Modern Management of Cardiometabolic Continuum: From Overweight/Obesity to Prediabetes/Type 2 Diabetes Mellitus. Recommendations from the Eastern and Southern Europe Diabetes and Obesity Expert Group.

The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in ß-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient's disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum.

Metastatic pituitary neuroendocrine neoplasms: A case report of a malignant prolactinoma.

We report a rare clinical case of a malignant prolactinoma in which the exponential increase of prolactin levels with minimal tumor growth and no response to treatment led to diagnosis of abdominal, thoracic, and vertebral metastases.

Cultural Translation and Validation of the Bariatric Quality of Life Index to European Portuguese.

INTRODUCTION: Obesity is a chronic noncommunicable disease, defined by a body mass index over 30 kg/m2. Its impact is not restricted to its association with higher risks of mortality and morbidity from other noncommunicable diseases, but also with a decrease in quality of life (QoL). There are several tools to assess QoL, from generic health-related tools to obesity-related specific ones. However, to assess QoL in patients undergoing bariatric surgery, only the Bariatric Analysis and Reporting Outcome System was available, which presented some significant problems. Therefore, the Bariatric Quality of Life (BQL) Index was developed. The aim of this study was the validation and cultural adaptation of the BQL Index for European Portuguese. METHODS: A cross-sectional study was conducted, with the presentation of two questionnaires to the participants: BQL Index and EQ-5D-3L (European Quality of Life 5 Dimensions and 3 Level) Index. Direct translation followed reviewing, back-translation, comparison, and pilot testing were performed. Retest was done six months after the baseline. The following psychometric properties were assessed: convergent validity using the Spearman r correlation coefficient between BQL Index and EQ-5D-3L Index; internal consistency based on Cronbach alpha coefficient; and reproducibility between test and retest through Spearman r correlation coefficient and intraclass correlation coefficient (ICC). RESULTS: A total of 260 participants were included, the mean age was 45 ± 10 years old, the mean body mass index was 44 ± 6.5 kg/m2 and 78% were females. The most frequent obesity-related comorbidities were osteoarticular disease (69%), anxiety/depression (60%), and hypertension (54%). The most common eating patterns were volume eater (67%) and sweet eater (62%). Quality of Life scores were 41.3 ± 9.3 for the BQL Index, 0.35 ± 0.19 for the EQ-5D-3L Index and 55.7 ± 19.8 for the EQ-5D-3L VAS. The translation yielded good convergent validity (r = 0.62), good internal consistency (alpha = 0.94), and good reproducibility (r = 0.62 and ICC = 0.79). CONCLUSION: Our translation exhibited good parametric properties, with validity within the original BQL values, higher internal consistency, and good reproducibility.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Preoperative Location Of Parathyroid Adenomas In Primary Hyperparathyroidism: The Role of Cervical Doppler Ultrasound.

INTRODUCTION: Parathyroid adenoma is the most frequent cause of primary hyperparathyroidism. In recent years, the preoperative location of parathyroid adenomas allowed minimally invasive surgical techniques that have become preferred over the traditional bilateral neck exploration. The more recent guidelines on this subject highlight the role of nuclear medicine imaging tests. The aim of this study was to review the current role of Doppler ultrasound (US) in assessing the preoperative location of parathyroid adenomas in patients with primary hyperparathyroidism. MATERIAL AND METHODS: Retrospective study based on data from patients with primary hyperparathyroidism that underwent parathyroidectomy between January 2013 and January 2022 at the Centro Hospitalar Universitário Lisboa Central. Statistical analysis was performed with IBM SPSS Statistics, version 26.0.0.0®. RESULTS: Parathyroidectomy was performed in 171 patients (77.8% females) with primary hyperparathyroidism. Cervical Doppler ultrasound was the most performed test (64.3%, n = 110) for preoperative location and detected a suspicious lesion in 98 patients (89.1%). The preoperative location of the parathyroid adenomas was assessed through the Doppler ultrasound and was compared with the surgical reports and histological findings; a correct identification was made in 76 patients (77.6%). Doppler ultrasound slightly underestimated the mean adenoma size (18.1 ± 7.7 mm preoperative versus 22 ± 8.4 mm postoperative). Calcium, parathyroid hormone levels, adenoma size and concomitant presence of thyroid nodules did not affect the accuracy of Doppler ultrasound. CONCLUSION: Doppler ultrasound showed high diagnostic accuracy even in patients with nodular thyroid disease regardless of calcium and parathyroid hormone levels and adenoma size. Furthermore, its safety, affordability and availability should favor its use as first line test in primary hyperparathyroidism to assess the preoperative location of parathyroid adenomas.

Pituitary metastasis as the first manifestation of lung carcinoma.

Pituitary metastases are rare. Clinical presentation could range from asymptomatic to panhypopituitarism or local symptoms. We present a case report of a 43-year-old male patient with a new onset headache, visual disturbances, and panhypopituitarism. The investigation led to the diagnosis of pituitary metastasis as the first manifestation of underlying lung cancer.

Quality of Life in Obese Patients from a Multidisciplinary Bariatric Consultation: A Cross-Sectional Study Comparing to a Non-Bariatric Population and to the General Population.

Obesity is a chronic disease defined by a body mass index of ≥30 kg/m2, which can result in a decrease in quality of life (QoL). Our study aim was to assess the QoL of an obese population of bariatric surgery (BS) candidates, and to compare it to both that of a non-bariatric obese population (C) and that of the general population. This was a cross-sectional study using: (1) the EQ-5D-3L instrument: comparing BS with the C population and with the Portuguese general population; and (2) the Bariatric Quality of Life (BQL) Index: comparing the two groups of obese patients. We included 228 BS and 68 C obese patients. BS patients had higher BMI (44 ± 6 kg/m2 vs. 41 ± 6.5 kg/m2; p < 0.001), higher waist circumference (130 ± 13 cm vs. 123 ± 17 cm; p = 0.03), and higher total body fat mass (49.9 ± 6.7% vs. 45 ± 6.7%; p < 0.001). QoL as evaluated by EQ-5D-3L was similar, but the BQL index showed lower QoL in BS patients (40.9 ± 8.9 vs. 44.2 ± 11.2; p = 0.01). Compared to the Portuguese general population, BS patients had lower QoL (VAS: 55 ± 19 vs. 74.9; p < 0.001; index: 0.33 ± 0.2 vs. 0.76; p < 0.001). Despite higher adiposity in the BS group, QoL was similar between the groups by EQ-5D-3L. Nevertheless, there was a decrease in the QoL for the BS patients as determined using the BQL, a tool with higher sensitivity to bariatric patients.

The Role of the Metabolome and Non-Coding RNA on Pheochromocytomas and Paragangliomas: An Update.

Pheochromocytoma and paragangliomas (PPGL) are rare neuroendocrine tumors. In some patients they exhibit malignant behavior characterized by the presence of metastases, limiting treatment options and survival rates. Therapeutic options are limited to surgery, localized radiotherapy, and a few systemic therapies. However, in several recent studies, non-coding RNA molecules are gaining increasing attention as markers of malignancy for PPGL. The understanding of PPGL development molecular mechanisms has improved in the last years, with some of the epigenetic regulatory mechanisms such as DNA and histones methylation, being better understood than RNA-based mechanisms. Metabolome deregulation in PPGL, with increased synthesis of molecules that facilitated tumor growth, results from the activation of hypoxia signaling pathways, affecting tumorigenesis. In addition, the assessment of these metabolites can be useful for the management of these tumors. This review summarizes recent discoveries linking metabolome and non-coding RNA to PPGL and their relevance for diagnosis and therapeutics.

Protein Intake, Adherence to Vitamin-Mineral Supplementation, and Dumping Syndrome in Patients Undergoing One Anastomosis Gastric Bypass.

INTRODUCTION: One anastomosis gastric bypass (OAGB) is an effective bariatric procedure. However, nutritional deficiencies or dumping syndrome (DS) may occur. The aim of this study was to assess adherence to nutritional recommendations and development of DS in a 3-year OAGB patient follow-up. METHODS: For 150 OAGB patients, in our center, data were collected through the electronic platform and by an individual telephone interview. The inclusion criterion is OAGB as a primary bariatric procedure, no revisional surgery, or no pregnancy. The adequacy of daily protein intake cutoff was defined as 60 g. Adherence to micronutrient supplementation protocol was considered if a minimum of 5 takes/week were reported. To evaluate the occurrence of DS, the Sigstad score questionnaire was used. For statistical analysis, a significance level less than 5% (p < 0.05) was considered. RESULTS: A total of 150 patients (80% females), BMI 44.3 ± 21.3 kg/m2, were subjected to the OAGB procedure. Of those, 128 fulfilled the study inclusion criteria. After 3 years, the mean %EBMIL was 78.4 ± 14.4. During the 3-year follow-up, the average protein intake was 60 g/day, and 48% reported an adequate daily protein intake. Adherence to the micronutrient supplementation protocol was reported by 70%. According to the Sigstad score questionnaire, DS was present in 24% of patients. CONCLUSION: A significant part of OAGB patients does not comply with the nutrition prescription assessed, emphasizing the need to improve team/patient communication strategies. Long-term studies are needed to characterize and assess the health impact of protein, vitamin, and mineral malnutrition in patients undergoing OAGB.

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus.

BACKGROUND: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. METHODS: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

Juvenile dermatomyositis forty years on: Case report.

We present a case report of a 42 year old female, diagnosed at the age of 3 with Juvenile Dermatomyositis. The clinical course was severe and refractory to immunosuppressive therapy. Currently, she is mostly affected by severe muscle atrophy, large joint contractures, calcinosis, and a lipodystrophy associated metabolic syndrome with hypertriglyceridemia, insulin resistance, high total testosterone and hepatic steatosis. She developed Hodgkin´s lymphoma in the course of her disease. Personalized therapeutic choices are discussed as regards juvenile dermatomyositis complications.

Factors related with adiponectinemia in obese and normal-weight women and with its variation in weight loss programs.

OBJECTIVE: To assess different factors influencing adiponectinemia in obese and normal-weight women; to identify factors associated with the variation (Δ) in adiponectinemia in obese women following a 6-month weight loss program, according to surgical/non-surgical interventions. METHODS: We studied 100 normal-weight women and 112 obese premenopausal women; none of them was on any medical treatment. Women were characterized for anthropometrics, daily macronutrient intake, smoking status, contraceptives use, adiponectin as well as IL-6 and TNF-α serum concentrations. RESULTS: Adiponectinemia was lower in obese women (p < 0.001), revealing an inverse association with waist-to-hip ratio (p < 0.001; r = -0.335). Normal-weight women presented lower adiponectinemia among smokers (p = 0.041); body fat, waist-to-hip ratio, TNF-α levels, carbohydrate intake, and smoking all influence adiponectinemia (r(2) = 0.436). After weight loss interventions, a significant modification in macronutrient intake occurs followed by anthropometrics decrease (chiefly after bariatric procedures) and adiponectinemia increase (similar after surgical and non-surgical interventions). After bariatric intervention, Δ adiponectinemia was inversely correlated to Δ waist circumference and Δ carbohydrate intake (r(2) = 0.706). CONCLUSION: Anthropometrics, diet, smoking, and TNF-α levels all influence adiponectinemia in normal-weight women, although explaining less than 50% of it. In obese women, anthropometrics modestly explain adiponectinemia. Opposite to non-surgical interventions, after bariatric surgery adiponectinemia increase is largely explained by diet composition and anthropometric changes.

Q192R polymorphism of the paraoxonase-1 gene as a risk factor for obesity in Portuguese women.

INTRODUCTION: Obesity became a major public health problem as a result of its increasing prevalence worldwide. Paraoxonase-1 (PON1) is an esterase able to protect membranes and lipoproteins from oxidative modifications. At the PON1 gene, several polymorphisms in the promoter and coding regions have been identified. The aims of this study were i) to assess PON1 L55M and Q192R polymorphisms as a risk factor for obesity in women; ii) to compare PON1 activity according to the expression of each allele in L55M and Q192R polymorphisms; iii) to compare PON1 activity between obese and normal-weight women. MATERIALS AND METHODS: We studied 75 healthy (35.9 ± 8.2 years) and 81 obese women (34.3 ± 8.2 years). Inclusion criteria for obese subjects were body mass index ≥ 30  kg/m² and absence of inflammatory/neoplasic conditions or kidney/hepatic dysfunction. The two PON1 polymorphisms were assessed by real-time PCR with TaqMan probes. PON1 enzymatic activity was assessed by spectrophotometric methods, using paraoxon as a substrate. RESULTS: No significant differences were found for PON1 activity between normal and obese women. Nevertheless, PON1 activity was greater (P < 0.01) for the RR genotype (in Q192R polymorphism) and for the LL genotype (in L55M polymorphism). The frequency of allele R of Q192R polymorphism was significantly higher in obese women (P < 0.05) and was associated with an increased risk of obesity (odds ratio = 2.0 - 95% confidence interval (1.04; 3.87)). CONCLUSION: L55M and Q192R polymorphisms influence PON1 activity. The allele R of the Q192R polymorphism is associated with an increased risk for development of obesity among Portuguese Caucasian premenopausal women.