Bio

Clinical Focus


  • Internal Medicine

Academic Appointments


Professional Education


  • Fellowship:Stanford University Endocrinology Fellowship (2014) CA
  • Residency:Brigham and Women's Hospital Internal Medicine Residency (2004) MA
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2004)
  • Medical Education:University of California Los Angeles School of Medicine (2000) CA

Publications

All Publications


  • Remote Lifestyle Coaching Plus a Connected Glucose Meter with Certified Diabetes Educator Support Improves Glucose and Weight Loss for People with Type 2 Diabetes JOURNAL OF DIABETES RESEARCH Bollyky, J. B., Bravata, D., Yang, J., Williamson, M., Schneider, J. 2018
  • Use of a Connected Glucose Meter and Certified Diabetes Educator Coaching to Decrease the Likelihood of Abnormal Blood Glucose Excursions: The Livongo for Diabetes Program JOURNAL OF MEDICAL INTERNET RESEARCH Downing, J., Bollyky, J., Schneider, J. 2017; 19 (7): e234

    Abstract

    The Livongo for Diabetes Program offers members (1) a cellular technology-enabled, two-way messaging device that measures blood glucose (BG), centrally stores the glucose data, and delivers messages back to the individual in real time; (2) unlimited BG test strips; and (3) access to a diabetes coaching team for questions, goal setting, and automated support for abnormal glucose excursions. The program is sponsored by at-risk self-insured employers, health plans and provider organizations where it is free to members with diabetes or it is available directly to the person with diabetes where they cover the cost.The objective of our study was to evaluate BG data from 4544 individuals with diabetes who were enrolled in the Livongo program from October 2014 through December 2015.Members used the Livongo glucose meter to measure their BG levels an average of 1.8 times per day. We estimated the probability of having a day with a BG reading outside of the normal range (70-180 mg/dL, or 3.9-10.0 mmol/L) in months 2 to 12 compared with month 1 of the program, using individual fixed effects to control for individual characteristics.Livongo members experienced an average 18.4% decrease in the likelihood of having a day with hypoglycemia (BG <70 mg/dL) and an average 16.4% decrease in hyperglycemia (BG >180 mg/dL) in months 2-12 compared with month 1 as the baseline. The biggest impact was seen on hyperglycemia for nonusers of insulin. We do not know all of the contributing factors such as medication or other treatment changes during the study period.These findings suggest that access to a connected glucose meter and certified diabetes educator coaching is associated with a decrease in the likelihood of abnormal glucose excursions, which can lead to diabetes-related health care savings.

    View details for DOI 10.2196/jmir.6659

    View details for Web of Science ID 000409225400001

    View details for PubMedID 28698167

    View details for PubMedCentralID PMC5527250

  • Elimination diet and the development of multiple tree-nut allergies. Pediatric research Elizur, A., Bollyky, J. B., Block, W. M. 2017

    Abstract

    BackgroundDespite its high prevalence, relatively little is known about the characteristics of patients with multiple tree-nut allergies.MethodsPatients (n=60, aged 4-15 years), recruited for a multiple food (tree nuts, peanut, milk, egg, soy, sesame, and wheat) oral immunotherapy (OIT) study, filled a questionnaire on their initial allergy evaluation. Medical records were reviewed. At OIT enrollment (median interval, 7.5 years), patients underwent oral food challenges (OFCs) to foods still eliminated.ResultsThere was significantly less evidence for eliminating tree nuts compared with other foods, as reflected by a lower rate of acute reaction to the offending food, either as the trigger for initial allergy evaluation (5.9% for tree-nuts vs. 20-40% for other foods, respectively P<0.001) or later in life (14.5% vs. 38-75%, respectively P=0.001), and a higher rate of negative skin prick test (SPT)/specific IgE (sIgE) at initial diagnosis (25% vs. <10%, P<0.001). SPT/sIgE increased significantly from past initial levels to present for tree nuts (P<0.001) and peanut (P=0.001) but not for other foods, and most OFCs performed at present were positive.ConclusionsTree nuts are often eliminated from the diet of multiple-food-allergic patients, despite their low probability for allergy. Sensitization and allergy to most tree nuts exist years later, suggesting that it developed during the period of elimination.Pediatric Research advance online publication, 14 June 2017; doi:10.1038/pr.2017.127.

    View details for DOI 10.1038/pr.2017.127

    View details for PubMedID 28549059

  • Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood-Allergic Children. journal of allergy and clinical immunology. In practice Andorf, S., Borres, M. P., Block, W., Tupa, D., Bollyky, J. B., Sampath, V., Elizur, A., Lidholm, J., Jones, J. E., Galli, S. J., Chinthrajah, R. S., Nadeau, K. C. 2017

    Abstract

    Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically.We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs).Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat.Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies.Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.

    View details for DOI 10.1016/j.jaip.2017.01.016

    View details for PubMedID 28351786

  • The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice. Clinical and experimental immunology Kuipers, H. F., Nagy, N., Ruppert, S. M., Sunkari, V. G., Marshall, P. L., Gebe, J. A., Ishak, H. D., Keswani, S. G., Bollyky, J., Frymoyer, A. R., Wight, T. N., Steinman, L., Bollyky, P. L. 2016; 185 (3): 372-381

    Abstract

    Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan synthesis in mouse models of cancer, autoimmunity, and a variety of other inflammatory disorders where hyaluronan (HA) has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration, and metabolism of 4-MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4-MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after one week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a one-week loading period on the drug is required for most protocols. At steady state, over 90% of the drug is present in plasma as the glucuronidated metabolite 4-methylumbelliferyl glucuronide (4-MUG), with the sulfated metabolite, 4-methylumbelliferyl sulfate (4-MUS) comprising most of the remainder. Chow containing 5% but not 0.65% 4-MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis as well as in the DORmO mouse model of autoimmune diabetes. While oral 4-MU was effective at preventing EAE, daily intraperitoneal injections of 4-MU were not. Factors potentially affecting 4-MU uptake and plasma concentrations in mice include its taste, short half-life and low bioavailability. These studies provide a practical resource for implementing oral 4-MU treatment protocols in mice. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/cei.12815

    View details for PubMedID 27218304

  • Opening clinical trial data: are the voluntary data-sharing portals enough? BMC MEDICINE Geifman, N., Bollyky, J., Bhattacharya, S., Butte, A. J. 2015; 13: 280

    Abstract

    Data generated by the numerous clinical trials conducted annually worldwide have the potential to be extremely beneficial to the scientific and patient communities. This potential is well recognized and efforts are being made to encourage the release of raw patient-level data from these trials to the public. The issue of sharing clinical trial data has recently gained attention, with many agreeing that this type of data should be made available for research in a timely manner. The availability of clinical trial data is most important for study reproducibility, meta-analyses, and improvement of study design. There is much discussion in the community over key data sharing issues, including the risks this practice holds. However, one aspect that remains to be adequately addressed is that of the accessibility, quality, and usability of the data being shared. Herein, experiences with the two current major platforms used to store and disseminate clinical trial data are described, discussing the issues encountered and suggesting possible solutions.

    View details for DOI 10.1186/s12916-015-0525-y

    View details for Web of Science ID 000365069700001

    View details for PubMedID 26560699

    View details for PubMedCentralID PMC4642633

  • Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective DIABETES-METABOLISM RESEARCH AND REVIEWS Bollyky, J. B., Xu, P., Butte, A. J., Wilson, D. M., Beam, C. A., Greenbaum, C. J. 2015; 31 (6): 588-594

    Abstract

    Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies.Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and <8 years. Data were compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey.Only 2.0% of the individuals overall were excluded from trial participation because of insufficient C-peptide values (<0.2 pmol/mL). A disproportionate number of these subjects were <8 years old. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly higher than age-matched healthy National Health and Nutrition Examination Survey population. Of the cohort, 24.5% were overweight or obese. Neither high-risk human leukocyte antigen type DR3 nor DR4 was present in 31% of adults and 21% of children.The ability of recent-onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies. Copyright © 2015 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/dmrr.2643

    View details for PubMedID 25689602

  • Review of Environmental Impact on the Epigenetic Regulation of Atopic Diseases. Current allergy and asthma reports Sabounchi, S., Bollyky, J., Nadeau, K. 2015; 15 (6): 33-?

    Abstract

    There has been significant increase in the prevalence of atopy over the past decade that cannot be explained by genetic predisposition. Environmental factors including nutrition, the uterine environment, and lifestyle factors are known to play a role in gene expression through epigenetic modifications. In this article, we review the literature on the environmental impact on epigenetic modulation of atopic diseases including asthma, food allergy, eczema, and allergic rhinitis. Recent public release of epigenomic data for hundreds of human tissues provides a powerful resource for further investigation of the molecular basis of atopic diseases.

    View details for DOI 10.1007/s11882-015-0533-1

    View details for PubMedID 26141578

  • Review of Environmental Impact on the Epigenetic Regulation of Atopic Diseases CURRENT ALLERGY AND ASTHMA REPORTS Sabounchi, S., Bollyky, J., Nadeau, K. 2015; 15 (6)

    Abstract

    There has been significant increase in the prevalence of atopy over the past decade that cannot be explained by genetic predisposition. Environmental factors including nutrition, the uterine environment, and lifestyle factors are known to play a role in gene expression through epigenetic modifications. In this article, we review the literature on the environmental impact on epigenetic modulation of atopic diseases including asthma, food allergy, eczema, and allergic rhinitis. Recent public release of epigenomic data for hundreds of human tissues provides a powerful resource for further investigation of the molecular basis of atopic diseases.

    View details for DOI 10.1007/s11882-015-0533-1

    View details for Web of Science ID 000357428700004

    View details for PubMedID 26141578

  • 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer. Frontiers in immunology Nagy, N., Kuipers, H. F., Frymoyer, A. R., Ishak, H. D., Bollyky, J. B., Wight, T. N., Bollyky, P. L. 2015; 6: 123-?

    Abstract

    Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug in Europe and Asia called "hymecromone" where it is used to treat biliary spasm. However, there is uncertainty regarding how 4-MU treatment provides benefit in these animal models and the potential long-term consequences of HA inhibition. Here, we review what is known about how HA contributes to immune dysregulation and tumor progression. Then, we review what is known about 4-MU and hymecromone in terms of mechanism of action, pharmacokinetics, and safety. Finally, we review recent studies detailing the use of 4-MU to treat animal models of cancer and autoimmunity.

    View details for DOI 10.3389/fimmu.2015.00123

    View details for PubMedID 25852691

  • Big data approach towards the characterization of normal peripheral immune cells with data from ImmPort Andorf, S., Bollyky, J., Bhattacharya, S., Shankar, R., Dunn, P., Thomson, E., Wiser, J., Butte, A. AMER ASSOC IMMUNOLOGISTS. 2014
  • Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial LANCET Wherrett, D. K., Bundy, B., Becker, D. J., Dimeglio, L. A., Gitelman, S. E., Goland, R., Gottlieb, P. A., Greenbaum, C. J., Herold, K. C., Marks, J. B., Monzavi, R., Moran, A., Orban, T., Palmer, J. P., Raskin, P., Rodriguez, H., Schatz, D., Wilson, D. M., Krischer, J. P., Skyler, J. S. 2011; 378 (9788): 319-327

    Abstract

    Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate aggressive autoimmunity. We aimed to assess whether immunisation with GAD formulated with aluminum hydroxide (GAD-alum) would preserve insulin production in recent-onset type 1 diabetes.Patients aged 3-45 years who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and Canada, and randomly assigned to receive one of three treatments: three injections of 20 μg GAD-alum, two injections of 20 μg GAD-alum and one of alum, or 3 injections of alum. Injections were given subcutaneously at baseline, 4 weeks later, and 8 weeks after the second injection. The randomisation sequence was computer generated at the TrialNet coordinating centre. Patients and study personnel were masked to treatment assignment. The primary outcome was the baseline-adjusted geometric mean area under the curve (AUC) of serum C-peptide during the first 2 h of a 4-h mixed meal tolerance test at 1 year. Secondary outcomes included changes in glycated haemoglobin A(1c) (HbA(1c)) and insulin dose, and safety. Analysis included all randomised patients with known measurements. This trial is registered with ClinicalTrials.gov, number NCT00529399.145 patients were enrolled and treated with GAD-alum (n=48), GAD-alum plus alum (n=49), or alum (n=48). At 1 year, the 2-h AUC of C-peptide, adjusted for age, sex, and baseline C-peptide value, was 0·412 nmol/L (95% CI 0·349-0·478) in the GAD-alum group, 0·382 nmol/L (0·322-0·446) in the GAD-alum plus alum group, and 0·413 nmol/L (0·351-0·477) in the alum group. The ratio of the population mean of the adjusted geometric mean 2-h AUC of C-peptide was 0·998 (95% CI 0·779-1·22; p=0·98) for GAD-alum versus alum, and 0·926 (0·720-1·13; p=0·50) for GAD-alum plus alum versus alum. HbA(1c), insulin use, and the occurrence and severity of adverse events did not differ between groups.Antigen-based immunotherapy therapy with two or three doses of subcutaneous GAD-alum across 4-12 weeks does not alter the course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigen-based therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune disease remains a challenge.US National Institutes of Health.

    View details for DOI 10.1016/S0140-6736(11)60895-7

    View details for Web of Science ID 000293615800029

    View details for PubMedID 21714999

  • Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial LANCET Orban, T., Bundy, B., Becker, D. J., Dimeglio, L. A., Gitelman, S. E., Goland, R., Gottlieb, P. A., Greenbaum, C. J., Marks, J. B., Monzavi, R., Moran, A., Raskin, P., Rodriguez, H., Russell, W. E., Schatz, D., Wherrett, D., Wilson, D. M., Krischer, J. P., Skyler, J. S. 2011; 378 (9789): 412-419

    Abstract

    The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. We evaluated the effect of abatacept in recent-onset type 1 diabetes.In this multicentre, double-blind, randomised controlled trial, patients aged 6-45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. Computer-generated permuted block randomisation was used, with a block size of 3 and stratified by participating site. Neither patients nor research personnel were aware of treatment assignments. The primary outcome was baseline-adjusted geometric mean 2-h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years' follow-up. Analysis was by intention to treat for all patients for whom data were available. This trial is registered at ClinicalTrials.gov, NCT00505375.112 patients were assigned to treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% (95% CI 6·1-112) higher at 2 years with abatacept (n=73, 0·378 nmol/L) than with placebo (n=30, 0·238 nmol/L; p=0·0029). The difference between groups was present throughout the trial, with an estimated 9·6 months' delay (95% CI 3·47-15·6) in C-peptide reduction with abatacept. There were few infusion-related adverse events (36 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six [17%] on placebo). There was no increase in infections (32 [42%] patients on abatacept vs 15 [43%] on placebo) or neutropenia (seven [9%] vs five [14%]).Co-stimulation modulation with abatacept slowed reduction in β-cell function over 2 years. The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions.US National Institutes of Health.

    View details for DOI 10.1016/S0140-6736(11)60886-6

    View details for Web of Science ID 000293615900032

    View details for PubMedID 21719096