Insulin Secretion in Type 1 Diabetes

  1. Chynna Steele1,
  2. William A. Hagopian2,
  3. Stephen Gitelman3,
  4. Umesh Masharani3,
  5. Melissa Cavaghan4,
  6. Kristina I. Rother5,
  7. David Donaldson6,
  8. David M. Harlan5,
  9. Jeffrey Bluestone3 and
  10. Kevan C. Herold1
  1. 1Department of Medicine, Division of Endocrinology, and the Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, New York
  2. 2Pacific Northwest Research Institute, Seattle, Washington
  3. 3Diabetes Center, University of California at San Francisco, San Francisco, California
  4. 4Department of Medicine, Indiana University, Indianapolis, Indiana
  5. 5Transplant and Autoimmunity Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
  6. 6Department of Pediatrics, University of Utah, Salt Lake City, Utah
  1. Address correspondence and reprint requests to Kevan C. Herold, MD, Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave., New York, NY 10032. E-mail: kh318{at}


Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing β-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non–steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of β-cell function at an average rate of 756 ± 132 pmol/month to a final value of 28 ± 8.4% of initial levels after 2 years. There was a significant correlation between the total insulin secretory response and control of glucose, measured by HbA1c (P = 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction.


  • C.S. is currently affiliated with The University of Chicago, Chicago, Illinois.

    • Accepted October 27, 2003.
    • Received August 25, 2003.
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