Neuroendocrine Tumor Markers and Enterochromaffin-Like Cell Hyper/Dysplasia in Type 1 Diabetes

  1. Christophe E.M. De Block, MD, PHD1,
  2. Gert Colpin1,
  3. Kristof Thielemans1,
  4. Willy Coopmans2,
  5. Johannes J.P.M. Bogers, MD, PHD3,
  6. Paul A. Pelckmans, MD, PHD4,
  7. Eric A.E. Van Marck, MD, PHD3,
  8. Viviane Van Hoof, MD, PHD5,
  9. Manou Martin, MSC6,
  10. Ivo H. De Leeuw, MD, PHD1,
  11. Roger Bouillon, MD, PHD2 and
  12. Luc F. Van Gaal, MD, PHD1
  1. 1Department of Endocrinology-Diabetology, University Hospital Antwerp, Edegem, Belgium
  2. 2Laboratory of Experimental Medicine and Endocrinology, University Hospital Gasthuisberg, Leuven, Belgium
  3. 3Department of Pathology, University Hospital Antwerp, Edegem, Belgium
  4. 4Department of Gastroenterology and Hepatology, University Hospital Antwerp, Edegem, Belgium
  5. 5Department of Biochemistry, University Hospital Antwerp, Edegem, Belgium
  6. 6Department of Hormonology, University Hospital Antwerp, Edegem, Belgium
  1. Address correspondence and reprint requests to Christophe De Block, MD, PhD, Department of Endocrinology-Diabetology, Faculty of Medicine, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium. E-mail: christophe.deblock{at}ua.ac.be

Abstract

OBJECTIVE—Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia.

RESEARCH DESIGN AND METHODS—Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA+ and 62 PCA−, aged 45 ± 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies.

RESULTS—PCA+ patients had higher gastrin (P < 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA− subjects. ECL cell hyper/dysplasia was present in seven PCA+ patients who showed higher CgA levels (P < 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (β = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA+ patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor.

CONCLUSIONS—PCA+ patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.

Footnotes

  • C.E.M.D.B., G.C., and K.T. contributed equally to this study and retain joint first authorship.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted March 12, 2004.
    • Received December 21, 2003.
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  1. doi: 10.2337/diacare.27.6.1387 Diabetes Care June 2004 vol. 27 no. 6 1387-1393
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