Elevated FIB-4 Is Associated with Higher Rates of Cardiovascular Disease and Extrahepatic Cancer History in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often complicated by steatotic liver disease, cardiovascular disease (CVD), and extrahepatic cancer. We investigated whether FIB-4, an indicator of liver fibrosis, is associated with a higher risk of CVD and extrahepatic cancer history in T2DM. METHODS: Two hundred and nine of 244 diabetics admitted to our center in one year were included and retrospectively evaluated. RESULTS: One hundred and fifty-two (72.7%) were males and 57 (27.3%) females. The mean age and FIB-4 were 64.3 ± 11 years, and 1.15 ± 0.5, respectively. One hundred and fifty patients (71.8%) had FIB-4 ≤ 1.3, and 59 (28.2%) had FIB-4 > 1.3. A history of CVD was presented in 76 (36.4%) patients, and of extrahepatic cancer in 39 (18.7%). Patients with CVD were significantly older than those without (68.4 ± 8.5 vs. 63.2 ± 11.5 years; p = 0.002), with significantly higher FIB-4 (1.26 ± 0.5 vs. 1.08 ± 0.5; p = 0.012). Patients with cancer were older, with higher FIB-4 compared to those without (68.2 ± 9.5 vs. 64.4 ± 10.9 years; p = 0.098 and 1.37 ± 0.6 vs. 1.1 ± 0.5; p = 0.004, respectively). FIB-4 > 1.3 was associated with a 2.1-fold probability for CVD (χ2 = 5.810; p = 0.025) and 2.7-fold probability for cancer history (χ2 = 7.603; p = 0.01). CONCLUSIONS: FIB-4 ≥ 1.3 is associated with a higher probability of CVD or extrahepatic cancer history. FIB-4 could potentially discriminate patients at risk, justifying stricter surveillance.

Pearls & Oy-sters: Thyroid-Associated Ophthalmopathy and Transient Neuromuscular Junction Disorder Due to Graves Disease.

The concomitant presentation of thyroid-associated ophthalmopathy (TAO) and ocular myasthenia gravis is well documented. In the course of Graves disease (GD), symptomatic transient neuromuscular junction disorder may occur due to the effect of thyroid hormones at the neuromuscular synapse. Diagnostic clues are the clinical and electrophysiologic remission synchronous with restoration of euthyroidism. Furthermore, the occurrence of thymic hyperplasia in GD poses further diagnostic and therapeutic considerations. These points are discussed in the case report of a 43-year-old male patient suffering from TAO and transient neuromuscular junction disorder due to GD.

Early age at menarche and the risk of gestational diabetes mellitus: a cohort study.

PURPOSE: To evaluate whether there is an association between age at menarche (AAM) and the risk of gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted, including 5390 pregnant women who were screened for GDM at Alexandra Hospital in Athens, Greece over a 15-year period (2000-2014). Maternal age, pre-pregnancy body mass index (BMI), height, family history of type 2 diabetes mellitus, parity, educational and smoking status, and AAM were recorded. The results were expressed as odds ratios (OR) with a 95% confidence interval (95% CI). RESULTS: Pregnant women with GDM experienced earlier menarche compared to normoglycemic women (12.9 ± 1.5 vs 13.1 ± 1.6, p < 0.001, respectively). The OR for a woman with AAM <12 years to develop GDM was 1.08 (95% CI 1.03-1.14), while the OR to be obese was 1.70 (95% CI 1.50-1.90). The multivariate logistic regression analysis showed that AAM is a risk factor for GDM. However, that effect was lost after adjusting for BMI. CONCLUSION: Early AAM may be associated with an increased risk of GDM. Therefore, it can be used to identify high-risk women and implement preconception interventions for GDM prevention. Future studies should be conducted to confirm these findings.

Nutrition of aging people with diabetes mellitus: Focus on sarcopenia.

As populations age, chronic diseases accumulate, and new health conditions emerge. One noteworthy pair that warrants further evaluation is diabetes mellitus and sarcopenia, given that the latter occurs in 28 % of the population aged over 50 who have diabetes mellitus. The management of both entails nutritional interventions, making the development of unified dietary recommendations an alluring strategy. This review aims to elucidate the current recommendations for the combined management of sarcopenia and diabetes, while featuring elements that require further research. The goal of nutritional management is to improve muscle mass and strength while regulating metabolic risk and glucose levels. To ensure muscle synthesis in the elderly, recommendations align at daily calorie intake that exceeds 30 kcal/kg, with adjustments based on comorbidities. Additionally, a protein intake of at least 1-1.2 g/kg/d is essential, emphasizing both daily and per-meal intake, and can be achieved through diet or branched-amino-acids supplements. Specific considerations for diabetes include restricted protein intake in diabetic nephropathy and exploring the potential link between branched amino acids and insulin resistance. Further recommendations that both promote metabolic health and have demonstrated at least a potential to increase muscle strength include prioritizing polyunsaturated fatty acids as a fat source and maintaining adequate levels of vitamin D. Clinicians should consult their patients on dietary optimization, but evidence is insufficient to recommend additional supplementation. Lastly, an emerging challenge of diabetes and sarcopenia is sarcopenic obesity, which requires the combination of a hypocaloric diet with increased protein intake.

Thyroid disorders induced by immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs that powerfully contribute to cancer therapy by harnessing the immune system to fight malignancies. However, their successful use as anti-cancer drugs is accompanied by a wide spectrum of immune-related adverse effects (irAEs), including endocrinopathies. Among them, thyroid dysfunction stands out as one of the most common endocrinopathies induced by ICI therapy and surfaces as a prominent concern. Destructive thyroiditis is the pathophysiological basis shared by the most common patterns of thyrotoxicosis followed by hypothyroidism and isolated hypothyroidism. Diagnostic approach is guided by clinical manifestation, laboratory evaluation and imaging modalities. Treatment approaches range from the substitution of levothyroxine to the utilization of beta blockers, depending on the extent of thyroid dysfunction's severity. While the medical community is dealing with the evolution and complexities of immunotherapy, recognizing and effectively managing ICI-induced thyroid dysfunction emerged as crucial for enhancing patient safety and achieving improved outcomes. The aim of this review is to navigate the significance of ICI-induced thyroid dysfunction unraveling the various patterns, underlying mechanisms, diagnostic approaches, and treatment strategies. It, also, highlights the impact of various factors such as cancer subtype, ICI dosage, age, and genetic susceptibility on the risk of experiencing dysfunction.

Gonadal dysfunction in women with diabetes mellitus.

It is well known that both type 1 and type 2 diabetes mellitus (DM) are related to increased risk for cardiovascular (CV) and chronic kidney disease (CKD). However, besides these prominently presented complications, DM has also been associated with reproductive dysfunctions. It seems that these disorders are met in up to 40% of women with DM and consist of delayed menarche, all types of menstrual disorders, such as amenorrhea, oligomenorrhea, menstrual irregularity, as well as menorrhagia, infertility, characteristics of polycystic ovary syndrome (PCOS) and early (or rarely late) menopause. In type 1 DM (T1DM), insulin treatment, although it has reduced the rates of insulinopenic-induced hypogonadotropic hypogonadism, an entity commonly presented in many women with the disease in the past decades, when it is used in excess it can also promote hyperandrogenism. Regarding type 2 DM (T2DM), insulin resistance (IR) and hyperinsulinemia have mainly been implicated in the pathogenesis of reproductive dysfunctions, as insulin can act as gonadotropin on the theca cells of the ovary and can lead to hyperandrogenism and inhibition of proper ovulation. This review aims to detail the reproductive dysfunctions associated with DM and provide scientific data to enlighten the underlying pathogenetic mechanisms.

Comparison of treatment with insulin detemir and NPH in women with gestational diabetes mellitus: glycemic control and pregnancy outcomes. A retrospective study.

PURPOSE: The objective of this retrospective study was to compare glycemic control, pregnancy outcomes, and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with (a) insulin detemir and (b) insulin neutral protamine Hagedorn (NPH). METHODS: A total of 192 women with GDM were included in the analysis. Ninety-eight women received detemir, while 94 women received NPH. Data regarding medical history, glycemic control, and time and mode of delivery, as well as neonatal outcomes, were recorded. RESULTS: Baseline characteristics were comparable between the two groups. There were no differences with respect to the week of insulin initiation, total insulin dose, duration of insulin therapy, daily insulin dose/weight in early and late pregnancy, or the number of insulin injections per day. Maternal overall weight gain during pregnancy and weight gain per week did not differ either. The detemir group had slightly lower HbA1c levels at the end of gestation [median: det 5.2% (33 mmol/mol) vs NPH 5.4% (36 mmol/mol), p=0.035). There were no cases of hypoglycemia or allergic reactions in the two groups. There were also no differences regarding neonatal outcomes according to the available data, given that data in some cases were missing. CONCLUSION: The use of insulin detemir was found to be equally effective and safe compared to NPH in women with GDM.

Smoking during pregnancy and gestational diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: To investigate whether maternal cigarette smoking during pregnancy is a risk factor for developing GDM. METHODS: MEDLINE, Scopus, CENTRAL and Google Scholar databases were searched from inception to December 2022 to identify eligible original articles. A systematic review and meta-analysis (weighted data, random-effects model) were performed. The primary outcome was the development of GDM in pregnant women. The results were expressed as odds ratios (OR) with 95% confidence interval (CI) (inverse variance method). Subgroup analysis was planned according to the maternal smoking status and GDM diagnostic criteria. Statistical heterogeneity was checked with the Chi-squared (Chi2) test and the I2 index was used to quantify it. The studies were evaluated for publication bias. RESULTS: Thirty-five studies, including 23,849,696 pregnant women, met the inclusion criteria. The pooled OR of smoking during pregnancy compared with non-smoking (never smokers and former smokers) was 1.06 (95% CI 0.95-1.19), p = 0.30; I2 = 90%; Chi2 = 344; df=34; p < 0.001. Subgroup analysis was performed according to the two-step Carpenter-Coustan diagnostic criteria, due to the high heterogeneity among the other applied methods. The pooled OR for the Carpenter-Coustan subgroup was 1.19 (95% CI 0.95-1.49), p = 0.12; I2 = 63%; Chi2 = 27; df=10; p < 0.002. Further subgroup analysis according to maternal smoking status was not performed due to missing data. CONCLUSION: There is no evidence to support an association between maternal cigarette smoking during pregnancy and the risk for GDM. Universally accepted diagnostic criteria for GDM must be adopted to reduce heterogeneity and clarify the association between smoking and GDM.

Patients with type 2 diabetes mellitus present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to healthy subjects: a prospective cohort study.

AIM: To compare the kinetics of neutralizing antibodies (NΑbs) against SARS-CoV-2 after vaccination with the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with T2DM and healthy controls. METHODS: NAb levels after the BNT162b2 mRNA vaccine were compared between 50 patients with non-insulin treated T2DM and 50 age-, gender-, and BMI-matched healthy controls up to 3 months after the second dose. The median age of both groups was 70 years. RESULTS: On day 1, mean NAbs of the control and T2DM groups were 14.64% (standard error, SE = 2.30) and 14.04% (SE = 2.14), respectively (p value = 0.926). Three weeks later, the mean NAb values were 39.98% (SE = 3.53) in the control group and 40.97% (SE = 3.99) in participants with T2DM (p value = 0.698). One month after the second vaccination, mean NAb values increased to 87.13% (SE = 2.94) in the control group and 89.00% (SE = 2.18) in the T2DM group. Three months after the second vaccine dose, the mean inhibitory titers decreased to 83.49% (SE = 3.82) (control group) and 76.36% (SE = 3.33) (T2DM group). On all occasions, no significant difference was found between the two groups (all p values > 0.05). CONCLUSIONS: Patients with T2DM present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to that of healthy subjects.

The effect of allopurinol on cardiovascular outcomes in patients with type 2 diabetes: a systematic review.

BACKGROUND: Cardiovascular disease (CVD) remains the main cause of death in patients with type 2 diabetes (T2D). Although hyperuricemia has been associated with multiple CV complications, it is not officially recognized as a target parameter for CVD risk reduction. AIM: To systematically review the literature in order to determine whether treating hyperuricemia with allopurinol in patients with T2D reduces CVD risk. METHODS: A thorough literature search in the PubMed, CENTRAL, and EMBASE databases from inception to August 2022 was performed. After application of selection criteria, 6 appropriate studies were identified. RESULTS: Detailed analysis of the data derived indicated that there is an association between allopurinol treatment and CV benefits, resulting in a reduced risk of CVD events and mortality rates. This association can be attributed mainly to the reduction of inflammation and oxidative burden, as well as to the improvement of glycemic and lipid profiles. CONCLUSIONS: This systematic review provides evidence that allopurinol may reduce CVD risk in patients with T2D. Randomized, placebo-controlled trials should be performed in order to confirm these findings and identify specific subgroups of patients who will benefit most.

Endocrine disruptors in ancient times and Greek mythology: the spring of Salmacis and the curse of Hermaphroditus.

According to Greek mythology, the spring waters of Salmacis (or Salmakis) feminized the god Hermaphroditus (or Hermaphroditos) and transformed his nature from male to half-male and half-female. The mythical properties of these waters are described in the writings of authors and philosophers of the Hellenistic period. It is evident that the spring of Salmacis and lake actually existed (located in Halicarnassus, today Bodrum, Turkey) and are not the product of poetic imagination. Hence, it could be hypothesized that there were certain natural elements in the waters that had a feminizing effect on the male reproductive axis. We now know, in fact, that naturally occurring environmental agents, also known as endocrine disruptors, can affect the endocrine and reproductive function of both males and females. However, since most endocrine disruptors today are manmade products of the modern industrial lifestyle, the presence and effect of naturally occurring disruptors in times preceding the Industrial Revolution are not widely discussed. It is thus against this background that we seek to formulate a differential diagnosis of male feminization attributable to the effect of natural environmental factors in the form of endocrine disruptors that will have existed in environments round the globe since time immemorial. We conclude that if there had been an accumulation of the mycotoxin zearalenone (ZEA) in the waters of Salmacis, chronic exposure to the lake's water could have resulted in the phenotypic changes described in the Salmacis myth.

Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study.

Background: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.

Recurring subacute thyroiditis after SARS-CoV-2 mRNA vaccine: A case report.

SARS-CoV-2 vaccination is the most powerful and promising tool against the COVID-19 pandemic. Millions of people have been vaccinated worldwide. Recently, few cases of subacute thyroiditis following SARS-CoV-2 vaccination with various types of vaccine have been reported. We describe here a 36-year-old woman who presented with subacute thyroiditis 10 days after she had received her first dose of the SARS-CoV-2 mRNA vaccine Comirnaty (Pfizer/BioNTech); the condition receded but then recurred 10 days after she received her second dose. As vaccination programmes proceed, clinicians' attention and vigilance for such cases will be increased. Physicians need to know that subacute thyroiditis is a mild and self-limiting condition in the majority of cases. Last but not least, the benefits of vaccination against COVID-19 outweigh the side-effects reported so far.

A manless adultery: the story of Bassa as related in a Marcus Valerius Martialis' epigram.

During the Golden Age of the Roman Empire, Rome was transformed into a magnificent city where architecture, the arts, and commerce flourished. An inconceivable amount of wealth was accumulated by a handful of noble families, while the masses starved. In such a context, moral values inevitably decline, while sexual mores are liberalized and ever more veer towards salacity. This reality was elegantly illustrated in short, often sarcastic poems known as epigrams. Herein, we present a case of a woman with enigmatic appearance of the external genitalia, exhibiting unrestrained homosexual activity, as described in an epigram by Marcus Valerius Martialis (a contemporary poet who lived in the 1st century AD). Based on the information provided in the ancient text, we formulate a differential diagnosis and deduce that this woman was, in fact, a case of congenital adrenal hyperplasia (CAH). To our knowledge, this is the earliest literary description worldwide of a case of CAH as a cause of homosexuality and unquenchable lust.

The effect of carotid revascularization on the ophthalmic artery flow: systematic review and meta-analysis.

INTRODUCTION: High-grade internal carotid stenosis results in impaired flow dynamics in the ocular circulation that may lead to a rare clinical entity; ophthalmic ischemic syndrome (OIS). The aim of this study was to investigate hemodynamic changes in the ophthalmic circulation after carotid revascularization, assessed with duplex ultrasonography (DUS), and their potential impact on ocular function in patients suffering from OIS. EVIDENCE ACQUISITION: A systematic review of the literature was performed according to the PRISMA guidelines. Medline, Embase and Central databases were searched. EVIDENCE SYNTHESIS: The analysis included fourteen cohort studies (589 patients) reporting on the hemodynamic effect of carotid revascularization on the ophthalmic circulation using DUS. Eighty-five per cent of patients were treated for symptomatic carotid stenosis. The pre- and postoperative ophthalmological evaluation was recorded in four studies (227 out of 358 patients [63%] diagnosed with OIS). Reversed ophthalmic artery (OA) flow prior to carotid revascularization was present in 86 cases (24%). Following carotid revascularization, a significant increase in peak systolic velocity (PSV) (mean difference [MD] 14.712 cm/s, 95% confidence interval [CI] 10.566-18.858, P<0.001, I2=96%) and a significant anterograde restoration of flow in the OA (OR: 2.047, 95% CI: 1.72-2.42, P<0.001, Ι2=0%) were recorded. Carotid revascularization resulted in regression of ischemic symptoms in 93.1% of patients (95% CI: 56.4-99.3%), P=0.001, I2=82%). CONCLUSIONS: Carotid revascularization may be associated with a significant flow restoration and PSV increase in the OA; as well as clinical improvement in ischemic ophthalmic symptoms in patients with OIS.

HbA1c presents low sensitivity as a post-pregnancy screening test for both diabetes and prediabetes in Greek women with history of gestational diabetes mellitus.

BACKGROUND AND AIM: Women with a history of gestational diabetes mellitus (GDM) are at increased risk for type 2 diabetes (T2D). It is thus recommended that an oral glucose tolerance test (OGTT) be performed after delivery. Recently, the use of glycated haemoglobin A1c (HbA1c) has been proposed as a simpler and faster method to diagnose glucose disorders. The aim of this study was to investigate whether HbA1c measurement can replace OGTT in the detection of prediabetes and T2D in women with a history of GDM. PATIENTS AND METHODS: We studied 1336 women (35.3 ± 5.8 years old) with a history of GDM 16.6 ± 28.2 months after delivery. All women were evaluated through an OGTT and a simultaneous HbA1c measurement. American Diabetes Association (ADA) criteria were used for the assessment of glucose disorders. Sensitivity and specificity of HbA1c were measured for the prediction of T2D and prediabetes, while Cohen's coefficient of agreement (k) was calculated. ROC analysis was performed to evaluate the sensitivity and specificity of HbA1c. RESULTS: Based on OGTT, 725 women (54.3%) were normal, 406 (30.4%) presented impaired fasting glucose (IFG), 48 (3.6%) impaired glucose tolerance (IGT), 74 (5.5%) combined IFG+IGT, and 83 presented with T2D (6.2%). By contrast, using HbA1c as a screening test, 1150 women (94.1%) were normal, while 49 (4.0%) had prediabetes and 23 (1.9%) T2D. Sensitivity of HbA1c for the diagnosis of prediabetes was 5.3% in comparison to OGTT, specificity was 99.2%, while for the diagnosis of T2D, the percentages were 29.6 and 100%, respectively. The consistency in classifying impaired glucose tolerance between HbA1c and OGTT was 59.7%. Cohen's coefficient of agreement was k = 0.116, indicating slight agreement. Performing a ROC curve, the optimal value of distinctive ability of HbA1c was 4.6% in the case of prediabetes, while for diabetes, it was 5.5%. CONCLUSION: This study provided evidence that HbA1c can identify fewer women with prediabetes and T2D than OGTT, indicating that HbA1c cannot be recommended as an alternative post-pregnancy screening method.

The impact of environmental temperature on the diagnosis of gestational diabetes mellitus.

OBJECTIVE: To investigate a probable impact of seasons on the diagnosis of GDM, as well as the specific effect of the environmental temperature on the diagnosis of this clinical entity. PATIENTS AND METHODS: Two observational studies, one retrospective and one prospective, were conducted in a referral center. Study A included retrospectively 7618 pregnant women who underwent a 3-h 100 g OGTT during the 3rd trimester of gestation. Study B prospectively included 768 pregnant women tested in the 3rd trimester of gestation with a 75 g OGTT. Temperature was recorded every day at 09:00 h. RESULTS: Retrospective Study A: GDM prevalence differed significantly by season: winter = 28.1%, summer = 39.2%, spring = 32.4% and autumn = 32.4% (P < 0.0001). The odds ratio for being diagnosed with GDM was much higher during summer 1.65 (95% CI: 1.43-1.90), with spring and autumn following with 1.23 (95% CI: 1.08-1.39) compared to winter. Glucose levels during OGTT were measured: significantly increased blood glucose values were observed at 60, 120 and 180 min in summer, which remained significant after adjustment for age, gestational age, BMI, weight gain during pregnancy and blood pressure. Prospective Study B: At temperatures above 25°C, the average glucose 60-min and 120-min levels were increased. The relative risk for abnormal glucose values at 60 min, when the environmental temperature increased over 25°C, was 2.2 (1.5-3.3). CONCLUSIONS: GDM prevalence in Greece presents seasonal variation, with higher risk during summer due to post glucose load level variations. These variations could be attributed to differences in environmental temperature.