Preservation of C-peptide secretion in subjects at high risk of developing type 1 diabetes mellitus - A new surrogate measure of non-progression?

Desmond Schatz, David Cuthbertson, Mark Atkinson, Michael Clare Salzer, William Winter, Andrew Muir, Janet Silverstein, Roberta Cook, Noel Maclaren, Jin-Xiong She, Carla Greenbaum, Jeffrey Krischer

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Individuals at high risk of developing type 1 diabetes mellitus can be identified using immunologic, genetic, and metabolic parameters. In the Diabetes Prevention Trial-1 (DPT-1), annual intravenous infusions of low doses of regular insulin, together with daily subcutaneous injection of a single low dose of Ultralente insulin at nighttime, failed to prevent or delay the onset of type 1 diabetes in high-risk non-diabetic relatives. In our study, we attempted to achieve β-cell rest by administering higher doses of neutral protamine Hagedorn (NPH) insulin twice daily to high-risk non-diabetic subjects in an effort to prevent or delay the onset of the disease. The maximum tolerable dose was given with the dose reduced for any hypoglycemia (mean dose 0.33 ± 0.15; range 0.09-0.66 units/kg/d). We treated 26 subjects who were confirmed to have islet cell antibodies (ICAs) and a low first-phase insulin response (FPIR) to intravenous glucose. Fourteen had normal glucose tolerance and 12 impaired glucose tolerance (IGT). The median duration of follow-up was 5.5 yr. Diabetes occurred in 10 of 12 subjects with IGT and five of 14 subjects with normal glucose tolerance. The cumulative incidence of diabetes was the same as with that seen in a matched, observation group (subjects followed prospectively as part of the University of Florida natural history studies) (age, sex, ICA, insulin autoantibodies, duration of ICA prior to enrollment, FPIR, and glucose intolerance; p = 0.39), as was the rate of progression (p = 0.79). There was a higher rate of progression to diabetes in the group with abnormal glucose tolerance at baseline than in those with normal baseline glucose tolerance (p = 0.003). Interestingly, in non-progressors, as opposed to progressors, there was no fall in C-peptide (peak and area under the curve) production regardless of the type of tolerance testing (mixed meal, oral or intravenous) over time (p < 0.001). In this study, in the dose and regimen of NPH insulin used, insulin did not delay or prevent the development of type 1 diabetes. However, preservation of C-peptide production in the prediabetic period appears to indicate non-progression to clinical disease and may serve as a new surrogate for determining response to preventative efforts.

Original languageEnglish (US)
Pages (from-to)72-79
Number of pages8
JournalPediatric Diabetes
Volume5
Issue number2
DOIs
StatePublished - Jun 1 2004
Externally publishedYes

Fingerprint

C-Peptide
Type 1 Diabetes Mellitus
Glucose Intolerance
Insulin
Glucose
Isophane Insulin
Ultralente Insulin
Subcutaneous Injections
Natural History
Hypoglycemia
Intravenous Infusions
Autoantibodies
Area Under Curve
Meals
Research Design
Observation
Incidence
islet cell antibody

Keywords

  • C-peptide
  • Insulin
  • Prediction
  • Prevention
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism

Cite this

Preservation of C-peptide secretion in subjects at high risk of developing type 1 diabetes mellitus - A new surrogate measure of non-progression? / Schatz, Desmond; Cuthbertson, David; Atkinson, Mark; Salzer, Michael Clare; Winter, William; Muir, Andrew; Silverstein, Janet; Cook, Roberta; Maclaren, Noel; She, Jin-Xiong; Greenbaum, Carla; Krischer, Jeffrey.

In: Pediatric Diabetes, Vol. 5, No. 2, 01.06.2004, p. 72-79.

Research output: Contribution to journalArticle

Schatz, D, Cuthbertson, D, Atkinson, M, Salzer, MC, Winter, W, Muir, A, Silverstein, J, Cook, R, Maclaren, N, She, J-X, Greenbaum, C & Krischer, J 2004, 'Preservation of C-peptide secretion in subjects at high risk of developing type 1 diabetes mellitus - A new surrogate measure of non-progression?', Pediatric Diabetes, vol. 5, no. 2, pp. 72-79. https://doi.org/10.1111/j.1399-543X.2004.00047.x
Schatz, Desmond ; Cuthbertson, David ; Atkinson, Mark ; Salzer, Michael Clare ; Winter, William ; Muir, Andrew ; Silverstein, Janet ; Cook, Roberta ; Maclaren, Noel ; She, Jin-Xiong ; Greenbaum, Carla ; Krischer, Jeffrey. / Preservation of C-peptide secretion in subjects at high risk of developing type 1 diabetes mellitus - A new surrogate measure of non-progression?. In: Pediatric Diabetes. 2004 ; Vol. 5, No. 2. pp. 72-79.
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