Sodium-Glucose Cotransporter 2 Inhibitors Should Be Avoided for the Inpatient Management of Hyperglycemia.

OBJECTIVE: Hyperglycemia in patients with type 2 diabetes mellitus is frequently encountered in the hospital setting. The recent guidelines for the management of inpatient hyperglycemia have included the use of dipeptidyl peptidase 4 inhibitors as an alternative to standard insulin therapy in select patients. This raises the question of the inpatient use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), which have gained increasing popularity in the outpatient setting because of beneficial cardiovascular and renal outcomes. This article describes the risks associated with the use of SGLT2i for the management of inpatient hyperglycemia. METHODS: A literature review was performed using PubMed and Google Scholar for studies assessing the inpatient use of SGLT2i. Search terms included "SGLT2 inhibitors," "euglycemic DKA," "inpatient hyperglycemia," "DPP4 inhibitors," "hypovolemia," and "urinary tract infections." Studies not written in English were excluded. Forty-eight articles were included. RESULTS: Review of the literature showed significant safety concerns with the use of SGLT2i for the inpatient management of hyperglycemia. Hospitalized patients treated with SGLT2i were at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections. When compared head-to-head, SGLT2i were not more effective for inpatient glycemic control than dipeptidyl peptidase 4 inhibitors and did not reduce insulin requirements when used in combination with insulin. Although SGLT2i can be considered for the treatment of congestive heart failure, they should be started close to or at the time of discharge. CONCLUSION: Although SGLT2i are a preferred pharmacotherapy class for the outpatient management of type 2 diabetes mellitus, there are considerable safety concerns when using them in a hospital setting, and avoidance is recommended.

Racial and ethnic differences in post-traumatic stress trajectories in breast cancer survivors.

PURPOSE: To describe differences in post-traumatic stress (PTS) symptoms over time among racial and ethnic minoritized breast cancer survivors (BCS) with comorbid diabetes. DESIGN: In a multisite longitudinal study, post-traumatic stress was evaluated at baseline, 6 and 12 months through self-reported questionnaires (Impact of Events Scale-Revised [IES-R]). PARTICIPANTS: One hundred and seventy-eight post-treatment BCS with diabetes were recruited from three tertiary medical centers. FINDINGS: Relative to non-Hispanic White women, minoritized women reported higher total IES-R scores at all time points. In the adjusted model, Latina women reported persistently higher IES-R total scores and Latina, and 'Other' women reported higher avoidance scores. CONCLUSIONS: Minoritized BCS with comorbid diabetes report higher rates of cancer related PTS that persist over 12 months. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Post diagnosis PTS evaluation and support is important in survivorship and primary care practices. Linkage to socially and culturally sensitive community support may be warranted.

A New Frontier in Telehealth Research: A National Telehealth Data Warehouse.

Importance: Given the rapid increase in telehealth utilization since the onset of the COVID-19 pandemic, it has become essential to examining the vast amount of available data on telehealth encounters to conduct more cogent, robust, and large-scope research studies to examine the utility, cost-impact, and effect on clinical outcomes that telehealth can potentially provide. However, the diversity of data collected by numerous telehealth organizations has made that type of analysis difficult. Objective: The University of Mississippi Medical Center (UMMC), a Telehealth Center of Excellence designated by the Health Resources and Services Administration, is creating a National Telehealth Data Warehouse. Design: UMMC will develop the data warehouse in Microsoft Azure and will use a data dictionary that was created by the Center for Telehealth and eHealth Law (CTeL) to support their national cost-benefit study on the use of telehealth during COVID-19. Impact: The data warehouse will provide unparalleled opportunities to conduct cost-benefit and cost-effectiveness analyses on telehealth, to develop and test quality measures specific to telehealth, and to understand how telehealth and reduce disparities in health care and expand access to care for everyone. The warehouse is expected to go live in the Summer of 2023.

The impact of cognitive impairment on self-regulatory styles in breast cancer survivors.

OBJECTIVE: Cognitive impairment (CI) is highly prevalent in breast cancer survivors (BCS), and can be a barrier to health-promoting behaviours. However, the ways in which CI may affect self-regulation or motivation to perform such behaviours have not been explored. We assessed if BCS with CI report greater extrinsic self-regulation compared to those without CI and if this relationship persists after controlling for depression. METHODS: We recruited BCS with diabetes and assessed cognition and motivation to perform healthy diabetes management behaviours (e.g., diet and exercise). Participants completed a cognitive battery evaluating attention, working memory, executive functioning (EF), processing speed (PS), language and memory. The Treatment Self-Regulation Questionnaire (TSRQ) assessed intrinsic versus extrinsic motivation. Depression was determined by a score ≥16 on the Center for Epidemiological Studies Depression Scale. Wilcoxon rank-sum test compared associations between CI and TSRQ scores. RESULTS: Participants were 118 older adults (mean age 65 years). Participants with CI in the following domains had higher extrinsic self-regulation scores compared to those without CI: attention (p < 0.01), PS (p = 0.01), EF (p < 0.01), language (p = 0.02; p = 0.04) and memory (p = 0.04; p = 0.03). After adjusting for depression, the relationship between CI and higher extrinsic self-regulation scores remained significant. CONCLUSIONS: BCS with CI appear to rely more on external sources of motivation to perform health behaviours, regardless of depression. Future studies and interventions to improve health behaviours should consider screening for CI and involving caregivers for those with CI to improve outcomes.

Racial and ethnic disparities in post-traumatic stress and illness coherence in breast cancer survivors with comorbid diabetes.

CONTEXT: Breast cancer survivors (BCS) with comorbid diabetes mellitus (DM) and of racial and ethnic minority status are at higher risk of cancer-related post-traumatic stress (PTS) and severe illness beliefs. These affective and cognitive outcomes influence self-management and treatment adherence in patients with chronic conditions, yet little is known regarding the interplay of these processes in diverse BCS with comorbid DM. OBJECTIVES: The purposes of this study were to (1) describe racial and ethnic differences in cancer-related PTS and illness perceptions; and (2) examine the relationship between PTS and illness perceptions in BCS with comorbid DM. METHODS: Female BCS with DM completed measures of cancer related stress (Impact of Events Scale-Revised) and cancer and DM illness perception (Illness Perception Questionnaire-Revised). Logistic regression analyses were used to assess the association between PTS, race and illness perceptions. RESULTS: Of the 135 BCS with comorbid DM, the mean (standard deviation) age was 65.3 (7.1) years, 38% were Black, 31% Non-Hispanic White (NHW), 13% Hispanic/Latina, and 18% were "other." Minority women were more likely to report cancer-related PTS (p < 0.01). In adjusted analyses, PTS was associated with chronicity (odds ratio [OR] = 9.79, p = 0.005), time-cycle (OR = 6.71, p = 0.001), negative consequences (OR = 3.95, p = 0.018), and negative emotional impact (OR = 12.63, p < 0.001) of cancer. CONCLUSION: Minority BCS with comorbid DM report higher rates of cancer-related PTS and lower cancer illness coherence relative to NHW survivors. Cancer-related PTS influences cancer and DM illness perceptions. Culturally sensitive care is needed to improve these outcomes in minority BCS. KEY MESSAGE: This article presents findings from a cross sectional cohort of an understudied population of racially and ethnically diverse BCS with comorbid diabetes. The results indicate that the occurrence of PTS is significantly higher in racial and ethnic minority women and is strongly associated with more severe illness perceptions.

Adapting a home telemonitoring intervention for underserved Hispanic/Latino patients with type 2 diabetes: an acceptability and feasibility study.

BACKGROUND: Home telemonitoring is a promising approach to optimizing outcomes for patients with Type 2 Diabetes; however, this care strategy has not been adapted for use with understudied and underserved Hispanic/Latinos (H/L) patients with Type 2 Diabetes. METHODS: A formative, Community-Based Participatory Research approach was used to adapt a home telemonitoring intervention to facilitate acceptability and feasibility for vulnerable H/L patients. Utilizing the ADAPT-ITT framework, key stakeholders were engaged over an 8-month iterative process using a combination of strategies, including focus groups and structured interviews. Nine Community Advisory Board, Patient Advisory, and Provider Panel Committee focus group discussions were conducted, in English and Spanish, to garner stakeholder input before intervention implementation. Focus groups and structured interviews were also conducted with 12 patients enrolled in a 1-month pilot study, to obtain feedback from patients in the home to further adapt the intervention. Focus groups and structured interviews were approximately 2 hours and 30 min, respectively. All focus groups and structured interviews were audio-recorded and professionally transcribed. Structural coding was used to mark responses to topical questions in the moderator and interview guides. RESULTS: Two major themes emerged from qualitative analyses of Community Advisory Board/subcommittee focus group data. The first major theme involved intervention components to maximize acceptance/usability. Subthemes included tablet screens (e.g., privacy/identity concerns; enlarging font sizes; lighter tablet to facilitate portability); cultural incongruence (e.g., language translation/literacy, foods, actors "who look like me"); nursing staff (e.g., ensuring accessibility; appointment flexibility); and, educational videos (e.g., the importance of information repetition). A second major theme involved suggested changes to the randomized control trial study structure to maximize participation, including a major restructuring of the consenting process and changes designed to optimize recruitment strategies. Themes from pilot participant focus group/structured interviews were similar to those of the Community Advisory Board such as the need to address and simplify a burdensome consenting process, the importance of assuring privacy, and an accessible, culturally congruent nurse. CONCLUSIONS: These findings identify important adaptation recommendations from the stakeholder and potential user perspective that should be considered when implementing home telemonitoring for underserved patients with Type 2 Diabetes. TRIAL REGISTRATION: NCT03960424; ClinicalTrials.gov (US National Institutes of Health). Registered 23 May 2019. Registered prior to data collection. https://www.clinicaltrials.gov/ct2/show/NCT03960424?term=NCT03960424&draw=2&rank=1.

Exploratory study of impact of cancer-related posttraumatic stress symptoms on diabetes self-management among cancer survivors.

OBJECTIVE: Posttraumatic stress symptoms (PTSS) can be triggered by a diagnosis of a potentially life-threatening illness such as cancer. Little is known about the impact of cancer-related PTSS symptoms on self-management behaviors for comorbid chronic medical conditions such as diabetes mellitus (DM). METHODS: We recruited patients with DM and a recent diagnosis of early-stage cancer from 2 medical centers in New York City. Cancer-related PTSS were assessed using the Impact of Events Scale (score ≥ 26). DM self-management behaviors (medication adherence, exercise, healthy diet, and glucose testing) were measured 3 months later. Logistic regression was used to assess the association between cancer-related PTSS symptoms and DM self-management behaviors, adjusting for gender, marital status, and anxiety symptoms. RESULTS: Of 56 participants recruited, 33% reported cancer-related PTSS symptoms. Elevated cancer-related PTSS symptoms were associated with lack of healthy diet (odds ratio: 0.08, 95% confidence interval: 0.01-0.62). CONCLUSIONS: Early-stage cancer survivors with cancer-related PTSS symptoms were less likely to adhere to some DM self-management behaviors. Providers should recognize the impact of cancer-related PTSS symptoms to better support comorbid disease management in cancer survivors.

Building the Evidence Base for Tele-Emergency Care: Efforts to Identify a Standardized Set of Outcome Measures.

BACKGROUND: To enhance the quality of emergency department (ED) care, some rural hospitals have adopted the use of telemedicine (tele-ED). Without a common set of metrics, it is difficult to quantify the impact of this technology. INTRODUCTION: To address this limitation, the Health Resources and Services Administration funded the identification and testing of a core set of measures that could be used to build a business case for the value of tele-ED care. METHODS: A comprehensive environmental scan was conducted to identify existing measures relevant to assessing ED care and the use of telemedicine. Identified measures were assessed against a set of criteria and pilot tested in rural hospitals. RESULTS: The environmental scan identified numerous ED-specific measures and a limited set of telehealth-specific measures, but no clearly defined measures specific to tele-ED. Applying evaluation criteria to the measures revealed that few have a well-established evidence base, and fewer have undergone the rigorous testing needed to establish statistical reliability and validity. Nevertheless, a parsimonious set of measures was identified that met many of the evaluation criteria. Pilot testing indicated that collecting data using these measures was feasible. DISCUSSION: For tele-ED benefits to be widely acknowledged, more research is required to demonstrate that care delivered using tele-ED care is as high quality, if not more so, than in-person care. This requires researchers to consistently use a set of clearly defined measures. CONCLUSION: The use of clearly defined and standardized measures will aid interpretation and permit replication in multiple studies, furthering acceptance of study findings.

Endocrine Dysfunction in Diamond-Blackfan Anemia (DBA): A Report from the DBA Registry (DBAR).

BACKGROUND: Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome. The mainstays of treatment involve chronic red cell transfusions, long-term glucocorticoid therapy, and stem cell transplantation. Systematic data concerning endocrine function in DBA are limited. We studied patients in the DBA Registry (DBAR) of North America to assess the prevalence of various endocrinopathies. PROCEDURE: In a pilot study, retrospective data were collected for 12 patients with DBA. Subsequently, patients with DBA aged 1-39 years were recruited prospectively. Combined, 57 patients were studied; 38 chronically transfused, 12 glucocorticoid-dependent, and seven in remission. Data were collected on anthropometric measurements, systematic screening of pituitary, thyroid, parathyroid, adrenal, pancreatic, and gonadal function, and ferritin levels. Descriptive statistics were tabulated and group differences were assessed. RESULTS: Fifty-three percent of patients had ≥ 1 endocrine disorder, including adrenal insufficiency (32%), hypogonadism (29%), hypothyroidism (14%), growth hormone dysfunction (7%), diabetes mellitus (2%), and/or diabetes insipidus (2%). Ten of the 33 patients with available heights had height standard deviation less than -2. Low 25-hydroxy vitamin D (25(OH)D) levels were present in 50%. A small proportion also had osteopenia, osteoporosis, or hypercalciuria. Most with adrenal insufficiency were glucocorticoid dependent; other endocrinopathies were more common in chronically transfused patients. CONCLUSIONS: Endocrine dysfunction is common in DBA, as early as the teenage years. Although prevalence is highest in transfused patients, patients taking glucocorticoids or in remission also have endocrine dysfunction. Longitudinal studies are needed to better understand the etiology and true prevalence of these disorders.

Advancing Medication Safety: Establishing a National Action Plan for Adverse Drug Event Prevention.

BACKGROUND: Adverse drug events (ADEs) are important contributors to preventable morbidity and mortality, comprising one third of all hospital adverse events. In response to growing evidence detailing the high prevalence of ADEs, particularly among vulnerable older adults, Congress requested that the Secretary of the Department of Health and Human Services (HHS) convene a Federal Interagency Steering Committee to establish a National Action Plan to focus on ADE prevention. In August 2014, the Office of Disease Prevention and Health Promotion released the final version of the National Action Plan for Adverse Drug Event Prevention. The Action Plan directly supports the goals of the HHS Strategic Plan and the Patient Protection and Affordable Care Act by providing guidance on tracking and preventing ADEs, as well as describing evidence-based tools and resources to enhance medication safety. ADE ACTION PLAN CONTENT: The Federal Interagency Steering Committee focused the Action Plan on ADEs that are clinically significant, account for the greatest number of measurable harms as identified by using existing surveillance tools, and are largely preventable. As such, the decision was made to target three medication classes: anticoagulants, diabetes agents (insulin and oral hypoglycemic agents), and opioids. The Action Plan is organized around four key areas: surveillance; evidence-based prevention; payment, policy incentives, and oversight; and research opportunities to advance medication safety. CONCLUSION: One measure of the ADE Action Plan's success will be the wider dissemination of information and educational resources to providers and patients (or consumers) regarding the risks associated with medications. Future Action Plan iterations are likely to consider other high-priority medication classes and update the recommendations.

Federal efforts to define and advance telehealth--a work in progress.

BACKGROUND: The integration of telecommunications and information systems in healthcare is not new or novel; indeed, it is the current practice of medicine and has been an integral part of medicine in remote locations for several decades. The U.S. Government has made a significant investment, measured in hundreds of millions of dollars, and therefore has a strong presence in the integration of telehealth/telemedicine in healthcare. However, the terminologies and definitions in the lexicon vary across agencies and departments of the U.S. Government. The objective of our survey was to identify and evaluate the definitions of telehealth/telemedicine across the U.S. Government to provide a better understanding of what each agency or department means when it uses these terms. METHODOLOGY: The U.S. Government, under the leadership of the Health Resources and Services Administration in the U.S. Department of Health and Human Services, established the Federal Telemedicine (FedTel) Working Group, through which all members responded to a survey on each agency or department's definition and use of terms associated with telehealth. RESULTS AND CONCLUSIONS: Twenty-six agencies represented by more than 100 individuals participating in the FedTel Working Group identified seven unique definitions of telehealth in current use across the U.S. Government. Although many definitions are similar, there are nuanced differences that reflect each organization's legislative intent and the population they serve. These definitions affect how telemedicine has been or is being applied across the healthcare landscape, reflecting the U.S. Government's widespread and influential role in healthcare access and service delivery. The evidence base suggests that a common nomenclature for defining telemedicine may benefit efforts to advance the use of this technology to address the changing nature of healthcare and new demands for services expected as a result of health reform.

Ensuring fidelity: key elements to consider in disseminating a diabetes telemanagement program for underserved Hispanic/Latinos living with type 2 diabetes.

Background: The Hispanic/Latino population has greater risk (estimated >50%) of developing type 2 diabetes (T2D) and developing it at a younger age. The American Diabetes Association estimates costs of diagnosed diabetes in 2017 was $327 billion; with medical costs 2.3x higher than patients without diabetes. The purpose of this manuscript is to describe the methodology utilized in a randomized controlled trial aimed at evaluating the efficacy of a diabetes telemanagement (DTM) program for Hispanic/Latino patients with T2D. The intent is to provide information for future investigators to ensure that this study can be accurately replicated. Methods: This study was a randomized controlled trial with 240 participants. Eligible patients (Hispanic/Latino, aged 18+, living with T2D) were randomized to Comprehensive Outpatient Management (COM) or DTM. DTM was comprised of usual care, including routine clinic visits every three months, as well as: Biometrics (a tablet, blood glucose meter, blood pressure monitor, and scale); Weekly Video Visits (facilitated in the patient's preferred language); and Educational Videos (including culturally congruent diabetes self-management education and quizzes). COM consisted of usual care including routine clinic visits every three months. For this study, COM patients received a glucometer, glucose test strips, and lancets. Establishing a therapeutic nurse-patient relationship was a fundamental component of our study for both groups. First contact (post-enrollment) centered on ensuring that patients and caregivers understood the program, building trust and rapport, creating a non-judgmental environment, determining language preference, and establishing scheduling availability (including evenings and weekends). DTM were provided with a tablet which allowed for self-paced education through videos and weekly video visits. The research team and Community Advisory Board identified appropriate educational video content, which was incorporated in diabetes educational topics. Video visits allowed us to assess patient involvement, motivation, and nonverbal communication. Communicating in Spanish, and awareness of diverse Hispanic/Latino backgrounds was critical, as using relevant and commonly-used terms can increase adherence and improve outcomes. Shared decision-making was encouraged to make realistic health care choices. Conclusion: Key elements discussed above provide a framework for future dissemination of an evidence-based DTM intervention to meet the needs of underserved Hispanic/Latino people living with T2D.

Lack of evidence for telehealth fraud.

Despite evidence to the contrary, U.S. policy makers, payers, and the public continue to express apprehension that the use of telehealth is associated with increased risk of fraud and abuse. The fraudulent use of telehealth is multifaceted and complex, ranging from potentially false claims to miscoding, inaccurate billing, and kickbacks. For the past 6 years, the U.S. Federal Government has undertaken research studies to examine potential fraud issues related to the use of telehealth, including up-coding time spent with the patient, misrepresentation of the service provided, and billing for services that were not rendered. This article reviews previous efforts to assess the risk of fraud associated with the delivery of virtual care in America, concluding that there is little evidence for higher levels of fraud and abuse related to the use of telehealth.

Assessing the Effect of Cancer Diagnosis on Beliefs about Comorbid Diabetes.

OBJECTIVES: Increasingly, patients diagnosed with cancer also live with chronic comorbidities, and it is important to understand the impact of a new cancer diagnosis on perceptions about preexisting conditions. This study assessed the effect of cancer diagnosis on beliefs about comorbid diabetes mellitus and assessed changes in beliefs about cancer and diabetes over time. DATA SOURCES: We recruited 75 patients with type 2 diabetes who were newly diagnosed with early-stage breast, prostate, lung, or colorectal cancer and 104 age-, sex-, and hemoglobin A1c-matched controls. Participants completed the Brief Illness Perception Questionnaire four times over 12 months. The authors examined within-patient and between-group differences in cancer and diabetes beliefs at baseline and over time. RESULTS: Overall, diabetes beliefs did not differ between cancer patients and controls at baseline. Cancer patients' beliefs about diabetes varied significantly over time; they reported less concern about cancer, less emotional effect, and greater cancer knowledge over time. Participants without cancer were significantly more likely to report that diabetes affected their life across all time points, though this effect did not persist after adjustment for sociodemographic variables. CONCLUSION: While all patients' diabetes beliefs were similar at baseline and 12 months, cancer patients' beliefs about both illnesses fluctuated during the months following cancer diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can play a key role in recognizing the effects of cancer diagnosis on beliefs about comorbid conditions and fluctuations in these beliefs during treatment. Assessing and communicating patient beliefs between oncology and other practitioners could produce more effective care plans based on patients' current outlook on their health.

Cancer beliefs and diet self-management among cancer survivors with comorbid diabetes.

PURPOSE: Illness beliefs impact disease self-management; however, little is known about the impact of patients' beliefs about one illness on the management of another illness. We sought to understand how cancer beliefs impact diet self-management for cancer survivors with diabetes and whether a change in beliefs leads to a change in dietary adherence. METHODS: Seventy-eight participants with diabetes and recently diagnosed early-stage breast, prostate, lung, or colon cancer were recruited. Participants were surveyed at enrollment and after 12 months about their cancer and diabetes illness beliefs and dietary adherence. Associations between beliefs about cancer and diabetes to diet adherence at baseline and at 12 months were assessed. Change in diet adherence was examined in relation to beliefs about each illness. RESULTS: The mean age was 62 years, and 23 (32%) identified as black non-Hispanic, 22 (31%) as white non-Hispanic, and 14 (19%) as Hispanic. Participants with more threatening beliefs about both cancer and diabetes at baseline had worse adherence to a diabetes diet than those with less threatening beliefs. However, at 12 months, those with more threatening cancer beliefs had better dietary adherence than participants with less threatening beliefs. Diabetes beliefs were not associated with diet adherence at 12 months. CONCLUSIONS: While threatening illness beliefs may initially result in worse diet adherence, over time these beliefs may result in increased activation for better self-care and improved diet adherence. IMPLICATIONS FOR CANCER SURVIVORS: Understanding how cancer beliefs impact diet self-management for diabetes may provide coping strategies to improve cancer survivors' management of comorbidities.

COVID-19 stressors for Hispanic/Latino patients living with type 2 diabetes: a qualitative study.

Background and aim: During the early stages of the COVID-19 pandemic, nationwide lockdowns caused disruption in the diets, physical activities, and lifestyles of patients with type 2 diabetes. Previous reports on the possible association between race/ethnicity, COVID-19, and mortality have shown that Hispanic/Latino patients with type 2 diabetes who are socioeconomically disadvantaged are disproportionately affected by this novel virus. The aim of this study was to explore stressors associated with changes in diabetes self-management behaviors. Our goal was to highlight the health disparities in these vulnerable racial/ethnic minority communities and underscore the need for effective interventions. Methods and participants: Participants were enrolled in part of a larger randomized controlled trial to compare diabetes telehealth management (DTM) with comprehensive outpatient management (COM) in terms of critical patient-centered outcomes among Hispanic/Latino patients with type 2 diabetes. We conducted a thematic analysis using patient notes collected from two research nurses between March 2020 and March 2021. Two authors read through the transcripts independently to identify overarching themes. Once the themes had been identified, both authors convened to compare themes and ensure that similar themes were identified within the transcripts. Any discrepancies were discussed by the larger study team until a consensus was reached. Results: Six themes emerged, each of which can be categorized as either a source or an outcome of stress. Sources of stress associated with the COVID-19 pandemic were (1) fear of contracting COVID-19, (2) disruptions from lockdowns, and (3) financial stressors (e.g., loss of income). Outcomes of COVID-19 stressors were (1) reduced diabetes management (e.g., reduced diabetes monitoring and physical activity), (2) suboptimal mental health outcomes (e.g., anxiety and depression), and (3) outcomes of financial stressors. Conclusion: The findings indicated that underserved Hispanic/Latino patients with type 2 diabetes encountered a number of stressors that led to the deterioration of diabetes self-management behaviors during the pandemic.

Identification of pigment epithelium-derived factor as an adipocyte-derived inflammatory factor.

Obesity is a major risk factor for insulin resistance, type 2 diabetes mellitus and cardiovascular disease. The pathophysiology of obesity is associated with chronic low-grade inflammation. Adipose tissue in obesity is significantly infiltrated by macrophages that secrete cytokines. The mechanisms of interaction between macrophages and adipocytes, leading to macrophage activation and increased cytokine release, remain to be elucidated. We reasoned that an adipocyte-derived factor might stimulate activation of macrophages. We have identified pigment epithelium-derived factor (PEDF) as a mediator of inflammation that is secreted by adipocytes and mediates macrophage activation. Recombinant PEDF activates macrophages to release tumor necrosis factor (TNF) and interleukin-1 (IL-1). The PEDF receptor adipose triglyceride lipase (ATGL) is required for PEDF-mediated macrophage activation. Selective inhibition of ATGL on macrophages attenuates PEDF-induced TNF production, and PEDF enhances the phosphorylation of p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases. PEDF administration to rats results in increased serum TNF levels, and insulin resistance. Together, these findings suggest that PEDF secreted by adipocytes contributes to the onset and maintenance of chronic inflammation in obesity, and may be a therapeutic target in ameliorating insulin resistance.

Galantamine alleviates inflammation and other obesity-associated complications in high-fat diet-fed mice.

Obesity, a serious and growing health threat, is associated with low-grade inflammation that plays a role in mediating its adverse consequences. Previously, we have discovered a role for neural cholinergic signaling in controlling inflammation, and demonstrated that the cholinergic agent galantamine suppresses excessive proinflammatory cytokine release. The main objective of this study was to examine the efficacy of galantamine, a clinically-approved drug, in alleviating obesity-related inflammation and associated complications. After 8 wks on a high-fat diet, C57BL/6J mice were treated with either galantamine (4 mg/kg, intraperitoneally [i.p.]) or saline for 4 wks in parallel with mice on a low-fat diet and treated with saline. Galantamine treatment of obese mice significantly reduced body weight, food intake, abdominal adiposity, plasma cytokine and adipokine levels, and significantly improved blood glucose, insulin resistance and hepatic steatosis. In addition, galantamine alleviated impaired insulin sensitivity and glucose intolerance significantly. These results indicate a previously unrecognized potential of galantamine in alleviating obesity, inflammation and other obesity-related complications in mice. These findings are of interest for studying the efficacy of this clinically-approved drug in the context of human obesity and metabolic syndrome.

Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia.

The autonomic nervous system maintains homeostasis through its sympathetic and parasympathetic divisions. During infection, cells of the immune system release cytokines and other mediators that cause fever, hypotension, and tissue injury. Although the effect of cytokines on the nervous system has been known for decades, only recently has it become evident that the autonomic nervous system, in turn, regulates cytokine production through neural pathways. We have previously shown that efferent vagus nerve signals regulate cytokine production through the nicotinic acetylcholine receptor subunit alpha7, a mechanism termed "the cholinergic antiinflammatory pathway." Here, we show that vagus nerve stimulation during endotoxemia specifically attenuates TNF production by spleen macrophages in the red pulp and the marginal zone. Administration of nicotine, a pharmacological agonist of alpha7, attenuated TNF immunoreactivity in these specific macrophage subpopulations. Synaptophysin-positive nerve endings were observed in close apposition to red pulp macrophages, but they do not express choline acetyltransferase or vesicular acetylcholine transporter. Surgical ablation of the splenic nerve and catecholamine depletion by reserpine indicate that these nerves are catecholaminergic and are required for functional inhibition of TNF production by vagus nerve stimulation. Thus, the cholinergic antiinflammatory pathway regulates TNF production in discrete macrophage populations via two serially connected neurons: one preganglionic, originating in the dorsal motor nucleus of the vagus nerve, and the second postganglionic, originating in the celiac-superior mesenteric plexus, and projecting in the splenic nerve.