Stephen Gitelman
Professor
[email protected]
+1 415 476-3748
+1 415 476-8214
UCSF Profiles

Biography

I am involved in a variety of different translational and clinical research projects, most related to diabetes. A number of the on-going studies are attempts to alter the course of autoimmune-mediated type 1 diabetes, often via immunomodulation, in order to preserve endogenous beta cell function. Some of the recent and on-going projects are described below.

Most of this work occurs in multi-center clinical trials. I am the Clinical Center director for the NIH sponsored program TrialNet, a multi-center research consortium that develops trials to delay or prevent the onset of type 1 diabetes in those at risk, or prolong endogenous insulin secretion (the honeymoon phase) in those with new onset disease. UCSF is one of 14 national centers for this 7-year study. Current studies include:
-natural history study to screen and predict who might develop type 1 diabetes
-a prevention trial with omega 3 fatty acids to determine if treatment during pregnancy or shortly after birth can serve as a primary means to prevent type 1 diabetes
-a new onset diabetes trial with mycophenolate mofetil with our without IL-2 receptor monoclonal antibody to determine if this will preserve endogenous insulin secretion
-a new onset study with anti-CD20 monoclonal antibody to determine if this will preserve endogenous insulin secretion
The consortium is continuing to develop additional prevention and new onset studies over time.

In addition, I have served as the site director for a novel study evaluating the role of an anti-CD3 monoclonal antibody in prolonging the honeymoon phase in those with new onset type 1 diabetes. The initial phase 1 / 2 study results were published in the N Engl J Med 2002, and our 2 year follow-up data was just published (Diabetes 2005). These exciting results were confirmed in an independent study with a related drug in Europe, and have spawned a series of studies to build on these initial findings. We are now launching an NIH-sponsored phase 2 study for new onset diabetes, evaluating the efficacy of antibody treatment every 12 months for 2 courses. In addition to these efforts, we have several additional NIH-funded new onset type 1 diabetes studies that will soon begin. We are evaluating the window of opportunity for anti-CD3 therapy, with a trial planned for subjects from 4 to 12 months from diagnosis. We are developing clinical trials the assess the effect of anti-CD3 therapy coupled with antigen, and another study coupling with an incretin hormone analgoue, exenatide, which may help with beta cell regeneration. Finally, I am the study principal investigator for a multi-center new onset type 1 diabetes trial with anti-thymocyte globulin, sponsored by the Immune Tolerance Network.

I am partnering with other members of the UCSF Diabetes Center to pursue other clinical trials, and translational studies that may help us better understand the pathogenesis of type 1 diabetes. Such studies include development of T cell assays; characterization of patients with novel disorders in carbohydrate metabolism; possible use of T regulatory cells as an immunotherapy. As technology advances, we anticipate to one day be able to use beta cells developed from stem cells as a definitive treatment for type 1 diabetes.

Education and Training

Post-Doc Fellow/Scholar, 1990 Medicine (Pediatrics), University of California, San Francisco
M.D., 1984 School of Medicine, University of North Carolina
Residency, School of Medicine, University of California, San Francisco

Publications

Wentworth JM, Bediaga NG, Giles LC, Ehlers M, Gitelman SE, Geyer S, Evans-Molina C, Harrison LC. Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables. Diabetologia. 2019 Jan; 62(1):33-40.
Haller MJ, Schatz DA, Skyler JS, Krischer JP, Bundy BN, Miller JL, Atkinson MA, Becker DJ, Baidal D, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Herold KC, Marks JB, Moran A, Rodriguez H, Russell W, Wilson DM, Greenbaum CJ. Low-Dose Anti-Thymocyte Globulin (ATG) Preserves ß-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes. Diabetes Care. 2018 09; 41(9):1917-1925.
Amon R, Ben-Arye SL, Engler L, Yu H, Lim N, Berre LL, Harris KM, Ehlers MR, Gitelman SE, Chen X, Soulillou JP, Padler-Karavani V. Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy. Oncotarget. 2017 Dec 22; 8(68):112236-112244.
Ferrara CT, Geyer SM, Evans-Molina C, Libman IM, Becker DJ, Wentworth JM, Moran A, Gitelman SE, Redondo MJ. The Role of Age and Excess Body Mass Index in Progression to Type 1 Diabetes in At-Risk Adults. J Clin Endocrinol Metab. 2017 12 01; 102(12):4596-4603.
Yang YY, Long RK, Ferrara CT, Gitelman SE, German MS, Yang SB. A new familial form of a late-onset, persistent hyperinsulinemic hypoglycemia of infancy caused by a novel mutation in KCNJ11. Channels (Austin). 2017 Nov 02; 11(6):636-647.
Ferrara CT, Gitelman SE. Type 1 Diabetes and Celiac Disease: Causal Association or True, True, Unrelated? Pediatrics. 2017 11; 140(5).
Salama A, Evanno G, Lim N, Rousse J, Le Berre L, Nicot A, Bach JM, Brouard S, Harris KM, Ehlers MR, Gitelman SE, Soulillou JP. Anti-Gal and Anti-Neu5Gc Responses in Nonimmunosuppressed Patients After Treatment With Rabbit Antithymocyte Polyclonal IgGs. Transplantation. 2017 10; 101(10):2501-2507.
Ferrara CT, Geyer SM, Liu YF, Evans-Molina C, Libman IM, Besser R, Becker DJ, Rodriguez H, Moran A, Gitelman SE, Redondo MJ. Excess BMI in Childhood: A Modifiable Risk Factor for Type 1 Diabetes Development? Diabetes Care. 2017 05; 40(5):698-701.
Ku E, McCulloch CE, Mauer M, Gitelman SE, Grimes BA, Hsu CY. Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes. Diabetes Care. 2016 12; 39(12):2218-2224.
Haller MJ, Gitelman SE, Gottlieb PA, Michels AW, Perry DJ, Schultz AR, Hulme MA, Shuster JJ, Zou B, Wasserfall CH, Posgai AL, Mathews CE, Brusko TM, Atkinson MA, Schatz DA. Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes. Diabetes. 2016 Dec; 65(12):3765-3775.
Gitelman SE, Bluestone JA. Regulatory T cell therapy for type 1 diabetes: May the force be with you. J Autoimmun. 2016 07; 71:78-87.
Boyle KD, Keyes-Elstein L, Ehlers MR, McNamara J, Rigby MR, Gitelman SE, Weiner LJ, Much KL, Herold KC. Two- and Four-Hour Tests Differ in Capture of C-Peptide Responses to a Mixed Meal in Type 1 Diabetes. Diabetes Care. 2016 06; 39(6):e76-8.
Gitelman SE, Gottlieb PA, Felner EI, Willi SM, Fisher LK, Moran A, Gottschalk M, Moore WV, Pinckney A, Keyes-Elstein L, Harris KM, Kanaparthi S, Phippard D, Ding L, Bluestone JA, Ehlers MR. Antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial. Diabetologia. 2016 06; 59(6):1153-61.
Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, Herold KC, Lares A, Lee MR, Li K, Liu W, Long SA, Masiello LM, Nguyen V, Putnam AL, Rieck M, Sayre PH, Tang Q. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015 Nov 25; 7(315):315ra189.
Wherrett DK, Chiang JL, Delamater AM, DiMeglio LA, Gitelman SE, Gottlieb PA, Herold KC, Lovell DJ, Orchard TJ, Ryan CM, Schatz DA, Wendler DS, Greenbaum CJ. Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: a consensus report. Diabetes Care. 2015 Oct; 38(10):1975-85.
Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Keyes-Elstein L, Long SA, Kanaparthi S, Lim N, Phippard D, Soppe CL, Fitzgibbon ML, McNamara J, Nepom GT, Ehlers MR. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015 Aug 03; 125(8):3285-96.
Haller MJ, Gitelman SE, Gottlieb PA, Michels AW, Rosenthal SM, Shuster JJ, Zou B, Brusko TM, Hulme MA, Wasserfall CH, Mathews CE, Atkinson MA, Schatz DA. Anti-thymocyte globulin/G-CSF treatment preserves ß cell function in patients with established type 1 diabetes. J Clin Invest. 2015 Jan; 125(1):448-55.
Beam CA, Gitelman SE, Palmer JP. Recommendations for the definition of clinical responder in insulin preservation studies. Diabetes. 2014 Sep; 63(9):3120-7.
Orban T, Bundy B, Becker DJ, Dimeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, Moran A, Peakman M, Raskin P, Russell WE, Schatz D, Wherrett DK, Wilson DM, Krischer JP, Skyler JS. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. Diabetes Care. 2014 Apr; 37(4):1069-75.
Rigby MR, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Patel CM, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Moran A, Russell WE, Pinckney A, Keyes-Elstein L, Howell M, Aggarwal S, Lim N, Phippard D, Nepom GT, McNamara J, Ehlers MR. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2013 Dec; 1(4):284-94.
Pescovitz MD, Greenbaum CJ, Bundy B, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, Moran A, Raskin P, Rodriguez H, Schatz DA, Wherrett DK, Wilson DM, Krischer JP, Skyler JS. B-lymphocyte depletion with rituximab and ß-cell function: two-year results. Diabetes Care. 2014 Feb; 37(2):453-9.
Gitelman SE, Gottlieb PA, Rigby MR, Felner EI, Willi SM, Fisher LK, Moran A, Gottschalk M, Moore WV, Pinckney A, Keyes-Elstein L, Aggarwal S, Phippard D, Sayre PH, Ding L, Bluestone JA, Ehlers MR. Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2013 Dec; 1(4):306-16.
Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, Boyle KD, Keyes-Elstein L, Aggarwal S, Phippard D, Sayre PH, McNamara J, Bluestone JA. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes. 2013 Nov; 62(11):3766-74.
Thomas HR, Gitelman SE. Altering the course of type 1 diabetes: an update on prevention and new-onset clinical trials. Pediatr Diabetes. 2013 Aug; 14(5):311-21.
Gerard-Gonzalez A, Gitelman SE, Cheng P, Dubose SN, Miller KM, Olson BA, Redondo MJ, Steck AK, Beck RW. Comparison of autoantibody-positive and autoantibody-negative pediatric participants enrolled in the T1D Exchange clinic registry. J Diabetes. 2013 Jun; 5(2):216-23.
Moran A, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Greenbaum CJ, Herold KC, Marks JB, Raskin P, Sanda S, Schatz D, Wherrett DK, Wilson DM, Krischer JP, Skyler JS, Pickersgill L, de Koning E, Ziegler AG, Böehm B, Badenhoop K, Schloot N, Bak JF, Pozzilli P, Mauricio D, Donath MY, Castaño L, Wägner A, Lervang HH, Perrild H, Mandrup-Poulsen T. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet. 2013 Jun 01; 381(9881):1905-15.
Lenders CM, Lee PD, Feldman HA, Wilson DM, Abrams SH, Gitelman SE, Klish WJ, Wertz MS, Taylor GA, Alongi RT, Chen TC, Holick MF. A cross-sectional study of osteocalcin and body fat measures among obese adolescents. Obesity (Silver Spring). 2013 Apr; 21(4):808-14.
Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and ß-cell death in type 1 diabetes. Diabetes. 2013 May; 62(5):1676-80.
Greenbaum CJ, Beam CA, Boulware D, Gitelman SE, Gottlieb PA, Herold KC, Lachin JM, McGee P, Palmer JP, Pescovitz MD, Krause-Steinrauf H, Skyler JS, Sosenko JM. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data. Diabetes. 2012 Aug; 61(8):2066-73.
Cheung CC, Cadnapaphornchai MA, Ranadive SA, Gitelman SE, Rosenthal SM. Persistent elevation of urine aquaporin-2 during water loading in a child with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by a R137L mutation in the V2 vasopressin receptor. Int J Pediatr Endocrinol. 2012 Feb 10; 2012(1):3.
Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, Moran A, Raskin P, Rodriguez H, Russell WE, Schatz D, Wherrett D, Wilson DM, Krischer JP, Skyler JS. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jul 30; 378(9789):412-9.
Wherrett DK, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Herold KC, Marks JB, Monzavi R, Moran A, Orban T, Palmer JP, Raskin P, Rodriguez H, Schatz D, Wilson DM, Krischer JP, Skyler JS. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet. 2011 Jul 23; 378(9788):319-27.
Glaser NS, Geller DH, Haqq A, Gitelman S, Malloy M. Detecting and treating hyperlipidemia in children with type 1 diabetes mellitus: are standard guidelines applicable to this special population? Pediatr Diabetes. 2011 Jun; 12(4 Pt 2):442-59.
Sullivan MM, O'Brien CR, Gitelman SE, Shapiro SE, Rushakoff RJ. Impact of an interactive online nursing educational module on insulin errors in hospitalized pediatric patients. Diabetes Care. 2010 Aug; 33(8):1744-6.
Rochdi MD, Vargas GA, Carpentier E, Oligny-Longpré G, Chen S, Kovoor A, Gitelman SE, Rosenthal SM, von Zastrow M, Bouvier M. Functional characterization of vasopressin type 2 receptor substitutions (R137H/C/L) leading to nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis: implications for treatments. Mol Pharmacol. 2010 May; 77(5):836-45.
Cho YH, Gitelman S, Rosenthal S, Ambler G. Long-term outcomes in a family with nephrogenic syndrome of inappropriate antidiuresis. Int J Pediatr Endocrinol. 2009; 2009:431527.
Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, McGee PF, Moran AM, Raskin P, Rodriguez H, Schatz DA, Wherrett D, Wilson DM, Lachin JM, Skyler JS. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009 Nov 26; 361(22):2143-52.
Gitelman SE, Haller MJ, Schatz D. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2009 Aug 12; 302(6):624; author reply 624-5.
Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF. Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr. 2009 Sep; 90(3):459-67.
Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, Sayre P, Bianchine P, Wong E, Seyfert-Margolis V, Bourcier K, Bluestone JA. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009 Aug; 132(2):166-73.
Huang EA, Gitelman SE. The effect of oral alpha-lipoic acid on oxidative stress in adolescents with type 1 diabetes mellitus. Pediatr Diabetes. 2008 Jun; 9(3 Pt 2):69-73.
Bremer AA, Nobuhara KK, Gitelman SE. Congenital hyperinsulinism in an infant caused by a macroscopic insulin-producing lesion. J Pediatr Endocrinol Metab. 2007 Mar; 20(3):437-40.
Rosenthal SM, Feldman BJ, Vargas GA, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD): a paradigm for activating mutations causing endocrine dysfunction. Pediatr Endocrinol Rev. 2006 Dec; 4 Suppl 1:66-70.
Seyfert-Margolis V, Gisler TD, Asare AL, Wang RS, Dosch HM, Brooks-Worrell B, Eisenbarth GS, Palmer JP, Greenbaum CJ, Gitelman SE, Nepom GT, Bluestone JA, Herold KC. Analysis of T-cell assays to measure autoimmune responses in subjects with type 1 diabetes: results of a blinded controlled study. Diabetes. 2006 Sep; 55(9):2588-94.
Gitelman SE, Feldman BJ, Rosenthal SM. Nephrogenic syndrome of inappropriate antidiuresis: a novel disorder in water balance in pediatric patients. Am J Med. 2006 Jul; 119(7 Suppl 1):S54-8.
Huang EA, Feldman BJ, Schwartz ID, Geller DH, Rosenthal SM, Gitelman SE. Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in children. J Pediatr. 2006 Jan; 148(1):128-31.
Sapru A, Gitelman SE, Bhatia S, Dubin RF, Newman TB, Flori H. Prevalence and characteristics of type 2 diabetes mellitus in 9-18 year-old children with diabetic ketoacidosis. J Pediatr Endocrinol Metab. 2005 Sep; 18(9):865-72.
Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun; 54(6):1763-9.
Feldman BJ, Rosenthal SM, Vargas GA, Fenwick RG, Huang EA, Matsuda-Abedini M, Lustig RH, Mathias RS, Portale AA, Miller WL, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005 May 05; 352(18):1884-90.
Wilson DM, Buckingham BA, Kunselman EL, Sullivan MM, Paguntalan HU, Gitelman SE. A two-center randomized controlled feasibility trial of insulin pump therapy in young children with diabetes. Diabetes Care. 2005 Jan; 28(1):15-9.
Conrad SC, Mastrototaro JJ, Gitelman SE. The use of a continuous glucose monitoring system in hypoglycemic disorders. J Pediatr Endocrinol Metab. 2004 Mar; 17(3):281-8.
Steele C, Hagopian WA, Gitelman S, Masharani U, Cavaghan M, Rother KI, Donaldson D, Harlan DM, Bluestone J, Herold KC. Insulin secretion in type 1 diabetes. Diabetes. 2004 Feb; 53(2):426-33.
Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30; 346(22):1692-8.
Conrad SC, McGrath MT, Gitelman SE. Transition from multiple daily injections to continuous subcutaneous insulin infusion in type 1 diabetes mellitus. J Pediatr. 2002 Feb; 140(2):235-40.
Greenspan LC, Gitelman SE, Leung MA, Glidden DV, Mathias RS. Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis. Pediatr Nephrol. 2002 Jan; 17(1):1-5.