Publications by authors named "Elizabeth J Murphy"

39 Publications

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

Nutrients 2021 Feb 26;13(3). Epub 2021 Feb 26.

Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.

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) ( = 28) was compared to a high-GL ( = 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 ( = 0.6, 0.3, and 0.8 at 20, 28, and 34 weeks, respectively) and also assessing the mean change over the study period ( = 0.6). Furthermore, there was no statistically significant difference between the two intervention groups for any of the other examined outcomes ( ≥ 0.07). In the pooled cohort, there was no significant effect of dietary GL on any metabolic or anthropometric outcome ( ≥ 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 ( = 0.046) and to deliver large-for-gestational-age (LGA) ( = 0.01) or macrosomic ( = 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.
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http://dx.doi.org/10.3390/nu13030748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996780PMC
February 2021

Assuring safety and efficacy of nurse triage for electronic consultation to improve access to specialty care.

BMJ Qual Saf 2021 Feb 4. Epub 2021 Feb 4.

Center for Innovation in Access and Quality at Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, California, USA

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http://dx.doi.org/10.1136/bmjqs-2020-012619DOI Listing
February 2021

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

J Endocr Soc 2021 Feb 27;5(2):bvaa185. Epub 2020 Nov 27.

Division of Endocrinology and Metabolism, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA.

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, In-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.
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http://dx.doi.org/10.1210/jendso/bvaa185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750930PMC
February 2021

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

J Clin Endocrinol Metab 2021 01;106(1):e377-e381

Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1210/clinem/dgaa704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665547PMC
January 2021

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

Am J Manag Care 2020 01 1;26(1):e21-e27. Epub 2020 Jan 1.

University of California, Berkeley, School of Public Health, 2121 Berkeley Way West, Room 5435, Berkeley, CA 94720. Email:

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.
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http://dx.doi.org/10.37765/ajmc.2020.42149DOI Listing
January 2020

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

Hum Mol Genet 2019 12;28(24):4208-4218

Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA.

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.
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http://dx.doi.org/10.1093/hmg/ddz262DOI Listing
December 2019

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

J Endocr Soc 2019 Aug 7;3(8):1485-1502. Epub 2019 Jun 7.

Division of Endocrinology, Diabetes, and Metabolism, University of Rochester Medical School, Rochester, New York.

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.
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http://dx.doi.org/10.1210/js.2019-00095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676069PMC
August 2019

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

Perm J 2019 ;23

Division of Endocrinology, Department of Medicine, University of California, San Francisco.

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.
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http://dx.doi.org/10.7812/TPP/18-097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380483PMC
September 2019

Evaluating diverse electronic consultation programs with a common framework.

BMC Health Serv Res 2018 Oct 24;18(1):814. Epub 2018 Oct 24.

Center for Innovation in Access and Quality at Priscilla Chan and Mark Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, 94110, USA.

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.
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http://dx.doi.org/10.1186/s12913-018-3626-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201558PMC
October 2018

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

Am J Physiol Endocrinol Metab 2018 07 20;315(1):E126-E132. Epub 2018 Mar 20.

KineMed, Emeryville, California.

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-C]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·min) on two occasions and a low dose (5 mg·kg fat-free mass·min) 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.
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http://dx.doi.org/10.1152/ajpendo.00470.2017DOI Listing
July 2018

Twelve-month outcomes of a randomized trial of a moderate-carbohydrate versus very low-carbohydrate diet in overweight adults with type 2 diabetes mellitus or prediabetes.

Nutr Diabetes 2017 12 21;7(12):304. Epub 2017 Dec 21.

University of California, San Francisco, CA, USA.

Dietary treatment is important in management of type 2 diabetes or prediabetes, but uncertainty exists about the optimal diet. We randomized adults (n = 34) with glycated hemoglobin (HbA1c) > 6.0% and elevated body weight (BMI > 25) to a very low-carbohydrate ketogenic (LCK) diet (n = 16) or a moderate-carbohydrate, calorie-restricted, low-fat (MCCR) diet (n = 18). All participants were encouraged to be physically active, get sufficient sleep, and practice behavioral adherence strategies based on positive affect and mindful eating. At 12 months, participants in the LCK group had greater reductions in HbA1c levels (estimated marginal mean (EMM) at baseline = 6.6%, at 12 mos = 6.1%) than participants in MCCR group (EMM at baseline = 6.9%, at 12 mos = 6.7%), p = .007. Participants in the LCK group lost more weight (EMM at baseline = 99.9 kg, at 12 mos = 92.0 kg) than participants in the MCCR group (EMM at baseline = 97.5 kg, at 12 mos = 95.8 kg), p < .001. The LCK participants experienced larger reductions in diabetes-related medication use; of participants who took sulfonylureas or dipeptidyl peptidase-4 inhibitors at baseline, 6/10 in the LCK group discontinued these medications compared with 0/6 in the MCCR group (p = .005). In a 12-month trial, adults with elevated HbA1c and body weight assigned to an LCK diet had greater reductions in HbA1c, lost more weight, and reduced more medications than those instructed to follow an MCCR diet.
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http://dx.doi.org/10.1038/s41387-017-0006-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865541PMC
December 2017

Growth hormone receptor antagonism with pegvisomant in insulin resistant non-diabetic men: A phase II pilot study.

F1000Res 2017 3;6:614. Epub 2017 May 3.

Department of Medicine, University of California, San Francisco, San Francisco, CA, 94143, USA.

Growth hormone (GH) is known to affect insulin and glucose metabolism.  Blocking its effects in acromegalic patients improves diabetes and glucose metabolism. We aimed to determine the effect of pegvisomant, a GH receptor antagonist, on insulin resistance, endogenous glucose production (EGP) and lipolysis in insulin resistant non-diabetic men.  Four men between the ages of 18-62 with a BMI of 18-35kg/m , with insulin resistance as defined by a HOMA-IR > 2.77, were treated for four weeks with pegvisomant 20 mg daily.  Inpatient metabolic assessments were performed before and after treatment. The main outcome measurements were: change after pegvisomant therapy in insulin sensitivity as measured by hyperinsulinemic euglycemic clamp; and EGP and lipolysis assessed by stable isotope tracer techniques. Insulin like growth factor-1 (IGF-1) concentrations decreased from 134.0 ± 41.5 (mean ± SD) to 72.0 ± 11.7 ng/mL (p = 0.04) after 4 weeks of therapy. Whole body insulin sensitivity index (M/I 3.2 ± 1.3 3.4 ± 2.4; = 0.82), as well as suppression of EGP (89.7 ± 26.9 83.5 ± 21.6%; p = 0.10) and Ra glycerol (59.4 ± 22.1% 61.2 ± 14.4%; p = 0.67) during the clamp were not changed significantly with pegvisomant treatment. Blockade of the GH receptor with pegvisomant for four weeks had no significant effect on insulin/glucose metabolism in a small phase II pilot study of non-diabetic insulin resistant participants without acromegaly.
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http://dx.doi.org/10.12688/f1000research.11359.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499778PMC
May 2017

Electronic consultation system demonstrates educational benefit for primary care providers.

J Telemed Telecare 2018 Aug 14;24(7):465-472. Epub 2017 Jun 14.

4 Department of Medicine, University of California, USA.

Background Electronic consultation systems allow primary care providers to receive timely speciality expertise via iterative electronic communication. The use of such systems is expanding across the USA with well-documented high levels of user satisfaction. We characterise the educational impact for primary care providers of a long-standing integrated electronic consultation and referral system. Methods Primary care providers' perceptions of the educational value inherent to electronic consultation system communication and the impact on their ability to manage common speciality clinical conditions and questions were examined by electronic survey using five-point Likert scales. Differences in primary care providers' perceptions were examined overall and by primary care providers' speciality, provider type and years of experience. Results Among 221 primary care provider participants (35% response rate), 83.9% agreed or strongly agreed that the integrated electronic consultation and referral system provided educational value. There were no significant differences in educational value reported by provider type (attending physician, mid-level provider, or trainee physician), primary care providers' speciality, or years of experience. Perceived benefit of the electronic consultation and referral system in clinical management appeared stronger for laboratory-based conditions (i.e. subclinical hypothyroidism) than more diffuse conditions (i.e. abdominal pain). Nurse practitioners/physician assistants and trainee physicians were more likely to report improved abilities to manage specific clinical conditions when using the electronic consultation and/or referral system than were attending physicians, as were primary care providers with ≤10 years experience, versus those with >20 years of experience. Conclusions Primary care providers report overwhelmingly positive perceptions of the educational value of an integrated electronic consultation and referral system. Nurse practitioners, physician assistants, trainee physicians and less-experienced primary care providers report the greatest clinical educational benefit, particularly for conditions involving lab-based diagnosis and management.
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http://dx.doi.org/10.1177/1357633X17711822DOI Listing
August 2018

The Challenges of Electronic Health Records and Diabetes Electronic Prescribing: Implications for Safety Net Care for Diverse Populations.

J Diabetes Res 2017 18;2017:8983237. Epub 2017 Jan 18.

Division of Endocrinology, Department of Medicine, University of California, San Francisco, 1001 Potrero Avenue, Box 0862, San Francisco, CA 94143, USA.

Widespread electronic health record (EHR) implementation creates new challenges in the diabetes care of complex and diverse populations, including safe medication prescribing for patients with limited health literacy and limited English proficiency. This review highlights how the EHR electronic prescribing transformation has affected diabetes care for vulnerable patients and offers recommendations for improving patient safety through EHR electronic prescribing design, implementation, policy, and research. Specifically, we present evidence for (1) the adoption of RxNorm; (2) standardized naming and picklist options for high alert medications such as insulin; (3) the widespread implementation of universal medication schedule and language-concordant labels, with the expansion of electronic prescription 140-character limit; (4) enhanced bidirectional communication with pharmacy partners; and (5) informatics and implementation research in safety net healthcare systems to examine how EHR tools and practices affect diverse vulnerable populations.
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http://dx.doi.org/10.1155/2017/8983237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286474PMC
June 2017

Group visits to encourage insulin initiation: targeting patient barriers.

J Clin Nurs 2017 Jun 8;26(11-12):1705-1713. Epub 2017 Feb 8.

University of California, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1111/jocn.13577DOI Listing
June 2017

In vivo triglyceride synthesis in subcutaneous adipose tissue of humans correlates with plasma HDL parameters.

Atherosclerosis 2016 08 13;251:147-152. Epub 2016 Jun 13.

Departments of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.

Backgrounds And Aims: Low concentrations of plasma HDL-C are associated with the development of atherosclerotic cardiovascular diseases and type 2 diabetes. Here we aimed to explore the relationship between the in vivo fractional synthesis of triglycerides (fTG) in subcutaneous (s.q.) abdominal adipose tissue (AT), HDL-C concentrations and HDL particle size composition in non-diabetic humans.

Methods: The fTG in s.q. abdominal AT was measured in 16 non-diabetic volunteers (7 women, 9 men; Age: 49 ± 20 years; BMI: 31 ± 5 kg/m; Fasting Plasma Glucose: 90 ± 10 mg/dl) after (2)H2O labeling. HDL-C concentration and subclasses, large (L-HDL), intermediate (I-HDL) and small (S-HDL) were measured.

Results: Linear regression analyses demonstrated significant associations of fTG with plasma concentration of HDL-C (r = 0.625,p = 0.009) and percent contribution of L-HDL (r = 0.798,p < 0.001), I-HDL (r = -0.765,p < 0.001) and S-HDL (r = -0.629, p = 0.009). When analyses were performed by gender, the associations remained significant in women (HDL-C: r = 0.822,p = 0.023; L-HDL: r = 0.892,p = 0.007; I-HDL: r = -0.927,p = 0.003) but not men.

Conclusions: Our study demonstrated an in vivo association between subcutaneous abdominal adipose tissue lipid dynamics and HDL parameters in humans, but this was true for women not men. Positive association with L-HDL and negative with I-HDL suggest that subcutaneous abdominal adipose tissue lipid dynamics may play an important role in production of mature functional HDL particles. Further studies evaluating the mechanism responsible for these associations and the observed gender differences are important and warranted to identify potential novel targets of intervention to increase the production of atheroprotective subclasses of HDL-Cs and thus decreasing the risks of development of atherosclerotic conditions.
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http://dx.doi.org/10.1016/j.atherosclerosis.2016.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983221PMC
August 2016

Comparison of multiple methods to measure maternal fat mass in late gestation.

Am J Clin Nutr 2016 Apr 17;103(4):1055-63. Epub 2016 Feb 17.

Oregon Health & Science University, Portland, OR;

Background: Measurements of maternal fat mass (FM) are important for studies of maternal and fetal health. Common methods of estimating FM have not been previously compared in pregnancy with measurements using more complete body composition models.

Objectives: The goal of this pilot study was to compare multiple methods that estimate FM, including 2-, 3- and 4-compartment models in pregnant women at term, and to determine how these measures compare with FM by dual-energy X-ray absorptiometry (DXA) 2 wk postpartum.

Design: Forty-one healthy pregnant women with prepregnancy body mass index (in kg/m(2)) 19 to 46 underwent skinfold thickness (SFT), bioelectrical impedance analysis (BIA), body density (Db) via air displacement plethysmography (ADP), and deuterium dilution of total body water (TBW) with and without adjustments for gestational age using van Raaij (VRJ) equations at 37-38 wk of gestation and 2 wk postpartum to derive 8 estimates of maternal FM. Deming regression analysis and Bland-Altman plots were used to compare methods of FM assessment.

Results: Systematic differences in FM estimates were found. Methods for FM estimates from lowest to highest were 4-compartment, DXA, TBW(VRJ), 3-compartment, Db(VRJ), BIA, air displacement plethysmography body density, and SFT ranging from a mean ± SD of 29.5 ± 13.2 kg via 4-compartment to 39.1 ± 11.7 kg via SFT. Compared with postpartum DXA values, Deming regressions revealed no substantial departures from trend lines in maternal FM in late pregnancy for any of the methods. The 4-compartment method showed substantial negative (underestimating) constant bias, and the air displacement plethysmography body density and SFT methods showed positive (overestimating) constant bias. ADP via Db(VRJ)and 3-compartment methods had the highest precision; BIA had the lowest.

Conclusions: ADP that uses gestational age-specific equations may provide a reasonable and practical measurement of maternal FM across a spectrum of body weights in late pregnancy. SFT would be acceptable for use in larger studies. This trial was registered at clinicaltrials.gov as NCT02586714.
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http://dx.doi.org/10.3945/ajcn.115.113464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807697PMC
April 2016

Leveraging an electronic referral system to build a medical neighborhood.

Healthc (Amst) 2015 Dec 2;3(4):202-8. Epub 2015 May 2.

Division of General Internal Medicine at San Francisco General Hospital, University of California, Box 1364, San Francisco, USA; Center for Innovation in Access and Quality, San Francisco General Hospital, Box 1364, San Francisco, USA. Electronic address:

Background: Electronic referral and consultation systems are gaining popularity, but their contribution to the patient centered medical home-neighborhood framework of coordinated care delivery is not clear. We examined how specialists leverage an electronic referral and consultation system to deliver specialty care, identified determinants of high-quality electronic specialist communication and measured the impact of feedback to specialists on communication quality.

Methods: Referral patterns were identified for 19 specialties using eReferral in the San Francisco public health care delivery system. Primary care provider (PCP) ratings of the quality (helpfulness and educational value) of consultative communication were measured. Using logistic regression, we identified determinants of high-quality specialist communication during pre-consultative exchange or virtual co-management. Predictors included: specialty and reviewer type, referral volume, percent of referrals never scheduled and time spent by reviewers on eReferral. A pre-post analysis examined the impact of feedback on communication quality.

Results: The percentage of referrals immediately scheduled (27.2-82.8%) and never scheduled (7.7-59.3%) varied by specialty, with medical reviewers (vs. surgical and women׳s health) and physician reviewers (vs. nurse practitioners) scheduling fewer referrals immediately (p<0.001). Prevalence of high-quality communication was 71%, impacted by referral volume (adjusted odds ratio=0.78, 95%CI 0.68-0.88 for each additional 1000 referrals/year) and time spent per referral (1.18, 1.04-1.35 for each additional 3min).

Conclusions: Specialists can use electronic referral and consultation systems to enhance specialty care delivery with consultative communication that is highly rated by PCPs.

Implications: These data can inform the structure and functionality of future electronic consultation systems to maximize care coordination.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.hjdsi.2015.04.001DOI Listing
December 2015

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

BMC Health Serv Res 2015 Dec 19;15:568. Epub 2015 Dec 19.

Center for Innovation in Access and Quality at San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, 94110, USA.

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.
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http://dx.doi.org/10.1186/s12913-015-1233-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684927PMC
December 2015

Practical Management Guide for Clinicians Who Treat Patients with Amiodarone.

Am J Med 2016 05 11;129(5):468-75. Epub 2015 Nov 11.

Department of Medicine, University of California, San Francisco, Calif; Division of Cardiology, Department of Medicine, San Francisco General Hospital, San Francisco, Calif.

Amiodarone, an iodinated benzofuran derivative with Class I, II, III, and IV antiarrhythmic properties, is the most commonly used antiarrhythmic drug used to treat supraventricular and ventricular arrhythmias. Appropriate use of this drug, with its severe and potentially life-threatening adverse effects, requires an essential understanding of its risk-benefit properties in order to ensure safety. The objective of this review is to afford clinicians who treat patients receiving amiodarone an appropriate management strategy for its safe use. The authors of this consensus management guide have thoroughly reviewed and evaluated the existing literature on amiodarone and apply this information, along with the collective experience of the authors, in its development. Provided are management guides on the intravenous and oral dosing of amiodarone, appropriate outpatient follow-up of patients taking the drug, its recognized adverse effects, and recommendations on when to consult specialists to help in patient management. All clinicians must be cognizant of the appropriate use, follow-up, and adverse reactions of amiodarone. The responsibility incurred by those treating such patients cannot be overemphasized.
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http://dx.doi.org/10.1016/j.amjmed.2015.08.039DOI Listing
May 2016

Metformin as Initial Oral Therapy in Type 2 Diabetes.

JAMA 2015 Jun 23-30;313(24):2484-5

Department of Medicine, University of California, San Francisco3Division of Endocrinology, San Francisco General Hospital, San Francisco, California.

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http://dx.doi.org/10.1001/jama.2015.2765DOI Listing
June 2015

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

BMC Complement Altern Med 2014 Jul 1;14:212. Epub 2014 Jul 1.

Osher Center for Integrative Medicine, University of California, 1545 Divisadero St,, San Francisco, CA 94115, USA.

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.
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http://dx.doi.org/10.1186/1472-6882-14-212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096416PMC
July 2014

A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes.

PLoS One 2014 9;9(4):e91027. Epub 2014 Apr 9.

University of California San Francisco, San Francisco, California, United States of America.

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091027PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981696PMC
January 2015

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

Am J Physiol Endocrinol Metab 2013 Oct 27;305(8):E999-E1006. Epub 2013 Aug 27.

Department of Medicine, Division of Endocrinology and Institute for Translational Science; University of Texas Medical Branch at Galveston, Texas;

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.
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http://dx.doi.org/10.1152/ajpendo.00194.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798696PMC
October 2013

eReferral--a new model for integrated care.

N Engl J Med 2013 Jun;368(26):2450-3

Department of Medicine, University of California, San Francisco, and Division of General Internal Medicine, San Francisco General Hospital, San Francisco, USA.

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http://dx.doi.org/10.1056/NEJMp1215594DOI Listing
June 2013

Regional cell proliferation in microdissected human prostate specimens after heavy water labeling in vivo: correlation with prostate epithelial cells isolated from seminal fluid.

Clin Cancer Res 2012 Jun 2;18(12):3250-60. Epub 2012 May 2.

KineMed, Inc, Emeryville, California 94608, USA.

Purpose: Prostate cancer is detected with increasing frequency but has a highly variable natural history and prognosis and active surveillance of men with low-risk prostate cancer would benefit greatly from minimally invasive methods to identify progression. We describe here two novel in vivo metrics of cell proliferation in men with prostate neoplasia.

Experimental Design: Three groups of men drank heavy water, a nonradioactive, stable isotopic tracer for 14 to 28 days: (i) healthy men, (ii) men scheduled for transrectal core needle biopsy, and (iii) men scheduled for radical prostatectomy. Prostate epithelial cells (PEC) were isolated from ejaculated seminal fluid in all subjects. Histologically graded lesions were microdissected from tissue slides obtained from subjects undergoing surgery and proliferation rates were measured from isolated cells via mass spectrometry.

Results: Proliferation rates of seminal PEC in healthy men (0.10%-0.27%/d) were stable on repeat sampling. Rates above 0.34%/d were seen only in patients with cancer where rates increased progressively from normal tissue through benign prostate hyperplasia, prostate intraepithelial neoplasia, and tumor grades III and IV in all subjects. Seminal PEC kinetics correlated highly with the most proliferative microdissected region in each subject (r(2) = 0.94).

Conclusions: Prostate cell proliferation can be measured in vivo from microdissected histopathology sections or noninvasively from seminal fluid where the latter reflects the most proliferative region of the gland. This approach may allow monitoring of progression in men with low-risk prostate cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-11-2988DOI Listing
June 2012

Dual-energy X-ray absorptiometry-based body volume measurement for 4-compartment body composition.

Am J Clin Nutr 2012 Jan 30;95(1):25-31. Epub 2011 Nov 30.

University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, USA.

Background: Total body volume (TBV), with the exclusion of internal air voids, is necessary to quantify body composition in Lohman's 4-compartment (4C) model.

Objective: This investigation sought to derive a novel, TBV measure with the use of only dual-energy X-ray absorptiometry (DXA) attenuation values for use in Lohman's 4C body composition model.

Design: Pixel-specific masses and volumes were calculated from low- and high-energy attenuation values with the use of first principle conversions of mass attenuation coefficients. Pixel masses and volumes were summed to derive body mass and total body volume. As proof of concept, 11 participants were recruited to have 4C measures taken: DXA, air-displacement plethysmography (ADP), and total body water (TBW). TBV measures with the use of only DXA (DXA-volume) and ADP-volume measures were compared for each participant. To see how body composition estimates were affected by these 2 methods, we used Lohman's 4C model to quantify percentage fat measures for each participant and compared them with conventional DXA measures.

Results: DXA-volume and ADP-volume measures were highly correlated (R(2) = 0.99) and showed no statistically significant bias. Percentage fat by DXA volume was highly correlated with ADP-volume percentage fat measures and DXA software-reported percentage fat measures (R(2) = 0.96 and R(2) = 0.98, respectively) but were slightly biased.

Conclusions: A novel method to calculate TBV with the use of a clinical DXA system was developed, compared against ADP as proof of principle, and used in Lohman's 4C body composition model. The DXA-volume approach eliminates many of the inherent inaccuracies associated with displacement measures for volume and, if validated in larger groups of participants, would simplify the acquisition of 4C body composition to a single DXA scan and TBW measure.
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http://dx.doi.org/10.3945/ajcn.111.019273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238462PMC
January 2012

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

Mol Med 2011 23;17(11-12):1374-82. Epub 2011 Sep 23.

The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, New York, United States of America.

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.
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http://dx.doi.org/10.2119/molmed.2011.00360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321822PMC
August 2012

Plasma bile acids are not associated with energy metabolism in humans.

Nutr Metab (Lond) 2010 Sep 3;7:73. Epub 2010 Sep 3.

Dept. of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.
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http://dx.doi.org/10.1186/1743-7075-7-73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2942888PMC
September 2010

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

Hepatology 2010 Oct;52(4):1455-64

Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

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.
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http://dx.doi.org/10.1002/hep.23831DOI Listing
October 2010