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ABSTRACT COVID-19 and obesity are two pandemic diseases that the world is currently facing. Both activate the immune system and mediate inflammation. A sequence of disease phases in patients with severe COVID-19 results in a cytokine storm, which amplifies the subclinical inflammation that already exists in patients with obesity. Pro-inflammatory cytokines and chemotactic factors increase insulin resistance in obesity. Therefore, a greater systemic inflammatory response is establishe, along with an increased risk of thrombotic phenomena and hyperglycemic conditions. These changes further impair pulmonary, cardiac, hepatic, and renal functions, in addition to hindering glycemic control in people with diabetes and pre-diabetes. This review explains the pathophysiological mechanisms of these two pandemic diseases, provides a deeper understanding of this harmful interaction and lists possible therapeutic strategies for this risk group.

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ABSTRACT Intermittent fasting (IF) is an increasingly popular method of weight loss, as an alternative to daily caloric restriction (DCR). Several forms of IF exist, such as alternate-day fasting or time-restricted feeding regimens. Some of its proponents claim several health benefits unrelated to caloric restriction or weight loss, which rely mainly on animal models. Although several studies published in the last few years confirm that IF can be a useful and safe therapeutical option for obesity and related disorders, no superiority to conventional caloric restriction diets have emerged. There are still several questions left answered. In this Review, we discuss some of the claims, unveiling myths, facts, and presumptions about several models of IF. The focus of this article is obesity, but there is a brief discussion of the potential benefits of IF on overall human health.

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ABSTRACT Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and β-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional β-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of β-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.

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ABSTRACT Subclinical hypothyroidism (Shypo) is an increasingly frequent condition in common medical practice. Its diagnosis continues to pose a challenge since a series of non-thyroidal and temporary conditions can elevate serum TSH levels. In addition, the consequences of Shypo are still up for debate. Although detrimental cardiovascular effects have been consistently demonstrated in the young, they are less evident in older adults (65-79 years), and even more so in the oldest old (≥80 years). In the absence of evidence of any benefits of treating Shypo in patients’ clinical manifestations and unfavorable outcomes, the most effective decision-making approach should include a thorough investigation of the patient's condition integrating all relevant clinical data, such as TSH levels, age, quality of life, comorbidities, cardiovascular risk, safety, and personal preferences. The decision-making process needs to take into account the risk of levothyroxine overtreatment and the resulting adverse consequences, such as reduction of bone mineral density, heart failure, and atrial fibrillation. Hence, current evidence suggests that individuals with TSH > 10 mU/L, who test positive for TPO Ab or are symptomatic may benefit from levothyroxine treatment. However, a more cautious and conservative approach is required in older (≥65 years of age), and oldest-old (≥80 years) patients, particularly those with frailty, in which the risk of treatment can outweigh potential benefits. The latter may benefit from a wait-and-see approach.

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ABSTRACT Objective: To verify the cytopathological Bethesda System classification of thyroid nodule fine-needle aspiration biopsy (FNAB) in MTC patients and to assess the role of preoperative serum calcitonin (CT) levels in the investigation of this neoplasm in medullary thyroid cancer (MTC) patients under observation at the Uopeccan (União Oeste Paranaense de Estudos e Combate ao Câncer). Materials and methods: This is a cross-sectional review of medical records of patients monitored at the thyroid cancer outpatient clinic of Uopeccan. Clinical and demographic data, laboratory tests, ultrasound images, and cytopathological findings of MTC patients were evaluated. Results and discussion: Among the 360 patients with thyroid cancer monitored in the outpatient clinic, 5.2% (n: 19/360) had MTC. The hereditary form was more prevalent (63.2%), and there was no sex preference. The most common ultrasound findings were hypoechogenicity, solid appearance and microcalcifications. The FNAB diagnoses showed a sensitivity of 47.1%, and the most common cytopathological report was Bethesda category III. Serum CT levels showed good sensitivity (84.6%) for the diagnosis of MTC, and sensitivity levels were directly associated with the size of the nodule and distant metastases. Conclusion: Bethesda category III was more prevalent in this group of MTC patients. Serum CT levels were more sensitive than cytopathology for diagnosis of this neoplasm and were able to identify all patients who could not be diagnosed by FNAB.

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ABSTRACT Objectives: To evaluate the effectiveness of adding dapagliflozin as an intensification strategy for the treatment of patients with uncontrolled type 2 diabetes mellitus (T2DM). Materials and methods: A historical cohort study was conducted in 123 adult patients over 18 years old who were diagnosed with uncontrolled T2DM, who received dapagliflozin add-on to their dual base treatment: metformin plus glibenclamide (n = 32), metformin plus saxagliptin (n = 29), metformin plus exenatide (n = 28), or metformin plus insulin (n = 34). The endpoints were evaluated using analysis of variance. Results: All the patients completed a 52-week follow-up. Overall, 52.85% of patients were female, the Hispanic population represented the largest proportion of patients in all groups (60.98%), and the mean ± SD patient age and body weight were 55.05 ± 7.58 years and 83.55 ± 9.65 kg, respectively. The mean ± SD duration of T2DM, glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG) were 5.93 ± 2.98 years, 8.1 ± 0.53%, and 166.03 ± 26.80 mg/dL, respectively. The grand mean changes of HbA1c, FPG, body weight and blood pressure showed a decreasing trend during the study period and it was statistically significant in all groups (p-value = <0.001). The proportion of patients achieving HbA1c target (<7%) was highest in the group that used a dapagliflozin add-on to metformin plus saxagliptin. Conclusion: The addition of dapagliflozin as an alternative for intensification of dual therapy consistently improved, not only FPG and HbA1c, but also body weight and blood pressure, with statistically significant results.

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ABSTRACT Objective: A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) and ADAMTS-5 normal expression levels are essential for ovulation and subsequent fertilization. The objective of the present study was to assess expression pattern of these genes in cumulus cells (CCs) taken from patients with polycystic ovary syndrome (PCOS) and to investigate any possible relationship with the oocyte quality. Subjects and methods: ADAMTS-4 and -5 expression levels within CCs containing oocytes at the metaphase II (MII) and germinal vesicle (GV) stages, taken from 35 patients with PCOS and 35 women with normal ovarian function, were investigated using RT-qPCR. Moreover, possible correlations between ADAMTS-4, ADAMTS-5, and progesterone receptors (PRs) expression as well as oocyte quality were evaluated. Results: ADAMTS-4 and -5 expression levels were dramatically diminished in the CCs of the PCOS patients when compared to the controls. ADAMTS-4 and -5 expression levels were correlated with each other and with the oocyte quality. Furthermore, lower expression levels of ADAMTS-4 and -5 in the PCOS patients were strongly correlated with the diminished PRs expression levels. Conclusions: Downregulation of ADAMTS-4 and -5 in the human CCs of the PCOS patients correlated with the decline in the PRs expression, and impaired oocyte quality may cause lower oocyte recovery, maturation, and fertilization rate.

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ABSTRACT Objective: To develop, adapt and validate an instrument named “CSII – Brazil” to assess users’ conceptual and procedural knowledge of continuous subcutaneous insulin infusion systems. Materials and methods: Methodological and exploratory study developed in three stages: a) instrument development; b) content validation and cultural adaptation (evaluation by a committee of experts and pre-test with CSII users); c) psychometric validation through instrument application in a sample of 60 patients by means of the web tool e-Surv. Internal consistency and reproducibility analyses were performed within IBM SPSS Statistics 20 programming environment. Results: The 16 multiple-choice question instrument successfully attained a content validity index of 0.97, showing satisfactory internal consistency, with 0.61 Cronbach's alpha [95% CI 0.462-0.746] and an intraclass correlation coefficient of 0.869 [95% CI: 0.789-0.919] between the test and retest scores. Conclusion: The CSII – Brazil instrument is considered adequate and validated to assess continuous subcutaneous infusion system users’ conceptual and procedural knowledge.

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ABSTRACT Objective: To describe the clinical characteristics, management, and fetal outcomes of patients diagnosed with gestational diabetes mellitus (GDM) or overt diabetes (OD) during pregnancy who followed up at a public healthcare referral center in Brazil. Materials and methods: A retrospective cohort study based on the medical records of women diagnosed with dysglycemia during pregnancy between January 2015 and July 2017 was conducted. Results: Out of 224 pregnant women evaluated, 70% were overweight/obese. GDM was observed in 78.6% of pregnant women, while 21.4% presented with OD. Approximately 59% of patients could be diagnosed with GDM or OD by fasting plasma glucose (FPG) alterations alone. Exclusive diet therapy was used in 50.9% of patients. The need for insulin therapy was higher in OD patients (60.4%) than in GDM patients (38.1%) (p = 0.006). Women who needed insulin (n = 96) had a mean initial dose of 0.33 IU/kg (±0.27) and a final value of 0.39 IU/kg (±0.34). The cesarean rate was 74.3%. The fetal outcomes evaluated were macrosomia (2.15%), large for gestational age (LGA) fetus (15.83%), intensive care unit (ICU) need (4.32%), Apgar score ≤7 (6.47%), hypoglycemia (14.39%) and jaundice (16.55%). Conclusions: Patients with GDM and OD presented with several similar clinical features. Approximately half of the patients presented with adequate glycemic control only with diet management. Patients with OD presented a higher need for insulin therapy. Although overweight and obesity were frequent within both groups, they could possibly explain many of our findings.

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ABSTRACT Objective: Internet usage for obtaining health-related information is widely popular among patients. However, there are still concerns about the reliability and comprehensibility of online information. The purpose of this study is to investigate the reliability and readability of osteoporosis-related websites. Materials and methods: On April 2, 2020, we searched the term “osteoporosis” on Google (https://www.google.com). We evaluated the first 200 uniform resource locators (URLs) in the query results regarding typology, the Journal of the American Medical Association (JAMA) scores, Health on the Net Foundation Code of conduct (HONcode) certification, Flesch–Kincaid Grade (FKG), and Simple Measure of Gobbledygook (SMOG) scores. The JAMA scoring system and HONcode stamp were used for assessing the reliability, whereas FKG and SMOG scores were used to assess the readability of online information. Results: Of the 151 analyzed websites, 57 (37.7%) were classified as highly reliable, and 19 (12.6%) were assigned with HONcode certification. The average FKG scores (8.81 ± 2.21) and SMOG scores (7.63 ± 1.81) were below the recommended grade, which is considered as easily readable. High reliable information was found to have higher readability scores, thereby representing the difficulty of readability. We observed a weak correlation between the increased reliability of information and decreased readability. Conclusion: Osteoporosis-related content on the internet generally has low reliability. High-reliable information is available online in scientific published materials, health portals, and news. Although the readability of the overall material is acceptable, the high-reliable websites still require high literacy and comprehension skills.

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ABSTRACT Objective: We assessed plasma adiponectin and its correlation with carotid intima-media-thickness (CIMT), as a marker of atherosclerosis, and urine albumin/creatinine ratio (ACR) in patients with non-alcoholic fatty liver disease (NAFLD). Subjects and methods: The study included 100 Egyptian subjects (50 patients with NAFLD with no history of diabetes or hypertension and 50 age and sex-matched normal healthy control subjects). Urine albumin/creatinine ratio (ACR) was assessed in all participants and fasting plasma adiponectin was measured using ELISA technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using high-resolution Doppler ultrasonography. Results: Mild albuminuria was detected in patients with NAFLD (mean urine ACR = 42 ± 30 mg/g). Plasma adiponectin was significantly lower and urine ACR and CIMT significantly higher in patients with NAFLD as compared with the control group (P < 0.001 for all). A significant negative correlation was found between plasma adiponectin and both urine ACR and CIMT in patients with NAFLD (P < 0.001 and < 0.05 respectively). A significant positive correlation was also found between CIMT and urine ACR in those patients (P < 0.05). Plasma adiponectin and urine ACR were independent determinants of CIMT in patients with NAFLD (P < 0.01 and < 0.05 respectively). Conclusion: Patients with NAFLD, without diabetes, have an increased risk of atherosclerosis and cardiovascular disease. Hypoadiponectinemia and low-grade albuminuria are important markers of that risk.

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ABSTRACT Objective: This study investigated the acute effects of high-intensity interval (HIIE) and moderate-intensity continuous (MICE) exercise on ghrelin levels in obese men. Subjects and methods: A total of 10 obese men (age 27.6 ± 1.8 years, body mass index 35.4 ± 4.5 kg/m², body fat 39.9 ± 2.1%) performed two exercise sessions in a randomized order: HIIE (10 × 1 min intervals at 90% of the maximal heart rate [HRmax] interspersed by 1 min of active recovery) and MICE (20 min at 70% of the HRmax). Ghrelin levels were assessed pre-, post- and 1h post-exercise, and energy intake was assessed 1h post-exercise through an ad libitum meal. Results: HIIE and MICE showed a trend to decrease ghrelin levels immediately post-exercise (-14.1 ± 21.6% and −9.6 ± 23.8%, respectively, p = 0.07) and decreased 1h post-exercise (-12.7 ± 31.8% and −13.8 ± 21.7%, respectively, p < 0.05). No changes were observed for post-exercise energy intake (p > 0.05). There was a positive correlation between the change in ghrelin levels and post-exercise energy intake only for HIIE (r = 0.63, p = 0.05). Conclusion: In summary, a single session of HIIE and MICE elicits a reduction on ghrelin levels without changing post-exercise energy intake in obese men.

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ABSTRACT Objectives: To evaluate the performance of telemonitoring in detecting clinical and psychological needs and adherence to the protective measures imposed by the COVID-19 pandemic in addition to providing remote assistance for patients with type 1 diabetes (T1D) in a public university center in Brazil. Subjects and methods: Telemonitoring protocol included phone calls and e-mails. Patients were asked to rate COVID-19-like symptoms, psychological symptoms, epidemiological issues, and adherence to diabetes management (insulin, exercise, and diet) using a 0-to-10 scale. An e-mail address and phone number were offered for further contact if needed. Clinical, demographic, and laboratorial data from the consultations before the pandemic were collected from medical records. Results: Among 321 patients with a previously scheduled consultation over the first 15 weeks of social distancing, 237 (73.8%) could be successfully contacted. Of these, 207 (87.3%) were exclusively evaluated by telemonitoring (190 only by phone or text message and 17 who were also reached by email), and 30 (12.7%) patients attended the consultation for medical reasons detected during the telephone screening. Overall, 44 (18.5%) patients reported COVID-19-like symptoms. One (2.3%) patient was hospitalized and subsequently died. Psychological symptoms were reported by 137 (60.4%) patients and 30 (12.7%) required remote psychological assistance. Appropriate social distancing was performed by 203 (87.9%) patients, and 221 (97.8%) referred use of masks. Conclusions: Telemonitoring T1D patients during the pandemic helped reduce the need for in-person consultations, detect clinical and psychological needs, and offer support to patients in addition to monitoring suspected COVID-19 cases and the adherence to protective measures.

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SUMMARY Pseudohypoparathyroidism comprehends an assorted group of genetically rare disorders that share end-organ resistance to parathyroid hormone. Genetic and epigenetic modifications on guanine nucleotide-binding protein alpha-stimulating gene locus are the most common underlying mechanisms associated with pseudohypoparathyroidism. Biochemical and molecular analysis stratify pseudohypoparathyroidism into types 1A, 1B, 1C, and 2. We describe an unusual case of sporadic pseudohypoparathyroidism type 1B. A 34-year-old Caucasian woman was admitted to the emergency department, with persistent asthenia, limb paresthesias, and tactile hyposensitivity. Her physical examination, previous personal and family histories were unsuspicious, except for mild, intermittent and self-limited complaints of paresthesia during her two pregnancies, but no detailed workup was done. No typical features of Albright hereditary osteodystrophy were observed. The initial laboratory investigation showed elevated parathyroid hormone level (311.2 pg/mL), hypocalcemia (albumin-corrected serum calcium 4.3 mg/dL), hypocalciuria, hyperphosphatemia, hypophosphaturia, and vitamin D deficiency. Combined calcium, vitamin D, and magnesium supplementation was commenced, with symptomatic and analytical improvement. Albeit resolution of vitamin D deficiency, the patient relapsed with mild and intermittent lower limb paresthesias. Pseudohypoparathyroidism was confirmed by molecular identification of the 3-kb STX16 deletion. The treatment was readjusted, and one year later, symptomatic remission was attained. Clinical and biochemical features, and their respective course, along with lack of distinctive features of Albright hereditary osteodystrophy pointed to pseudohypoparathyroidism type 1B. A careful follow-up is needed to avoid complications and recurrence. Once correction of hypocalcemia and hyperphosphatemia is achieved, with no reported complications and recurrence, a good prognosis is anticipated, comparable to the general population.

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ABSTRACT This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs.77%, respectively, p = 0.03).