What parents think about giving nonnutritive sweeteners to their children: A pilot study

Objective. To evaluate parental attitudes toward providing foods and beverages with nonnutritive sweeteners (NNS) to their children and to explore parental ability to recognize NNS in packaged foods and beverages. Methods. 120 parents of children ≥ 1 and ≤18 years of age completed brief questionnaires upon entering or exiting a grocery store. Parental attitudes toward NNS were assessed using an interviewer-assisted survey. Parental selection of packaged food and beverages (with and without NNS) was evaluated during a shopping simulation activity. Parental ability to identify products with NNS was tested with a NNS recognition test. Results. Most parents (72%) disagreed with the statement “NNS are safe for my child to consume.” This was not reflected during the shopping simulation activity because about one-quarter of items selected by parents contained NNS. Parents correctly identified only 23% of NNS-containing items presented as foods or beverages which were sweetened with NNS. Conclusions. The negative parental attitudes toward providing NNS to their children raise the question whether parents are willing to replace added sugars with NNS in an effort to reduce their child’s calorie intake. Our findings also suggest that food labeling should be revised in order for consumers to more easily identify NNS in foods and beverages

Consumption of Low-calorie Sweeteners in the United States 2009-12

We have previously demonstrated that low-calorie sweetener (LCS) consumption increased in the United States (US) between 1999 and 2008 (from 9% to 15 % in kids and from 27% to 32% in adults), but little is known about current consumption. We therefore analyzed National Health and Nutrition Examination Survey (NHANES) data collected in 2011-12 and compared LCS consumption patterns across socio-demographic subgroups. Dietary sources of LCS were identified using NHANES food descriptions. Prevalence of consumption nationally and by age, race, gender, socio-economic status, educational attainment, were estimated using two 24-hour dietary recalls. F-tests were used to evaluate differences in consumption across socio-demographic subgroups. Forty-two percent of the adults and 26% percent of children reported consuming an LCS-containing food or beverage in 2009-12. Thirty-one percent of adults consumed beverages and 11% consumed foods sweetened with LCS. In addition, 14% reported addition of LCS from packets to their foods or beverages. Similar findings were observed among children, with 19% and 8% consuming LCS-containing beverages and foods, respectively. Less than 1% of children reported consuming LCS packets. LCS consumption was highest among non-Hispanic white (47%) compared to non-Hispanic black (29%), and Hispanic (32%) adults (

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

Buddy Study: Partners for better health in adolescents with type 2 diabetes

AIM: To investigate whether assigning young, healthy and motivated lay volunteer partners (“buddies”) to adolescents with type 2 diabetes improves hemoglobin A1c (HbA1c). METHODS: Adolescents with type 2 diabetes were randomized to partnering with a “buddy” or to conventional treatment. During the initial screening visit, which coincided with a routine outpatient diabetes clinic visit, patients with type 2 diabetes underwent a physical examination, detailed medical history, laboratory measurement of HbA1c, and completed two questionnaires (Pediatric Quality of Life Inventory and Children’s Depression Inventory) to assess their overall quality of life and the presence of depressive symptoms. Patients were then randomized to the intervention (the buddy system) or conventional treatment (standard care). All patients were scheduled to return for follow-up at 3- and 6-mo after their initial visit. HbA1c was determined at all visits (i.e., at screening and at the 3- and 6-mo follow-up visits) and quality of life and depressive symptoms were evaluated at the screening visit and were reassessed at the 6-mo visit. RESULTS: Ten adolescents, recruited from a pool of approximately 200 adolescents, enrolled over a two-year time period, leading to premature termination of the study. In contrast, we easily recruited motivated lay volunteers. We found no change in HbA1c from the initial to the 6-mo visit in either group, yet our small sample size limited systematic assessment of this outcome. Participants repeatedly missed clinic appointments, failed to conduct self-glucose-monitoring and rarely brought their glucometers to clinic visits. Total quality of life scores (72.6 ± 6.06) at screening were similar to previously reported scores in adolescents with type 2 diabetes (75.7 ± 15.0) and lower than scores reported in normal-weight (81.2 ± 0.9), overweight (83.5 ± 1.8), and obese youths without diabetes (78.5 ± 1.8) or in adolescents with type 1 diabetes (80.5 ± 13.1). Among adolescents who returned for their 6-mo visit, there were no differences in total quality of life scores (70.2 ± 9.18) between screening and follow-up. CONCLUSION: Our approach, effective in adults with type 2 diabetes, was unsuccessful among adolescents and emphasizes the need for innovative strategies for diabetes treatment in adolescent patients

Evidence That IRS-2 Phosphorylation Is Required for Insulin Action in Hepatocytes

Insulin receptor substrates (IRSs) are tyrosine-phosphorylated following stimulation with insulin, insulin-like growth factors (IGFs), and interleukins. A key question is whether different IRSs play different roles to mediate insulin's metabolic and growth-promoting effects. In a novel system of insulin receptor-deficient hepatocytes, insulin fails to (i) stimulate glucose phosphorylation, (ii) enhance glycogen synthesis, (iii) suppress glucose production, and (iv) promote mitogenesis. However, insulin's ability to induce IRS-1 and gab-1 phosphorylation and binding to phosphatidylinositol (PI) 3-kinase is unaffected, by virtue of the compensatory actions of IGF-1 receptors. In contrast, phosphorylation of IRS-2 and generation of IRS-2/PI 3-kinase complexes are markedly reduced. Thus, absence of insulin receptors selectively reduces IRS-2, but not IRS-1 phosphorylation, and the impairment of IRS-2 activation is associated with lack of insulin effects. To address whether phosphorylation of additional IRSs is also affected, we analyzed phosphotyrosine-containing proteins in PI 3-kinase immunoprecipitates from insulin-treated cells. However, these experiments indicate that IRS-1 and IRS-2 are the main PI 3-kinase-bound proteins in hepatocytes. These data identify IRS-2 as the main effector of both the metabolic and growth-promoting actions of insulin through PI 3-kinase in hepatocytes, and IRS-1 as the main substrate mediating the mitogenic actions of IGF-1 receptors

JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies

BACKGROUND. Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment

Safety and efficacy of low-dose sirolimus in the PIK3CA-Related Overgrowth Spectrum

Purpose PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Methods Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. Results Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of –7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently. Conclusion This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk–benefit evaluations for sirolimus treatment in PROS

Seroprevalence of 34 Human Papillomavirus Types in the German General Population

The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life