Prediction of resting energy expenditure for adolescents with severe obesity: A multi-centre analysis.

BACKGROUND AND OBJECTIVES: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations. METHODS: Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites. Data were randomly divided into development (N = 438) and validation (N = 118) cohorts. A predictive equation was developed using Elastic Net regression, using sex, race, ethnicity, weight, height, BMI percent of the 95th%ile (BMIp95), waist circumference, hip circumference, waist/hip ratio, age, Tanner stage, fat and fat-free mass. This equation was verified in the validation cohort and compared with 11 prior equations. RESULTS: Data from the total cohort (n = 556, age 15 ± 1.7 years, 77% female, BMIp95 3.3 ± 0.94) were utilized. The best fit equation was REE = -2048 + 18.17 × (Height in cm) - 2.57 × (Weight in kg) + 7.88 × (BMIp95) + 189 × (1 = male, 0 = female), R2 = 0.466, and mean bias of 23 kcal/day. CONCLUSION: This new equation provides an updated REE prediction that accounts for severe obesity and metabolic complications frequently observed in contemporary youth.

A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

Estimating insulin sensitivity and ß-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model.

Efficient and accurate methods to estimate insulin sensitivity (SI) and ß-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.NEW & NOTEWORTHY The pathogenesis of type 2 diabetes (T2D) is determined by a balance between insulin sensitivity (SI) and ß-cell function (BCF), which can be determined by gold standard direct measurements or estimated by fitting differential equation models to oral glucose tolerance tests (OGTTs). We propose and validate a new differential equation model that is simpler to use than current models and requires less data while maintaining good correlation and agreement with gold standards. Matlab and Python code is freely available.

Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI. CONCLUSION: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.

Reevaluating First-line Therapies in Youth-Onset Type 2 Diabetes.

The prevalence of youth-onset type 2 diabetes is growing worldwide and current first-line treatment with metformin and intensive behavior and lifestyle changes are suboptimal in over 50% of youth within 2 years of diagnosis. This perspective article is a call to action for reevaluation of existing strategies and critical appraisal of metformin as first-line therapy in youth-onset type 2 diabetes. Increased attention should be given to novel therapeutics approved in youth, including glucagon-like 1 receptor agonists, sodium glucose cotransporter-2, and sociocultural interventions that will promote diabetes self-management.

Perceived Accuracy Around Undetectable = Untransmitable Among Sexual and Gender Minorities Using Smartphones in India.

Sexual and gender minorities (SGM) using online venues in India are usually not reached by government HIV interventions, remaining an understudied yet important population. We investigated sociodemographic characteristics, sexual behaviours along with familiarity, knowledge, and correlated factors around perceived accuracy of the Undetectable = Untransmittable (U = U) slogan. Grindr users in India completed an online, cross-sectional survey in May-June 2022. We included individuals ≥ 18 years old who reported sex with men (excluding those who were born female and or identified as cis-gender female). Associations with perceived U = U accuracy were estimated using adjusted prevalence odds ratios (aPOR) with 95% confidence intervals (95% CI). The survey was completed by 3,126 eligible participants. The median age was 28 years and most participants lived in urban areas and had graduate or postgraduate education. HIV prevalence was 3.1%. Only 14% reported familiarity with the U = U slogan and after an explanation was provided, 25% perceived it as completely accurate. This was associated with knowing their HIV status (HIV Negative aPOR 1.37 [95%CI 1.1, 1.71], HIV Positive aPOR 3.39 [95%CI 2.11, 5.46]), having heard of PrEP (aPOR1.58 [95%CI 1.29,1.92]) or have used PrEP (aPOR1.56 [95%CI 1.15, 2.12]) along with use of party drugs (aPOR1.51 [95%CI 1.0 2.10]), being in touch with NGOs (aPOR 1.61 [95%CI 1.27, 2.02], p < .001) and having attended LGBTQIA + events (aPOR1.38 [95%CI 1.1, 1.73]). SGMs in India had low familiarity and low perceived accuracy around U = U. Education about U = U and innovating new strategies to reach this hidden population could reduce stigma around HIV in India.

RESUMEN: Las minorías sexuales y de género (MSG) que utilizan sitios en línea en la India, generalmente no son alcanzadas por el gobierno a través de sus intervenciones contra el VIH aunque siguen siendo una población importante, pero poco estudiada. Se investigaron las características sociodemográficas, el comportamiento sexual y, adicionalmente, la familiaridad, el conocimiento y la percepción de exactitud sobre el eslogan Indetectable = Intransmisible (I = I). Los usuarios indios de Grindr completaron una encuesta transversal en línea entre mayo y junio del 2022. Se incluyeron a personas ≥ 18 años que informaron haber tenido relaciones sexuales con hombres (se excluyeron aquellas asignadas como mujer al nacer y que se identificaron como mujeres cisgénero). Las asociaciones con la precisión percibida de I = I se estimaron con razones de probabilidad de prevalencia ajustadas (aPR) con intervalos de confianza a 95% (IC 95%). En total, 3,126 participantes elegibles completaron la encuesta. La mediana de edad fue de 28 años, la mayoría vivían en áreas urbanas y eran graduados o posgraduados. La prevalencia del VIH fue de 3.1%. Solo 14% informó que conocía el eslogan I = I, pero incrementó a 25% después de que se proporcionó una explicación y lo percibieron como completamente exacto. Esto se asoció con conocer su estado serológico (aPR VIH negativo = 1.37 [IC 95%: 1.1, 1.71]; aPR VIH positivo = 3.39 [IC 95%: 2.11, 5.46]), tener conocimiento de la profilaxis preexposición (PrEP) (aPR = 1.58 [IC 95%: 1.29,1.92]), haber usado la PrEP (aPR = 1.56 [IC 95% 1.15, 2.12]), usado drogas con fines recreativos (aPR = 1.51 [IC 95%: 1.0, 2.10]), estar en contacto con las ONG (aPOR 1.61 [95%CI 1.27, 2.02], p < .001) y haber asistido a eventos LGBTIQA+ (aPR = 1.38 [IC 95%: 1.0, 2.10]). Las MSG en India tuvieron poco conocimiento y poca percepción de exactitud sobre el eslogan I = I. La educación sobre I = I y otras estrategias innovadoras de prevención para el VIH en esta población podría ayudar a reducir el estigma en torno a esta enfermedad en la India.

Striatal dopamine tone is positively associated with body mass index in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers.

The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [18F]fallypride and [11C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m2). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [11C]raclopride (r= -0.51; p<0.0001) but not [18F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [18F]fallypride has greater binding affinity to dopamine type-2 receptors than [11C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.

Virtual Learning and Youth-Onset Type 2 Diabetes During the COVID-19 Pandemic.

INTRODUCTION: Cases and severity of presentation of youth-onset type 2 diabetes (Y-T2D) increased during the COVID-19 pandemic, yet the potential drivers of this rise remain unknown. During this time public health mandates paused in-person education and limited social interactions, resulting in radical lifestyle changes. We hypothesized that the incidence and severity of presentation of Y-T2D increased during virtual learning amidst the COVID-19 pandemic. MATERIALS AND METHODS: We conducted a single center retrospective chart review to identify all newly diagnosed cases of Y-T2D (n=387) at a pediatric tertiary care center in Washington, DC during three pre-determined learning periods as defined by learning modality in Washington, DC Public Schools: pre-pandemic in-person learning (3/11/2018-3/13/2020), pandemic virtual learning (3/14/2020-8/29/2021), and pandemic in-person learning (8/30/2021-3/10/2022) periods. RESULTS: Incident cases were stable during pre-pandemic in-person learning (3.9 cases/month, 95% CI: 2.8 - 5.4 cases/month), increased to a peak during virtual learning (18.7 cases/month, 95% CI: 15.9 - 22.1 cases/month), and declined with return to in-person learning (4.3 cases/month, 95% CI: 2.8 - 6.8 cases/month). Y-T2D incidence was 16.9 (95% CI: 9.8-29.1, p<0.001) and 5.1-fold higher (95% CI: 2.9-9.1, p<0.001) among non-Hispanic Black and Latinx youth, respectively, throughout the study period. Overall COVID-19 infection rates at diagnosis were low (2.5%) and were not associated with diabetes incidence (p=0.26). DISCUSSION/CONCLUSIONS: This study provides timely insights into an important and modifiable correlate of Y-T2D incidence, its disproportionate impact on underserved communities, and the need to consider the effects on long-term health outcomes and pre-existing healthcare inequities when designing public policy.

Estimating Insulin Sensitivity and Beta-Cell Function from the Oral Glucose Tolerance Test: Validation of a new Insulin Sensitivity and Secretion (ISS) Model.

Efficient and accurate methods to estimate insulin sensitivity (SI) and beta-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes. Many methods exist, ranging in input data and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic models (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new ISS (Insulin Secretion and Sensitivity) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. The model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. The model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including post-challenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts including individuals at high risk of prediabetes (adult women with a wide range of BMI and adolescents with obesity). The new model had strong correlation with gold-standard estimates from intravenous glucose tolerance tests and hyperinsulinemic-euglycemic clamp. The ISS model has broad clinical applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.

One-hour glucose is an earlier marker of dysglycemia than two-hour glucose.

AIMS: The timing of increase in 1-hour PG and its utility as an earlier predictor of both prediabetes (PreDM) and type 2 diabetes (T2D) compared to 2-hour PG (2 h-PG) are unknown. To evaluate the timing of crossing of the 1 h-PG ≥ 155 mg/dl (8.6 mmol/L) for PreDM and 209 mg/dl (11.6 mmol/L) for T2D and respective current 2 h-PG thresholds of 140 mg/dl (7.8 mmol/L) and 200 mg/dl (11.1 mmol/L). METHODS: Secondary analysis of 201 Southwest Native Americans who were followed longitudinally for 6-10 years and had at least 3 OGTTs. RESULTS: We identified a subset of 43 individuals who first developed PreDM by both 1 h-PG and 2 h-PG criteria during the study. For most (32/43,74%), 1 h-PG ≥ 155 mg/dl was observed before 2 h-PG reached 140 mg/dl (median [IQR]: 1.7 [-0.25, 4.59] y; mean ± SEM: 5.3 ± 1.9 y). We also identified a subset of 33 individuals who first developed T2D during the study. For most (25/33, 75%), 1 h-PG reached 209 mg/dl earlier (median 1.0 [-0.56, 2.02] y; mean ± SEM: 1.6 ± 0.8 y) than 2 h-PG reached 200 mg/dl, diagnostic of T2D. CONCLUSIONS: 1 h-PG ≥ 155 mg/dl is an earlier marker of elevated risk for PreDM and T2D than 2 h-PG ≥ 140 mg/dl.

Access to sexual and reproductive health services among South African young people living with and without HIV during the COVID-19 pandemic.

OBJECTIVE: To examine sexual and reproductive health (SRH) service access among South African young people during the COVID-19 pandemic. STUDY DESIGN: We utilized cross-sectional data collected from February to October 2021 in Cape Town among young people 13-24 years of age living with and without HIV. RESULTS: Two hundred and fifteen young people living with HIV (YPLWH) and 320 young people living without HIV were included. Young people reported an unmet need for SRH services during COVID-19, and 28% of YPLWH reported missing an HIV care appointment during the COVID-19 lockdowns. CONCLUSIONS: Expanding access to SRH services for young people during disruptive events is critical to reduce disparities in HIV and other SRH outcomes.

Assessing trends and reasons for unsuccessful implant discontinuation in Burkina Faso and Kenya between 2016 and 2020: a cross-sectional study.

OBJECTIVES: Contraceptive implant use has grown considerably in the last decade, particularly among women in Burkina Faso and Kenya, where implant use is among the highest globally. We aim to quantify the proportion of current implant users who have unsuccessfully attempted implant removal in Burkina Faso and Kenya and document reasons for and location of unsuccessful removal. METHODS: We use nationally representative data collected between 2016 and 2020 from a cross-section of women of reproductive age in Burkina Faso and Kenya to estimate the prevalence of implant use, proportion of current implant users who unsuccessfully attempted removal and proportion of all removal attempts that have been unsuccessful. We describe reasons for and barriers to removal, including the type of facility where successful and unsuccessful attempts occurred. FINDINGS: The total number of participants ranged from 3221 (2017) to 6590 (2020) in Burkina Faso and from 5864 (2017) to 9469 (2019) in Kenya. Over a 4 year period, the percentage of current implant users reporting an unsuccessful implant discontinuation declined from 9% (95% CI: 7% to 12%) to 2% (95% CI: 1% to 3%) in Kenya and from 7% (95% CI: 4% to 14%) to 3% (95% CI: 2% to 6%) in Burkina Faso. Common barriers to removal included being counselled against removal by the provider or told to return a different day. CONCLUSION: Unsuccessful implant discontinuation has decreased in recent years. Despite progress, substantial numbers of women desire having their contraceptive implant removed but are unable to do so. Greater attention to health systems barriers preventing implant removal is imperative to protect reproductive autonomy and ensure women can achieve their reproductive goals.

Metabolomic Profiling of an Ultraprocessed Dietary Pattern in a Domiciled Randomized Controlled Crossover Feeding Trial.

BACKGROUND: Objective markers of ultraprocessed foods (UPF) may improve the assessment of UPF intake and provide insight into how UPF influences health. OBJECTIVES: To identify metabolites that differed between dietary patterns (DPs) high in or void of UPF according to Nova classification. METHODS: In a randomized, crossover, controlled-feeding trial (clinicaltrials.govNCT03407053), 20 domiciled healthy participants (mean ± standard deviation: age 31 ± 7 y, body mass index [kg/m2] 22 ± 11.6) consumed ad libitum a UPF-DP (80% UPF) and an unprocessed DP (UN-DP; 0% UPF) for 2 wk each. Metabolites were measured using liquid chromatography with tandem mass spectrometry in ethylenediaminetetraacetic acid plasma, collected at week 2 and 24-h, and spot urine, collected at weeks 1 and 2, of each DP. Linear mixed models, adjusted for energy intake, were used to identify metabolites that differed between DPs. RESULTS: After multiple comparisons correction, 257 out of 993 plasma and 606 out of 1279 24-h urine metabolites differed between UPF-DP and UN-DP. Overall, 21 known and 9 unknown metabolites differed between DPs across all time points and biospecimen types. Six metabolites were higher (4-hydroxy-L-glutamic acid, N-acetylaminooctanoic acid, 2-methoxyhydroquinone sulfate, 4-ethylphenylsulfate, 4-vinylphenol sulfate, and acesulfame) and 14 were lower following the UPF-DP; pimelic acid, was lower in plasma but higher in urine following the UPF-DP. CONCLUSIONS: Consuming a DP high in, compared with 1 void of, UPF has a measurable impact on the short-term human metabolome. Observed differential metabolites could serve as candidate biomarkers of UPF intake or metabolic response in larger samples with varying UPF-DPs. This trial was registered at clinicaltrials.gov as NCT03407053 and NCT03878108.

Childhood Obesity and Cardiovascular Disease Risk.

PURPOSE OF REVIEW: The global epidemic of youth-onset obesity is tightly linked to the rising burden of cardiometabolic disease across the lifespan. While the link between childhood obesity and cardiovascular disease is established, this contemporary review summarizes recent and novel advances in this field that elucidate the mechanisms and impact of this public health issue. RECENT FINDINGS: The review highlights the emerging data supporting the relationship between childhood adverse events, social determinants of health, and systemic and institutional systems as etiological factors. We also provide updates on new screening and treatment approaches including updated nutrition and dietary guidelines and benchmarks for pediatric obesity screening, novel pharmacological agents for pediatric obesity and type 2 diabetes such as glucagon-like 1 peptide receptor agonists, and we discuss the long-term safety and efficacy data on surgical management of pediatric obesity. The global burden of pediatric obesity continues to rise and is associated with accelerated and early vascular aging especially in youth with obesity and type 2 diabetes. Socio-ecological determinants of risk mediate and moderate the relationship of childhood obesity with cardiometabolic disease. Recognizing the importance of neighborhood level influences as etiological factors in the development of cardiovascular disease is critical for designing effective policies and interventions. Novel surgical and pharmacological interventions are effective pediatric weight-loss interventions, but future research is needed to assess whether these agents, within a socio-ecological framework, will be associated with abatement of the pediatric obesity epidemic and related increased cardiovascular disease risk.

The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes.

Disclosure summary: Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose. Background: Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes gastrointestinal (GI) side effects, which may contribute to reduced treatment adherence and efficacy. Prebiotic intake may reduce metformin's side effects by shifting microbiota composition and activity. Objective: The aims of this study were to determine the feasibility and tolerability of a prebiotic supplement to improve metformin-induced GI symptoms and explore the changes in glycemia and shifts in the microbiota diversity. Methods: In a two-phase pilot clinical trial, we compared, stool frequency and stool form every 1-2 days, and composite lower GI symptoms (weekly) at initiation of daily metformin combined with either a daily prebiotic or a placebo shake in a 1-week randomized double-blind crossover design (Phase 1), followed by a 1-month open-labeled extension (Phase 2). Plasma glycemic markers and stool samples were collected before and after each phase. Results: Six Y-T2DM (17.2 ± 1.7y (mean ± SD), 67% male, BMI (42 ± 9 kg/m2), HbA1c (6.4 ± 0.6%)) completed the intervention. Stool frequency, stool composition, and GI symptom scores did not differ by group or study phase. There were no serious or severe adverse events reported, and no differences in metabolic or glycemic markers. After one week Phase 1metformin/placebo Proteobacteria, Enterobacteriaceae, and Enterobacteriales were identified as candidate biomarkers of metformin effects. Principle coordinate analyses of beta diversity suggested that the metformin/prebiotic intervention was associated with distinct shifts in the microbiome signatures at one week and one month. Conclusion: Administration of a prebiotic fiber supplement during short-term metformin therapy was well tolerated in Y-T2DM and associated with modest shifts in microbial composition. This study provides a proof-of-concept for feasibility exploring prebiotic-metformin-microbiome interactions as a basis for adjunctive metformin therapy. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04209075.

No significant salt or sweet taste preference or sensitivity differences following ad libitum consumption of ultra-processed and unprocessed diets: a randomized controlled pilot study.

Ultra-processed food consumption has increased worldwide, yet little is known about the potential links with taste preference and sensitivity. This exploratory study aimed to (i) compare sweet and salty taste detection thresholds and preferences following consumption of ultra-processed and unprocessed diets, (ii) investigate whether sweet and salty taste sensitivity and preference were associated with taste substrates (i.e. sodium and sugar) and ad libitum nutrient intake, and (iii) examine associations of taste detection thresholds and preferences with blood pressure (BP) and anthropometric measures following consumption of ultra-processed and unprocessed diets. In a randomized crossover study, participants (N = 20) received ultra-processed or unprocessed foods for 2 weeks, followed by the alternate diet. Baseline food intake data were collected prior to admission. Taste detection thresholds and preferences were measured at the end of each diet arm. Taste-substrate/nutrient intake, body mass index (BMI), and body weight (BW) were measured daily. No significant differences were observed in participant salt and sweet detection thresholds or preferences after 2 weeks on ultra-processed or unprocessed diets. There was no significant association between salt and sweet taste detection thresholds, preferences, and nutrient intakes on either diet arm. A positive correlation was observed between salt taste preference and systolic BP (r = 0.59; P = 0.01), BW (r = 0.47, P = 0.04), and BMI (r = 0.50; P = 0.03) following consumption of the ultra-processed diet. Thus, a 2-week consumption of an ultra-processed diet does not appear to acutely impact sweet or salty taste sensitivity or preference. Trial Registration: ClinicalTrials.gov Identifier NCT03407053.

Contraceptive stockouts in Western Kenya: a mixed-methods mystery client study.

BACKGROUND: The prevalence of modern contraception use is higher in Kenya than in most countries in Sub-Saharan Africa. The uptake has however slowed down in recent years, which, among other factors, has been attributed to challenges in the supply chain and increasing stockouts of family planning commodities. Research on the frequency of contraceptive stockouts and its consequences for women in Kenya is still limited and mainly based on facility audits. METHODS: This study employs a set of methods that includes mystery clients, focus group discussions, key informant interviews, and journey mapping workshops. Using this multi-method approach, we aim to quantify the frequency of method denial resulting from contraceptive stockout and describe the impact of stockouts on the lived experiences of women seeking contraception in Western Kenya. RESULTS: Contraceptives were found to be out of stock in 19% of visits made to health facilities by mystery clients, with all contraceptive methods stocked out in 9% of visits. Women experienced stockouts as a sizeable barrier to accessing their preferred method of contraception and a reason for taking up non-preferred methods, which has dire consequences for heath, autonomy, and the ability to prevent unintended pregnancy. Reasons for contraceptive stockouts are many and complex, and often linked to challenges in the supply chain - including inefficient planning, procurement, and distribution of family planning commodities. CONCLUSIONS: Contraceptive stockouts are frequent and negatively impact patients, providers, and communities. Based on the findings of this study, the authors identify areas where funding and sustained action have the potential to ameliorate the frequency and severity of contraceptive stockouts, including more regular deliveries, in-person data collection, and use of data for forecasting, and point to areas where further research is needed.

Pandemic policies and breastfeeding: A cross-sectional study during the onset of COVID-19 in the United States.

The United States is one of the few countries, and the only high-income country, that does not federally mandate protection of postpartum employment through paid postpartum maternity and family leave policies. At the onset of the COVID-19 pandemic in the U.S., stay-at-home orders were implemented nationally, creating a natural experiment in which to document the effects of de facto paid leave on infant feeding practices in the first postpartum year. The purpose of this cross-sectional, mixed-methods study was to describe infant and young child feeding intentions, practices, decision-making, and experiences during the first wave of the COVID-19 pandemic in the U.S. Quantitative and qualitative data were collected March 27-May 31, 2020 via online survey among a convenience sample of respondents, ages 18 years and older, who were currently feeding a child 2 years of age or younger, yielding 1,437 eligible responses. Nearly all (97%) respondents indicated an intention to feed their infant exclusively with human milk in the first 6 months. A majority of respondents who were breastfeeding (66%) reported no change in breastfeeding frequency after the implementation of COVID-19 stay-at-home orders. However, thirty-one percent indicated that they breastfed more frequently due to stay-at-home orders and delayed plans to wean their infant or young child. Key themes drawn from the qualitative data were: emerging knowledge and perceptions of the relationship between COVID-19 and breastfeeding, perceptions of immune factors in human milk, and the social construction of COVID-19 and infant and young child feeding perceptions and knowledge. There were immediate positive effects of stay-at-home policies on human milk feeding practices, even during a time of considerable uncertainty about the safety of breastfeeding and the transmissibility of SARS-CoV-2 via human milk, constrained access to health care services and COVID-19 testing, and no effective COVID-19 vaccines. Federally mandated paid postpartum and family leave are essential to achieving more equitable lactation outcomes.

Evaluating the feasibility of the Community Score Card and subsequent contraceptive behavior in Kisumu, Kenya.

BACKGROUND: Women seeking family planning services from public-sector facilities in low- and middle-income countries sometimes face provider-imposed barriers to care. Social accountability is an approach that could address provider-imposed barriers by empowering communities to hold their service providers to account for service quality. Yet little is known about the feasibility and potential impact of such efforts in the context of contraceptive care. We piloted a social accountability intervention-the Community Score Card (CSC)-in three public healthcare facilities in western Kenya and use a mix of quantitative and qualitative methodologies to describe the feasibility and impact on family planning service provision. METHODS: We implemented and evaluated the CSC in a convenience sample of three public-sector facility-community dyads in Kisumu County, Kenya. Within each dyad, communities met to identify and prioritize needs, develop corresponding indicators, and used a score card to rate the quality of family planning service provision and monitor improvement. To ensure young, unmarried people had a voice in identifying the unique challenges they face, youth working groups (YWG) led all CSC activities. The feasibility and impact of CSC activities were evaluated using mystery client visits, unannounced visits, focus group discussions with YWG members and providers, repeated assessment of score card indicators, and service delivery statistics. RESULTS: The involvement of community health volunteers and supportive community members - as well as the willingness of some providers to consider changes to their own behaviors-were key score card facilitators. Conversely, community bias against family planning was a barrier to wider participation in score card activities and the intractability of some provider behaviors led to only small shifts in quality improvement. Service statistics did not reveal an increase in the percent of women receiving family planning services. CONCLUSION: Successful and impactful implementation of the CSC in the Kenyan context requires intensive community and provider sensitization, and pandemic conditions may have muted the impact on contraceptive uptake in this small pilot effort. Further investigation is needed to understand whether the CSC - or other social accountability efforts - can result in improved contraceptive access.

Transitioning care in youth-onset type 1 and type 2 diabetes: a scoping review protocol using the socio-ecological model framework.

INTRODUCTION: The transition from paediatric to adult diabetes care in youth-onset diabetes (type 1 diabetes mellitus, Y-T1DM and type 2 diabetes mellitus, Y-T2DM) is associated with worsening glycaemic control, missed clinical visits, decreased medication adherence and the emergence of cardiometabolic complications. The socio-ecological challenges that influence transitioning to adult diabetes care may be distinct between Y-T1DM and Y-T2DM. The goal of this scoping review is to map the state of the literature on transitioning care in Y-T2DM compared with Y-T1DM and to identify the main sources and types of evidence available. The objectives are : (1) to identify the factors within the socio-ecological framework (individual, relationship, community, societal) associated with transitioning to adult care in Y-T2DM compared with Y- T1DM, and (2) to identify knowledge gaps related to transitioning to adult care. METHODS: The scoping review protocol and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews guidelines. A systematic search of scientific databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health, Scopus and APA PsycNet will be undertaken for articles between 1 January 1990 and 30 September 2022. Study designs will include peer-reviewed experimental and quasi-experimental published studies without language or country-specific restrictions. We will exclude articles on other diabetes subtypes and will exclude non-peer reviewed articles such as opinion papers, anecdotal reports or supplementary commentaries. ANALYSIS: References will be collated, sorted and extracted using Covidence. Factors associated with transition from paediatric to adult diabetes care in Y-T1DM and Y-T2DM will be identified using the socio-ecological framework and results will be presented in narrative format, tables, and summary graphs. ETHICS AND DISSEMINATION: Ethical approval will not be applicable for this review. TRIAL REGISTRATION NUMBER: https://osf.io/k2pwc.