Association of Dietary Inflammatory Index and Thyroid Function in Patients with Hashimoto's Thyroiditis: An Observational Cross-Sectional Multicenter Study.

Background and Objectives: The available research suggests that dietary patterns with high inflammatory potential, as indicated by a high DII score, may exacerbate inflammation and potentially influence thyroid function. Therefore, the aim of this study was to investigate the associations between the inflammatory potential of a diet and thyroid function in adults with Hashimoto's thyroiditis (HT). Materials and Methods: A total of 149 adults diagnosed with Hashimoto's thyroiditis were enrolled in this observational, cross-sectional, multicenter study. The Dietary Inflammatory Index (DII®) was calculated using a 141-item food frequency questionnaire (FFQ). The serum levels of the thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPO-Ab), and high-sensitivity C-reactive protein (hsCRP) were determined. Results: The DII® scores ranged from -3.49 (most anti-inflammatory) to +4.68 (most pro-inflammatory), whereas three DII® tertile ranges were defined as <-1.4, -1.39 to +1.20, and >+1.21, respectively. Participants in tertile 1 (more anti-inflammatory diet) had significantly higher levels of fT4 than those adhering to a more pro-inflammatory diet (p = 0.007). The levels of hsCRP and TSH appeared to increase with increasing the DII® score, but without statistical significance. A significant association was found between the DII® and TSH (ß = 0.42, p < 0.001) and between DII® and free thyroxine (ß = 0.19, p < 0.001). After adjustment for age, gender, energy intake, and physical activity, a significant positive correlation remained between the DII® and TSH (ß = 0.33, p = 0.002) and between the DII® and body mass index (BMI) (ß = 0.14, p = 0.04). Conclusions: Adherence to an anti-inflammatory diet appears to be beneficial in patients with Hashimoto's thyroiditis, suggesting that dietary modification aimed at lowering DII® levels may be a valuable strategy to improve clinical outcomes in these patients.

Primary hyperparathyroidism-induced acute pancreatitis in pregnancy: A systematic review with a diagnostic-treatment algorithm.

BACKGROUND: Primary hyperparathyroidism (PHPT)-induced acute pancreatitis (AP) during pregnancy has rarely been described. Due to this rarity, there are no diagnostic or treatment algorithms for pregnant patients. AIM: To determine appropriate diagnostic methods, therapeutic options, and factors related to maternal and fetal outcomes for PHPT-induced AP in pregnancy. METHODS: A literature search of articles in English, Japanese, German, Spanish, and Italian was performed using PubMed (1946-2023), PubMed Central (1900-2023), and Google Scholar. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol was followed. The search terms included "pancreatite acuta," "iperparatiroidismo primario," "gravidanza," "travaglio," "puerperio," "postpartum," "akute pankreatitis," "primärer hyperparathyreoidismus," "Schwangerschaft," "Wehen," "Wochenbett," "pancreatitis aguda," "hiperparatiroidismo primario," "embarazo," "parto," "puerperio," "posparto," "acute pancreatitis," "primary hyperparathyroidism," "pregnancy," "labor," "puerperium," and "postpartum." Additional studies were identified by reviewing the reference lists of retrieved studies. Demographic, imaging, surgical, obstetric, and outcome data were obtained. RESULTS: Fifty-four cases were collected from the 51 studies. The median maternal age was 29 years. PHPT-induced AP starts at the 20th gestational week; higher gestational weeks were seen in mothers who died (mean gestational week 28). Median values of amylase (1399, Q1-Q3 = 519-2072), lipase (2072, Q1-Q3 = 893-2804), serum calcium (3.5, Q1-Q3 = 3.1-3.9), and parathormone (PTH) (384, Q1-Q3 = 123-910) were reported. In 46 cases, adenoma was the cause of PHPT, followed by 2 cases of carcinoma and 1 case of hyperplasia. In the remaining 5 cases, the diagnosis was not reported. Neck ultrasound was positive in 34 cases, whereas sestamibi was performed in 3 cases, and neck computed tomography or magnetic resonance imaging was performed in 9 cases (the enlarged parathyroid gland was not localized in 3 cases). Surgery was the preferred treatment during pregnancy in 33 cases (median week of gestation 25, Q1-Q3 = 20-30) and postpartum in 12 cases. The timing was not reported in the remaining 9 cases, or surgery was not performed. AP was managed surgically in 11 cases and conservatively in 43 (79.6%) cases. Maternal and fetal mortality was 9.3% (5 cases). Surgery was more common in deceased mothers (60.0% vs 16.3%; P = 0.052), and PTH values tended to be higher in this group (910 pg/mL vs 302 pg/mL; P = 0.059). Maternal mortality was higher with higher serum lipase levels and earlier delivery week. Higher calcium (4.1 mmol/L vs 3.3 mmol/L; P = 0.009) and PTH (1914 pg/mL vs 302 pg/mL; P = 0.003) values increased fetal/child mortality, as well as abortions (40.0% vs 0.0%; P = 0.007) and complex deliveries (60.0% vs 8.2%; P = 0.01). CONCLUSION: If serum calcium is not tested during admission, definitive diagnosis of PHPT-induced AP in pregnancy is delayed, while early diagnosis and immediate intervention lead to excellent maternal and fetal outcomes.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure.

BACKGROUND: Sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have shown efficacy in reducing heart failure (HF) burden in a very heterogeneous groups of patients, raising doubts about some contemporary assumptions of their mechanism of action. We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy. Two groups of patients were included in the study: the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control. AIM: To evaluate the outcomes regarding natriuretic peptide, oxidative stress, inflammation, blood pressure, heart rate, cardiac function, and body weight. METHODS: The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and systolic and diastolic blood pressure. To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up, a rise in stroke volume index, body mass index (BMI) decrease, and lack of heart rate increase, linear regression analysis was performed. RESULTS: There was a greater reduction of MPO, hsCRP, GLS, and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up. Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI, while the predictor of stroke volume index increase was SGLT2i therapy itself. CONCLUSION: SGLT2i affect body composition, reduce cardiac load, improve diastolic/systolic function, and attenuate the sympathetic response. Glycemic control contributes to the improvement of heart function, blood pressure control, oxidative stress, and reduction in inflammation.

Laboratory medicine and sports: where are we now?

Laboratory medicine in sport and exercise has significantly developed during the last decades with the awareness that physical activity contributes to improved health status, and is present in monitoring both professional and recreational athletes. Training and competitions can modify concentrations of a variety of laboratory parameters, so the accurate laboratory data interpretation includes controlled and known preanalytical and analytical variables to prevent misleading interpretations. The paper represents a comprehensive summary of the lectures presented during the 35th Annual Symposium of the Croatian Society of Medical Biochemistry and Laboratory Medicine. It describes management of frequent sport injuries and sums up current knowledge of selected areas in laboratory medicine and sports including biological variation, changes in biochemical parameters and glycemic status. Additionally, the paper polemicizes sex hormone disorders in sports, encourages and comments research in recreational sports and laboratory medicine. In order to give the wider view, the connection of legal training protocols as well as monitoring prohibited substances in training is also considered through the eyes of laboratory medicine.

Challenges and pitfalls of youth-onset type 2 diabetes.

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) are increasing. The rise in frequency and severity of childhood obesity, inclination to sedentary lifestyle, and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications. Indeed, youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM, with greater insulin resistance and more rapid deterioration of beta cell function. Therefore, intermediate complications such as microalbuminuria develop in late childhood or early adulthood, while end-stage complications develop in mid-life. Due to the lack of efficacy and safety data, several drugs available for the treatment of adults with T2DM have not been approved in youth, reducing the pharmacological treatment options. In this mini review, we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

Managing end-stage carcinoid heart disease: A case report and literature review.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients' quality of life. Cardiovascular complications of GEP-NENs, primarily tricuspid and pulmonary valve disease, and right-sided heart failure, are the leading cause of death, even compared to metastatic disease. CASE SUMMARY: We present a case of a 35-year-old patient with progressive dyspnea, back pain, polyneuropathic leg pain, and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases. During the initial presentation, serum biomarkers were not evaluated, and the patient received five cycles of doxorubicin, which he did not tolerate well, so he refused further therapy and was lost to follow-up. After 10 years, he presented to the emergency room with signs and symptoms of right-sided heart failure. Panneuroendocrine markers, serum chromogranin A, and urinary 5-hydroxyindoleacetic acid were extremely elevated (900 ng/mL and 2178 µmol/L), and transabdominal ultrasound confirmed hepatic metastases. Computed tomography (CT) showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis. Furthermore, an Octreoscan showed lesions in the heart, thoracic spine, duodenum, and ascendent colon. A standard transthoracic echocardiogram confirmed findings of carcinoid heart disease. The patient was not a candidate for valve replacement. He started octreotide acetate treatment, and the dose escalated to 80 mg IM monthly. Although biochemical response and symptomatic improvement were noted, the patient died. CONCLUSION: Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors, usually with liver metastases, which manifests as right-sided heart valve dysfunction leading to right-sided heart failure. Carcinoid heart disease and tumor burden are major prognostic factors of poor survival. Therefore, they must be actively sought by available biochemical markers and imaging techniques. Moreover, imaging techniques aiding tumor detection and staging, somatostatin receptor positron emission tomography/CT, and CT or magnetic resonance imaging, should be performed at the time of diagnosis and in 3- to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery. Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered, while any delay can worsen right-sided ventricular failure.

Expect the unexpected: Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism.

Hyperparathyroidism (HPT) is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone (PTH), causing disturbances in calcium homeostasis. Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia. Brown tumors are rare, benign, tumor-like bone lesions, occurring in 1.5% to 4.5% of patients with HPT, as a complication of an uncontrolled disease pathway, and are nowadays rarely seen in clinical practice. The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass. Furthermore, it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion. The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium, phosphorus, and PTH. Although when present, brown tumor is quite pathognomonic for HPT, the histologic finding often suggests a giant cell tumor, while clinical presentation might suggest other more frequent pathologies such as metastatic tumors. Treatment of brown tumors frequently focuses on managing the underlying HPT, which can often lead to regression and resolution of the lesion, without the need for surgical intervention. However, in refractory cases or when dealing with large symptomatic lesions, surgical treatment may be necessary.

Metformin and pancreatic neuroendocrine tumors: A systematic review and meta-analysis.

BACKGROUND: Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET. AIM: To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET. METHODS: A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival. RESULTS: A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with I² = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; P < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; P < 0.001). The study heterogeneity was intermediate, with I² = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET. CONCLUSION: T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Compensated Advanced Chronic Liver Disease and Steatosis in Patients with Type 2 Diabetes as Assessed through Shear Wave Measurements and Attenuation Measurements.

Patients with type 2 diabetes (T2D) are at risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the prevalence of compensated advanced chronic liver disease (cACLD) and steatosis in patients with T2D using the new non-invasive diagnostic methods of shear wave measurements (SWMs) and attenuation (ATT) measurements in comparison with those of vibration-controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), which served as the reference methods. Among 214 T2D patients, steatosis at any grade and cACLD were revealed in 134 (62.6%) and 19 (8.9%) patients, respectively. SWMs showed a high correlation with VCTE (Spearman's ρ = 0.641), whereas SWMs produced lower (mean of -0.7 kPa) liver stiffness measurements (LSMs) overall. At a LSM of >11.0 kPa (Youden), SWMs had an AUROC of 0.951 that was used to diagnose cACLD (defined as a LSM of >15 kPa through VCTE) with 84.2% sensitivity and 96.4% specificity. The performance of ATT measurements in diagnosing liver steatosis at any grade (defined as the CAP of ≥274 dB/m) was suboptimal (AUROC of 0.744 at the ATT measurement cut-off of >0.63 dB/cm/MHz (Youden) with 59% sensitivity and 81.2% specificity). In conclusion, the prevalence of liver steatosis and previously unrecognized cACLD in patients with T2D is high and SWMs appear to be a reliable diagnostic method for this purpose, whereas further investigation is needed to optimize the diagnostic performance of ATT measurements.

Thyroid Stimulating Hormone as a Possible Additional COVID-19 Outcome Marker.

Background and Objectives: The interaction between thyroid and SARS-CoV-2 is complex and not yet fully understood. This study aimed to identify a predictive value of serum TSH levels on the short-term and middle-term outcomes of patients hospitalized for COVID-19. Materials and Methods: We retrospectively analyzed electronic records (ERs) data for hospitalized COVID-19 patients between March 2020 and June 2021 and their ERs during outpatient visits, 6-8 weeks post-discharge, in cases of known serum TSH levels and no previous thyroid disorder. The short-term (length of hospital stay, MSCT findings of lung involvement, required level of oxygen supplementation, admission to the ICU, and death) and middle-term outcomes after 6 to 8 weeks post-discharge (MSCT findings of lung involvement) were analyzed. Results: There were 580 patients included: 302 males and 278 females, average age of 66.39 ± 13.31 years, with no known thyroid disease (TSH mean 1.16 ± 1.8; median 0.80; no value higher than 6.0 mIU/L were included). Higher TSH was observed in patients with less severe outcomes and was associated with significantly higher SpO2 during hospitalization. Patients who required overall more oxygen supplementation or HFOT, mechanical ventilation, and patients who were more frequently admitted to the ICU or were more often treated with corticosteroids had lower TSH than those who did not show these indicators of disease severity. Lower TSH was also present in non-survivors when compared to survivors (all p < 0.01). Patients with low TSH during hospitalization more often had persistent lung involvement during the post-COVID-19 period (p = 0.028). In the post-COVID-19 period, there was an overall, statistically significant increase in the TSH levels when compared to TSH during hospitalization (p < 0.001). Conclusions: Low/suppressed serum TSH levels during acute COVID-19 may be an additional laboratory test that should be included in the prediction of unfavorable short- and middle-term outcomes.

Flash Glucose Monitoring in Croatia: The Optimal Number of Scans per Day to Achieve Good Glycemic Control in Type 1 Diabetes.

Background and Objectives: The purpose of this study is to determine the optimal number of scans per day required for attaining good glycemic regulation. Materials and Methods: The association of scanning frequency and glucometrics was analyzed according to bins of scanning frequency and bins of time in range (TIR) in the Croatian population of type 1 diabetes (T1DM) patients. Results: Intermittently scanned continuous glucose monitoring (isCGM) Libre users in Croatia performed on average 13 ± 7.4 scans per day. According to bins of scanning frequency, bin 5 with 11.2 ± 02 daily scans was sufficient for achieving meaningful improvements in glycemic regulation, while decreasing severe hypoglycemia required an increasing number of scans up to bin 10 (31 ± 0.9), yet with no effect on TIR improvement. When data were analyzed according to bins of TIR, an average of 16.3 ± 10.5 scans daily was associated with a TIR of 94.09 ± 3.49% and a coefficient of variation (CV) of 22.97 ± 4.94%. Improvement was shown between each successive bin of TIR but, of notice, the number of scans performed per day was 16.3 ± 10.5 according to TIR-based analysis and 31.9 ± 13.5 in bin 10 according to scan frequency analysis. Conclusions: In conclusion, an optimal average number of scans per day is 16.3 in order to achieve glucose stability and to minimize the burden associated with over-scanning.

Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the commonest malignancies associated with significant cancer-related death. The identification of chemo-preventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is intriguing. Metformin, a first-line agent used in the treatment of type 2 diabetes mellitus (T2DM), has been associated with inhibition of HCC growth. AIM: To determine whether metformin can prevent adverse events (i.e., death, tumor progression, and recurrence) after any HCC treatment in T2DM patients. METHODS: A systematic review of the published literature was undertaken focused on the role of metformin on outcomes in patients with T2DM and HCC receiving any tumor therapy. A search of the PubMed and Cochrane Central Register of Con-trolled Trials Databases was conducted. RESULTS: A total of 13 studies (n = 14886 patients) were included in this review. With regard to the risk of death, a decreased risk was reported in cases receiving metformin, although this decrease was not statistically significant [odds ratio (OR) = 0.89, P = 0.42]. When only patients treated with curative strategies were considered, a more marked correlation between metformin and favorable cases was reported (OR = 0.70, P = 0.068). When analyzing palliative treatment, there was no statistical significance in terms of the correlation between metformin and favorable cases (OR = 0.74, P = 0.66). As for the risks of progressive disease and recurrence, no obvious correlation between metformin use and reduced risk was reported. When sub-analyses were performed for patients from different regions, the results for patients from Eastern countries showed a tendency for decreased risk of death in T2DM cases receiving metformin (OR = 0.69, P = 0.17), but the same was not seen in patients from Western countries (OR = 1.19, P = 0.31). CONCLUSION: Metformin failed to show a marked impact in preventing adverse effects after HCC treatment. A trend was reported in T2DM cases receiving curative therapies in relation to the risk of death, especially in patients from Eastern regions. Great heterogeneity was reported among the different studies. Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.

Association between cardiorespiratory fitness level and insulin resistance in adolescents with various obesity categories.

BACKGROUND: An association between cardiorespiratory fitness (CRF) and insulin resistance in obese adolescents, especially in those with various obesity categories, has not been systematically studied. There is a lack of knowledge about the effects of CRF on insulin resistance in severely obese adolescents, despite their continuous rise. AIM: To investigate the association between CRF and insulin resistance in obese adolescents, with special emphasis on severely obese adolescents. METHODS: We performed a prospective, cross-sectional study that included 200 pubertal adolescents, 10 years to 18 years of age, who were referred to a tertiary care center due to obesity. According to body mass index (BMI), adolescents were classified as mildly obese (BMI 100% to 120% of the 95th percentile for age and sex) or severely obese (BMI ≥ 120% of the 95th percentile for age and sex or ≥ 35 kg/m2, whichever was lower). Participant body composition was assessed by bioelectrical impedance analysis. A homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Maximal oxygen uptake (VO2max) was determined from submaximal treadmill exercise test. CRF was expressed as VO2max scaled by total body weight (TBW) (mL/min/kg TBW) or by fat free mass (FFM) (mL/min/kg FFM), and then categorized as poor, intermediate, or good, according to VO2max terciles. Data were analyzed by statistical software package SPSS (IBM SPSS Statistics for Windows, Version 24.0). P < 0.05 was considered statistically significant. RESULTS: A weak negative correlation between CRF and HOMA-IR was found [Spearman's rank correlation coefficient (rs) = -0.28, P < 0.01 for CRFTBW; (rs) = -0.21, P < 0.01 for CRFFFM]. One-way analysis of variance (ANOVA) revealed a significant main effect of CRF on HOMA-IR [F(2200) = 6.840, P = 0.001 for CRFTBW; F(2200) = 3.883, P = 0.022 for CRFFFM]. Subsequent analyses showed that obese adolescents with poor CRF had higher HOMA-IR than obese adolescents with good CRF (P = 0.001 for CRFTBW; P = 0.018 for CRFFFM). Two-way ANOVA with Bonferroni correction confirmed significant effect of interaction of CRF level and obesity category on HOMA-IR [F(2200) = 3.292, P = 0.039 for CRFTBW]. Severely obese adolescents had higher HOMA-IR than those who were mildly obese, with either good or poor CRF. However, HOMA-IR did not differ between severely obese adolescents with good and mildly obese adolescents with poor CRF. CONCLUSION: CRF is an important determinant of insulin resistance in obese adolescents, regardless of obesity category. Therefore, CRF assessment should be a part of diagnostic procedure, and its improvement should be a therapeutic goal.

Impact of SGLT2 inhibitors on the mechanisms of myocardial dysfunction in type 2 diabetes: A prospective non-randomized observational study in patients with type 2 diabetes mellitus without overt heart disease.

AIMS: This prospective observational study evaluated the possible mechanisms of action of SGLT2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) without overt heart disease. METHODS: The study was designed to verify whether SGLT2i impact biomarkers of: myocardial stress-NT-proBNP, inflammation-high sensitivity C-reactive protein, oxidative stress -myeloperoxidase, functional and structural echocardiographic parameters, in patients with T2DM on metformin (heart failure stages A and B) who needed treatment intensification with a second antidiabetic agent. The patients were divided in two groups - the ones planned to receive SGLT2i or DPP-4 inhibitor (except saxagliptin). At baseline, and after six months of therapy, 64 patients underwent blood analysis, physical and echocardiography examination. RESULTS: There were no significant differences between the two groups in terms of biomarkers of myocyte and oxidative stress, inflammation and blood pressure. Body mass index, triglycerides, aspartate aminotransferase, uric acid, E/E', deceleration time and systolic pressure in the pulmonary artery significantly decreased, while stroke volume, indexed stroke volume, high-density lipoprotein, hematocrit and hemoglobin significantly increased in the group on SGLT2i. CONCLUSIONS: According to the results, SGLT2i mechanisms of action comprise rapid changes in body composition and metabolic parameters, reduced cardiac load and improvement in diastolic and systolic parameters.

Semaglutide-eye-catching results.

Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and, more recently, at higher doses, for the treatment of obesity. Both diseases are reaching epidemic proportions and often coexist, posing patients with a high risk for cardiovascular disease and death. Therefore, an agent such as semaglutide, which offers clinically significant weight loss and cardiovascular benefits, is essential and will be increasingly used in high-risk patients. However, during the SUSTAIN clinical trial program (Semaglutide Unabated Sustainability in treat-ment of type 2 diabetes), a safety issue concerning the progression and worsening of diabetic retinopathy emerged. The existing explanation so far mainly supports the role of the magnitude and speed of HbA1c reduction, a phenomenon also associated with insulin treatment and bariatric surgery. Whether and to which extent the effect is direct is still a matter of debate and an intriguing topic to investigate for suitable preventative and rehabilitative purposes. In this minireview, we will summarize the available data and suggest guidelines for a comprehensive semaglutide clinical utilization until new evidence becomes available.

Management of Glycemia during Acute Aerobic and Resistance Training in Patients with Diabetes Type 1: A Croatian Pilot Study.

(1) Background: The increased risk of developing hypoglycemia and worsening of glycemic stability during exercise is a major cause of concern for patients with type 1 diabetes mellitus (T1DM). (2) Aim: This pilot study aimed to assess glycemic stability and hypoglycemic episodes during and after aerobic versus resistance exercises using a flash glucose monitoring system in patients with T1DM. (3) Participants and Methods: We conducted a randomized crossover prospective study including 14 adult patients with T1DM. Patients were randomized according to the type of exercise (aerobic vs. resistance) with a recovery period of three days between a change of groups. Glucose stability and hypoglycemic episodes were evaluated during and 24 h after the exercise. Growth hormone (GH), cortisol, and lactate levels were determined at rest, 0, 30, and 60 min post-exercise period. (4) Results: The median age of patients was 53 years, with a median HbA1c of 7.1% and a duration of diabetes of 30 years. During both training sessions, there was a drop in glucose levels immediately after the exercise (0'), followed by an increase at 30' and 60', although the difference was not statistically significant. However, glucose levels significantly decreased from 60' to 24 h in the post-exercise period (p = 0.001) for both types of exercise. Glycemic stability was comparable prior to and after exercise for both training sessions. No differences in the number of hypoglycemic episodes, duration of hypoglycemia, and average glucose level in 24 h post-exercise period were observed between groups. Time to hypoglycemia onset was prolonged after the resistance as opposed to aerobic training (13 vs. 8 h, p = NS). There were no nocturnal hypoglycemic episodes (between 0 and 6 a.m.) after the resistance compared to aerobic exercise (4 vs. 0, p = NS). GH and cortisol responses were similar between the two sessions, while lactate levels were significantly more increased after resistance training. (5) Conclusion: Both exercise regimes induced similar blood glucose responses during and immediately following acute exercise.

Ocular myasthenia gravis-like symptoms associated with erenumab: Case report.

OBJECTIVE: We present a case of a patient who developed myasthenia gravis (MG)-like symptoms during erenumab treatment. CASE REPORT: The patient had a years-long history of chronic migraine with visual and sensory aura. Two months after the beginning of erenumab therapy, she reported intermittent bilateral weakness of the eyelids, with ptosis. The eyelid ptosis was severe enough to block the patient's vision. The symptoms would usually last between 5 and 10 minutes and resolve completely spontaneously, but they repeated on a daily basis. Antibodies against acetylcholine receptors and muscle-specific kinase were all negative, and other work-up excluded the usual etiology of ptosis. Since the cause of symptoms was not detected, we suspected they were induced by erenumab. The treatment was discontinued, and after 7 weeks from the last dose of erenumab, ocular symptoms resolved completely. In the presented case, other possible causes of MG-like symptoms were excluded by diagnostic tests and clinical course of the disease. The temporal relationship between the administration of erenumab and occurrence of ptosis, with regression of the symptoms after the drug discontinuation supports the hypothesis of causal relationship with erenumab. According to the Naranjo's Adverse Drug Reaction Probability Scale, erenumab-related MG-like symptoms were rated 'probable'. Reviewing the literature, we identified no similar case reports. CONCLUSION: Drug-induced MG-like symptoms might be life threatening. Therefore, clinicians should be aware of these adverse reactions during the use of erenumab.

THE IMPACT OF TOTAL PHYSICAL ACTIVITY ON MICROVASCULAR COMPLICATIONS IN TYPE 1 DIABETES MELLITUS PATIENTS.

The incidence of diabetes is increasing worldwide, emphasizing an emerging need for blood glucose control optimization to prevent the development of chronic complications and improve the quality of life. This retrospective cohort study aimed to investigate the effects of total physical activity on microvascular diabetic complication development in patients with type 1 diabetes mellitus (T1DM). The study included 71 T1DM patients, average age 41 years and HbA1c 7.78%. Most patients (82.1%) reported having hypoglycemia, while the minority of patients developed microvascular complications, mostly nonproliferative retinopathy (17.7%). All subjects included in the study were moderately or vigorously physically active. No association was observed between total physical activity and regulation of glycemia, hypoglycemic incidents, or development of microvascular complications. Until sufficient data from prospective studies become available, our data support the findings of no negative effect of higher intensity physical activity on the development of microvascular complications in T1DM patients.

Prehabilitation of overweight and obese patients with dysglycemia awaiting bariatric surgery: Predicting the success of obesity treatment.

Bariatric surgery offers the best health results in overweight and obese patients but is not a risk and/or complication-free treatment. In cases with additional hyperglycemia, the burden of surgery can be even higher and alter both short-term and long-term outcomes. Although bariatric surgery offers glycemic improvements and in the case of early onset diabetes disease remission, weight loss results are lower than for obese patients without diabetes. Different multimodal programs, usually including interventions related to patients' performance, nutritional and psychological status as well as currently available pharmacotherapy before the surgery itself might considerably improve the immediate and late postoperative course. However, there are still no clear guidelines addressing the prehabilitation of obese patients with dysglycemia undergoing bariatric surgery and therefore no unique protocols to improve patients' health. In this minireview, we summarize the current knowledge on prehabilitation before bariatric surgery procedures in patients with obesity and dysglycemia.