitancy by making the necessary interventions. Correcting misconceptions about vaccinations is a prerequisite for ensuring personal and public health, especially in the context of a pandemic or epidemic. Moreover, ensuring the efficacy and safety of vaccines, especially in cases of modern technology applications, is a fundamental factor in addressing people's concerns about vaccines. For this purpose, medical authorities and organizations must provide accurate and clear information on vaccines so as to eliminate misinformation. Furthermore, clinicians should cultivate their communication skills in order to convey the appropriate messages to prospective recipients of vaccinations.

Insulin requirements during lactation in women with diabetes mellitus type 1 in comparison with pre-pregnancy levels: A 10-year retrospective study.

The metabolic profile variability of women with diabetes mellitus type 1 (DM1) during breastfeeding, leads to a reassessment in managing glycemia, mainly to prevent hypoglycemia. In this retrospective study we assessed insulin needs, vis-à-vis breastfeeding in DM1. A 10.7% reduction of daily insulin dosage, compared to pre-pregnancy insulin needs, was noted in women who breastfed exclusively versus 10.8% in those who supplemented breastfeeding (p = NS). Women who experienced hypoglycemic episodes, tended (but not significantly) to be younger (p = 0.10), with longer duration of DM1 and more weight gain in pregnancy. Exclusive breastfeeding was associated with younger age (p = 0.04), regardless of hypoglycemia (p = 0.25).

Metformin: Sex/Gender Differences in Its Uses and Effects-Narrative Review.

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.

An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes.

Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists ("glitazones") are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that point to their usefulness. The use of glitazones has always been controversial both for the type of patients who must take these drugs and for the side effects associated with them. Unfortunately, the recent guidelines do not include them among the preferred drugs for the treatment of hyperglycemia and rosiglitazone is out of the market in many countries due to an adverse cardiovascular risk profile. Even though real-life studies have proven otherwise, and their pleiotropic effects have been highlighted, they have been unable to achieve primacy in the choice of antihyperglycemic drugs. It would be appropriate to demonstrate the usefulness of pioglitazone and its therapeutic benefit with further cardiovascular safety studies.

Increased Glucocorticoid Receptor Alpha Expression and Signaling in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: Critical illness is characterized by increased serum cortisol concentrations and bioavailability resulting from the activation of the hypothalamic-pituitary-adrenal axis, which constitutes an essential part of the stress response. The actions of glucocorticoids are mediated by a ubiquitous intracellular receptor protein, the glucocorticoid receptor. So far, data on coronavirus disease 2019 and glucocorticoid receptor alpha expression are lacking. DESIGN: Prospective observational study. SETTING: One academic multidisciplinary ICU. SUBJECTS: Twenty-six adult coronavirus disease 2019 patients; 33 adult noncoronavirus disease 2019 patients, matched for age, sex, and disease severity, constituted the control group. All patients were steroid-free. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Glucocorticoid receptor alpha, glucocorticoid-inducible leucine zipper expression, and serum cortisol were measured on ICU admission. In coronavirus disease 2019 patients, glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper messenger RNA expression were upregulated (4.7-fold, p < 0.01 and 14-fold, p < 0.0001, respectively), and cortisol was higher (20.3 vs 14.3 µg/dL, p < 0.01) compared with the control group. CONCLUSIONS: ICU coronavirus disease 2019 patients showed upregulated glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper expression, along with cortisol levels, compared with ICU noncoronavirus disease 2019 patients. Thus, on ICU admission, critical coronavirus disease 2019 appears to be associated with hypercortisolemia, and increased synthesis of glucocorticoid receptor alpha and induced proteins.

Pituitary-Adrenal Responses and Glucocorticoid Receptor Expression in Critically Ill Patients with COVID-19.

The hypothalamus-pituitary-adrenal (HPA) axis was described as the principal component of the stress response 85 years ago, along with the acute-phase reaction, and the defense response at the tissue level. The orchestration of these processes is essential since systemic inflammation is a double-edged sword; whereas inflammation that is timely and of appropriate magnitude is beneficial, exuberant systemic inflammation incites tissue damage with potentially devastating consequences. Apart from its beneficial cardiovascular and metabolic effects, cortisol exerts a significant immunoregulatory role, a major attribute being that it restrains the excessive inflammatory reaction, thereby preventing unwanted tissue damage. In this review, we will discuss the role of the HPA axis in the normal stress response and in critical illness, especially in critically ill patients with coronavirus disease 2019 (COVID-19). Finally, a chapter will be dedicated to the findings from clinical studies in critical illness and COVID-19 on the expression of the mediator of glucocorticoid actions, the glucocorticoid receptor (GCR).

Inherited/Genetically-Associated Pheochromocytoma/ Paraganglioma Syndromes and COVID-19.

In some subjects with inherited pheochromocytoma/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1α) stabilization/activation could lead to an increase in angiotensin converting enzymes (ACE). This would result in the stimulation of angiotensin (AT) II production and, hence, reduce the availability of ACE 2. The latter would provide decreased numbers of binding sites for the spike protein of SARS-CoV-2 and, therefore, result in less points of viral entry into cells. Thus, subjects with HIF1α-associated PPG syndromes may benefit from an inherent protective effect against COVID-19. Such an implication of HIF1α vis-à-vis COVID-19 could open ways of therapeutic interventions.

Glycemia, Beta-Cell Function and Sensitivity to Insulin in Mildly to Critically Ill Covid-19 Patients.

Background and objectives: Critically and non-critically ill patients with SARS-CoV-2 infection (Covid-19) may present with higher-than-expected glycemia, even in the absence of diabetes. With this study we aimed to assess glucose, glycemic gap (GlyG) and insulin secretion/sensitivity measures in patients with Covid-19. Materials and Methods: We studied, upon admission, 157 patients with Covid-19 (84: in wards and 73: in intensive care units; ICU); 135 had no history of diabetes. We measured blood glucose upon admission as well as glycated hemoglobin (A1c), plasma insulin and C-peptide. We calculated the GlyG and the Homeostasis Model Assessment 2 (HOMA2) estimates of steady state beta cell function (HOMA2%B) and insulin sensitivity (HOMA2%S). Statistical assessment was done with analysis or the Kruskal-Wallis test. Results: Compared to patients in the wards without diabetes, patients with diabetes in the wards, as well as patients in the ICU (without or with diabetes) had higher admission glycemia. The GlyG was significantly higher in patients without diabetes in the ICU compared to patients without diabetes in the wards, while HOMA2%B based on glucose and insulin was significantly higher in the ICU patients compared to patients in the wards. Of all the parameters, HOMA2%S based on C-peptide/glucose was higher in survivors (n = 133). Conclusions: In our series of patients with Covid-19, a substantial number of patients with and without diabetes had admission hyperglycemia and those who were critically ill may have had compromised insulin secretion and lowered sensitivity to insulin. These findings lend credence to reports of association between Covid-19 and hyperglycemia/secondary diabetes.

Antidiabetic drugs and blood pressure changes.

New era antidiabetic drugs are characterized by cardiovascular safety, including specific outcome benefits observed in randomized clinical trials (RCTs). It has been postulated that the favorable effects of new antidiabetic agents are related both to better control of blood pressure (BP) levels and to activation of multiple anti-atherosclerotic properties. In this review, we aimed to assess whether antidiabetic drugs have a pressor effect in glucose control and outcome-oriented RCTs, and to summarize the activated pathophysiological mechanisms relevant to BP control following the use of different antidiabetic drug classes. We also tried to determine which, if any, are the BP-lowering effects of more intense vs less intense glucose-lowering strategy irrespectively of trial antidiabetic regimen. To provide more robust results and evidence-based argumentation, a meta-analysis of placebo-controlled antidiabetic drug RCTs was undertaken to estimate the ongoing BP reduction for all considered and each separate drug class alone. This quantitative synthesis might be helpful for the clinician 1) to select or avoid the use of some classes of antidiabetic agents with a potential favorable or adverse pressor effect, respectively 2) to organize the overall drug regimen in patients with diabetes mellitus and minimize side effects because of concomitant use of drugs with established pressor effect (i.e. antihypertensive agents). This review was also organized to indicate whether BP change associated with different antidiabetic treatments may explain the specific macrovascular outcome benefits. Between all antidiabetic drugs including exogenous insulin, only sodium-glucose cotransporter 2 inhibitors produce a clinically important BP-lowering effect, but this BP reduction alone cannot explain the observed cardiovascular benefit.

Decreased glucocorticoid receptor expression during critical illness.

INTRODUCTION: In critically ill patients, the hypothalamic-pituitary-adrenal axis is activated, resulting in increased serum cortisol concentrations. However, in some patients, especially those with sepsis, cortisol levels are relatively low for the degree of illness severity. Therefore, in the present project, we aim to characterize the time course of glucocorticoid receptor (GCR) alpha and beta expression in peripheral polymorphonuclear cells of critically ill septic or nonseptic patients using real-time PCR. DESIGN: A prospective observational study conducted on 32 critically ill adults not receiving steroids, in a university-affiliated, multidisciplinary intensive care unit (ICU). Blood samples were collected for measurement of glucocorticoid receptor expression within 24-48 hours of admission to the ICU and at days 4, 8 and 13 after admission, reflecting the acute and chronic phase of the illness. RESULTS: During ICU stay, patients expressed over time reduced levels of both GCR-α and GCR-ß mRNA. More specifically, GCR-α mRNA expression was decreased fourfold 4 days after admission (P < 0.0001) and remained low up to 2 weeks after admission (P < 0.001). On the other hand, GCR-ß mRNA levels remained stable shortly after admission, but approx. one week after admission, its levels decreased threefold (P < 0.01) and remained reduced up to 2 weeks after admission (P < 0.001). DISCUSSION: Our results suggest that critically ill patients have highly variable expression of alpha and beta GCR, and moreover, the levels of both receptors decrease during ICU stay. Taken together, these might explain the differential responsiveness of patients to exogenous steroid administration or to endogenous cortisol secretion.

A Bayesian look at the new 2019 guidelines for imaging of pheochromocytoma/paraganglioma with emphasis on extra-adrenal disease.

Dear Editor, In this journal, a few years ago, we presented a Bayesian (critical) appraisal of the-then recent-American Endocrine Society's guidelines regarding the diagnosis and management of pheochromocytoma/paraganglioma (PPG). This year, the European Society of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging have introduced new guidelines regarding functional imaging (i.e. by means of Nuclear Medicine modalities) of PPG. In light of this, we believe that it is appropriate to present a new relevant Bayesian assessment. In the new guidelines the following functional imaging modalities are covered: iodine-123-metaiodobenzylguanidine (123I-MIBG) single photon emission tomography (SPET), indium-111-diethylenetriamine pentaacetic acid (111In-DTPA)-pentetreotide (111In-pentetreotide) SPET, fluorine-18-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET), 18F-fluorodeoxyglucose (18F-FDG) PET and PET with various gallium-68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (168Ga-DOTA)-coupled somatostatin agonists (68Ga-SSTa). Based on a pretest probability of 15% for extra-adrenal disease and the reported sensitivity and specificity for each modality, we calculated likelihood ratios (LR) for a positive and a negative test (LR+ and LR-, respectively). In the absence of a given specificity in the guidelines we used levels of 55% for 18F-FDG and 85% for 68Ga-SSTa (the latter is a level that we used in our previous assessment), which have been validated in a recent meta-analysis. Using LR+ and LR- with Fagan's nomograms we calculated the post-test probability of extra-adrenal PPG. Only the LR+ for 18F-FDOPA was over 10 and no LR- was lower than 0.1, shifting to an important degree the probability of a diagnosis (clinicians have to bear in mind that an LR- may not be useful, since absence of radionuclide uptake does not imply absence of PPG if biochemistry is positive). It is evident that functional imaging of PPG has become more diversified and tailored according to each patient's history and genetic background. Nevertheless, the diagnostic characteristics of all methods (biochemical and imaging) are still not perfect; they are rather complimentary to each other. Biochemical evaluation should be done first, since functional imaging of PPG is advised to be performed in patients with biochemically-proven disease.

Subjective social status, social network and health disparities: empirical evidence from Greece.

BACKGROUND: Several studies suggest that socioeconomic status affects (SES) affects self-rated health (SRH), both in Greece and internationally. However, prior research mainly uses objective measures of SES, instead of subjective evaluations of individuals' social status. Based on this, this paper aims to examine (a) the impact of the economic dowturn on SRH in Greece and (b) the relationship between subjective social status (SSS), social network and SRH. METHODS: The descriptive analysis is based on four cross-sectional surveys conducted by the National School of Public Health, Athens, Greece (2002, 2006, 2011, 2015), while the data for the empirical investigation were derived from the 2015 survey (Health + Welfare Survey GR). The empirical strategy is based on an ordinal logistic regression model, aiming to examine how several variables affect SRH. Size of social network and SSS are among the independent variables employed for the empirical analysis RESULTS: According to our findings, average SRH has deteriorated, and the percentage of the population that reports very good/good SRH has also decreased. Moreover, our empirical analysis suggests that age, existence of a chronic disease, size of social network and SSS affect SRH in Greece. CONCLUSION: Our findings are consistent with the existing literature and confirm a social gradient in health. According to our analysis, health disparities can be largely attributed to socioeconomic inequalities. The adverse economic climate has impact on socioeconomic differences which in turn affect health disparities. Based on these, policy initiatives are necessasy in order to mitigate the negative impact on health and the disparities caused by economic dowturn and the occuring socioeconomic inequalities.

Economic crisis, austerity and unmet healthcare needs: the case of Greece.

BACKGROUND: The programme for fiscal consolidation in Greece has led to income decrease and several changes in health policy. In this context, this study aims to assess how economic crisis affected unmet healthcare needs in Greece. METHODS: Time series analysis was performed for the years 2004 through 2011 using the EU-SILC database. The dependent variable was the percentage of people who had medical needs but did not use healthcare services. Median income, unemployment and time period were used as independent variables. We also compared self-reported unmet healthcare needs drawn from a national survey conducted in pre-crisis 2006 with a similar survey from 2011 (after the onset of the crisis). A common questionnaire was used in both years to assess unmet healthcare needs, including year of survey, gender, age, health status, chronic disease, educational level, income, employment, health insurance status, and prefecture. The outcome of interest was unmet healthcare needs due to financial reasons. Ordinary least squares, as well as logistic regression analysis were conducted to analyze the results. RESULTS: Unmet healthcare needs increased after the enactment of austerity measures, while the year of participation in the survey was significantly associated with unmet healthcare needs. Income, educational level, employment status, and having insurance, private or public, were also significant determinants of unmet healthcare needs due to financial reasons. CONCLUSIONS: The adverse economic environment has significantly affected unmet health needs. Therefore health policy actions and social policy measures are essential in order to mitigate the negative impact on access to healthcare services and health status.

In prostate cancer, low adiponectin levels are not associated with insulin resistance.

PURPOSE: Adiponectin, an adipose tissue-derived hormone with insulin-sensitizing effect, has been inversely associated with several hormonally dependent malignancies. Prostate cancer is associated with low levels of adiponectin, which have been proposed as an independent risk factor for this malignancy. Aim of this study was to examine whether hypoadiponectinaemia in prostate is associated with insulin resistance. EXPERIMENTAL DESIGN: Plasma samples and covariate data in the context of a case-control study of 300 Greek men were evaluated including 75 patients with prostate cancer, 75 patients with benign prostatic hyperplasia (BPH) and 150 age-matched healthy controls. RESULTS: Patients with prostate cancer had significantly lower plasma adiponectin levels compared with the other two groups, that is BPH patients and healthy controls (7.4 ± 5 ng/mL vs. 11.5 ± 6.4 ng/mL and 12.8 ± 8 ng/mL, respectively). On the other hand, no statistically significant differences were found between patients with prostate cancer and the other two groups for both HOMA-IR and QUICKI (P-value = 0.551). As expected, in all three groups, the levels of adiponectin correlated negatively with HOMA-IR (rho = -0.214, P-value = 0.006), QUICKI (rho = 0.214, P-value = 0.006) and insulin levels (rho = 0.942, P-value < 0.001). CONCLUSION: In spite of what would have been expected from the relevant literature, our data suggest that the hypoadiponectinaemia in prostatic cancer does not appear to be associated with insulin resistance.

Quantifying the economic benefits of prevention in a healthcare setting with severe financial constraints: the case of hypertension control.

Hypertension significantly contributes to the increased cardiovascular morbidity and mortality, thus leading to rising healthcare costs. The objective of this study was to quantify the clinical and economic benefits of optimal systolic blood pressure (SBP), in a setting under severe financial constraints, as in the case of Greece. Hence, a Markov model projecting 10-year outcomes and costs was adopted, in order to compare two scenarios. The first one depicted the "current setting", where all hypertensives in Greece presented an average SBP of 164 mmHg, while the second scenario namely "optimal SBP control" represented a hypothesis in which the whole population of hypertensives would achieve optimal SBP (i.e. <140 mmHg). Cardiovascular events' occurrence was estimated for four sub-models (according to gender and smoking status). Costs were calculated from the Greek healthcare system's perspective (discounted at a 3% annual rate). Findings showed that compared to the "current setting", universal "optimal SBP control" could, within a 10-year period, reduce the occurrence of non-fatal events and deaths, by 80 and 61 cases/1000 male smokers; 59 and 37 cases/1000 men non-smokers; whereas the respective figures for women were 69 and 57 cases/1000 women smokers; and accordingly, 52 and 28 cases/1000 women non-smokers. Considering health expenditures, they could be reduced by approximately €83 million per year. Therefore, prevention of cardiovascular events through BP control could result in reduced morbidity, thereby in substantial cost savings. Based on clinical and economic outcomes, interventions that promote BP control should be a health policy priority.

A probabilistic assessment of the diagnosis of paraganglioma/pheochromocytoma based on clinical criteria and biochemical/imaging findings.

UNLABELLED: Paragangliomas (PGL) and pheochromocytomas (P) are rare neural-crest-derived neoplasms. Very recently guidelines on diagnosis and treatment of PGL/P have been presented by the US Endocrine Society. In the following overview we assessed the implementation of these guidelines with probabilistic reasoning (calculating with Fagan nomograms the post-test probability of PGL/P for a given pre-test probability). CONCLUSION: Biochemical evaluation of PGL/P showed excellent diagnostic characteristics with post-test probabilities that are very different from the pre-test probabilities, thus a positive biochemical test is usually indicative of disease whereas a negative one usually rules out disease. The post-test probabilities of anatomical and functional imaging modalities (i.e. in nuclear medicine) were different from the pre-test probabilities but to a lesser degree than the biochemical tests; furthermore in biochemically-proven PGL/P a negative imaging modality is not useful, while a positive one may indicate only one of multiple foci of metastatic/extra-adrenal disease. Thus, regarding imaging modalities, they should be combined in order to get the most of their characteristics for the localization of PGL/P.