Volume 1029, Issue 1 p. 260-277

Oral Insulin Therapy to Prevent Progression of Immune-Mediated (Type 1) Diabetes

BERRIN ERGUN-LONGMIRE

BERRIN ERGUN-LONGMIRE

Division of Pediatric Endocrinology, New York-Presbyterian Hospital, Weill Medical College of Cornell University, New York, New York

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JOHN MARKER

JOHN MARKER

Tulane Medical School, New Orleans, Louisiana

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ADINA ZEIDLER

ADINA ZEIDLER

Department of Medicine, University of Southern California, Los Angeles, California

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ROBERT RAPAPORT

ROBERT RAPAPORT

Department of Pediatrics, Mount Sinai Medical Center, New York, New York

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PHILIP RASKIN

PHILIP RASKIN

University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

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BRUCE BODE

BRUCE BODE

Endocrine Associates, Atlanta, Georgia

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DESMOND SCHATZ

DESMOND SCHATZ

Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida

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ALFONSO VARGAS

ALFONSO VARGAS

Department of Pediatrics, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, Louisiana

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DOUGLAS ROGERS

DOUGLAS ROGERS

Cleveland Clinic, Cleveland, Ohio

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SHERWYN SCHWARTZ

SHERWYN SCHWARTZ

Diabetes and Glandular Disease Clinic, San Antonio, Texas

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JOHN MALONE

JOHN MALONE

University of South Florida Diabetes Center, St. Petersburg, Florida

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JEFFREY KRISCHER

JEFFREY KRISCHER

H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida

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NOEL K. MACLAREN

Corresponding Author

NOEL K. MACLAREN

Bioseek Clinics, New York, New York 10022, USA

Address for correspondence: Noel K. Maclaren, M.D., Bioseek Clinics, 5 East 57th Street, 16th Floor, New York, NY 10022. Voice: 212-371-0658; fax: 212-371-3744. [email protected]Search for more papers by this author
First published: 12 January 2006
Citations: 48

Abstract

Abstract: Repeated ingestion of insulin has been suggested as an immune tolerization therapy to prevent immune-mediated (type 1) diabetes. We performed a placebo-controlled, two-dose, oral insulin tolerance trial in newly diagnosed (< 2 years) diabetic patients who had required insulin replacement for less than 4 weeks and were found to have cytoplasmic islet cell autoantibodies (ICAs). No oral hypoglycemic agents were permitted during the trial. Endogenous insulin reserves were estimated at six-month intervals by plasma C-peptide responses to a mixed meal. Positive ICAs were found in 262 (31%) of the 846 patients screened. Of the 197 who agreed to participate, 187 could be followed for 6 to 36 months. Endogenous insulin retention was dependent upon initial stimulated C-peptide response, age at diabetes onset, and numbers of specific islet cell autoantibodies found. Oral insulin improved plasma C-peptide responses in patients diagnosed at ages greater than 20 years, best seen at the low (1 mg/day) over the high (10 mg/day) insulin dose (P= .003 and P= .01, respectively). In patients diagnosed before age 20 years, the 1 mg dose was ineffective, whereas the 10 mg dose actually accelerated C-peptide loss (P= .003). There were no adverse effects. If confirmed, these findings suggest that diabetic patients over age 20 years with ICA evidence of late-onset immune-mediated diabetes should be considered for oral insulin at 1 mg/day to better retain endogenous insulin secretion.