Joslin Diabetes Center

The objective of this study was to evaluate the Diabetes Eating Problems Survey-Revised (DEPS-R) against the Eating Disorder Diagnostic Interview (EDDI). Specific aims were to (1) assess the ability of the DEPS-R to identify Diagnostic and Statistical Manual-5 (DSM-5) eating disorders, including sensitivity and specificity of the current DEPS-R cutoff ≥20 and (2) report the correlation of each item to the presence of any eating disorder. Baseline data from 293 women (14-35 years) with type 1 diabetes (T1D) and body image concerns enrolled in a multinational randomized controlled trial were examined. Receiver operating characteristic (ROC) analysis, univariate logistic regression and two-sample t-test were performed. The ROC analysis demonstrated good accuracy of the DEPS-R with an area under the curve (AUC) of 0.82 (95% CI 0.79-0.94). The cutoff of ≥20 yielded a sensitivity of 87.5% (95% CI 83.6%-91.3%) and a specificity of 60.4% (95% CI 54.8%-66.0%). Univariate logistic regression identified 12 items as significantly correlated with the presence of any eating disorder. The highest odds ratios (OR) were observed for items 9 (OR = 3.64), 8 (OR = 2.85), 13 (OR = 2.36), 14 (OR = 2.23), 15 (OR = 1.99) and 5 (OR = 1.99). This is the first study to investigate the ability of the DEPS-R to identify DSM-5 eating disorder diagnosis established via a diagnostic interview using a ROC-analysis. DEPS-R cutoff ≥20 correctly identified most cases with eating disorders but showed moderate specificity, considered acceptable as an initial screening tool for disordered eating. In clinical care, specific DEPS-R items may be emphasized to explore the presence of disordered eating behaviours and eating disorders.

The RHONE-X study (ClinicalTrials.gov identifier, NCT04432831) evaluated long-term safety and tolerability (primary end points), and efficacy (exploratory end points) of faricimab, a dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) inhibitor, using a treat-and-extend (T&E) protocol in patients with diabetic macular edema (DME). Global phase 3, multicenter, nonrandomized, 2-year open-label extension study of the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) studies. Of 1622 patients who completed YOSEMITE and RHINE, 1474 patients (91%) were included in the RHONE-X trial. Patients transitioned from faricimab every 8 weeks (Q8W), faricimab T&E, or aflibercept 2.0 mg Q8W in YOSEMITE and RHINE to the RHONE-X study without requiring monthly initiation doses. All received faricimab T&E at up to 16-week intervals based on best-corrected visual acuity (BCVA) and central subfield thickness (CST), per YOSEMITE and RHINE criteria. Patients attended every month during the initial 4-month masked period, then only for T&E dosing visits (open-label arm). Analysis windows were defined for the RHONE-X study years 1, 1.5, and 2 to account for visit asynchronicity. The primary end point was incidence and severity of ocular and nonocular adverse events (AEs). Exploratory end points included change from baseline BCVA and CST, proportion of patients with absence of DME (CST < 325 μm), and treatment durability. Overall, 1204 patients (82%) completed the RHONE-X trial. The incidence of AEs leading to treatment discontinuation (1.5%) and rates of intraocular inflammation (1.3%) were low. Overall, faricimab T&E maintained visual and anatomic improvements achieved in YOSEMITE and RHINE. Adjusted mean BCVA improvements from YOSEMITE and RHINE baseline to the end of the RHONE-X trial were +10.1 letters (faricimab T&E), +11.4 letters (faricimab T&E [prior Q8W]), and +9.5 letters (faricimab T&E [prior aflibercept]); CST reductions were -198.3 μm, -202.5 μm, and -204.9 μm, respectively. At study end, more than 90% of patients achieved DME absence, regardless of prior treatment. Median number of injections over the RHONE-X trial (2 years) were 7 (faricimab T&E), 8 (faricimab T&E [prior Q8W]), and 8 (faricimab T&E [prior aflibercept]). By the RHONE-X trial completion, approximately 80% of patients received faricimab at ≥Q12W intervals. Faricimab, a dual Ang-2 and VEGF-A inhibitor, provided long-term safety, efficacy, and durability in patients with DME treated using a T&E regimen. Sustained visual and anatomic improvements were observed, with extended dosing intervals and reduced treatment burden. Faricimab was well tolerated, with a safety profile consistent with the YOSEMITE and RHINE trials. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Severe hypoglycemic events (SHEs) impose substantial clinical and economic burden on people with type 1 diabetes (pwT1D), yet real-world data describing this burden remain limited in the U.S. hospital setting. This study examined T1D-related complications and direct medical costs in pwT1D hospitalized or treated in the emergency department (ED) for hypoglycemia. IQVIA's PharMetrics Plus database was used to identify adults with T1D who experienced at least 1 hypoglycemic event requiring an inpatient hospitalization or ED visit from April 2016-April 2020. The SHE date was defined as the date of the first hospital-treated SHE: a claim with a hypoglycemia diagnosis and an inpatient hospitalization or ED visit. Patients were followed up until the end of continuous enrollment or end of the study period (April 30, 2022). Prevalence of T1D-related complications were descriptively summarized, and all-cause direct medical costs were calculated as per-patient-per-year (PPPY). The study was conducted during a period of early adoption of advanced diabetes technologies, such as hybrid closed-loop systems, and only included direct medical costs, potentially underestimating total costs. Among 4627 adults with T1D and hospital-treated SHEs, mean age was 41.4years, 57.3% were male, and 93.4% had commercial insurance. Common comorbidities included hypertension (24.6%), anxiety (9.5%), and depression (9.3%). Prevalence of retinopathy, neuropathy, chronic kidney disease (any stage), coronary artery disease, and peripheral vascular disease were 38.6%, 38.6%, 17.7%, 13.2%, and 11.4%, respectively. Total all-cause direct medical costs averaged $52,849 PPPY in 2022 USD ($59,719 in 2025 USD), driven primarily by inpatient hospitalization (mean-$22,981 in 2022 USD, $25,968 in 2025 USD). Among patients with a hospitalization, mean (SD) number of hospitalizations (PPPY) were 1.5 (3.6) and the average length of stay per patient (PPPY) was 5.0 (20.7) days. High T1D-related complication rates and elevated direct medical costs highlight the complexity of pwT1D who experienced hospital-treated SHEs.

To determine how Erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation affects the proliferation and transcriptional programs of MLO-Y4 osteocyte-like cells. Although Er:YAG lasers are widely used in periodontal hard tissue therapy, how they affect osteocytes remain elusive. MLO-Y4 cells were seeded before 72 h Er:YAG laser irradiation at energy fluences of 3.1, 6.0, and 8.9 J/cm2. Cell surface temperature and Hspa1a expression were measured to evaluate thermal effects. Cell proliferation and cytotoxicity were assessed by the Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays. RNA sequencing (RNA-seq) was performed 6 h after 6.0 J/cm2 laser irradiation versus nonirradiated controls. According to surface temperature and Hspa1a expression, no major thermal effects were observed at 6.0 J/cm2. The CCK-8 assay revealed significantly increased proliferative activity, although LDH levels were slightly but significantly increased at 6.0 J/cm2 laser irradiation. RNA-seq identified 337 differentially expressed genes (DEGs). Expression of mechanical stimulation-associated genes, including Epha2, Itga5, and Tcf7, was highly upregulated in the laser-irradiated cells. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed upregulation of the PI3K-Akt signaling pathway in the laser-irradiated cells. Upregulated DEGs belonged to the "euchromatin" cellular component Gene Ontology term in the laser-irradiated cells. Gene set enrichment analysis showed enrichment of the Transforming Growth Factor Beta (TGF-β) signaling gene set and downregulation of mechanistic target of rapamycin (mTORC1) signaling gene set in the laser-irradiated cells. Er:YAG laser irradiation at 6.0 J/cm2 promotes MLO-Y4 osteocyte-like cell proliferation via altering gene expression, possibly by activating PI3K-Akt and TGF-β signaling while suppressing mTORC1 signaling.

Brown adipose tissue (BAT) plays a key role in non-shivering thermogenesis and is a promising target for enhancing energy expenditure to combat obesity. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme that catalyzes the conversion of epoxy fatty acids into less active diols. We have reported that local administration of the sEH inhibitor, t-TUCB, to the endogenous interscapular BAT (iBAT) of diet-induced obese mice decreased serum triglycerides and enhanced the expression of essential genes associated with lipid metabolism. Here, the effects of sEH inhibition by t-AUCB were assessed on human brown adipocyte (HuBr) differentiation and in nude mice transplanted with t-AUCB-treated HuBr. HuBr cells were differentiated with t-AUCB (1-10 µM) or the vehicle (0.1% DMSO). HuBr differentiated with t-AUCB at 5 μM (AUCB 5) or DMSO was mixed with matrix gel and transplanted into the nude mice. The mice were then fed a high-fat diet for eight weeks. The mice receiving AUCB 5-treated HuBr exhibited markedly reduced lipid accumulation in the iBAT compared with DMSO or matrix-only controls, along with increased protein expression of thermogenic PGC1α and UCP1, fatty acid transporter CD36, and CPT1A in the iBAT, while the NFκB inflammatory pathways were suppressed in both the AUCB 5 and DMSO groups. Moreover, the PGC1α and CPT1A protein levels were elevated, and the adipocyte sizes were decreased in the epididymal white adipose tissue of the AUCB 5 group. Our findings indicate that the transplantation of HuBr treated with AUCB 5 may stimulate thermogenesis, enhance lipid metabolism, and reduce inflammation in iBAT.

Antigen-specific therapy is needed to induce tolerance in type 1 diabetes at early disease stages or in combination with immunotherapy. We conducted a phase I trial in type 1 diabetes of a novel plasmid construct expressing the islet antigen preproinsulin (PPI) and immunomodulatory cytokines transforming growth factor-β1 (TGF-β1), interleukin-10 (IL-10), and IL-2. The therapy was safe and well tolerated. Dose-dependent changes in DNA plasmid levels and type 1 interferon signatures were detected; however, global and antigen-specific immune changes to PPI, IL-2, IL-10, or TGF-β1 were not observed. Further trials are needed to assess efficacy.