Citations

Early postprandial glucagon concentrations are higher in type 1 diabetes (T1D) than in individuals with no diabetes (ND). To determine the cause, we infused stable [13C9, 15N1]glucagon before, during, and after a mixed meal in 16 ND and 16 T1D individuals to measure glucagon turnover. In a subcohort of 9 ND and 12 T1D individuals, we estimated [13C9, 15N1]glucagon kinetics during steady state. A linear, single-compartment model described [13C9, 15N1]glucagon kinetics and allowed precise estimation of the volume of distribution (VD) and clearance rate (CL). Model parameters were similar between groups, with the VD of [13C9, 15N1]glucagon at 42.1 ± 3.3 mL/kg, implying that [13C9, 15N1]glucagon distributes in a single compartment and with VD approximating the plasma volume and CL at 10.6 ± 0.9 mL/kg/min. Higher early (0–120 min after meal ingestion) postprandial glucagon concentrations (1,907.9 ± 373.4 vs. −93.6 ± 240.5 pg/mL · 120 min P < 0.001) observed in T1D was due to higher rates of glucagon appearance (3.39 ± 2.8 vs. −3.95 ± 2.0 ng/kg · 120 min, P < 0.04) and disappearance (2.13 ± 2.6 vs. −5.28 ± 2.1 ng/kg · 120 min, P < 0.04) compared with ND. We have determined postprandial glucagon turnover in humans and have demonstrated that changes in postprandial glucagon concentrations in T1D are due to increased rates of glucagon turnover during the early postprandial period. Article Highlights This study was conducted to determine postprandial glucagon metabolism in people with and without type 1 diabetes. We wanted to determine the cause for higher early postprandial glucagon concentrations in type 1 diabetes. We found that higher early postprandial glucagon turnover is the cause of higher early postprandial glucagon concentrations in type 1 diabetes Strategies that decrease early post prandial glucagon fluxes could improve postprandial glucose concentrations in type 1 diabetes.

Objective To evaluate the safety and efficacy of Grayson's presurgical nasoalveolar molding (PNAM) technique on nasal and alveolar morphology in infants with unilateral cleft lip and palate (UCLP). Design Systematic review and meta-analysis. Setting : Multicenter international literature across clinical and academic institutions. Patients, Participants Infants with UCLP reported in 21 eligible studies (n = 534), of whom 368 received PNAM. Interventions Presurgical nasoalveolar molding (PNAM) according to the Grayson protocol. Main Outcome Measure(s) : Changes in nasal symmetry (nostril width ratio, columellar angle) and alveolar morphology (alveolar gap dimensions, intertuberosity distance). Results PNAM was performed for an average duration of 96 days with 11 adjustments per patient. Pooled analyses demonstrated significant improvements in nasal symmetry: nostril width ratio decreased from 2.4 (95% CI, 1.7–3.1; I² = 98%) to 1.8 (95% CI, 0.9–2.6; I² = 97%), and the columellar angle increased from 52° (95% CI, 42.0–62.8; I² = 100%) to 70° (95% CI, 59.1–80.6; I² = 98%). Alveolar gap narrowed from 10.7 mm (95% CI, 9.5–11.9; I² = 92%) to 3.9 mm (95% CI, 3.1–4.8; I² = 93%). Intertuberosity distance increased slightly, from 31.3 mm (95% CI, 29.3–33.3; I² = 95%) to 31.8 mm (95% CI, 28.9–34.8; I² = 98%). Conclusions Grayson's PNAM appears to improve nasal and alveolar morphology in infants with UCLP prior to definitive surgery. Standardized outcome measures and long-term prospective studies are needed to confirm these findings and refine clinical protocols.

Importance The ideal duration of androgen deprivation therapy (ADT) for treating localized prostate cancer is unknown due to variable adherence and treatment durations tested in clinical trials. Objective To determine the ideal duration of ADT for patients with prostate cancer treated with radiotherapy. Data Sources This individual patient data meta-analysis of 13 randomized phase 3 clinical trials evaluated the use of radiotherapy alone or with ADT. It included patients with a median follow-up of 11.3 (IQR, 9.5-14.5) years and ADT duration of 0 to 36 months. Most patients (7392 [72%]) included had National Comprehensive Cancer Network high-risk or very high-risk disease. Study Selection For this meta-analysis, a systematic literature search from 1980 to 2020 was performed in trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), MEDLINE (1966-2020), Embase (1982-2020), Web of Science, and Scopus to identify trials. Data Extraction and Synthesis Intention-to-treat and as-treated analyses were performed. The number needed to treat to prevent 1 distant metastasis at 10 years was calculated based on prognostic risk group. The analyses were conducted from January 5 to August 15, 2023. Main Outcomes and Measures The primary end point for this study was overall survival, defined as time to death or last follow-up from randomization. Secondary end points included biochemical recurrence, distant metastasis (DM), prostate cancer–specific mortality, and other-cause mortality. Results The median (IQR) age among the 10 266 male patients was 70 (65-74) years. Longer durations of ADT were associated with nonlinear improvement in relative benefits of DM, prostate cancer–specific mortality, and overall survival, with reduced estimated benefits beyond 9 to 12 months of ADT based on the end point. There was a near-linear increase in other-cause mortality associated with long-term ADT use (hazard ratio, 1.28; 95% CI, 1.09-1.50; P = .002 for 28 vs 0 months of ADT). The optimal ADT duration based on 10-year DM was 0, 6, 12 months, and undefined for patients with 1 intermediate-risk factor, 2 or more intermediate-risk factors, and National Comprehensive Cancer Network high-risk and very high-risk disease, respectively. Conclusions and Relevance The results of this meta-analysis suggest that, for men with localized prostate cancer treated with definitive radiotherapy and ADT, there are relative and absolute benefits from increasing durations of ADT that help provide individualized risk estimates.

Greater degrees of aerobic fitness are associated with greater insulin-mediated muscle glucose uptake. Insulin regulates adipose tissue lipolysis, whether aerobic fitness affects insulin’s ability to regulate lipolysis is unknown. We found that greater fitness is associated with improved adipose tissue insulin responsiveness independent of age, sex, BMI, visceral adipose tissue, body fat (kg), percent body fat, and adipocyte size. This suggests that exercise, if it improves fitness, may improve both adipose tissue and muscle function.

Abstract Twohey, E, Dobbs, WC, Malone, CM, Fields, JB, Jones, MT, and Jagim, AR. The use of a consumer-grade bioelectrical impedance analysis device for weight certification in collegiate wrestling: Implications for minimal wrestling weight determination. J Strength Cond Res 39(12): 1321–1326, 2025—Wrestlers are required to complete a preseason weight certification assessment, which includes a weigh-in, a hydration test, and a body fat percentage (BF%) measurement. This information is then used to establish their minimal wrestling weight (MWW) and minimal weight class. Skinfold (SKF) is the primary method used for determining body fat for collegiate wrestling, yet impedance devices are being considered for use in the future. The purpose of this study was to examine differences in body fat and the resulting MWW values derived from SKF and a consumer-grade multifrequency bioelectrical impedance analysis (MFBIA) device. Thirty-one collegiate male wrestlers produced a urine sample for urine specific gravity assessment to ensure adequate hydration status. Subjects then completed a weigh-in, followed by 2 body composition assessments using a (a) MFBIA device and (b) skinfold calipers to determine body density and BF%. No significant differences were observed for estimates of BF% (SKF: 13.4 ± 2.8% vs. MFBIA: 14.0 ± 3.3%; p = 0.198) or computed MWW values (SKF: 69.8 ± 8.7 kg vs. MFBIA: 69.4 ± 9.7 kg; p = 0.348) between devices. When determining the minimal weight class for each device, there were discrepancies in 11 of the 31 wrestlers (35%). Although the current MFBIA device can provide an acceptable estimate of BF% and similar resulting MWW value at the group level, the methods cannot be used interchangeably.

Aging plays a major role in the development of numerous chronic diseases, one of which is a marked decline in skeletal health. Beyond diminishing bone mass and strength, mammals of advanced age experience a decline in skeletal mechanotransduction—that is, the ability of the skeleton to respond adaptively to mechanical perturbation. One possibility for the loss of mechanotransduction in bone with aging is an age-associated increase in the population density of senescent cells—those cells that have undergone irreversible cell cycle arrest, resistance to apoptosis, and production of a modified secretome (the SASP) that has damaging effects to nearby healthy (non-senescent) cells. We investigated whether the presence of senescent cells might drive some of the diminished mechanical response observed in aged bone, by testing the hypothesis that the clearance of senescent cells via intermittent senolytic treatment promotes mechanical responsiveness in an aged skeleton. C57BL/6 mice aged 6 months and 22 months were treated weekly with the senolytic cocktail Dasatinib and Quercetin (D + Q) for 1 month, then subjected to low level in vivo mechanical loading of the ulna for 1 week. The 6-month-old mice exhibited a doubling of load-induced ulnar periosteal bone formation when treated with D + Q, compared to vehicle-treated mice, but the periosteal response to loading was not significantly altered by D + Q in the aged (22-month) mice. We further probed the efficacy of D + Q in mechanotransduction by switching to an endocortical model—the axial tibia loading system. Here, the 22-month-old mice had nearly double the load-induced endocortical bone formation compared to vehicle-treated mice. We further assayed the cortical bone gene expression profile in loaded and control tibias from treatment-naïve 6-month and 22-month mice, to determine whether there is significant overlap between mechanically induced signaling genes and SASP genes. We found significant load-induced changes among several SASP genes, suggesting that inhibition of the SASP (i.e., senomorphics) might interfere with mechanical signaling from otherwise healthy cells. In summary, clearance of senescent cells via intermittent D + Q treatment is effective at improving endocortical mechanical responsiveness in the aged skeleton, which is commonly diminished throughout the course of aging.