Case Report: Post-gastrectomy reactive hyperinsulinemic hypoglicaemia: glucose trends before and after canagliflozin treatment

The pathogenesis of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia is not yet fully clarified. Recent studies suggest an up-regulation of the intestinal glucose transporter SGLT-1 aimed to prevent carbohydrate malabsorption. The overexpression of SGLT-1 could therefore represents one of the mechanisms underlying the wide glycemic excursions found in patients after gastrectomy, but studies investigating the use of SGLT-1/SGLT-2 inhibitors in patients with post-gastrectomy reactive hyperinsulinemic hypoglycaemia are very scant in the literature. We report the case of a 37-year-old non diabetic man who frequently presented symptoms of hypoglycaemia in the postprandial period. In 2012, he underwent Roux en-Y gastric bypass (RYGB) and after two years, he started to experience typical symptoms of reactive hyperinsulinaemic hypoglycaemia. We suggested healthy modifications of dietary habits and periodic follow-up visits with a dietitian. After three months, the patient still presented symptoms of reactive hypoglycaemia; we provided him with Flash Glucose Monitoring (FGM) to assess trend of glucose levels in interstitial fluid during the day and we decided to introduce canagliflozin 300 mg/day before the main meal. Hypoglycaemic events previously referred by the patient and clearly recorded by FGM completely disappeared taking canagliflozin. We found a reduction of time spent in hypoglycaemia, an improvement of glycemic variability and an increase of time in target range. It was also noted a reduction of time spent in hyperglicemia with consequent improvement of average glucose values and of glucose main indicator. This is the first report with FGM supporting a role of canagliflozin in the management of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia. Our preliminary results are very limited but in line with those of the literature and showed for the first time a reduction of hypoglycaemic events and an improvement of glycemic variability through a flash glucose monitoring system. Further studies are mandatory to confirm this therapeutic opportunity

Effects of the composition of the pre-peak diet fed from 18 to 29 wk of age on egg production, egg quality, and the development of the gastrointestinal tract of brown-egg laying hens from 18 to 61 wk

SUMMARY: The effects of the nutritional characteristics of the diet fed from 18 to 29 wk of age on egg production and the development of the gastrointestinal tract (GIT) were studied in brown egg-laying hens from 18 to 61 wk of age. The experimental design was completely randomized with 4 pre-peak diets that contained 2.68 Mcal AMEn/kg, organized as a 2 × 2 factorial, with the standardized ileal digestible lysine content (DLys, 0.78 vs. 0.86%) and level of crude fiber (CF, 3.40 vs. 4.80%) of the diets as main effects. From 30 to 61 wk of age all hens were fed a common commercial diet with 2.78 Mcal AMEn/kg, 0.71% DLys, and 3.40% CF. Each treatment was replicated 16 times. The composition of the pre-peak diet did not affect hen production, egg quality, or any of the GIT traits studied at any age, except ceca length that was longer at 29 wk of age in hens fed the high CF diet (12.5 vs. 11.5 cm/kg BW; P < 0.05). In summary, an increase in DLys from 0.78 to 0.86% or of CF from 3.40 to 4.80% of the diet fed from 18 to 29 wk of age, did not affect hen production, egg quality, or GIT traits of the hens from 18 to 61 wk of age. The data indicate that pre-peak diets with 2.68 Mcal AMEn/kg, 0.78% DLys, and 3.40 to 4.80% CF are adequate to sustain egg production throughout the whole egg cycle, once the hens were fed a common commercial diet

Testing for BRAF (V600E) Mutation in Thyroid Nodules with Fine-Needle Aspiration (FNA) Read as Suspicious for Malignancy (Bethesda V, Thy4, TIR4): a Systematic Review and Meta-analysis.

In patients with thyroid fine-needle aspiration (FNA) report of suspicious for malignancy (SFM), both lobectomy and thyroidectomy might be considered. BRAF mutation analysis could guide towards accurate surgical therapy. The primary outcome was the reliability of BRAF (V600E) in detecting malignancy in nodules with FNA reading of SFM. The secondary outcome was to analyze its positive predictive value (PPV) and negative predictive value (NPV) considering the surgical histology as gold standard. A literature search of online databases was performed in June 2019. BRAF prevalence among thyroid nodules with FNA read as SFM according to the most popular classification systems (i.e., Bethesda V, Thy4, TIR4 category) was searched. The random-effects model was used. Three hundred sixty original articles were identified and 34 were finally included in the study. There were 1428 thyroid nodules with FNA read as SFM and 1287 (90.1%) lesions underwent surgery with a cancer rate 89.6%. The pooled prevalence of BRAF (V600E) mutation among all nodules with SFM cytology was 47% (95% CI = 40 to 54, I2 = 85.5%). Pooled PPV and NPV of BRAF testing were 99% (95% CI, 97-99) and 24% (95% CI, 16-32), respectively. BRAF (V600E) mutation was found in about one in two nodules with thyroid FNA read as SFM, its PPV to detect cancers was excellent, and its NPV was very poor. The routine BRAF testing in FNA read as SFM cannot be recommended. BRAF (V600E) test may be useful to extend surgical approach in selected cases with further suspicious clinical/ultrasound features

GLP-1 receptor agonists vs. SGLT-2 inhibitors: the gap seems to be leveling off

Cardiovascular disease (CVD) remains the leading cause of death in patients with type 2 diabetes (T2D). Older age, prior heart failure (HF) and CV events, peripheral artery disease, and kidney complications can identify a subgroup of patients with T2D at high risk of mortality who are likely to achieve the greatest benefit from newer glucose-lowering agents. Both glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors can reduce CV risk in patients with T2D, and both are recommended by the American Diabetes Association to reduce the risk of major cardiovascular events (MACE). The magnitude of the benefits of GLP-1RA and SGLT-2 inhibitors on MACE are similar, ranging from 12 to 14% reduction of risk, but only GLP-1RA may reduce the risk of stroke. The most striking difference between the two classes of drugs relates to the amelioration on hospitalization for HF, as the benefit of SGLT-2 inhibitors surpass by threefold that obtained with GLP-1RA. Despite this, GLP-1RA also exert a significant benefit on HF which suggest their use when SGLT-2 inhibitors are contraindicated or not tolerated. The difference between the two classes is less impressive for the kidney outcome. Overall, the results of CVOTs published so far seems to suggest that the gap between the cardiorenal benefits of SGLT-2 and GLP-1RA is narrowing

Up and down waves of glycemic control and lower-extremity amputation in diabetes

Lower extremity amputations (LEA) are associated with a high mortality and medical expenditure. Diabetes accounts for 45% to 70% of LEA and is one of the most potent risk factors for peripheral artery diseases (PAD). The existence of a link between the recent relaxation of glycemic targets and the resurgence of LEA is suggested from the analysis of adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2010 and 2015, when diabetes-related LEA increased by more than 25% associated with a decline in glycemic control. Indeed, in “the perfect wave” of NHANES, including the years 2007–2010, there was the highest number of diabetic people with hemoglobin A1c (HbA1c), non-high-density lipoprotein (HDL) cholesterol and blood pressure levels at their respective targets, associated with the lowest number of LEA. Until now, the ACCORD study, testing the role of aggressive vs conventional glucose control, and the LEADER trial, evaluating the effects of liraglutide versus placebo, have shown a reduced incidence of LEA in people with type 2 diabetes. The results of ongoing clinical trials involving glucagon-like peptide-1 receptor agonists (GLP-1RA, liraglutide or semaglutide) hopefully will tell us whether the wider use of these drugs may provide additional vascular benefits for diabetic people affected by PAD to decrease their risk of LEA

Impact of COVID-19 on the thyroid gland: an update

Coronavirus disease 2019 (COVID-19) is the pandemic of the new millennium. COVID-19 can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. Data on the relationship between COVID-19 and thyroid have been emerging, and rapidly increasing since March 2020. The thyroid gland and the virus infection with its associated inflammatory-immune responses are known to be engaged in complex interplay. SARS-CoV-2 uses ACE2 combined with the transmembrane protease serine 2 (TMPRSS2) as the key molecular complex to infect the host cells. Interestingly, ACE2 and TMPRSS2 expression levels are high in the thyroid gland and more than in the lungs. Our literature search provided greater evidence that the thyroid gland and the entire hypothalamic–pituitary–thyroid (HPT) axis could be relevant targets of damage by SARS-CoV-2. Specifically, COVID-19-related thyroid disorders include thyrotoxicosis, hypothyroidism, as well as nonthyroidal illness syndrome. Moreover, we noticed that treatment plans for thyroid cancer are considerably changing in the direction of more teleconsultations and less diagnostic and therapeutical procedures. The current review includes findings that could be changed soon by new results on the topic, considering the rapidity of worldwide research on COVID-19

Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes

Hospitalization for major diabetes complications, including myocardial infarction, stroke, lower-extremity amputation, and end-stage kidney disease, is on the rise and represents a great health burden for patients with type 2 diabetes (T2D), in particular for older people. Newer glucose-lowering medications have generated some optimism on the possibility to influence the natural history of cardiorenal complications of T2D. This review summarizes work in the area of sodium–glucose cotransporter 2 inhibitors (SGLT-2i) treatment and prevention of cardiorenal complications in patients with T2D (major adverse cardiovascular events, hospitalization for heart failure, kidney outcomes), with a particular emphasis on the effect of age, the role of primary versus secondary prevention and the possible extension of their cardiorenal benefits to the entire class of SGLT-2i

Neutropenia in patients with hyperthyroidism: Systematic review and meta-analysis

Background and Objective: Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new-onset hyperthyroidism. The aim of this systematic review and meta-analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting. Methods: A comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non-English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta-analysis was performed with DerSimonian and Laird method (random-effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I2 statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two-sided P-value of &lt;.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included. Results: The literature search yielded 1880 studies of which 13 studies were included for systematic review and meta-analysis. Results of the meta-analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves’ hyperthyroidism was 10% (CI 5%-19%, I2 88.6%) and summary mean ANC value in neutropenic was 1.4&nbsp;±&nbsp;0.3&nbsp;×&nbsp;109/L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not&nbsp;statistically&nbsp;significant or not calculable. Conclusions: Graves’ disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too

The dilemma of 18F-FDG PET/CT thyroid incidentaloma: what we should expect from FNA. A systematic review and meta-analysis.

&lt;sup&gt;18&lt;/sup&gt; F-FDG thyroid incidentaloma (TI) occurs in ~2% of PET/CT examinations with a cancer prevalence of up to 35-40%. Guidelines recommend fine-needle aspiration cytology (FNA) if a focal &lt;sup&gt;18&lt;/sup&gt; F-FDG TI corresponds to a sonographic nodule &gt;1 cm. The aim of this systematic review and meta-analysis was to provide evidence-based data on the diagnostic distribution of &lt;sup&gt;18&lt;/sup&gt; F-FDG TIs in the six Bethesda systems for reporting thyroid cytopathology (BETHESDA) subcategories. Original studies reporting &lt;sup&gt;18&lt;/sup&gt; F-FDG TIs and cytologically classified according to BETHESDA were included. Six separate meta-analyses were performed to obtain the pooled prevalence (95% confidence interval, 95% CI) of &lt;sup&gt;18&lt;/sup&gt; F-FDG TIs in the six BETHESDA subcategories. Fifteen studies were finally included. Nine studies were from Asian/Eastern and six from Western countries. FNA data according to BETHESDA was available in 2304 cases. The pooled prevalence of &lt;sup&gt;18&lt;/sup&gt; F-FDG TIs according to BETHESDA was BETHESDA I 10% (6-14), BETHESDA II 45% (37-53), BETHESDA III 8% (3-13), BETHESDA IV 8% (5-12), BETHESDA V 6% (4-9), BETHESDA VI 19% (13-25). A significantly different prevalence was found in the BETHESDA IV between Asian/Eastern (2%) and Western (19%) studies. Two-thirds of focal &lt;sup&gt;18&lt;/sup&gt; F-FDG TIs undergoing FNA have either malignant (BETHESDA VI) or benign (BETHESDA II) cytology while a minority will have indeterminate (BETHESDA III or IV) FNA results. Significant differences between Asian/Eastern and Western studies are also present in the prevalence of indeterminate FNA results