The role of low glycemic index and load diets in medical nutrition therapy for type 2 diabetes: an update.

The increasing prevalence of type 2 diabetes mellitus (T2DM) and its microvascular and macrovascular complications necessitate an optimal approach to prevention and management. Medical nutrition therapy serves as the cornerstone of diabetes care, reducing reliance on diabetic medications for glycemic control and mitigating cardiovascular risk. The broadening field of research in the effect of low glycemic index (GI) and/or glycemic load (GL) diets on individuals with T2DM has yielded promising results in the existing literature. Adopting low-GI and GL dietary patterns contributes to minimizing fluctuations in blood glucose levels, thus presenting a good strategy for achieving enhanced glycemic control. Furthermore, the above dietary practices may offer a viable alternative and practical approach to weight management in individuals with T2DM. However, clinical practice guidelines for diabetes dietary management show inconsistency regarding the certainty of evidence supporting the implementation of low-GI/GL nutritional patterns. This review aims to thoroughly evaluate the available data on the effectiveness of low-GI and low-GL diets in managing glycemic control and reducing cardiovascular risk factors.

Two rare cases of benign struma ovarii with malignant recurrence.

Summary: Struma ovarii is an ovarian teratoma that comprises 2-5% of all ovarian teratomas. Malignant transformation of struma ovarii occurs in less than 5% of all cases, and metastatic disease is even rarer. We report two cases initially diagnosed with benign struma ovarii that presented malignant transformation, specifically highly differentiated follicular carcinoma of the ovary (HDFCO), some years after the first diagnosis. Case 1 concerns a 37-year-old female featuring HDFCO of the right ovary with multiple metastatic foci, who was diagnosed with benign struma ovarii 14 years ago. Case 2 concerns a 26-year-old female diagnosed with HDFCO of the left ovary. This patient was initially diagnosed with benign struma ovarii 6 years ago that recurred 4 years after the diagnosis. Both patients were treated with surgery, adjunctive total thyroidectomy, and radioactive iodine (131I) therapy. Learning points: Malignant transformation of struma ovarii is very rare (<5%). Diagnosis of HDFCO without extra ovarian dissemination is difficult due to the resemblance of its histological appearance with normal thyroid tissue. There is no consensus on the postoperative treatment of malignant struma ovarii (MSO). Clinical and histological features of MSO should be assessed for the postoperative treatment decisions. TSH suppression and thyroglobulin level measurements are necessary for patient follow-up.

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.

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.

Thyroid autoimmunity following alemtuzumab treatment in multiple sclerosis patients: a prospective study.

Autoimmune thyroid disease (AITD) is the most common adverse effect in alemtuzumab (ALZ) treated relapsing-remitting (RR) multiple sclerosis (MS) patients. The objective of this prospective study was to analyze the occurrence, timing of onset, clinical course, and laboratory characteristics of AITD post-ALZ. We evaluated 35 RRMS patients treated with ALZ at a single academic MS center; clinical and laboratory data were collected before ALZ initiation and thereafter quarterly on follow-up with a median of 43.5 months. Seventeen out of 31 patients (54.8%) with no prior history of thyroid dysfunction developed AITD with a mean onset of 19.4 months ± 10.2 (SD) after the first ALZ cycle; Graves' disease (GD) (n = 9); hypothyroidism with positive stimulating thyrotropin receptor antibodies (TRAb) (n = 1); Hashimoto thyroiditis (HT) (n = 6); HT with hypothyroidism (n = 1). Interestingly, seven of nine (77.7%) GD patients showed a fluctuating course. Three out of four patients with preexisting thyroid disease remained stable, whereas one with prior HT and hypothyroidism developed fluctuating GD. All patients with GD commenced antithyroid drugs (ATDs); five continued on "block and replace" treatment; one required radioactive iodine, and one total thyroidectomy. Our analysis showed earlier onset of ALZ-induced AITD in comparison to most other ALZ cohorts; overall, these patients required complex therapeutic approaches of the AITD. We observed a higher rate of fluctuating GD, with earlier onset and lower remission rate than previously reported, which in the majority of patients required prolonged "block and replace" therapy in the minimum dose of each therapeutic agent or more definitive interventions.

Basic Concepts and Hormonal Regulators of the Stress System.

BACKGROUND: Human organisms have to cope with a large number of external or internal stressful stimuli that threaten - or are perceived as threatening - their internal dynamic balance or homeostasis. To face these disturbing forces, or stressors, organisms have developed a complex neuroendocrine system, the stress system, which consists of the hypothalamic-pituitary-adrenal axis and the locus caeruleus/norepinephrine-autonomic nervous system. SUMMARY: Upon exposure to stressors beyond a certain threshold, the activation of the stress system leads to a series of physiological and behavioral adaptations that help achieve homeostasis and increase the chances of survival. When, however, the stress response to stressors is inadequate, excessive, or prolonged, the resultant maladaptation may lead to the development of several stress-related pathologic conditions. Adverse environmental events, especially during critical periods of life, such as prenatal life, childhood, and puberty/adolescence, in combination with the underlying genetic background, may leave deep, long-term epigenetic imprints in the human expressed genome. KEY MESSAGES: In this review, we describe the components of the stress system and its functional interactions with other homeostatic systems of the organism; we present the hormonal regulators of the stress response, and we discuss the development of stress-related pathologies.

Sleep Apnea and Cardiovascular Risk in Patients with Prediabetes and Type 2 Diabetes.

Obstructive sleep apnea (OSA) is a common but largely undiagnosed clinical condition, which is turning into a serious public health issue. Of note is that its prevalence is gradually increasing in parallel with the obesity and type 2 diabetes mellitus (T2DM) epidemics. The aim of this article is to comprehensively review the literature in order to evaluate the cardiovascular (CV) risk among patients with OSA and prediabetes or T2DM. OSA seems to be an independent risk factor for the development as well as the progression of T2DM, whereas it is associated with T2DM-related macrovascular and microvascular complications. OSA may also act as a potential risk factor for the presentation and development of CV disease, such as hypertension, coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation and other cardiac arrythmias, as well as stroke. OSA and T2DM also share common pathophysiological mechanisms leading to atherosclerosis. Considering that the coexistence of OSA and T2DM is an independent and cumulative risk factor for CV mortality, more so than the two diseases separately, clinicians and healthcare professionals should be aware of and screen for OSA in patients with T2DM. Notably, targeted therapy for both conditions seems to substantially improve CV prognosis.

A rare case of poorly differentiated mixed neuroendocrine-nonneuroendocrine tumor of the caecum with long term survival: A case report.

A 59-year-old woman presented with flushing attacks accompanied by tachycardia and hypotension, which lasted approximately 30 to 60 minutes, underwent 18 years ago a gastrointestinal tumor resection. The histologic examination revealed a poorly differentiated mixed neuroendocrine/adenocarcinoma located in the caecum with regional metastases. Postoperatively, the patient received combined chemotherapy of 5-fluorouracil with interferon for six months and since has remained asymptomatic. Her examination revealed positivity for chromogranin A (CgA) and a-Fetoprotein (aFP) (580 ng/24 h, normal range 27-94, and 10 IU/mL, normal range 0-6, respectively). Urinary 5-hydroxy indole acetic acid excretion was remarkably high (41.8 mg/24 h, normal range 2-10 mg/24 h). An abdominal Magnetic Resonance Imaging scan revealed multiple focal loci in the liver whose histological examination revealed a carcinoid tumor confirmed by an Octreoscan. Additional uptake was noted on the right shoulder and the right sternum-clavicle joint confirmed by Tc-99m MDP scan. The patient received somatostatin analogue therapy followed by long-acting release octreotide analogue therapy (30 mg/month) showing a partial improvement of relevant biomarkers. Two years later, carcinoid syndrome symptoms reappeared and due to the tumors expression of somatostatin receptors the patient received peptide receptor radionuclide therapy with 177Lu-DOTATATE that resulted in both clinical and biochemical improvements.

Diabetes and COVID-19; A Bidirectional Interplay.

There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.

Thyroid disorders and cardiovascular manifestations: an update.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health, social, and economic issue. Thyroid disorders are very common and affect >10% of the adult population in total. The aim of this review is to describe the physiologic role of thyroid hormones on cardiovascular system, to present cardiovascular manifestations in patients with thyroid disorders, emphasizing in molecular mechanisms and biochemical pathways, and to summarize current knowledge of treatment options. Thyroid hormone receptors are located both in myocardium and vessels, and changes in their concentrations affect cardiovascular function. Hyperthyroidism or hypothyroidism, both clinical and subclinical, without the indicated therapeutical management, may contribute to the progression of CVD. According to recent studies, even middle changes in thyroid hormones levels increase cardiovascular mortality from 20% to 80%. In more details, thyroid disorders seem to have serious effects on the cardiovascular system via plenty mechanisms, including dyslipidemia, hypertension, systolic and diastolic myocardial dysfunction, as well endothelial dysfunction. On top of clinical thyroid disorders management, current therapeutics focus on younger patients with subclinical hypothyroidism and elderly patients with subclinical hyperthyroidism.

IgG4-related autoimmune manifestations in Alemtuzumab-treated multiple sclerosis patients.

We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highest IgG4-levels were more prone to thyroid-related autoimmune manifestations and specific autoimmune adverse events such as Crohn's disease, Graves' disease, and hemolytic anemia. Compared to baseline, total IgG-levels showed a trend towards reduced levels following two-courses of Alemtuzumab, but no significant change of C3 and/or C4-levels was observed. In conclusion, monitoring of IgG4-levels can serve as a marker for secondary autoimmunity risk in multiple sclerosis patients treated with Alemtuzumab.

The Effects of Different Hormones on Supraventricular and Ventricular Premature Contractions in Healthy Premenopausal Women.

Background and Objectives: The effects of gender differences on cardiac parameters have been well-established. In this study, we aimed to evaluate the possible associations of plasma levels of different sex hormones with premature atrial or ventricular contractions in premenopausal women. Materials and Methods: We conducted a prospective study which included women in late reproductive age who presented with palpitations during an eight-month period. A 12-lead electrocardiography, a transthoracic echocardiogram, blood samples, and 24-hour rhythm Holter were conducted on the third day of the menstrual cycle. Results Overall, 93 healthy premenopausal women with a median age of 42 years were enrolled. QTc interval was within normal limits in all patients. The 24 h range of premature atrial contractions (PACs) and premature ventricular contractions (PVCs) was 0-6450 and was 0-21,230, respectively. The median number of PVCs was 540 and the median number of PACs was 212, respectively. In total, 51 patients (54.8%) had a frequency of PVCs > 500/24 h and 37 patients (39.8%) had a frequency of PACs > 500/24 h, respectively. No statistically significant association was shown between any hormone and the frequency of PACs. Regarding PVCs, patients with a PVCs frequency > 500/24 h had higher estradiol levels compared to patients with PVCs less than 500/24 h (median 60 pg/mL versus 42 pg/mL, p = 0.02, OR: 1.01). No association was found between PVCs and other hormones. Conclusions: In premenopausal healthy women, higher estradiol levels are independently associated with increased PVCs. This suggests that estradiol in late reproductive stages may exert proarrhythmic effects.

Medullary thyroid carcinoma (MTC): unusual metastatic sites.

SUMMARY: Medullary thyroid carcinoma (MTC) has a varying clinical course; distant metastases are frequently present even at diagnosis. We present two MTC cases with unusual metastatic sites. Two female patients are presented with slow progressive MTC. The first case developed distant metastases 23 years after diagnosis and underwent locoregional therapies. At the same time a breast mass developed representing MTC metastasis. Treatment with vandetanib led to long-term disease stabilization. The second patient is presented with metastases in the pancreas 13 years after diagnosis. Shortly, a painful mass developed in the mandible and metastasis of MTC was diagnosed. Disease progression was recorded 20 months after the initiation of local and systemic therapy. Such cases have only rarely been reported in the literature and highlight the need for prompt recognition of unexpected MTC metastases. LEARNING POINTS: Unusual sites of metastasis may appear in patients with medullary thyroid carcinoma (MTC) years after the initial diagnosis. Although rare, unexpected MTC metastases highlight the need for prompt recognition and appropriate treatment. Local recurrences accompanied by inappropriately low calcitonin levels should prompt further investigation for possible distant metastatic disease. Systemic treatment with tyrosine kinase inhibitors may be effective even in patients with unusual metastases from MTC.

Early and late endocrine complications of COVID-19.

Endocrine system plays a vital role in controlling human homeostasis. Understanding the possible effects of COVID-19 on endocrine glands is crucial to prevent and manage endocrine disorders before and during hospitalization in COVID-19-infected patients as well as to follow them up properly upon recovery. Many endocrine glands such as pancreas, hypothalamus and pituitary, thyroid, adrenal glands, testes, and ovaries have been found to express angiotensin-converting enzyme 2 receptors, the main binding site of the virus. Since the pandemic outbreak, various publications focus on the aggravation of preexisting endocrine diseases by COVID-19 infection or the adverse prognosis of the disease in endocrine patients. However, data on endocrine disorders both during the phase of the infection (early complications) and upon recovery (late complications) are scarce. The aim of this review is to identify and discuss early and late endocrine complications of COVID-19. The majority of the available data refer to glucose dysregulation and its reciprocal effect on COVID-19 infection with the main interest focusing on the presentation of new onset of diabetes mellitus. Thyroid dysfunction with low triiodothyronine, low thyroid stimulating hormone, or subacute thyroiditis has been reported. Adrenal dysregulation and impaired spermatogenesis in affected men have been also reported. Complications of other endocrine glands are still not clear. Considering the recent onset of COVID-19 infection, the available follow-up data are limited, and therefore, long-term studies are required to evaluate certain effects of COVID-19 on the endocrine glands.

Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions.

CONTEXT: Association of central diabetes insipidus (CDI) and pituitary stalk thickening (PST) may have several etiologies (including malignancies) and differential diagnosis remains often difficult. OBJECTIVE: The purpose of this study was to identify which clinical, biochemical or radiological features could help clinicians to make an etiological diagnosis, especially distinguishing neoplastic from non-neoplastic pituitary stalk lesions. DESIGNS AND METHODS: We retrospectively analyzed clinical, biochemical, radiological and histological data of 38 adult patients diagnosed with CDI and PST of proven etiology. RESULTS: Of the 38 pituitary stalk lesions included, 11 (29%) were neoplastic. A histopathological diagnosis was obtained in 22/38 (58%) patients. The three most frequently observed etiologies of PST were neuroinfundibulitis (34%), germinoma (21%) and histiocytosis (18%). Pituitary stalk thickness was larger for neoplastic lesions, particularly germinomas. Male gender and a very young age were statistically associated with a risk of germinoma. At least one anterior pituitary deficit was observed in nearly 60% of patients. Patients with neoplastic PST were more affected by multiple anterior pituitary dysfunction than patients with benign PST. A high serum prolactin level was individually the best predictor of a neoplastic origin (90% sensitivity and 60% specificity for a serum prolactin level 1.27-fold above the normal upper limit (ULN)). CONCLUSION: We confirm a relatively high risk of malignancy in adult patients presenting with the association of CDI and PST. Young age, male gender, a very large thickening of the stalk, multiple anterior pituitary deficits and prolactin above 1.3× ULN increase the likelihood of a neoplastic origin.