24-h energy expenditure in people with type 1 diabetes: impact on equations for clinical estimation of energy expenditure.

BACKGROUND/OBJECTIVES: Type 1 diabetes (T1D) is associated with an increase in resting metabolic rate (RMR), but the impact of T1D on other components of 24-h energy expenditure (24-h EE) is not known. Also, there is a lack of equations to estimate 24-h EE in patients with T1D. The aims of this analysis were to compare 24-h EE and its components in young adults with T1D and healthy controls across the spectrum of body mass index (BMI) and derive T1D-specific equations from clinical variables. SUBJECTS/METHODS: Thirty-three young adults with T1D diagnosed ≥1 year prior and 33 healthy controls matched for sex, age and BMI were included in this analysis. We measured 24-h EE inside a whole room indirect calorimeter (WRIC) and body composition with dual x-ray absorptiometry. RESULTS: Participants with T1D had significantly higher 24-h EE than healthy controls (T1D = 2047 ± 23 kcal/day vs control= 1908 ± 23 kcal/day; P < 0.01). We derived equations to estimate 24-h EE with both body composition (fat free mass + fat mass) and anthropometric (weight + height) models, which provided high coefficients of determination (R2 = 0.912 for both). A clinical model that did not incorporate spontaneous physical activity yielded high coefficients of determination as well (R2 = 0.897 and R2 = 0.880 for body composition and anthropometric models, respectively). CONCLUSION: These results confirm that young adults with established T1D have increased 24-h EE relative to controls without T1D. The derived equations from clinically available variables can assist clinicians with energy prescriptions for weight management in patients with T1D.

Nutritional Status, Dietary Intake, and Nutrition-Related Interventions Among Older Adults With Type 1 Diabetes: A Systematic Review and Call for More Evidence Toward Clinical Guidelines.

There is an emerging population of older adults (≥65 years) living with type 1 diabetes. Optimizing health through nutrition during this life stage is challenged by multiple and ongoing changes in diabetes management, comorbidities, and lifestyle factors. There is a need to understand nutritional status, dietary intake, and nutrition-related interventions that may maximize well-being throughout the life span in type 1 diabetes, in addition to nutrition recommendations from clinical guidelines and consensus reports. Three reviewers used Cochrane guidelines to screen original research (January 1993-2023) and guidelines (2012-2023) in two databases (MEDLINE and CENTRAL) to characterize nutrition evidence in this population. We found limited original research explicitly focused on nutrition and diet in adults ≥65 years of age with type 1 diabetes (six experimental studies, five observational studies) and meta-analyses/reviews (one scoping review), since in the majority of analyses individuals ≥65 years of age were combined with those age ≥18 years, with diverse diabetes durations, and also individuals with type 1 and type 2 diabetes were combined. Further, existing clinical guidelines (n = 10) lacked specificity and evidence to guide clinical practice and self-management behaviors in this population. From a scientific perspective, little is known about nutrition and diet among older adults with type 1 diabetes, including baseline nutrition status, dietary intake and eating behaviors, and the impact of nutrition interventions on key clinical and patient-oriented outcomes. This likely reflects the population's recent emergence and unique considerations. Addressing these gaps is foundational to developing evidence-based nutrition practices and guidelines for older adults living with type 1 diabetes.

A Single Arm Phase 2 Trial of Trametinib in Patients With Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.

PURPOSE: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 operating as an oncogenic driver through activation of MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE. PATIENTS AND METHODS: A phase 2 trial of trametinib was conducted in patients with locally advanced or metastatic EHE. Eligibility requirements included evidence of tumor progression or presence of EHE-related pain requiring opiates for management prior to enrollment. The primary endpoint was objective response rate (ORR) per RECIST1.1 in cases with TAZ-CAMTA1 confirmed by fusion-FISH. Secondary objectives were to estimate ORR for all patients, median PFS, 2-year OS rate, patient safety, and change in patient-reported global health and pain scores per PROMIS questionnaires. RESULTS: 44 patients enrolled and 42 started trametinib. TAZ-CAMTA1 was detected in 27 tumor samples. The ORR was 3.7% (95% CI: 0.094, 19.0), median PFS was 10.4 months (95% CI: 7.1, NA), and 2-year OS rate was 33.3% (95% CI: 19.1, 58.2) in the target population. Median pain intensity and interference scores improved significantly after 4 weeks of trametinib in patients using opiates. Common AEs related to trametinib were rash, fatigue, nausea/vomiting, diarrhea/constipation, alopecia and edema; one Grade 5 ARDS/pneumonitis was related to trametinib. CONCLUSIONS: Trametinib was associated with reduction in EHE-related pain and median PFS of more than 6 months providing palliative benefit in patients with advanced EHE, but the trial did not meet the ORR goal.

Eating behaviors and estimated body fat percentage among adolescents with type 1 diabetes.

AIMS: Estimate associations between select eating behaviors and estimated body fat percentage (eBFP) and explore effect modification by sex among adolescents with type 1 diabetes (T1D). METHODS: This analysis included 257 adolescents (mean age 14.9 ± 1.14 years; 49.8 % female) with baseline hemoglobin A1c (HbA1c) between 8 and 13 % (64 mmol/mol-119 mmol/mol) from a randomized trial designed to improve glycemia. Eating behaviors and eBFP were determined from surveys and validated equations respectively. Linear mixed models were used to estimate associations. Effect modification was assessed via stratified plots, stratified associations, and interaction terms. RESULTS: Disordered eating, dietary restraint, and eBFP were significantly higher among females while external eating was higher among males. Disordered eating (ß: 0.49, 95 %CI: 0.24, 0.73, p = 0.0001) and restraint (ß: 1.11, 95 %CI: 0.29, 1.92, p = 0.0081) were positively associated with eBFP while external eating was not (ß: -0.19, 95 %CI: -0.470, 0.096, p = 0.20). Interactions with sex were not significant (p-value range: 0.28-0.64). CONCLUSION: Disordered eating and dietary restraint were positively associated with eBFP, highlighting the potential salience of these eating behaviors to cardiometabolic risk for both female and male adolescents. Prospective studies should investigate whether these eating behaviors predict eBFP longitudinally to inform obesity prevention strategies in T1D.

Post-Exercise Protein Intake May Reduce Time in Hypoglycemia Following Moderate-Intensity Continuous Exercise among Adults with Type 1 Diabetes.

Little is known about the role of post-exercise protein intake on post-exercise glycemia. Secondary analyses were conducted to evaluate the role of post-exercise protein intake on post-exercise glycemia using data from an exercise pilot study. Adults with T1D (n = 11), with an average age of 33.0 ± 11.4 years and BMI of 25.1 ± 3.4, participated in isoenergetic sessions of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Participants completed food records on the days of exercise and provided continuous glucose monitoring data throughout the study, from which time in range (TIR, 70-180 mg/dL), time above range (TAR, >180 mg/dL), and time below range (TBR, <70 mg/dL) were calculated from exercise cessation until the following morning. Mixed effects regression models, adjusted for carbohydrate intake, diabetes duration, and lean mass, assessed the relationship between post-exercise protein intake on TIR, TAR, and TBR following exercise. No association was observed between protein intake and TIR, TAR, or TBR (p-values ≥ 0.07); however, a borderline significant reduction of -1.9% (95% CI: -3.9%, 0.0%; p = 0.05) TBR per 20 g protein was observed following MICT in analyses stratified by exercise mode. Increasing post-exercise protein intake may be a promising strategy to mitigate the risk of hypoglycemia following MICT.

Atezolizumab for Advanced Alveolar Soft Part Sarcoma.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported. METHODS: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action. RESULTS: A total of 52 patients were evaluated. An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses. The median time to response was 3.6 months (range, 2.1 to 19.1), the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months. Seven patients took a treatment break after 2 years of treatment, and their responses were maintained through the data-cutoff date. No treatment-related grade 4 or 5 adverse events were recorded. Responses were noted despite variable baseline expression of programmed death 1 and PD-L1. CONCLUSIONS: Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03141684.).

Hypoechoic Halo Imaging Findings Following Femoropopliteal Artery Stent Implantation: Risk Factors and Clinical Outcomes.

BACKGROUND: Hypoechoic peri-stent areas in duplex ultrasonography (DUS) (ie, "halo") have been noted following femoropopliteal artery stenting. OBJECTIVES: This study sought to investigate the prevalence, risk factors, and potential safety implications of hypoechoic halos identified with DUS following stent implantation in the IMPERIAL (ELUVIA Drug-Eluting Stent Versus Zilver PTX Stent) and EMINENT (Trial Comparing ELUVIA Versus Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery) trials. METHODS: The IMPERIAL and EMINENT studies of femoropopliteal artery stenting included polymer-based drug-eluting stent, nonpolymer drug-coated stent, and bare metal stent treatment arms. A dedicated DUS protocol was implemented for core laboratory assessment of halo presence at study follow-up visits. Logistic regressions were used to investigate risk factors for a halo sign and its impact on clinically driven target lesion revascularization and primary patency. RESULTS: Diagnostic DUS imaging from 659 patients was obtained at time points ranging from 6 months to 5 years post-stent implantation. Halo prevalence ranged from 20% to 35% of patients with diagnostic DUS and was present at all time intervals. Halos were identified surrounding all stent types. In analyses of patients with diagnostic imaging from at least 2 visits, halo presence typically persisted, with occasional cases of regression and development at later times. No statistically significant association was found for halo status (ie, halo vs no halo) on 1-year clinically driven target lesion revascularization (OR: 1.27; 95% CI: 0.70-2.30; P = 0.4240) or primary patency (OR: 0.68; 95% CI: 0.43-1.07; P = 0.0927). CONCLUSIONS: A hypoechoic halo following a femoropopliteal stent procedure is a common occurrence associated with all studied stent types. The presence of a halo appears to be benign with no associated clinical sequelae or effect on target vessel revascularization rates within 1 year of stent implantation.

An Overview of Diet and Physical Activity for Healthy Weight in Adolescents and Young Adults with Type 1 Diabetes: Lessons Learned from the ACT1ON Consortium.

The prevalence of overweight and obesity in young people with type 1 diabetes (T1D) now parallels that of the general population. Excess adiposity increases the risk of cardiovascular disease, which is already elevated up to 10-fold in T1D, underscoring a compelling need to address weight management as part of routine T1D care. Sustainable weight management requires both diet and physical activity (PA). Diet and PA approaches must be optimized towards the underlying metabolic and behavioral challenges unique to T1D to support glycemic control throughout the day. Diet strategies for people with T1D need to take into consideration glycemic management, metabolic status, clinical goals, personal preferences, and sociocultural considerations. A major barrier to weight management in this high-risk population is the challenge of integrating regular PA with day-to-day management of T1D. Specifically, exercise poses a substantial challenge due to the increased risk of hypoglycemia and/or hyperglycemia. Indeed, about two-thirds of individuals with T1D do not engage in the recommended amount of PA. Hypoglycemia presents a serious health risk, yet prevention and treatment often necessitates the consumption of additional calories, which may prohibit weight loss over time. Exercising safely is a concern and challenge with weight management and maintaining cardiometabolic health for individuals living with T1D and many healthcare professionals. Thus, a tremendous opportunity exists to improve exercise participation and cardiometabolic outcomes in this population. This article will review dietary strategies, the role of combined PA and diet for weight management, current resources for PA and glucose management, barriers to PA adherence in adults with T1D, as well as findings and lessons learned from the Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON).

A Retrospective Multi-Institutional Cohort Analysis of Clinical Characteristics and Outcomes in Dedifferentiated Chondrosarcoma.

BACKGROUND: Dedifferentiated chondrosarcoma (DDCS) is a rare subset of chondrosarcoma. It is an aggressive neoplasm characterized by a high rate of recurrent and metastatic disease with overall poor outcomes. Systemic therapy is often used to treat DDCS; however, the optimal regimen and timing are not well defined, with current guidelines recommending following osteosarcoma protocols. METHODS: We conducted a multi-institutional retrospective analysis of clinical characteristics and outcomes of patients with DDCS. Between 1 January 2004 and 1 January 2022, the databases from five academic sarcoma centers were reviewed. Patient and tumor factors, including age, sex, tumor size, site, location, the treatments rendered, and survival outcomes, were collected. RESULTS: Seventy-four patients were identified and included in the analysis. Most patients presented with localized disease. Surgical resection was the mainstay of therapy. Chemotherapy was used predominantly in the metastatic setting. Partial responses were low (n = 4; 9%) and occurred upon treatment with doxorubicin with cisplatin or ifosfamide and single-agent pembrolizumab. For all other regimens, stable disease was the best response. Prolonged stable disease occurred with the use of pazopanib and immune checkpoint inhibitors. CONCLUSIONS: DDCS has poor outcomes and conventional chemotherapy has limited benefit. Future studies should focus on defining the possible role of molecularly targeted therapies and immunotherapy in the treatment of DDCS.

A High Protein Diet Is Associated with Improved Glycemic Control Following Exercise among Adolescents with Type 1 Diabetes.

Nutritional strategies are needed to aid people with type 1 diabetes (T1D) in managing glycemia following exercise. Secondary analyses were conducted from a randomized trial of an adaptive behavioral intervention to assess the relationship between post-exercise and daily protein (g/kg) intake on glycemia following moderate-to-vigorous physical activity (MVPA) among adolescents with T1D. Adolescents (n = 112) with T1D, 14.5 (13.8, 15.7) years of age, and 36.6% overweight or obese, provided measures of glycemia using continuous glucose monitoring (percent time above range [TAR, >180 mg/dL], time-in-range [TIR, 70-180 mg/dL], time-below-range [TBR, <70 mg/dL]), self-reported physical activity (previous day physical activity recalls), and 24 h dietary recall data at baseline and 6 months post-intervention. Mixed effects regression models adjusted for design (randomization assignment, study site), demographic, clinical, anthropometric, dietary, physical activity, and timing covariates estimated the association between post-exercise and daily protein intake on TAR, TIR, and TBR from the cessation of MVPA bouts until the following morning. Daily protein intakes of ≥1.2 g/kg/day were associated with 6.9% (p = 0.03) greater TIR and -8.0% (p = 0.02) less TAR following exercise, however, no association was observed between post-exercise protein intake and post-exercise glycemia. Following current sports nutrition guidelines for daily protein intake may promote improved glycemia following exercise among adolescents with T1D.

Food Insecurity and Adequacy of Dietary Intake in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes.

BACKGROUND: Household food insecurity is associated with poor dietary intake in the general population, but little is known about this association in persons with diabetes. OBJECTIVE: We examined the degree of adherence to the dietary reference intakes and 2020-2025 Dietary Guidelines for Americans overall and according to food security status and diabetes type among youth and young adults (YYA) with youth-onset diabetes. DESIGN, PARTICIPANTS, AND SETTING: The SEARCH for Diabetes in Youth study includes 1,197 YYA with type 1 diabetes (mean age = 21 ± 5 years) and 319 YYA with type 2 diabetes (25 ± 4 years). Participants (or parents if younger than age 18 years) completed the US Department of Agriculture Household Food Security Survey Module, wherein ≥3 affirmations indicate food insecurity. MAIN OUTCOME MEASURES: Diet was assessed via food frequency questionnaire and compared with age- and sex-specific dietary reference intakes for 10 nutrients and dietary components (calcium; fiber; magnesium; potassium; sodium; vitamins C, D, and E; added sugar; and saturated fat). STATISTICAL ANALYSES PERFORMED: Median regression models controlled for sex- and type-specific means for age, diabetes duration, and daily energy intake. RESULTS: Prevalence of guideline adherence was overarchingly poor, with <40% of participants meeting recommendations for eight of 10 nutrients and dietary components; however, higher adherence (>47%) was observed for vitamin C and added sugars. YYA with type 1 diabetes who were food insecure were more likely to meet recommendations for calcium, magnesium, and vitamin E (P < 0.05), and less likely for sodium (P < 0.05) than those with food security. In adjusted models, YYA with type 1 diabetes who were food secure had closer median adherence to sodium (P = 0.002) and fiber (P = 0.042) guidelines than those food insecure. No associations were observed in YYA with type 2 diabetes. CONCLUSIONS: Food insecurity is associated with lesser adherence to fiber and sodium guidelines in YYA with type 1 diabetes, which may lead to diabetes complications and other chronic diseases.

Diabetes Stigma and Clinical Outcomes in Adolescents and Young Adults: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To examine the association between diabetes stigma and HbA1c, treatment plan and acute and chronic complications in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: The SEARCH for Diabetes in Youth study is a multicenter cohort study that collected questionnaire, laboratory, and physical examination data about AYAs with diabetes diagnosed in childhood. A five-question survey assessed frequency of perceived diabetes-related stigma, generating a total diabetes stigma score. We used multivariable linear modeling, stratified by diabetes type, to examine the association of diabetes stigma with clinical factors, adjusting for sociodemographic characteristics, clinic site, diabetes duration, health insurance, treatment plan, and HbA1c. RESULTS: Of 1,608 respondents, 78% had type 1 diabetes, 56% were female, and 48% were non-Hispanic White. The mean (SD) age at study visit was 21.7 (5.1) years (range, 10-24.9). The mean (SD) HbA1c was 9.2% (2.3%; 77 mmol/mol [2.0 mmol/mol]). Higher diabetes stigma scores were associated with female sex and higher HbA1c (P < 0.01) for all participants. No significant association between diabetes stigma score and technology use was observed. In participants with type 2 diabetes, higher diabetes stigma scores were associated with insulin use (P = 0.04). Independent of HbA1c, higher diabetes stigma scores were associated with some acute complications for AYAs with type 1 diabetes and some chronic complications for AYAs with type 1 or type 2 diabetes. CONCLUSIONS: Diabetes stigma in AYAs is associated with worse diabetes outcomes and is important to address when providing comprehensive diabetes care.

Estimating incidence of type 1 and type 2 diabetes using prevalence data: the SEARCH for Diabetes in Youth study.

BACKGROUND: Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts. The aim of this study was to examine whether a partial differential equation (PDE) can be used to estimate diabetes incidence from prevalence in youth. METHODS: We used age-, sex-, and race/ethnicity-specific estimates of prevalence in 2001 and 2009 as reported in the SEARCH for Diabetes in Youth study. Using these data, a PDE was applied to estimate the average incidence rates of type 1 and type 2 diabetes for the period between 2001 and 2009. Estimates were compared to annual incidence rates observed in SEARCH. Precision of the estimates was evaluated using 95% bootstrap confidence intervals. RESULTS: Despite the long period between prevalence measures, the estimated average incidence rates mirror the average of the observed annual incidence rates. Absolute values of the age-standardized sex- and type-specific mean relative errors are below 8%. CONCLUSIONS: Incidence of diabetes can be accurately estimated from prevalence. Since only cross-sectional prevalence data is required, employing this methodology in future studies may result in considerable cost savings.

Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity.

BACKGROUND: Diet, a key component of type 1 diabetes (T1D) management, modulates the intestinal microbiota and its metabolically active byproducts-including SCFA-through fermentation of dietary carbohydrates such as fiber. However, the diet-microbiome relationship remains largely unexplored in longstanding T1D. OBJECTIVES: We evaluated whether increased carbohydrate intake, including fiber, is associated with increased SCFA-producing gut microbes, SCFA, and intestinal microbial diversity among young adults with longstanding T1D and overweight or obesity. METHODS: Young adult men and women with T1D for ≥1 y, aged 19-30 y, and BMI of 27.0-39.9 kg/m2 at baseline provided stool samples at baseline and 3, 6, and 9 mo of a randomized dietary weight loss trial. Diet was assessed by 1-2 24-h recalls. The abundance of SCFA-producing microbes was measured using 16S rRNA gene sequencing. GC-MS measured fecal SCFA (acetate, butyrate, propionate, and total) concentrations. Adjusted and Bonferroni-corrected generalized estimating equations modeled associations of dietary fiber (total, soluble, and pectins) and carbohydrate (available carbohydrate, and fructose) with microbiome-related outcomes. Primary analyses were restricted to data collected before COVID-19 interruptions. RESULTS: Fiber (total and soluble) and carbohydrates (available and fructose) were positively associated with total SCFA and acetate concentrations (n = 40 participants, 52 visits). Each 10 g/d of total and soluble fiber intake was associated with an additional 8.8 µmol/g (95% CI: 4.5, 12.8 µmol/g; P = 0.006) and 24.0 µmol/g (95% CI: 12.9, 35.1 µmol/g; P = 0.003) of fecal acetate, respectively. Available carbohydrate intake was positively associated with SCFA producers Roseburia and Ruminococcus gnavus. All diet variables except pectin were inversely associated with normalized abundance of Bacteroides and Alistipes. Fructose was inversely associated with Akkermansia abundance. CONCLUSIONS: In young adults with longstanding T1D, fiber and carbohydrate intake were associated positively with fecal SCFA but had variable associations with SCFA-producing gut microbes. Controlled feeding studies should determine whether gut microbes and SCFA can be directly manipulated in T1D.

Projections of Type 1 and Type 2 Diabetes Burden in the U.S. Population Aged <20 Years Through 2060: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To project the prevalence and number of youths with diabetes and trends in racial and ethnic disparities in the U.S. through 2060. RESEARCH DESIGN AND METHODS: Based on a mathematical model and data from the SEARCH for Diabetes in Youth study for calendar years 2002-2017, we projected the future prevalence of type 1 and type 2 diabetes among youth aged <20 years while considering different scenarios of future trends in incidence. RESULTS: The number of youths with diabetes will increase from 213,000 (95% CI 209,000; 218,000) (type 1 diabetes 185,000, type 2 diabetes 28,000) in 2017 to 239,000 (95% CI 209,000; 282,000) (type 1 diabetes 191,000, type 2 diabetes 48,000) in 2060 if the incidence remains constant as observed in 2017. Corresponding relative increases were 3% (95% CI -9%; 21%) for type 1 diabetes and 69% (95% CI 43%; 109%) for type 2 diabetes. Assuming that increasing trends in incidence observed between 2002 and 2017 continue, the projected number of youths with diabetes will be 526,000 (95% CI 335,000; 893,000) (type 1 diabetes 306,000, type 2 diabetes 220,000). Corresponding relative increases would be 65% (95% CI 12%; 158%) for type 1 diabetes and 673% (95% CI 362%; 1,341%) for type 2 diabetes. In both scenarios, substantial widening of racial and ethnic disparities in type 2 diabetes prevalence are expected, with the highest prevalence among non-Hispanic Black youth. CONCLUSIONS: The number of youths with diabetes in the U.S. is likely to substantially increase in future decades, which emphasizes the need for prevention to attenuate this trend.

Associations of disordered eating with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes.

BACKGROUND AND AIMS: Disordered eating (DE) in type 1 diabetes (T1D) includes insulin restriction for weight loss with serious complications. Gut microbiota-derived short chain fatty acids (SCFA) may benefit host metabolism but are reduced in T1D. We evaluated the hypothesis that DE and insulin restriction were associated with reduced SCFA-producing gut microbes, SCFA, and intestinal microbial diversity in adults with T1D. METHODS AND RESULTS: We collected stool samples at four timepoints in a hypothesis-generating gut microbiome pilot study ancillary to a weight management pilot in young adults with T1D. 16S ribosomal RNA gene sequencing measured the normalized abundance of SCFA-producing intestinal microbes. Gas-chromatography mass-spectrometry measured SCFA (total, acetate, butyrate, and propionate). The Diabetes Eating Problem Survey-Revised (DEPS-R) assessed DE and insulin restriction. Covariate-adjusted and Bonferroni-corrected generalized estimating equations modeled the associations. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 data. Data were available for 45 participants at 109 visits, which included 42 participants at 65 visits pre-COVID-19. Participants reported restricting insulin "At least sometimes" at 53.3% of visits. Pre-COVID-19, each 5-point DEPS-R increase was associated with a -0.34 (95% CI -0.56, -0.13, p = 0.07) lower normalized abundance of genus Anaerostipes; and the normalized abundance of Lachnospira genus was -0.94 (95% CI -1.5, -0.42), p = 0.02 lower when insulin restriction was reported "At least sometimes" compared to "Rarely or Never". CONCLUSION: DE and insulin restriction were associated with a reduced abundance of SCFA-producing gut microbes pre-COVID-19. Additional studies are needed to confirm these associations to inform microbiota-based therapies in T1D.

Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results.

AIMS: Co-management of weight and glycaemia is critical yet challenging in type 1 diabetes (T1D). We evaluated the effect of a hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diet without calorie restriction on weight and glycaemia in young adults with T1D and overweight or obesity. MATERIALS AND METHODS: We implemented a 9-month Sequential, Multiple Assignment, Randomized Trial pilot among adults aged 19-30 years with T1D for ≥1 year and body mass index 27-39.9 kg/m2 . Re-randomization occurred at 3 and 6 months if the assigned diet was not acceptable or not effective. We report results from the initial 3-month diet period and re-randomization statistics before shutdowns due to COVID-19 for primary [weight, haemoglobin A1c (HbA1c), percentage of time below range <70 mg/dl] and secondary outcomes [body fat percentage, percentage of time in range (70-180 mg/dl), and percentage of time below range <54 mg/dl]. Models adjusted for design, demographic and clinical covariates tested changes in outcomes and diet differences. RESULTS: Adjusted weight and HbA1c (n = 38) changed by -2.7 kg (95% CI -3.8, -1.5, P < .0001) and -0.91 percentage points (95% CI -1.5, -0.30, P = .005), respectively, while adjusted body fat percentage remained stable, on average (P = .21). Hypoglycaemia indices remained unchanged following adjustment (n = 28, P > .05). Variability in all outcomes, including weight change, was considerable (57.9% were re-randomized primarily due to loss of <2% body weight). No outcomes varied by diet. CONCLUSIONS: Three months of a diet, irrespective of macronutrient distribution or caloric restriction, resulted in weight loss while improving or maintaining HbA1c levels without increasing hypoglycaemia in adults with T1D.

The Intestinal Microbiota and Short-Chain Fatty Acids in Association with Advanced Metrics of Glycemia and Adiposity Among Young Adults with Type 1 Diabetes and Overweight or Obesity.

Background: Comanagement of glycemia and adiposity is the cornerstone of cardiometabolic risk reduction in type 1 diabetes (T1D), but targets are often not met. The intestinal microbiota and microbiota-derived short-chain fatty acids (SCFAs) influence glycemia and adiposity but have not been sufficiently investigated in longstanding T1D. Objectives: We evaluated the hypothesis that an increased abundance of SCFA-producing gut microbes, fecal SCFAs, and intestinal microbial diversity were associated with improved glycemia but increased adiposity in young adults with longstanding T1D. Methods: Participants provided stool samples at ≤4 time points (NCT03651622: https://clinicaltrials.gov/ct2/show/NCT03651622). Sequencing of the 16S ribosomal RNA gene measured abundances of SCFA-producing intestinal microbes. GC-MS measured total and specific SCFAs (acetate, butyrate, propionate). DXA (body fat percentage and percentage lean mass) and anthropometrics (BMI) measured adiposity. Continuous glucose monitoring [percentage of time in range (70-180 mg/dL), above range (>180 mg/dL), and below range (54-69 mg/dL)] and glycated hemoglobin (i.e., HbA1c) assessed glycemia. Adjusted and Bonferroni-corrected generalized estimating equations modeled the associations of SCFA-producing gut microbes, fecal SCFAs, and intestinal microbial diversity with glycemia and adiposity. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 visits. Results: Data were available for ≤45 participants at 101 visits (including 40 participants at 54 visits pre-COVID-19). Abundance of Eubacterium hallii was associated inversely with BMI (all data). Pre-COVID-19, increased fecal propionate was associated with increased percentage of time above range and reduced percentage of time in target and below range; and abundances of 3 SCFA-producing taxa (Ruminococcus gnavus, Eubacterium ventriosum, and Lachnospira) were associated inversely with body fat percentage, of which two microbes were positively associated with percentage lean mass. Abundance of Anaerostipes was associated with reduced percentage of time in range (all data) and with increased body fat percentage and reduced percentage lean mass (pre-COVID-19). Conclusions: Unexpectedly, fecal propionate was associated with detriment to glycemia, whereas most SCFA-producing intestinal microbes were associated with benefit to adiposity. Future studies should confirm these associations and determine their potential causal linkages in T1D.This study is registered at clinical.trials.gov (NCT03651622; https://clinicaltrials.gov/ct2/show/NCT03651622).

The Impact of TSC-1 and -2 Mutations on Response to Therapy in Malignant PEComa: A Multicenter Retrospective Analysis.

BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy. METHODS: This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations. RESULTS: No significant differences in survival were identified between TSC-1 and TSC-2 mutated PEComa or TSC-1/-2 versus other mutations. No significant difference was seen in progression-free survival (PFS) after first-line therapy between mTOR inhibition versus other systemic therapies. CONCLUSIONS: We were unable to detect differences in survival based on genomic alterations or PFS between mTOR inhibition versus other systemic therapies. Future studies should seek to identify other drivers of TSC-1/-2 silencing that could predict response to mTOR inhibition.