Evaluating the Clinical Effect of Personal Continuous Glucose Monitoring in a Diverse Population With Type 2 Diabetes.

Objective: To determine the clinical effect of personal continuous glucose monitoring (CGM) in a diverse population with type 2 diabetes (T2D). Research Design and Methods: A report was created from the electronic health record identifying adults prescribed CGM at an urban family medicine clinic between January 1, 2019, and February 23, 2022. An "index date" was identified as the start of CGM. The closest hemoglobin A1c (A1c) 6 months or more after the index date was identified as the "follow-up date." The primary outcome of this study was to compare the percentage of individuals meeting the MN Community Measure (MNCM) D5 HbA1c goal of <8% at the follow-up date versus the index date. Results: Seventy-two patients were identified after the exclusion criteria were applied. Approximately one-third of patients required utilization of an interpreter and 76% of patients were of a racial or ethnic minority. The mean HbA1c prior to CGM use was 9.8%, with 16.7% of the population meeting the MNCM D5 A1c goal of <8%. At the follow-up date, the mean A1c was 8.4% (mean difference -1.4%; p < 0.001), with 41.7% of the population meeting goal (mean difference +25%; p < 0.001). Subgroup analyses affirm that the results of the primary outcome were sustained despite insulin use status. Conclusion: A diverse population with T2D had a significant reduction in A1c and was more likely to meet the MNCM D5 A1c goal of <8% after an average of 6 months using personal CGM.

Acacia Gum Is Well Tolerated While Increasing Satiety and Lowering Peak Blood Glucose Response in Healthy Human Subjects.

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.

Endogenous HLA-DQ8αß programs superantigens (SEG/SEI) to silence toxicity and unleash a tumoricidal network with long-term melanoma survival.

BACKGROUND: As the most powerful T cell agonists known, superantigens (SAgs) have enormous potential for cancer immunotherapy. Their development has languished due to high incidence (60%-80%) of seroreactive neutralizing antibodies in humans and tumor necrosis factor-α (TNFα)-mediated cardiopulmonary toxicity. Such toxicity has narrowed their therapeutic index while neutralizing antibodies have nullified their therapeutic effects. METHODS: Female HLA-DQ8 (DQA*0301/DQB*0302) tg mice expressing the human major histocompatibility complex II (MHCII) HLA-DQ8 allele on a high proportion of PBL, spleen and lymph node cells were used. In the established tumor model, staphylococcal enterotoxin G and staphylococcal enterotoxin I (SEG/ SEI) (50 µg each) were injected on days 6 and 9 following tumor inoculation. Lymphoid, myeloid cells and tumor cell digests from tumor tissue were assayed using flow cytometry or quantitated using a cytometric bead array. Tumor density, necrotic and viable areas were quantitated using the ImageJ software. RESULTS: In a discovery-driven effort to address these problems we introduce a heretofore unrecognized binary complex comprizing SEG/SEI SAgs linked to the endogenous human MHCII HLA-DQ8 allele in humanized mice. By contrast to staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) deployed previously in clinical trials, SEG and SEI does not exhibit neutralizing antibodies in humans or TNFα-mediated toxicity in humanized HLA-DQ8 mice. In the latter model wherein SAg behavior is known to be 'human-like', SEG/SEI induced a powerful tumoricidal response and long-term survival against established melanoma in 82% of mice. Other SAgs deployed in the same model displayed toxic shock. Initially, HLA-DQ8 mediated melanoma antigen priming, after which SEG/SEI unleashed a broad CD4+ and CD8+ antitumor network marked by expansion of melanoma reactive T cells and interferon-γ (IFNy) in the tumor microenvironment (TME). SEG/SEI further initiated chemotactic recruitment of tumor reactive T cells to the TME converting the tumor from 'cold' to a 'hot'. Long-term survivors displayed remarkable resistance to parental tumor rechallenge along with the appearance of tumor specific memory and tumor reactive T memory cells. CONCLUSIONS: Collectively, these findings show for the first time that the SEG/SEI-(HLA-DQ8) empowers priming, expansion and recruitment of a population of tumor reactive T cells culminating in tumor specific memory and long-term survival devoid of toxicity. These properties distinguish SEG/SEI from other SAgs used previously in human tumor immunotherapy. Consolidation of these principles within the SEG/SEI-(HLA-DQ8) complex constitutes a conceptually new therapeutic weapon with compelling translational potential.

Effects of mechanical injury on the tribological rehydration and lubrication of articular cartilage.

Healthy articular cartilage is crucial to joint function, as it provides the low friction and load bearing surface necessary for joint articulation. Nonetheless, joint injury places patients at increased risk of experiencing both accelerated cartilage degeneration and wear, and joint dysfunction due to post-traumatic osteoarthritis (PTOA). In this study, we used our ex vivo convergent stationary contact area (cSCA) explant testing configuration to demonstrate that high-speed sliding of healthy tissues against glass could drive consistent and reproducible recovery of compression-induced cartilage deformation, through the mechanism of 'tribological rehydration'. In contrast, the presence of physical cartilage damage, mimicking those injuries known to precipitate PTOA, could compromise tribological rehydration and the sliding-driven recovery of cartilage function. Full-thickness cartilage injuries (i.e. fissures and chondral defects) markedly suppressed sliding-driven tribological rehydration. In contrast, impaction to cartilage, which caused surface associated damage, had little effect on the immediate tribomechanical response of explants to sliding (deformation/strain, tribological rehydration, and friction/lubricity). By leveraging the unique ability of the cSCA configuration to support tribological rehydration, this study permitted the first direct ex vivo investigation of injury-dependent strain and friction outcomes in cartilage under testing conditions that replicate and maintain physiologically-relevant levels of fluid load support and frictional outcomes under high sliding speeds (80 mm/s) and moderate compressive stresses (~0.3 MPa). Understanding how injury alters cartilage tribomechanics during sliding sheds light on mechanisms by which cartilage's long-term resilience and low frictional properties are maintained, and can guide studies investigating the functional consequences of physical injury and joint articulation on cartilage health, disease, and rehabilitation.