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Glucose induced insulin release in b-thalassemia heterozygotes

Sara T.O. Saad; Mario J.A. Saad

Hemocentro - UNICAMP, Caixa Postal 6198, 13081 Campinas, SP, Brasil

ABSTRACT

The human b-globin gene cluster and the insulin gene have been assigned to the short arm of chromosome 11 with evidence for linkage (Lebo et al., 1983). In order to investigate if heterozigosity for b-thalassemia (b-thal) is linked to an abnormality in insulin secretion, an intravenous glucose tolerance test (IVGTT) was performed on nine b-thal patients and on 15 healthy subjects. No significant differences were observed between the mean plasma glucose levels of the patients with b-thal and those of the control group at any time of the IVGTT, and the glucose disappearance rate was similar in the two groups. Serum insulin levels before and after glucose infusion in patients with b-thal were not significantly different from normals. All indexes of first phase glucose induced insulin release were also similar in the two groups. Previous reports have demonstrated that in sickle cell anemia and associated with the sickle cell trait there is abnormal insulin secretion. However, the results of the IVGTT in the present study suggest that there is no alteration in insulin release in b-that patients, possibly because the decreased insulin secretion is an independent genetic abnormality in linkage disequilibrium with the B^s gene but not with b-thal genes.

Keywords: b-thalassemia heterozygotes.

REFERENCES

Antonarakis, S.E., Phillips III, J.A., Mallonee, R.L., Kazazian, H.H., Fearon, E.R., Waber, P.G., Kronenberg, H.M., Ullrich, A. and Meyers, DA. (1983). b-globin locus is linked to the parathyroid hormone (PTH) locus and lies between the insulin and PTH loci in man. Proc. Natl. Acad. Sci. 80: 6615-6619.

Costa, F., Tavella, M.H. and Zago, MA. (1990). Bases moleculares das b-talassemias no Brasil. Congresso da Sociedade Brasileira de Hematologia, Campinas.

Craighead, J.E. (1978). Current views of etiology of insulin-dependent Diabetes Mellitus. N. Engl. J. Med. 299: 1439-1445.

Felig, P., Baxter, J.D., Broadus, A.E. and Frohman, L.A. (1986). Endocrinology and metabolism (McGraw-Hill, New York).

Ganda, O.P., Srikanta, S., Brink, S.J., Morris, MA., Gleason, R.E., Soelner, J.S. and Eisenbarth, G.S. (1984). Differential sensitivity to 13-cell secretagogues in "early" type I diabetes mellitus. Diabetes 33:516-521.

Hampton, S.M., Morgan, L.M., Tredger, J.A., Cramb, R. and Marks, V. (1986). Insulin and C-peptide levels after oral and intravenous glucose. Diabetes 35: 612-616.

Lebo, R.V., Chakravarti, A., Buetow, K.H., Cheung, M.C., Cann, H., Cordell, B. and Goodman, H. (1983). Recombination within and between the human insulin and b-globin gene loci. Proc. Natl. Acad. Sci. 80: 4808-4812.

Maniatis, T., Fritsch, E.F., Lauer, J. and Lawn, RM. (1980). The molecular genetics of human hemoglobins. Annu. Rev. Genet. 14: 145-178.

Pembrey, M.E., Mac Wade, P. and Weatherall, D.J. (1972). Reliable routine estimation of small amounts of foetal haemoglobin by alkaly desnaturation. J. Clin. Pathol. 25: 738-740.

Reid, H.L., Dimitrios, P.P., Oli, J.M. and Kaine, W. (1988). Concurrent sickle cell disease and Diabetes Mellitus. Trop. Geogr. Med. 41: 205-208.

Saad, S.T.O., Braga, G.S. and Saad, M.J.A. (1989). Decreased C-peptide secretion in sickle cell anemia. Acta Haemat. 82: 81-84.

Saad, M.J.A., Saad, S.T.O. and Braga, G.S. Decreased insulin response to glucose in sickle cell trait. Diabete et Metabolisme (in press).

Smith, C.P., Archibald, H.R., Thomas, J.M., Tarn, A.C., Williams, A.J.K., Gale, E.A.M. and Savage, M.O. (1988). Basal and stimulated insulin levels rise with advancing puberty. Clin. Endocrinol. 28: 7-14.

Soeldner, J.S. and Slone, D. (1965). Critical variables in the radioimmunoassay of serum insulin using the double antibody technique. Diabetes 14: 771-779.

Somogyi, M. (1945). Determination of blood sugar. J. Biol. Chem. 160: 69-73.

Srikanta, S., Ganda, O.P., Rabizadeh, A., Soeldner, J.S. and Eisenbarth, G.S. (1985). First degree relatives of patients with type I diabetes mellitus. Islet cell antibodies and insulin secretion. N. Engl. J. Med. 313: 461-464.

Weatherall, D.J. (1989). The thalassemias. In: Hematology (Williams, W.J., Beutler, E., Erslev, A.J., Lichtman, M.A. eds.). McCraw-Hill Inc., New York, pp. 510-539.

Weatherall, D.J. and Clegg, J.B. (1983). The thalassaemia syndromes. Blackwell Scientific Publ., Oxford, pp. 744-769.

Zago, MA., Costa, F.F. and Bottura, C. (1982). Teste de solubilidade quantitativo modificado em hemolisados normais e em variantes da hemoglobina. Rev. Paul. Med. 100: 15-17.