Obesity treatment in patients both with and without diabetes: current options and perspectives.

Increasing prevalence of obesity and its complications in practically all developed countries worldwide is one of the most cardinal problems of current healthcare. Obesity is an important risk factor for the development of type 2 diabetes mellitus and it is closely interconnected with arterial hypertension, dyslipidemia and other diseases commonly referred to as metabolic syndrome or insulin resistance syndrome. Overall, this combination of diseases markedly increases risk of cardiovascular morbidity and mortality. In this paper, we provide a review of current possibilities of pharmacological modulation of body weight in patients with obesity both with and without diabetes. We also briefly mention the treatment possibilities using bariatric surgery and endoscopy, and discuss the perspectives of pharmacological modulation of body weight in patients with diabetes in the context of ongoing research programmes.

ANTHROPOMETRIC FEATURES ARE NOT PREDICTIVE OF 72-HOUR FAST DURATION IN INSULINOMAS.

OBJECTIVE: The 72-hour fast is used to document Whipple's triad and understand the mechanism of hypoglycemia. Although hypoglycemia develops within 24 hours in the majority of fasts, identifying possible determinants of fast duration may help to predict the need for admission. Therefore, we determined the relation between anthropometric features on fast duration and assessed end of fast parameters on maximal tumor size, extent of disease, or tumor recurrence. METHODS: A retrospective analysis of patients with insulinoma in the past 25 years who underwent a 72-hour fast was conducted. Electronic medical records were reviewed to obtain anthropometric patient data and tumor characteristics. RESULTS: A total of 233 patients underwent the 72-hour fast. The mean age at diagnosis was 50 ± 16 years, with a body mass index (BMI) of 29 ± 7 kg/m2, and 66% (153 of 233) were female. Duration of fast was not associated with gender (P = .2), age (P = .3), or BMI (P = .7). A shorter fast duration was inversely related to end of fast C-peptide (P = .0075) but not insulin (P = .13) or proinsulin (P = .28) concentration. End of fast C-peptide was associated with increased tumor size (P = .036) and multiplicity (P =.01). Proinsulin was associated with increased tumor size (P<.01) and malignancy (P = .018). CONCLUSION: Duration of fast was not significantly related age, gender, weight, or BMI, although end-of-fast C-peptide and proinsulin may provide some information regarding tumor characteristics. Consequently, the duration of fast cannot be predicted a priori and should be allowed to run for the planned length unless hypoglycemia develops. Abbreviation: BMI = body mass index.

Tissue architecture delineates field cancerization in BRAFV600E-induced tumor development.

Cancer cells hijack developmental growth mechanisms but whether tissue morphogenesis and architecture modify tumorigenesis is unknown. Here, we characterized a new mouse model of sporadic thyroid carcinogenesis based on inducible expression of BRAF carrying a Val600 Glu (V600E) point mutation (BRAFV600E) from the thyroglobulin promoter (TgCreERT2). Spontaneous activation of this Braf-mutant allele due to leaky activity of the Cre recombinase revealed that intrinsic properties of thyroid follicles determined BRAF-mutant cell fate. Papillary thyroid carcinomas developed multicentrically within a normal microenvironment. Each tumor originated from a single follicle that provided a confined space for growth of a distinct tumor phenotype. Lineage tracing revealed oligoclonal tumor development in infancy and early selection of BRAFV600E kinase inhibitor-resistant clones. Somatic mutations were few, non-recurrent and limited to advanced tumors. Female mice developed larger tumors than males, reproducing the gender difference of human thyroid cancer. These data indicate that BRAFV600E-induced tumorigenesis is spatiotemporally regulated depending on the maturity and heterogeneity of follicles. Moreover, thyroid tissue organization seems to determine whether a BRAF-mutant lineage becomes a cancerized lineage. The TgCreERT2;BrafCA/+ sporadic thyroid cancer mouse model provides a new tool to evaluate drug therapy at different stages of tumor evolution.

Effect of Complex Weight-Reducing Interventions on Rhythm Control in Obese Individuals with Atrial Fibrillation Following Catheter Ablation: A Study Protocol.

INTRODUCTION: Obesity and atrial fibrillation (AF) pose a significant burden on healthcare systems worldwide. Reduction of body weight has been documented to reduce the risk of AF. Little is known about the effect of different weight-reducing interventions including bariatric surgery in obese individuals on the risk of arrhythmia recurrence following catheter ablation (CA) for AF, and about the pathophysiological mechanisms linking these two conditions. METHODS: The Effect of complex weigHt-reducing interventiOns on rhythm control in oBese subjects wITh Atrial Fibrillation (HOBIT-AF) is a single-blinded, parallel-group randomised controlled trial with 18-month follow-up to assess the effect of complex weight-reducing interventions supported by the use of smart technologies and bariatric surgery on the arrhythmia burden in obese individuals following CA for AF. One hundred and sixty individuals (age 18-70 years, body mass index ≥ 30 kg/m2) will be randomised in a 1:1 fashion to undergo a structured weight reduction programme and sleeve gastrectomy (when indicated and preferred by the patient) aiming to achieve greater than 10% weight reduction from baseline (intervention group) or standard post-ablation medical care (control group). Two-week continuous ECG monitoring will be used 3 and 18 months after CA to assess the arrhythmia burden. Other investigations will include transthoracic echocardiography with quantification of epicardial adipose tissue, and markers of low-grade inflammation and circulating adipokines. PLANNED OUTCOMES: The main objective is to assess the effect of complex weight-reducing interventions on the arrhythmia burden and quality of life. Subgroup analyses to identify patient subgroups preferentially benefiting from weight loss related to a decrease in arrhythmia burden will be performed. Exploratory objectives will include investigation of potential mechanisms linking weight reduction with amelioration of arrhythmia burden such as changes in markers of low-grade inflammation, circulating adipokines, cytokines, monocytes or reduction of epicardial adipose tissue volume. TRIAL REGISTRATION: NCT04560387.

Impact of Hashimoto's thyroiditis, TSH levels, and anti-thyroid antibody positivity on differentiated thyroid carcinoma incidence.

INTRODUCTION: The relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) is controversial. While most surgical studies report a high incidence of malignancy among patients with HT, cytological studies do not. The role of autoantibodies in the incidence of malignancy is unclear. MATERIAL AND METHODS: A single-centre retrospective observational study was conducted in patients evaluated for thyroid nodules by US-guided fine-needle aspiration cytology (FNAC) and, if indicated, by surgery. The levels of thyroid-stimulating hormone (TSH) and anti-thyroid antibodies were measured at the time of FNAC. RESULTS: Of 4947 patients, 599 (12.1%) were diagnosed with HT. A malignant/suspicious cytological result was found in 14.2% of the patients with HT and in 15.2% of the others. The odds ratio (OR) for malignancy in HT was 0.921 (0.716-1.183, p = 0.51). Of 1603 patients who underwent surgery, differentiated thyroid carcinoma was found in 29.5% of the HT patients and in 15.2% of the others (OR 2.33, 95% confidence interval CI, 1.403-3.854, p < 0,001). Low TSH (< 0.4 mIU/L) decreased the malignancy rate in the entire patient population, both when considering the cytological results and the surgical results. This was not confirmed in the subgroup diagnosed with HT. No relationship was observed between autoantibodies against thyroid peroxidase (ATP) or thyroglobulin (ATG) and malignancy rate. CONCLUSIONS: No association between HT and thyroid cancer was observed cytologically; a positive relationship in histological series was caused by selection bias. Low TSH levels decreased the risk of TC in patients with nodular goitre, but this has not been proven in patients with HT.