Hormonal responses to non-nutritive sweeteners in water and diet soda.

BACKGROUND: Non-nutritive sweeteners (NNS), especially in form of diet soda, have been linked to metabolic derangements (e.g. obesity and diabetes) in epidemiologic studies. We aimed to test acute metabolic effects of NNS in isolation (water or seltzer) and in diet sodas. METHODS: We conducted a four-period, cross-over study at the National Institutes of Health Clinical Center (Bethesda, Maryland). Thirty healthy adults consumed 355 mL water with 0 mg, 68 mg, 170 mg, and 250 mg sucralose, and 31 individuals consumed 355 mL caffeine-free Diet Rite Cola™, Diet Mountain Dew™ (18 mg sucralose, 18 mg acesulfame-potassium, 57 mg aspartame), and seltzer water with NNS (68 mg sucralose and 41 mg acesulfame-potassium, equivalent to Diet Rite Cola™) in randomized order, prior to oral glucose tolerance tests. Blood samples were collected serially for 130 min. Measures included GLP-1, GIP, glucose, insulin, C-peptide, glucose absorption, gastric emptying, and subjective hunger and satiety ratings. RESULTS: Diet sodas augmented active GLP-1 (Diet Rite Cola™ vs. seltzer water, AUC, p = 0.039; Diet Mountain Dew™ vs. seltzer water, AUC, p = 0.07), but gastric emptying and satiety were unaffected. Insulin concentrations were nominally higher following all NNS conditions without altering glycemia. Sucralose alone (at any concentration) did not affect metabolic outcomes. CONCLUSIONS: Diet sodas but not NNS in water augmented GLP-1 responses to oral glucose. Whether the trends toward higher insulin concentrations after NNS are of clinical importance remains to be determined. Our findings emphasize the need to test metabolic effects of NNS after chronic consumption. TRIAL REGISTRATION: The data for this manuscript were gathered from clinical trial #NCT01200940

Patients with MEN1 are at an increased risk for venous thromboembolism VTE risk in MEN1

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing to the development of multiple functional and non-functional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (<1%) and ACTH-producing tumors (<5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have increased risk of VTE. Methods: We queried a prospective natural history study of germline mutation positive MEN1 patients (n=286) between 1991-2019 for all lifetime events of VTE. Search terms were: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban and apixaban. Incidence rates were calculated accounting for age and sex. Comparison was made to published incidence rates in healthy populations, different types of cancer, and Cushing's syndrome. Results: Thirty-six subjects (median age 45 years, range 16-75) experienced a VTE event, yielding a prevalence rate of 12.9%. The age-sex adjusted incidence rate of VTE is 9.11 per 1,000 patient-years, with a sex-adjusted lifetime incidence rate of 2.81 per 1,000 patient-years. MEN1-associated lifetime incidence rates are ~two-fold higher than the estimated annual incidence rate in the general population and are comparable to known risk in the setting of various types of cancer. Approximately 80% were diagnosed with pancreatic NETs, of which 24% were insulinomas. Fourteen patients (42%) experienced peri-operative VTE events. Conclusions: MEN1 patients have an increased risk of VTE. Further mechanistic investigation and validation from other MEN1 cohorts are needed to confirm the increased prevalence of VTE in MEN1

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Understanding the Metabolic and Health Effects of Low-calorie Sweeteners: Methodological Considerations and Implications for Future Research.

Consumption of foods, beverages, and packets containing low-calorie sweeteners (LCS) has increased markedly across gender, age, race/ethnicity, weight status, and socioeconomic subgroups. However, well-controlled intervention studies rigorously evaluating the health effects of LCS in humans are limited. One of the key questions is whether LCS are indeed a beneficial strategy for weight management and prevention of obesity. The current review discusses several methodological considerations in the design and interpretation of these studies. Specifically, we focus on the selection of study participants, inclusion of an appropriate control, importance of considering habitual LCS exposure, selection of specific LCS, dose and route of LCS administration, choice of study outcomes, and the context and generalizability of the study findings. These critical considerations will guide the design of future studies and thus assist in understanding the health effects of LCS

Plasma concentrations of sucralose in children and adults

<p>We aimed to measure concentrations of the commonly used artificial sweetener sucralose, following ingestion of doses reflecting a range of consumption and to compare concentrations in children and adults. Eleven adults consumed 355 mL water containing 0 mg (control), 68, 170, or 250 mg sucralose (equivalent to 1–4 diet sodas). A second group of adults (<i>n</i> = 11) consumed 355 mL Diet Rite Cola™ (68 mg sucralose and 41 mg acesulfame-potassium (ace-K)) or 68 mg sucralose and 41 mg ace-K in seltzer. Beverages were provided at separate visits in randomized order, prior to an oral glucose tolerance test. Eleven children consumed 0 or 68 mg sucralose in 240 mL water, in an identical study design. Blood was collected before beverage ingestion and serially for 120 min. Sucralose doses (corrected for weight) resulted in similar plasma concentrations in children and adults. Concentrations were comparable whether sucralose was administered in water, combined with ace-K, or in diet soda. Due to their lower body weight and blood volume, children have markedly higher plasma sucralose concentrations after the consumption of a typical diet soda, emphasizing the need to determine the clinical implications of sucralose use in children.</p