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Soluble CD8 antigen, stimulated C-peptide and islet cell antibodies are predictors of insulin requirement in newly diagnosed patients with unclassifiable diabetes

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Abstract

To evaluate the predictive factors of insulin requirement in newly diagnosed patients with unclassifiable diabetes, 54 consecutive patients, aged less than 35 years, were prospectively followed for 3 years or more. At entry, haemoglobin HbAlc, basal and stimulated C-peptide concentrations, HLA phenotype, islet cell antibodies (ICA) status, and serum levels of soluble CD8 antigen (sCD8) were evaluated. After a median time of 9 (range 2–32) months, 31 patients (group 1) required insulin therapy, whereas 23 patients (group 2) remained non-insulin-requiring after 36 months. Group 1 patients were younger (P<0.05) and had higher HbAlc and sCD8 serum levels (P<0.001, respectively), a higher frequency of ICA positivity and of HLA DR3 and/or DR4 phenotype (P<0.005 andP<0.0001, respectively), and lower C-peptide concentrations (P<0.005 andP<0.0001, basal and stimulated, respectively) than group 2. The sensitivity, specificity, positive and negative predictive value, and overall accuracy for the subsequent insulin requirement were: sCD8 serum levels (>737 U/ml), 100%, 65%, 79%, 100% and 85%, respectively; stimulated C-peptide (<0.60 nmol/l), 71%, 96%, 96%, 74% and 81%, respectively; and ICA positivity (>20 JDFU), 45%, 91%, 87%, 55% and 65%, respectively. Thus, higher sCD8 serum levels, low stimulated C-peptide concentrations and ICA positivity are the most powerful predictors of subsequent recourse to insulin therapy in young, newly detected patients with unclassifiable diabetes.

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References

  1. Landin-Olsson M, Karlsson A, Lernmark A, Sundkvist G et al, Islet and thyrogastric antibodies in 633 consecutive 15- to 34-yr-old patients in the diabetes incidence study in Sweden. Diabetes 41:1022–1027, 1992

    PubMed  Google Scholar 

  2. Hother-Nielsen O, Faber O, Schwartz-Sorensen N, Beck-Nielsen H, Classification of newly diagnosed diabetic patients as insulin-requiring or non insulin-requiring based on clinical and biochemical variables. Diabetes Care 11:531–537, 1988

    PubMed  Google Scholar 

  3. Landin-Olsson M, Nilsson KO, Lernmark A, Sundkvist G, Islet cell antibodies and fasting C-peptide predict insulin requirement at diagnosis of diabetes mellitus. Diabetologia 33:56–568, 1990

    Google Scholar 

  4. Bottazzo GF, Dean BM, McNally JM, McKay EH, Swift PGF, Gamble DR, In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 313:353–360, 1985

    PubMed  Google Scholar 

  5. Santamaria P, Nakhleh RE, Sutherland DE, Barbosa J, Characterization of T lymphocytes infiltrating human pancreas allograft affected by isletitis and recurrent diabetes. Diabetes 41:53–61, 1992

    PubMed  Google Scholar 

  6. Fujimoto J, Levy S, Levy R, Spontaneous release of the Leu-2 (T8) molecule from human T cells. J Exp Med 159:752–766, 1983

    Google Scholar 

  7. Tomkinson BE, Brown MC, Ip SH, Carrabis SH, Sullivan JL, Soluble CD8 during T cell activation. J Immunol 142:2230–2236, 1989

    PubMed  Google Scholar 

  8. Di Cesare E, Previti M, Ingemi C, Bagnato GF, Cucinotta D, High serum levels of soluble CD8 in insulin-dependent diabetes. Clin Exp Immunol 95:283–286, 1994

    PubMed  Google Scholar 

  9. WHO Study Group Report of Diabetes Mellitus, Technical Report 1985, series n 727. WHO, Geneva, 1985

    Google Scholar 

  10. Cole R, Soldner J, Dunne P, Bunn H, A rapid method for determination of glycosylated hemoglobin using high pressure liquid chromatography. Metabolism 27:289–301, 1978

    PubMed  Google Scholar 

  11. Heding LS, Radio immunological determination of C-peptide in serum. Diahetologia 11:541–548, 1975

    Google Scholar 

  12. Terasaki PI, HLA DR joint report. In: Terasaki PI(eds) Histocompatibilith testing. UCLA Tissue Typing Laboratory, Los Angeles, p 506, 1980

    Google Scholar 

  13. Boitard C, Bonifacio E, Bottazzo GF, Gleichmann H, Molenaar J, Immunology and Diabetes Workshop: report on the third international (stage 3) workshop of the standardisation of cytoplasmatic islet cell antibodies. Diabetologia 31:451–452, 1988

    PubMed  Google Scholar 

  14. O'Rahilly S, Spivey R, Holman RR, Nugent Z, Clark A, Turner RC, Type 2 diabetes early onset: a distinct clinical and genetic syndrome. Br Med J 294:923–928, 1987

    Google Scholar 

  15. Pagano GF, Cavallo-Perin P, Cavalot F, Dall'Omo Masciola P et al, Genetic, immunologic, and environmental heterogeneity of IDDM. Diabetes 36:859–863, 1987

    PubMed  Google Scholar 

  16. Tarn AC, Dean BM,Schwartz G, Thomas JM, Ingram D, Bottazzo GF, Gale EAM, Predicting insulin-dependent diabetes. Lancet I:845–850, 1988

    Google Scholar 

  17. Bonifacio E, Bingley PJ, Shattock M, Dean BM, Dunger D, Gale EAM, Bottazzo G, Quantification of islet cell antibodies and prediction of insulin dependent diabetes. Lancet 335:147–149, 1990

    PubMed  Google Scholar 

  18. Di Mario U, Irvine W, Borsey D, Kyner J, Weston J, Galfo C, Immune abnormalities in diabetic patients not requiring insulin at diagnosis. Diabetologia 25:392–395, 1983

    PubMed  Google Scholar 

  19. Christie M, Genovese S, Cassidy D, Bosi E, Brown T, Lai M, Bonifacio E, Bottazzo GF, Antibodies to islet 37k antigen, but not to glutamate decarboxylase, discriminate rapid progression to IDDM in endocrine autoimmunity. Diabetes 43:1254–1259, 1994

    PubMed  Google Scholar 

  20. Faber OK, Binder C, C-peptide response to glucagon. A test for the residual B-cell function in diabetes mellitus. Diabetes 26:605–610, 1977

    PubMed  Google Scholar 

  21. Gjiessing HJ, Matzen LE, Faber OK, Froland A, Fasting plasma glucagon stimulated C-peptide, and urinary C-peptide in relation to clinical type of diabetes. Diabetologia 32:305–311, 1989

    PubMed  Google Scholar 

  22. Madsbad S, Krarup T, McNair P, Christiansen C, Faber OK, Transbol I et al, Practical clinical value of the C-peptide response to glucagon stimulation in the choice of treatment in diabetes mellitus. Acta Med Scand 210:153–156, 1981

    PubMed  Google Scholar 

  23. Koskinen P, Viikari J, Irjala K, Kaiola HL, Seppala P, C-peptide determination in the choice of treatment in diabetes mellitus. Scand J Clin Lab Invest 45:589–597, 1985

    PubMed  Google Scholar 

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Di Bonito, P., De Bellis, A., Capaldo, B. et al. Soluble CD8 antigen, stimulated C-peptide and islet cell antibodies are predictors of insulin requirement in newly diagnosed patients with unclassifiable diabetes. Acta Diabetol 33, 220–224 (1996). https://doi.org/10.1007/BF02048547

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  • DOI: https://doi.org/10.1007/BF02048547

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