Stephen Gitelman, MD

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.
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
  1. Preferences for Risks and Benefits of Islet Cell Transplantation for Persons With Type 1 Diabetes With History of Episodes of Severe Hypoglycemia: A Discrete-Choice Experiment to Inform Regulatory Decisions.
  2. IL-6 receptor blockade does not slow β cell loss in new-onset type 1 diabetes.
  3. The effects of low-dose IL-2 on Treg adoptive cell therapy in patients with Type 1 diabetes.
  4. Simplifying prediction of disease progression in pre-symptomatic type 1 diabetes using a single blood sample.
  5. Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
  6. Youth with Type 1 Diabetes Had Improvement in Continuous Glucose Monitoring Metrics During the COVID-19 Pandemic.
  7. Low-Dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report.
  8. Continuous Glucose Monitoring to Diagnose Hypoglycemia Due to Late Dumping Syndrome in Children After Gastric Surgeries.
  9. Comparing Beta Cell Preservation Across Clinical Trials in Recent-Onset Type 1 Diabetes.
  10. Exenatide extended release in patients with type 1 diabetes with and without residual insulin production.
  11. Clinical trial data validate the C-peptide estimate model in type 1 diabetes.
  12. Excess BMI Accelerates Islet Autoimmunity in Older Children and Adolescents.
  13. Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes.
  14. Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes.
  15. Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome.
  16. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.
  17. Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data.
  18. Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables.
  19. Low-Dose Anti-Thymocyte Globulin (ATG) Preserves ß-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes.
  20. Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy.
  21. The Role of Age and Excess Body Mass Index in Progression to Type 1 Diabetes in At-Risk Adults.
  22. A new familial form of a late-onset, persistent hyperinsulinemic hypoglycemia of infancy caused by a novel mutation in KCNJ11.
  23. Type 1 Diabetes and Celiac Disease: Causal Association or True, True, Unrelated?
  24. Anti-Gal and Anti-Neu5Gc Responses in Nonimmunosuppressed Patients After Treatment With Rabbit Antithymocyte Polyclonal IgGs.
  25. Excess BMI in Childhood: A Modifiable Risk Factor for Type 1 Diabetes Development?
  26. Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes.
  27. Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.
  28. Regulatory T cell therapy for type 1 diabetes: May the force be with you.
  29. Two- and Four-Hour Tests Differ in Capture of C-Peptide Responses to a Mixed Meal in Type 1 Diabetes.
  30. Antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial.
  31. Type 1 diabetes immunotherapy using polyclonal regulatory T cells.
  32. Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: a consensus report.
  33. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients.
  34. Anti-thymocyte globulin/G-CSF treatment preserves ß cell function in patients with established type 1 diabetes.
  35. Recommendations for the definition of clinical responder in insulin preservation studies.
  36. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment.
  37. 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.
  38. B-lymphocyte depletion with rituximab and ß-cell function: two-year results.
  39. Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial.
  40. 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.
  41. Altering the course of type 1 diabetes: an update on prevention and new-onset clinical trials.
  42. Combined pancreatic islet and kidney transplantation in a child with unstable type 1 diabetes and end-stage renal disease.
  43. Comparison of autoantibody-positive and autoantibody-negative pediatric participants enrolled in the T1D Exchange clinic registry.
  44. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials.
  45. A cross-sectional study of osteocalcin and body fat measures among obese adolescents.
  46. Immune therapy and ß-cell death in type 1 diabetes.
  47. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.
  48. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data.
  49. 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.
  50. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial.
  51. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial.
  52. Detecting and treating hyperlipidemia in children with type 1 diabetes mellitus: are standard guidelines applicable to this special population?
  53. Impact of an interactive online nursing educational module on insulin errors in hospitalized pediatric patients.
  54. 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.
  55. Long-term outcomes in a family with nephrogenic syndrome of inappropriate antidiuresis.
  56. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function.
  57. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus.
  58. Relation of body fat indexes to vitamin D status and deficiency among obese adolescents.
  59. 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.
  60. The effect of oral alpha-lipoic acid on oxidative stress in adolescents with type 1 diabetes mellitus.
  61. Congenital hyperinsulinism in an infant caused by a macroscopic insulin-producing lesion.
  62. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD): a paradigm for activating mutations causing endocrine dysfunction.
  63. Analysis of T-cell assays to measure autoimmune responses in subjects with type 1 diabetes: results of a blinded controlled study.
  64. Nephrogenic syndrome of inappropriate antidiuresis: a novel disorder in water balance in pediatric patients.
  65. Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in children.
  66. Prevalence and characteristics of type 2 diabetes mellitus in 9-18 year-old children with diabetic ketoacidosis.
  67. 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.
  68. Nephrogenic syndrome of inappropriate antidiuresis.
  69. A two-center randomized controlled feasibility trial of insulin pump therapy in young children with diabetes.
  70. The use of a continuous glucose monitoring system in hypoglycemic disorders.
  71. Insulin secretion in type 1 diabetes.
  72. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus.
  73. Transition from multiple daily injections to continuous subcutaneous insulin infusion in type 1 diabetes mellitus.
  74. Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis.
  75. Peptide mapping and characterisation of glycation patterns of the glima 38 antigen recognised by autoantibodies in Type I diabetic patients.
  76. Inhibition of TGF-beta receptor signaling in osteoblasts leads to decreased bone remodeling and increased trabecular bone mass.
  77. Smooth muscle expresses bone morphogenetic protein (Vgr-1/BMP-6) in human fetal intestine.
  78. Neonatal hyperinsulinism.
  79. Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing's disease.
  80. Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents.
  81. Structure and sequence of the mouse Bmp6 gene.
  82. Immunoreactive inhibin, müllerian inhibitory substance, and activin as biochemical markers for juvenile granulosa cell tumors.
  83. A promoter within intron 35 of the human C4A gene initiates abundant adrenal-specific transcription of a 1 kb RNA: location of a cryptic CYP21 promoter element?
  84. Vgr-1/BMP-6 induces osteoblastic differentiation of pluripotential mesenchymal cells.
  85. Toward a molecular understanding of skeletal development.
  86. Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.
  87. Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B.
  88. Abundant adrenal-specific transcription of the human P450c21A "pseudogene".
  89. Mental retardation locus in Xp21 chromosome microdeletion.
  90. Congenital lipoid adrenal hyperplasia--genes for P450scc, side chain cleavage enzyme, are normal.
  91. Analysis of the duplicated human C4/P450c21/X gene cluster.
  92. Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus.
  93. Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus.
  94. Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.
  95. Cloning of the LH/CG receptor: implications for a unique G-protein coupled receptor.
  96. Transcript encoded on the opposite strand of the human steroid 21-hydroxylase/complement component C4 gene locus.
  97. Purification of calmodulin from Chlamydomonas: calmodulin occurs in cell bodies and flagella.