Early nutritional risk detection and intervention in COVID-19 hospitalized patients through the implementation of electronic automatized alarms.

INTRODUCTION: Hospitalized COVID-19 patients may present acute malnutrition which could influence morbidity and mortality. In the first wave of the pandemic severe weight loss was observed in many hospitalized patients. This pilot study evaluates the usefulness of an electronic automatized alarm for the early quantification of a low food intake as a predictor of the risk of malnutrition using COVID-19 disease as a model of severe illness. METHODS: Observational prospective nutritional screening with a daily automatized warning message to the Endocrinology and Nutrition Service provided by the Information Systems. All adult patients admitted for COVID-19 from November 2020 to February 2021 were included. When diet intake was <50% during consecutive 48h, an automated message was generated identifying the patient as "at nutritional risk (NR)" and additional specialist nutritional evaluation and therapy was performed within the next 24h. RESULTS: 205 patients out of 1176 (17.4%) were detected by automatized alarm and were considered as presenting high NR; 100% were concordant by the validated nutritional screening SNAQ. Nutritional support after detection was: 77.6% dietary adaptation+oral supplements; 9.3% enteral nutrition (EN); 1.5% parenteral nutrition (PN); 1% EN+PN and 10.7% no intervention is performed due to an end-of-life situation. Median weight loss during admission was 2.5kg (p25 0.25-p75: 6kg). Global mortality was 6.7% while in those detected by automatized alarm was 31.5%. CONCLUSIONS: The implementation of an electronic NR screening tool was feasible and allowed the early nutritional assessment and intervention in COVID-19 hospitalized patients and can be useful in patients hospitalized for other pathologies.

The double burden: type 1 diabetes and heart failure-a comprehensive review.

Heart failure (HF) is increasing at an alarming rate, primary due to the rising in aging, obesity and diabetes. Notably, individuals with type 1 diabetes (T1D) face a significantly elevated risk of HF, leading to more hospitalizations and increased case fatality rates. Several risk factors contribute to HF in T1D, including poor glycemic control, female gender, smoking, hypertension, elevated BMI, and albuminuria. However, early and intensive glycemic control can mitigate the long-term risk of HF in individuals with T1D. The pathophysiology of diabetes-associated HF is complex and multifactorial, and the underlying mechanisms in T1D remain incompletely elucidated. In terms of treatment, much of the evidence comes from type 2 diabetes (T2D) populations, so applying it to T1D requires caution. Sodium-glucose cotransporter 2 inhibitors have shown benefits in HF outcomes, even in non-diabetic populations. However, most of the information about HF and the evidence from cardiovascular safety trials related to glucose lowering medications refer to T2D. Glycemic control is key, but the link between hypoglycemia and HF hospitalization risk requires further study. Glycemic variability, common in T1D, is an independent HF risk factor. Technological advances offer the potential to improve glycemic control, including glycemic variability, and may play a role in preventing HF. In summary, HF in T1D is a complex challenge with unique dimensions. This review focuses on HF in individuals with T1D, exploring its epidemiology, risk factors, pathophysiology, diagnosis and treatment, which is crucial for developing tailored prevention and management strategies for this population.

Longitudinal trajectories of maternal TSH in healthy pregnant women in Catalonia.

Objective: Longitudinal evaluation of thyroid function throughout pregnancy in the same subject could offer precise information about its dynamics as a physiological mechanism of adaption to the requirements. In this study, we evaluated longitudinal trajectories of maternal thyroid function during pregnancy by a latent class growth analysis and explored their association with maternal-fetal outcomes. Methods: A prospective observational study was carried out, including 414 healthy pregnant women, from the first trimester to delivery. Thyroid function and autoimmunity were measured in the three trimesters. Clinical data during pregnancy were obtained. Longitudinal mixed model techniques were performed to explore trajectories of gestational thyroid function. Results: Three different longitudinal trajectories were obtained from maternal thyrotropin (TSH) levels: low-increasing TSH (class 1) in 86% of cases, high-increasing TSH (class 2) in 9.7%, and decreasing TSH (class 3) in 4.3%. No statistical differences in free thyroxine levels were found among the three classes. Differences in maternal age (P = 0.027) and initial maternal weight (P = 0.043) were observed among the groups. In logistic regression analysis, maternal age correlated with longitudinal trajectories. The three longitudinal classes remain when women with thyroid autoimmunity (TAI) are excluded. Multinomial logistic regression showed maternal age correlated with longitudinal trajectories independently of TAI status. Conclusions: Three differentiated TSH trajectories were found in healthy pregnant women living in Catalonia, as previously described. No association with obstetric outcomes was observed in these different chronological thyroid pathways, but maternal age might condition the longitudinal mechanism of thyroid function regulation throughout pregnancy.

Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus.

Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9-3440.5) pg/mL vs. 1396.05 (820.3-2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6-79.8) ng/mL vs. 34.1 (24.09-55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09-1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12-4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09-1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21-7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11-3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D.

Dysglycemia in young women attenuates the protective effect against fatty liver disease.

Introduction: Sexual dimorphism has been reported in non-alcoholic fatty liver disease (NAFLD), similar to the sex differences evident with cardiovascular disease. Type 2 diabetes mellitus (T2D) significantly increases the risk and severity of NAFLD, but there is scarce information on whether T2D or altered glucose metabolism can modify the prevalence of NAFLD in men and women of reproductive age. Purpose: To investigate the relationship between age, sex and NAFLD in subjects with and without dysglycemia. Materials and methods: We analyzed 2,790 patients. NAFLD was characterized using established diagnostic criteria: one or more positive results on the fatty liver index and hepatic ultrasound. Liver fibrosis (liver stiffness measurement [LSM] ≥8.0 kPa) was assessed by Fibroscan®. For analysis purposes, we included both T2D and prediabetes under the predefined condition of dysglycemia. Results: The global prevalence of NAFLD was higher in men than in women (50% and 34%; P<0.001), and the prevalence increased with age in both sexes. Older women (≥ 50 years) had a higher prevalence than younger women (<50 years), both in the overall cohort and in non-dysglycemic subjects. In dysglycemic subjects, the prevalence of NAFLD was slightly higher in men (68% vs 61%, p=0.021); in younger subjects, there were no differences in the prevalence of NAFLD between men and women (68% vs 64%, respectively; p=0.635). We found an interaction between dysglycemia and female sex (odds ratio [OR] 1.6 95% confidence interval [CI] 1.0-2.4, p=0.030), and between and age ≥50 years (OR 0.6, 95% CI 0.3-1.0, p=0.046). The global prevalence of LSM ≥8.0 kPa was higher in men compared with women (8% vs 4%; p< 0.001). This prevalence increased with age, mainly in men. We did not find any association between liver fibrosis and age and gender. Conclusions: While the global prevalence of NAFLD is higher in men than in women across all ages, younger women with dysglycemia have a similar risk of developing NAFLD as men of a similar age. Therefore, the presence of dysglycemia may erase the protective effect of female sex against fatty liver disease.

Comparison of Glycemic Variability and Hypoglycemic Events in Hospitalized Older Adults Treated with Basal Insulin plus Vildagliptin and Basal-Bolus Insulin Regimen: A Prospective Randomized Study.

Background: The basal−bolus insulin regimen is recommended in hospitalized patients with diabetes mellitus (DM), but has an increased risk of hypoglycemia. We aimed to compare dipeptidyl peptidase 4 inhibitors (DPP4-i) and basal−bolus insulin glycemic outcomes in hospitalized type 2 DM patients. Methods and patients: Our prospective randomized study included 102 elderly T2DM patients (82 ± 9 years, HbA1c 6.6% ± 1.9). Glycemic control: A variability coefficient assessed by continuous glucose monitoring (Free Style® sensor), mean insulin dose and hypoglycemia rates obtained with the two treatments were analyzed. Results: No differences were found between groups in glycemic control (mean daily glycemia during the first 10 days: 152.6 ± 38.5 vs. 154.2 ± 26.3 mg/dL; p = 0.8). The total doses Kg/day were 0.40 vs. 0.20, respectively (p < 0.001). A lower number of hypoglycemic events (9% vs. 15%; p < 0.04) and lower glycemic coefficient of variation (22% vs. 28%; p < 0.0002) were observed in the basal−DPP4-i compared to the basal−bolus regimen group. Conclusions: Treatment of inpatient hyperglycemia with basal insulin plus DPP4-i is an effective and safe regimen in old subjects with T2DM, with a similar mean daily glucose concentration, but lower glycemic variability and fewer hypoglycemic episodes compared to the basal bolus insulin regimen.

Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects: A population-based study.

Objective: To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia. Material and Methods: A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively. Results: Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa. Conclusions: In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD.

Reference Intervals of Thyroid Function Tests Assessed by Immunoassay and Mass Spectrometry in Healthy Pregnant Women Living in Catalonia.

BACKGROUND: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain). METHODS: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect® immunoassay (Abbott) and FT4 by two immunoassays, Architect® (Abbott) and Cobas® (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T. RESULTS: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03-3.78; 2T: 0.51-3.53; 3T: 0.50-4.32; p < 0.0001) and FT4 (pmol/L) progressively decreased (Architect® 1T: 10.42-15.96; 2T: 8.37-12.74; 3T: 8.24-12.49; p < 0.0001; and Cobas®: 1T: 11.46-19.05; 2T: 9.65-14.67; 3T: 8.88-14.54; p < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75-18.27. Despite the 1T FT4 results measured by LC/MS/MS and with the two immunoassays being significantly correlated, the results obtained by the three methods were found to be non-interchangeable. CONCLUSIONS: We established trimester-specific RIs for TSH and for FT4 with immunoassays in our population. We also validated the 1T FT4 using LC/MS/MS to confirm the results of FT4 lower than the 2.5th percentile or higher than the 97.5th percentile.

Hypoglycemia after bariatric surgery: importance of exhaustive hormonal study.

SUMMARY: Hypoglycemia is an uncommon clinical problem in non-diabetic patients or patients not being treated for diabetes mellitus. It is a rare, but well-established complication of bariatric surgery and, in some cases, it can be the only symptom of another medical problem. A 50-year-old woman with a history of partially recovered hypopituitarism after transsphenoidal surgery for a non-functioning pituitary macroadenoma complained about symptomatic hypoglycemia after sleeve gastrectomy surgery. Our initial studies failed to determine the cause for these episodes and treatment with acarbose (suspecting a dumping syndrome) was not helpful. Finally, laboratory findings revealed growth hormone (GH) deficiency. The patient received treatment with GH, with the resolution of symptoms after 3 months of treatment. Our case suggests that all causes of hypoglycemia should be considered and studied after bariatric surgery. An improvement in insulin-resistance following bariatric surgery can trigger clinical manifestations of GH deficiency. LEARNING POINTS: Postprandial hypoglycemia after bariatric surgery is usually due to dumping syndrome. Even after bariatric surgery, all causes of hypoglycemia should be considered and studied. After significant weight loss, insulin sensitivity is usually restored and can trigger clinical manifestations of GH deficiency. Hypoglycemia is a rare symptom of GH deficiency.

Obesity and GLP-1.

Obesity is an important public health issue that has been on the rise over the last decades. It calls for effective prevention and treatment. Bariatric surgery is the most effective medical therapy for weight loss in morbid obesity, but we are in need for less aggressive treatments. Glucagon-like-peptide-1 receptor agonists are a group of incretin-based drugs that have proven to be productive for obesity treatment. Through activation of the GLP-1 receptor they not only have an important role stimulating insulin secretion after meals, but with their extrapancreatic actions, both peripheral and central, they also help reduce body weight by promoting satiety and delaying gastric emptying. Liraglutide in a dose of 3 mg is currently the only drug of this group that is approved by the FDA to treat obesity, with weight losses up to 8.5 kg in relatively short periods of time. Here we review the data so far collected of GLP-1 use for obesity with and without diabetes, including the recent data of oral semaglutide.

Microbiota, Fiber, and NAFLD: Is There Any Connection?

Gut microbiota can contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD). In fact, some specific changes of gut microbiota are observed in patients in what is called dysbiota. There has been a lot of investigation by using a variety of interventions, including diet, showing the possibility to modify components of gastrointestinal dysbiota towards healthy and multivariate microbiota to restore physiologic status. One of the main focuses has been dietary fiber (DF), in which most of its variants are prebiotics. The highest effective treatment for NAFLD is, so far, weight loss achieved by caloric restriction. DF supplementation with oligofructose facilitates weight loss, enhances the production of beneficial metabolites, decreases some pathogenic bacteria population by increasing Bifidobacteria, and has effects on intestinal barrier permeability. DF use has been associated with improvement in diverse metabolic diseases, including NAFLD, by modifying gut microbiota. Additionally, it has been shown that a higher insoluble fiber consumption (≥7.5 g/day) revealed improvements in 3 different scores of liver fibrosis. Further research is needed, but given the evidence available, it is reasonable to prescribe its consumption in early stages of NAFLD in order to prevent disease progression.

Endocrine adverse events related to immune-oncology agents: retrospective experience of a single institution.

BACKGROUND: Immune-oncology agents (IOA) represent a turning point in the treatment of several solid tumors (ST). Although their toxicity compares favorably with other treatments, IOA associate immune-related adverse events (IR-AE), among which endocrine-related AE stand out. We retrospectively evaluated the occurrence of endocrine (E) IR-AE in a cohort of patients with several ST treated with IOA. In addition, we assessed the correlation between likelihood of survival and the occurrence of IR-AE. METHODS: We collected data on clinical and molecular characteristics, efficacy and AE of 260 patients with ST treated with IOA from 2013 to 2017. We excluded patients with prior conditions or treatments potentially affecting thyroid test results. RESULTS: Lung cancer was the most prevalent diagnosis (70.2%). EIR-AE appeared in 18.1% of patients (total of 38 EIR-AE) and consisted of hypothyroidism, hyperthyroidism, pituitary disorders and type 1 diabetes mellitus in 60.5%, 21.1%, 15.8% and 2.6% of patients, respectively. EIR-AE were associated mainly to nivolumab, nivolumab plus ipilimumab (41.2% and 26.5%) and appeared after a median of 4.2 cycles of treatment. Specific therapy was required in 65.8% patients. There were significant differences in both progression-free survival (PFS) and overall survival (OS) for patients who experienced EIR-AE compared to those who did not [PFS: 56.7 (NC-NC) vs. 27.7 (14.3-41.3) months, P=0.008; OS: NC (NC-NC) vs. 31.4 (20.7-42.1) months, P=0.001]. CONCLUSIONS: The incidence of EIR-AE in our study is similar to other series. Patients who develop EIR-AE might have a better prognosis compared to those who do not experience them.