Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP.

While much work has been done in associating differentially methylated positions (DMPs) to type 2 diabetes (T2D) across different populations, not much attention has been placed on identifying its possible functional consequences. We explored methylation changes in the peripheral blood of Filipinos with T2D and identified 177 associated DMPs. Most of these DMPs were associated with genes involved in metabolism, inflammation and the cell cycle. Three of these DMPs map to the TXNIP gene body, replicating previous findings from epigenome-wide association studies (EWAS) of T2D. The TXNIP downmethylation coincided with increased transcription at the 3' UTR, H3K36me3 histone markings and Sp1 binding, suggesting spurious transcription initiation at the TXNIP 3' UTR as a functional consequence of T2D methylation changes. We also explored potential epigenetic determinants to increased incidence of T2D in Filipino immigrants in the USA and found three DMPs associated with the interaction of T2D and immigration. Two of these DMPs were located near MAP2K7 and PRMT1, which may point towards dysregulated stress response and inflammation as a contributing factor to T2D among Filipino immigrants.

Dose-dependent quantitative effects of acute fructose administration on hepatic de novo lipogenesis in healthy humans.

Fructose feeding increases hepatic de novo lipogenesis (DNL) and is associated with nonalcoholic fatty liver disease. Little is known, however, about individual variation in susceptibility to fructose stimulation of DNL. In this three-period crossover study, 17 healthy male subjects were enrolled to evaluate the within- and between-subject variability of acute fructose feeding on hepatic fractional DNL. During each assessment, [1-13C1]acetate was infused to measure DNL in the fasting state and during fructose feeding. Subjects randomly received a high dose of fructose (10 mg·kg fat-free mass-1·min-1) on two occasions and a low dose (5 mg·kg fat-free mass-1·min-1) on another. Fructose solutions were administered orally every 30 min for 9.5 h. Ten subjects completed all three study periods. DNL was assessed as the fractional contribution of newly synthesized palmitate into very-low-density lipoprotein triglycerides using mass isotopomer distribution analysis. Mean fasting DNL was 5.3 ± 2.8%, with significant within- and between-subject variability. DNL increased dose dependently during fructose feeding to 15 ± 2% for low- and 29 ± 2% for high-dose fructose. The DNL response to high-dose fructose was very reproducible within an individual ( r = 0.93, P < 0.001) and independent of fasting DNL. However, it was variable between individuals and significantly correlated to influx of unlabeled acetyl-CoA ( r = 0.7, P < 0.001). Unlike fasting DNL, fructose-stimulated DNL is a robust and reproducible measure of hepatic lipogenic activity for a given individual and may be a useful indicator of metabolic disease susceptibility and treatment response.

Evaluating diverse electronic consultation programs with a common framework.

BACKGROUND: Electronic consultation is an emerging mode of specialty care delivery that allows primary care providers and their patients to obtain specialist expertise without an in-person visit. While studies of individual programs have demonstrated benefits related to timely access to specialty care, electronic consultation programs have not achieved widespread use in the United States. The lack of common evaluation metrics across health systems and concerns related to the generalizability of existing evaluation efforts may be hampering further growth. We sought to identify gaps in knowledge related to the implementation of electronic consultation programs and develop a set of shared evaluation measures to promote further diffusion. METHODS: Using a case study approach, we apply the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) and the Quadruple Aim frameworks of evaluation to examine electronic consultation implementation across diverse delivery systems. Data are from 4 early adopter healthcare delivery systems (San Francisco Health Network, Mayo Clinic, Veterans Administration, Champlain Local Health Integration Network) that represent varied organizational structures, care for different patient populations, and have well-established multi-specialty electronic consultation programs. Data sources include published and unpublished quantitative data from each electronic consultation database and qualitative data from systems' end-users. RESULTS: Organizational drivers of electronic consultation implementation were similar across the systems (challenges with timely and/or efficient access to specialty care), though unique system-level facilitators and barriers influenced reach, adoption and design. Effectiveness of implementation was consistent, with improved patient access to timely, perceived high-quality specialty expertise with few negative consequences, garnering high satisfaction among end-users. Data about patient-specific clinical outcomes are lacking, as are policies that provide guidance on the legal implications of electronic consultation and ideal remuneration strategies. CONCLUSION: A core set of effectiveness and implementation metrics rooted in the Quadruple Aim may promote data-driven improvements and further diffusion of successful electronic consultation programs.

Group visits to encourage insulin initiation: targeting patient barriers.

AIMS AND OBJECTIVES: To evaluate the effect of an 'insulin introduction' group visit on insulin initiation and A1C in adults with type 2 diabetes. BACKGROUND: The clinical course of type 2 diabetes involves eventual beta-cell failure and the need for insulin therapy. Patient psychological insulin resistance, provider-related delays and system barriers to timely initiation of insulin are common. Group visits are widely accepted by patients and represent a potential strategy for improving insulin initiation. DESIGN: A single two-hour group visit in English or Spanish, facilitated by advanced practice nurses, addressed psychological insulin resistance and encouraged mock injections to overcome needle anxiety. METHODS: A retrospective review of 273 patients referred from 2008-2012, determined characteristics of group attenders, rates of mock self-injection, rates of insulin initiation and changes in A1C from baseline to 2-6 and 7-12 months postgroup. Change in A1C was compared to patients referred to the group who did not attend ('nonattenders'). RESULTS: Of 241 patients eligible for analysis, 87·6% were racial/ethnic minorities with an average A1C of 9·99%. Group attendance rate was 66%; 92% performed a mock injection, 55% subsequently started insulin. By 2-6 months, A1C decreased by 1·37% among group attenders, and by 1·6% in those who did a mock injection and started insulin. Fewer nonattenders started insulin in primary care (40%), experiencing an A1C reduction of 0·56% by 2-6 months. A1C improvements were sustained by 7-12 months among group attenders and nonattenders who started insulin. RELEVANCE TO CLINICAL PRACTICE: Nurses can effectively address patient fears and engage patients in reframing insulin therapy within group visits. CONCLUSIONS: This one-time nurse-facilitated group visit addressing psychological barriers to insulin in a predominantly minority patient population resulted in increased insulin initiation rates and clinically meaningful A1C reductions.

Facilitators and barriers to implementing electronic referral and/or consultation systems: a qualitative study of 16 health organizations.

BACKGROUND: Access to specialty care remains a challenge for primary care providers and patients. Implementation of electronic referral and/or consultation (eCR) systems provides an opportunity for innovations in the delivery of specialty care. We conducted key informant interviews to identify drivers, facilitators, barriers and evaluation metrics of diverse eCR systems to inform widespread implementation of this model of specialty care delivery. METHODS: Interviews were conducted with leaders of 16 diverse health care delivery organizations between January 2013 and April 2014. A limited snowball sampling approach was used for recruitment. Content analysis was used to examine key informant interview transcripts. RESULTS: Electronic referral systems, which provide referral management and triage by specialists, were developed to enhance tracking and operational efficiency. Electronic consultation systems, which encourage bi-directional communication between primary care and specialist providers facilitating longitudinal virtual co-management, were developed to improve access to specialty expertise. Integrated eCR systems leverage both functionalities to enhance the delivery of coordinated, specialty care at the population level. Elements of successful eCR system implementation included executive and clinician leadership, established funding models for specialist clinician reimbursement, and a commitment to optimizing clinician workflows. CONCLUSIONS: eCR systems have great potential to streamline access to and enhance the coordination of specialty care delivery. While different eCR models help solve different organizational challenges, all require institutional investments for successful implementation, such as funding for program management, leadership and clinician incentives.

A yoga intervention for type 2 diabetes risk reduction: a pilot randomized controlled trial.

BACKGROUND: Type 2 diabetes is a major health problem in many countries including India. Yoga may be an effective type 2 diabetes prevention strategy in India, particularly given its cultural familiarity. METHODS: This was a parallel, randomized controlled pilot study to collect feasibility and preliminary efficacy data on yoga for diabetes risk factors among people at high risk of diabetes. Primary outcomes included: changes in BMI, waist circumference, fasting blood glucose, postprandial blood glucose, insulin, insulin resistance, blood pressure, and cholesterol. We also looked at measures of psychological well-being including changes in depression, anxiety, positive and negative affect and perceived stress. Forty-one participants with elevated fasting blood glucose in Bangalore, India were randomized to either yoga (n = 21) or a walking control (n = 20). Participants were asked to either attend yoga classes or complete monitored walking 3-6 days per week for eight weeks. Randomization and allocation was performed using computer-generated random numbers and group assignments delivered in sealed, opaque envelopes generated by off-site study staff. Data were analyzed based on intention to treat. RESULTS: This study was feasible in terms of recruitment, retention and adherence. In addition, yoga participants had significantly greater reductions in weight, waist circumference and BMI versus control (weight -0.8 ± 2.1 vs. 1.4 ± 3.6, p = 0.02; waist circumference -4.2 ± 4.8 vs. 0.7 ± 4.2, p < 0.01; BMI -0.2 ± 0.8 vs. 0.6 ± 1.6, p = 0.05). There were no between group differences in fasting blood glucose, postprandial blood glucose, insulin resistance or any other factors related to diabetes risk or psychological well-being. There were significant reductions in systolic and diastolic blood pressure, total cholesterol, anxiety, depression, negative affect and perceived stress in both the yoga intervention and walking control over the course of the study. CONCLUSION: Among Indians with elevated fasting blood glucose, we found that participation in an 8-week yoga intervention was feasible and resulted in greater weight loss and reduction in waist circumference when compared to a walking control. Yoga offers a promising lifestyle intervention for decreasing weight-related type 2 diabetes risk factors and potentially increasing psychological well-being. TRIAL REGISTRATION: ClinicalTrials.gov Identified NCT00090506.

Altered subcutaneous abdominal adipose tissue lipid synthesis in obese, insulin-resistant humans.

The purpose of this study was to evaluate the variability of subcutaneous abdominal adipose tissue (AT) dynamics in obese subjects with a wide range of insulin sensitivity (IS) and the correlation between these two metabolic measures. Ten obese (BMI 30-40 kg/m²) nondiabetic subjects with (n = 6) and without (n = 4) the metabolic syndrome were studied following a 12-wk ²H2O labeling period. Subcutaneous abdominal AT biopsies were collected. Deuterium incorporation into triglyceride (TG)-glycerol and TG-palmitate were measured by gas chromatography-mass spectrometry for the calculation of fractional TG synthesis (fTG) and fractional de novo lipogenesis (fDNL). Muscle IS and insulin-mediated nonesterified fatty acid (NEFA) suppression (a measure for adipose IS) indexes were derived from the oral glucose tolerance test (OGTT). The ability of subcutaneous abdominal AT to synthesize lipids varied significantly in obese subjects (fTG range 7-28%, fDNL range 1.1-4.6%) with significantly lower values (>35% reduction) for both parameters in obese with the metabolic syndrome. fTG correlated positively with muscle IS (r = 0.64, P = 0.04) and inversely with NEFA suppression during the OGTT (r = -0.69, P = 0.03). These results demonstrate a large variability in subcutaneous abdominal AT lipid turnover in obesity. Moreover, a reduced capacity for subcutaneous abdominal AT fat storage is associated with muscle and adipose tissue insulin resistance as well as with the metabolic syndrome, thus identifying a form of obesity at heightened risk for type 2 diabetes and cardiovascular disease.

24-hydroxycholesterol replacement rate measured in blood is a non-invasive biomarker of brain demyelination and remyelination in cuprizone-treated mice.

In mice, dietary cuprizone causes brain demyelination with subsequent spontaneous remyelination upon return to normal chow. Heavy water (2H2O) labeling with mass spectrometric analysis can be used to measure brain de novo synthesis of several myelin components including cholesterol, phospholipids, galactocereboside (GalC) and myelin-associated proteins. 24-hydroxycholesterol (24-OHC), the major metabolite of brain cholesterol, is detected in blood and is believed to be specifically derived from CNS cholesterol metabolism. We assessed changes in syntheses of myelin components in brain and of blood sterols during cuprizone-induced experimental demyelination and remyelination, with and without thyroid hormone (T3) treatment. Mice were fed cuprizone for 4 weeks, then returned to control diet and treated with either placebo or T3 (0.005 mg/day). 2H2O was administered for the last 14 days of cuprizone diet, and for either 6, 12 or 19 days of treatment during recovery from cuprizone, after which blood and corpus callosum (CC) samples were collected (n = 5/time point/treatment). 2H incorporation into cholesterol and 24-OHC in blood and CC, and incorporation into phospholipid (PL)-palmitate, GalC, myelin basic protein (MBP) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) in CC were measured. Cuprizone significantly (p < 0.05) decreased syntheses of cholesterol, 24-OHC, GalC, MBP, CNPase and PL-palmitate in the CC and these effects were all reversed during recovery. T3 treatment significantly (p < 0.05) increased syntheses of cholesterol, 24-OHC and palmitate compared to placebo. 24-OHC and cholesterol turnover rates in brain and blood were nearly identical and 24-OHC rates in blood paralleled rates in CC, indicating that blood 24-OHC derives primarily from the brain and reflects oligodendrocyte function. In summary, changes in synthesis of several lipid and protein components in brain during cuprizone-induced demyelination and remyelination are measurable through stable isotope labeling. Blood 24-OHC turnover rates closely reflect flux rates of brain cholesterol in response to cuprizone and T3, which alter oligodendrocyte function. Labeling of blood 24-OHC has potential as a non-invasive marker of brain de novo cholesterol synthesis and breakdown rates in demyelinating conditions.

Intraclonal complexity in chronic lymphocytic leukemia: fractions enriched in recently born/divided and older/quiescent cells.

The failure of chemotherapeutic regimens to eradicate cancers often results from the outgrowth of minor subclones with more dangerous genomic abnormalities or with self-renewing capacity. To explore such intratumor complexities in B-cell chronic lymphocytic leukemia (CLL), we measured B-cell kinetics in vivo by quantifying deuterium ((2)H)-labeled cells as an indicator of a cell that had divided. Separating CLL clones on the basis of reciprocal densities of chemokine (C-X-C motif) receptor 4 (CXCR4) and cluster designation 5 (CD5) revealed that the CXCR4(dim)CD5(bright) (proliferative) fraction contained more (2)H-labeled DNA and hence divided cells than the CXCR4(bright)CD5(dim) (resting) fraction. This enrichment was confirmed by the relative expression of two cell cycle-associated molecules in the same fractions, Ki-67 and minichromosome maintenance protein 6 (MCM6). Comparisons of global gene expression between the CXCR4(dim)CD5(bright) and CXCR4(bright)CD5(dim) fractions indicated higher levels of pro-proliferation and antiapoptotic genes and genes involved in oxidative injury in the proliferative fraction. An extended immunophenotype was also defined, providing a wider range of surface molecules characteristic of each fraction. These intraclonal analyses suggest a model of CLL cell biology in which the leukemic clone contains a spectrum of cells from the proliferative fraction, enriched in recently divided robust cells that are lymphoid tissue emigrants, to the resting fraction enriched in older, less vital cells that need to immigrate to lymphoid tissue or die. The model also suggests several targets preferentially expressed in the two populations amenable for therapeutic attack. Finally, the study lays the groundwork for future analyses that might provide a more robust understanding of the development and clonal evolution of this currently incurable disease.

Improved glycemic control with colesevelam treatment in patients with type 2 diabetes is not directly associated with changes in bile acid metabolism.

UNLABELLED: Bile acids (BAs) are essential for fat absorption and appear to modulate glucose and energy metabolism. Colesevelam, a BA sequestrant, improves glycemic control in type 2 diabetes mellitus (T2DM). We aimed to characterize the alterations in BA metabolism associated with T2DM and colesevelam treatment and to establish whether metabolic consequences of T2DM and colesevelam are related to changes in BA metabolism. Male subjects with T2DM (n = 16) and controls (n = 12) were matched for age and body mass index. BA pool sizes and synthesis/input rates were determined before and after 2 and 8 weeks of colesevelam treatment. T2DM subjects had higher cholic acid (CA) synthesis rate, higher deoxycholic acid (DCA) input rate, and enlarged DCA pool size. Colesevelam resulted in a preferential increase in CA synthesis in both groups. CA pool size was increased whereas chenodeoxycholic acid and DCA pool sizes were decreased upon treatment. Fasting and postprandial fibroblast growth factor 19 (FGF19) levels did not differ between controls and diabetics, but were decreased by treatment in both groups. Colesevelam treatment reduced hemoglobin A1C by 0.7% (P < 0.01) in diabetics. Yet, no relationships between BA kinetic parameters and changes in glucose metabolism were found in T2DM or with colesevelam treatment. CONCLUSION: Our results reveal significant changes in BA metabolism in T2DM, particularly affecting CA and DCA. Colesevelam treatment reduced FGF19 signaling associated with increased BA synthesis, particularly of CA, and resulted in a more hydrophilic BA pool without altering total BA pool size. However, these changes could not be related to the improved glycemic control in T2DM.

In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia.

Clonal evolution and outgrowth of cellular variants with additional chromosomal abnormalities are major causes of disease progression in chronic lymphocytic leukemia (CLL). Because new DNA lesions occur during S phase, proliferating cells are at the core of this problem. In this study, we used in vivo deuterium ((2)H) labeling of CLL cells to better understand the phenotype of proliferating cells in 13 leukemic clones. In each case, there was heterogeneity in cellular proliferation, with a higher fraction of newly produced CD38+ cells compared with CD38- counterparts. On average, there were 2-fold higher percentages of newly born cells in the CD38+ fraction than in CD38- cells; when analyzed on an individual patient basis, CD38+ (2)H-labeled cells ranged from 6.6% to 73%. Based on distinct kinetic patterns, interclonal heterogeneity was also observed. Specifically, 4 patients exhibited a delayed appearance of newly produced CD38+ cells in the blood, higher leukemic cell CXC chemokine receptor 4 (CXCR4) levels, and increased risk for lymphoid organ infiltration and poor outcome. Our data refine the proliferative compartment in CLL based on CD38 expression and suggest a relationship between in vivo kinetics, expression of a protein involved in CLL cell retention and trafficking to solid tissues, and clinical outcome.

Calcium Stimulation Test for Insulinoma Localization in an End-stage Renal Disease Patient on Diazoxide.

Insulinomas are rare, and even rarer in patients with end-stage renal disease (ESRD). Clear criteria for the biochemical diagnosis of insulinomas in patients with renal failure have not been established, and hypoglycemia is often attributed to the renal disease itself, frequently leading to a delay in diagnosis. We describe a case of a patient who presented with asymptomatic recurrent hypoglycemia during hemodialysis. Disease progression and biochemical testing strongly suggested an insulinoma. Computed tomography (CT) of the abdomen and pelvis, 111In-pentetreotide scintigraphy and endoscopic ultrasound did not localize a pancreatic tumor. A calcium stimulation test was performed while the patient was taking diazoxide due to severe hypoglycemia with fasting for a couple of hours without treatment. The test showed a marked increase in insulin after calcium infusion in the dorsal pancreatic artery, localizing the tumor to the body and tail of the gland. Exploratory surgery easily identified a tumor at the body of the pancreas and pathology confirmed an insulin-secreting pancreatic neuroendocrine tumor. On follow-up, there was resolution of the hypoglycemia. We review the challenges of diagnosing an insulinoma in ESRD and describe a successful intra-arterial calcium stimulation test done in an ESRD patient while continuing diazoxide.

Innovations in Diabetes Care for a Better "New Normal" Beyond COVID-19.

The coronavirus disease pandemic has created opportunities for innovation in diabetes care that were not possible before. From the lens of this "new normal" state, we have an opportunity to rapidly implement, test, and iterate models of diabetes care to achieve the quadruple aim of improving medical outcomes, patient experience, provider satisfaction, and reducing costs. In this perspective, we discuss several innovative diabetes models of care which promote collaborative care models and improve access to high-quality specialty diabetes care. We discuss ongoing threats to diabetes care innovation, and offer practical solutions to foster evolution and sustain current strides made during the pandemic.

Effect of a Low-Glycemic Load Diet Intervention on Maternal and Pregnancy Outcomes in Obese Pregnant Women.

The increased prevalence of obese, pregnant women who have a higher risk of glucose intolerance warrants the need for nutritional interventions to improve maternal glucose homeostasis. In this study, the effect of a low-glycemic load (GL) (n = 28) was compared to a high-GL (n = 34) dietary intervention during the second half of pregnancy in obese women (body mass index (BMI) > 30 or a body fat >35%). Anthropometric and metabolic parameters were assessed at baseline (20 week) and at 28 and 34 weeks gestation. For the primary outcome 3h-glucose-iAUC (3h-incremental area under the curve), mean between-group differences were non-significant at every study timepoint (p = 0.6, 0.3, and 0.8 at 20, 28, and 34 weeks, respectively) and also assessing the mean change over the study period (p = 0.6). Furthermore, there was no statistically significant difference between the two intervention groups for any of the other examined outcomes (p ≥ 0.07). In the pooled cohort, there was no significant effect of dietary GL on any metabolic or anthropometric outcome (p ≥ 0.2). A post hoc analysis comparing the study women to a cohort of overweight or obese pregnant women who received only routine care showed that the non-study women were more likely to gain excess weight (p = 0.046) and to deliver large-for-gestational-age (LGA) (p = 0.01) or macrosomic (p = 0.006) infants. Thus, a low-GL diet consumed during the last half of pregnancy did not improve pregnancy outcomes in obese women, but in comparison to non-study women, dietary counseling reduced the risk of adverse outcomes.

e-Consult implementation success: lessons from 5 county-based delivery systems.

OBJECTIVES: Electronic consultation, or e-consult, systems improve specialty care access by conveying specialist expertise to primary care clinicians (PCCs) without requiring specialist visits. Our study evaluates organizational factors for e-consult implementation across 5 publicly financed, county-based health systems in California. Each system serves 40,000 to 180,000 culturally and linguistically diverse patients across 4 to 19 primary care locations. STUDY DESIGN: We interviewed leaders whose systems received grant funding between 2015 and 2017 to plan and implement e-consult. Interviews discussed platform selection, electronic health record (EHR) compatibility, PCC and specialist opinions, and project governance. We also collected implementing systems' platform operations metrics. METHODS: Mixed methods, including semistructured interviews and quantitative platform metrics. Interviews were analyzed in alignment with the Consolidated Framework for Implementation Research inner setting domain. RESULTS: Three of the 5 systems successfully implemented e-consults. System 1 sustained implementation across 27 specialties, system 2 achieved fragmented implementation, and system 3 reported early-stage implementation. Existing PCC-specialist relationships emerged as the strongest facilitator. E-consult-EHR technology integration was also important, although an add-on platform enabled e-consult expansion in system 2. Although all systems faced challenges, such as project management resourcing, systems 4 and 5 abandoned implementation amid compound climate and readiness barriers. CONCLUSIONS: Successful e-consult implementations in public delivery systems leveraged (1) prior primary care and specialty care clinician relationships and (2) integrated EHR and e-consult platforms. This contrasts with common expectations that new technology will overcome care delivery gaps. Findings add to existing e-consult implementation literature that emphasizes reimbursement and leadership champions.

Compensation, Productivity, and Other Demographics of Academic Divisions of Endocrinology, Diabetes, and Metabolism.

The landscape for academic endocrinology divisions has continued to evolve rapidly;thus, finding reliable data that can be used as benchmarks has become more difficult. Resources are available for salary and relative value units, with the Association of American Medical Colleges, Medical Group Management Association, and Faculty Practice Solutions Center the most commonly used databases. However, details regarding how these data are collected and what they include are unclear. For example, does the income include bonus and/or incentive payments? How are work relative value units defined (individual rendering vs supervising advanced practitioners or fellows or residents)? How is a clinical full-time equivalent defined? In addition, other important data that would be relevant to running an academic division of endocrinology are not available from these, or any other resources, including support staff numbers and compensation or fellowship funding and training information. Therefore, an unmet need exists for reliable data that divisions can use to help shape their visions and goals. To address this demand, the Association of Endocrine Chiefs and Directors, in collaboration with the Endocrine Society, developed a detailed survey for members to address the financial, productivity, composition, and educational issues that they regularly face. Twenty academic institutions throughout the United States completed in the survey in 2018. In the present report, we have provided the results of the survey and some initial interpretations of the findings. Our hope is that the information presented will prove useful as academic endocrinology divisions continue to evolve.

Challenges and Successes with Food Resource Referrals for Food-Insecure Patients with Diabetes.

INTRODUCTION: Clinics increasingly screen patients for food insecurity, but little is known about the efficacy of referring food-insecure patients to community-based food resources. OBJECTIVE: To evaluate the implementation of a tailored community food resource referral program in a safety-net diabetes clinic. METHODS: We conducted semistructured phone interviews with food-insecure patients participating in a screening and referral program in a diabetes clinic affiliated with a safety-net hospital. In this qualitative study, we describe barriers to and facilitators of successful food resource referrals from the patient's perspective. RESULTS: The prevalence of food insecurity was high (60%). Provision of written and verbal information alone about community food resources resulted in low linkage rates (0%-4%), even with individually tailored referrals. Misperceptions about eligibility, fears around government program registration, inaccessibility, lack of information retention, competing priorities, an inability to cook, stigma, and a perceived sense of stability with existing food support were major barriers to use. Personnel-guided, in-clinic enrollment to a food resource facilitated a higher connection rate (31%). DISCUSSION: Results of this study suggest that screening for food insecurity followed by a list of food resources for those screening positive may not adequately address patient barriers to using community-based food resources. For food insecurity screening programs in the clinical setting to be effective, systems must not only distribute food resource information but also assist patients in enrollment processes.