The failure of pancreatic β cells to adapt to an increasing demand for insulin is the major mechanism by which patients progress from insulin resistance to type 2 diabetes (T2D) and is thought to be related to dysfunctional lipid homeostasis within those cells. In multiple animal models of diabetes, females demonstrate relative protection from β cell failure. We previously found that the hormone 17β-estradiol (E2) in part mediates this benefit. Here, we show that treating male Zucker diabetic fatty (ZDF) rats with E2 suppressed synthesis and accumulation of fatty acids and glycerolipids in islets and protected against β cell failure. The antilipogenic actions of E2 were recapitulated by pharmacological activation of estrogen receptor α (ERα) or ERβ in a rat β cell line and in cultured ZDF rat, mouse, and human islets. Pancreas-specific null deletion of ERα in mice (PERα -/-) prevented reduction of lipid synthesis by E2 via a direct action in islets, and PERα -/-mice were predisposed to islet lipid accumulation and β cell dysfunction in response to feeding with a high-fat diet. ER activation inhibited β cell lipid synthesis by suppressing the expression (and activity) of fatty acid synthase via a nonclassical pathway dependent on activated Stat3. Accordingly, pancreas-specific deletion of Stat3 in mice curtailed ER-mediated suppression of lipid synthesis. These data suggest that extranuclear ERs may be promising therapeutic targets to prevent β cell failure in T2D.

Objective Integrating patient-reported outcomes (PROs) into electronic health records (EHRs) can improve patient-provider communication and delivery of care. However, new system implementation in health-care institutions is often accompanied by a change in clinical workflow and organizational culture. This study examines how well an EHR-integrated PRO system fits clinical workflows and individual needs of different provider groups within 2 clinics. Materials and Methods Northwestern Medicine developed and implemented an EHR-integrated PRO system within the orthopedics and oncology departments. We conducted interviews with 11 providers who had interacted with the system. Through thematic analysis, we synthesized themes regarding provider perspectives on clinical workflow, individual needs, and system features. Results Our findings show that EHR-integrated PROs facilitate targeted conversation with patients and automated triage for psychosocial care. However, physicians, psychosocial providers, and medical assistants faced different challenges in their use of the PRO system. Barriers mainly stemmed from a lack of actionable data, workflow disruption, technical issues, and a lack of incentives. Discussion This study sheds light on the ecosystem around EHR-integrated PRO systems (such as user needs and organizational factors). We present recommendations to address challenges facing PRO implementation, such as optimizing data collection and auto-referral processes, improving data visualizations, designing effective educational materials, and prioritizing the primary user group. Conclusion PRO integration into routine care can be beneficial but also require effective technology design and workflow configuration to reach full potential use. This study provides insights into how patient-generated health data can be better integrated into clinical practice and care delivery processes.

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Evidence suggests that chronic low level cadmium exposure impairs the function of insulin-producing β cells and may be associated with type-2 diabetes mellitus. Herein, we describe the cadmium content in primary human islets and define the uptake kinetics and effects of environmentally relevant cadmium concentrations in cultured β cells. The average cadmium content in islets from 10 non-diabetic human subjects was 29 ± 7 nmol/g protein (range 7 to 72 nmol/g protein). Exposure of the β-cell line MIN6 to CdCl2 concentrations between 0.1 and 1.0 µmol/L resulted in a dose- and time-dependent uptake of cadmium over 72 h. This uptake resulted in an induction of metallthionein expression, likely enhancing cellular cadmium accumulation. Furthermore, cadmium accumulation resulted in an inhibition of glucose stimulated insulin secretion in MIN6 cells and primary mouse islets. Our results indicate that this impairment in β-cell function is not due to an increase in cell death or due to an increase in oxidative stress. We conclude that mouse β cells accumulate cadmium in a dose- and time-dependent manner over a prolonged time course at environmentally relevant concentrations. This uptake leads to a functional impairment of β-cell function without significant alterations in cell viability, expression of genes important for β-cell function or increase in oxidative stress.

OBJECTIVEThe Patient-Reported Outcomes Measurement Information System (PROMIS), which is funded by the National Institutes of Health, is a set of adaptive, responsive assessment tools that measures patient-reported health status. PROMIS measures have not been validated for surgical patients with cervical spine disorders. The objective of this project is to evaluate the validity (e.g., convergent validity, known-groups validity, responsiveness to change) of PROMIS computer adaptive tests (CATs) for pain behavior, pain interference, and physical function in patients undergoing cervical spine surgery.METHODSThe legacy outcome measures Neck Disability Index (NDI) and SF-12 were used as comparisons with PROMIS measures. PROMIS CATs, NDI-10, and SF-12 measures were administered prospectively to 59 consecutive tertiary hospital patients who were treated surgically for degenerative cervical spine disorders. A subscore of NDI-5 was calculated from NDI-10 by eliminating the lifting, headaches, pain intensity, reading, and driving sections and multiplying the final score by 4. Assessments were administered preoperatively (baseline) and postoperatively at 6 weeks and 3 months. Patients presenting for revision surgery, tumor, infection, or trauma were excluded. Participants completed the measures in Assessment Center, an online data collection tool accessed by using a secure login and password on a tablet computer. Subgroup analysis was also performed based on a primary diagnosis of either cervical radiculopathy or cervical myelopathy.RESULTSConvergent validity for PROMIS CATs was supported with multiple statistically significant correlations with the existing legacy measures, NDI and SF-12, at baseline. Furthermore, PROMIS CATs demonstrated known-group validity and identified clinically significant improvements in all measures after surgical intervention. In the cervical radiculopathy and myelopathic cohorts, the PROMIS measures demonstrated similar responsiveness to the SF-12 and NDI scores in the patients who self-identified as having postoperative clinical improvement. PROMIS CATs required a mean total of 3.2 minutes for PROMIS pain behavior (mean ± SD 0.9 ± 0.5 minutes), pain interference (1.2 ± 1.9 minutes), and physical function (1.1 ± 1.4 minutes) and compared favorably with 3.4 minutes for NDI and 4.1 minutes for SF-12.CONCLUSIONSThis study verifies that PROMIS CATs demonstrate convergent and known-groups validity and comparable responsiveness to change as existing legacy measures. The PROMIS measures required less time for completion than legacy measures. The validity and efficiency of the PROMIS measures in surgical patients with cervical spine disorders suggest an improvement over legacy measures and an opportunity for incorporation into clinical practice.