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Oral Insulin Therapy to Prevent Progression of Immune-Mediated (Type 1) Diabetes
aDivision of Pediatric Endocrinology, New York-Presbyterian Hospital, Weill Medical College of Cornell University, New York, New York bTulane Medical School, New Orleans, Louisiana cDepartment of Medicine, University of Southern California, Los Angeles, California dDepartment of Pediatrics, Mount Sinai Medical Center, New York, New York eUniversity of Texas Southwestern Medical Center at Dallas, Dallas, Texas fEndocrine Associates, Atlanta, Georgia gDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, Florida hDepartment of Pediatrics, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, Louisiana iCleveland Clinic, Cleveland, Ohio jDiabetes and Glandular Disease Clinic, San Antonio, Texas kUniversity of South Florida Diabetes Center, St. Petersburg, Florida lH. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida mBioseek 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. maclaren{at}endoclinics.com
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.
Key Words: type 1 diabetes • immune-mediated diabetes • oral insulin tolerance therapy • endogenous insulin reserve • mixed meal tolerance testing • islet cell autoantibodies (ICA) • GAD65 • IA-2 autoantibodies • insulin autoantibodies • HLA-DR/DQ phenotypes
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