Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Jul;92(1):509–513. doi: 10.1172/JCI116595

Decreased insulin response to glucose in islet cell antibody-negative siblings of type 1 diabetic children.

J C Carel 1, C Boitard 1, P F Bougnères 1
PMCID: PMC293639  PMID: 8326015

Abstract

Measurement of beta-cell function is an important marker of progression to diabetes in individuals at risk for the disease. Although the peak incidence for the disease occurs before 17 years of age, normal values for insulin secretion were not available in this age group. We performed a simplified intravenous glucose tolerance test in 167 normal children, and in 98 islet cell antibody (ICA)-negative and 12 ICA-positive siblings of diabetic patients. Their age range was 1-16 yr. The first phase of insulin secretion, evaluated as the sum of plasma insulin concentrations at 1 and 3 min, increased with age and was significantly lower in ICA-negative siblings (86 +/- 6 microU/ml, P < 0.002) than in normal controls (115 +/- 6 microU/ml). This difference was not apparent before 8 yr of age. None of the ICA-negative siblings developed diabetes after an average of 4.5 yr. ICA-positive siblings at first study had a first phase insulin response similar to that of ICA negative siblings, but significantly lower than that of the normal controls (74 +/- 13 microU/ml, P < 0.02). The reason for the decreased insulin secretion in ICA-negative siblings is unknown, but could involve a defect in the growth of beta-cell mass or insulin secretion that could be part of the multifactorial pathogenesis of type 1 diabetes.

Full text

PDF
509

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen C., Palta M., D'Alessio D. J. Risk of diabetes in siblings and other relatives of IDDM subjects. Diabetes. 1991 Jul;40(7):831–836. doi: 10.2337/diab.40.7.831. [DOI] [PubMed] [Google Scholar]
  2. Amiel S. A., Sherwin R. S., Simonson D. C., Lauritano A. A., Tamborlane W. V. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med. 1986 Jul 24;315(4):215–219. doi: 10.1056/NEJM198607243150402. [DOI] [PubMed] [Google Scholar]
  3. Barbosa J., Cohen R. A., Chavers B., Michael A. F., Steffes M., Hoogwerf B., Szalapski E., Mauer M. Muscle extracellular membrane immunofluorescence and HLA as possible markers of prediabetes. Lancet. 1980 Aug 16;2(8190):330–333. doi: 10.1016/s0140-6736(80)90337-2. [DOI] [PubMed] [Google Scholar]
  4. Beer S. F., Heaton D. A., Alberti K. G., Pyke D. A., Leslie R. D. Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins. Diabetologia. 1990 Aug;33(8):497–502. doi: 10.1007/BF00405112. [DOI] [PubMed] [Google Scholar]
  5. Bleich D., Jackson R. A., Soeldner J. S., Eisenbarth G. S. Analysis of metabolic progression to type I diabetes in ICA+ relatives of patients with type I diabetes. Diabetes Care. 1990 Feb;13(2):111–118. doi: 10.2337/diacare.13.2.111. [DOI] [PubMed] [Google Scholar]
  6. Bloch C. A., Clemons P., Sperling M. A. Puberty decreases insulin sensitivity. J Pediatr. 1987 Mar;110(3):481–487. doi: 10.1016/s0022-3476(87)80522-x. [DOI] [PubMed] [Google Scholar]
  7. Boitard C., Bonifacio E., Bottazzo G. F., Gleichmann H., Molenaar J. Immunology and Diabetes Workshop: report on the Third International (Stage 3) Workshop on the Standardisation of Cytoplasmic Islet Cell Antibodies. Held in New York, New York, October 1987. Diabetologia. 1988 Jul;31(7):451–452. doi: 10.1007/BF00271591. [DOI] [PubMed] [Google Scholar]
  8. Bougnères P. F., Landais P., Mairesse A. M., Jais J. P., Jos J., Peyraud J., Wieliczko M. C., Chavoix P., Garandeau P., Asensi D. Improvement of diabetic control and acceptability of a three-injection insulin regimen in diabetic adolescents. A multicenter controlled study. Diabetes Care. 1993 Jan;16(1):94–102. doi: 10.2337/diacare.16.1.94. [DOI] [PubMed] [Google Scholar]
  9. Caillat-Zucman S., Garchon H. J., Timsit J., Assan R., Boitard C., Djilali-Saiah I., Bougnères P., Bach J. F. Age-dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus. J Clin Invest. 1992 Dec;90(6):2242–2250. doi: 10.1172/JCI116110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Caprio S., Plewe G., Diamond M. P., Simonson D. C., Boulware S. D., Sherwin R. S., Tamborlane W. V. Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J Pediatr. 1989 Jun;114(6):963–967. doi: 10.1016/s0022-3476(89)80438-x. [DOI] [PubMed] [Google Scholar]
  11. Castaño L., Boîtard C., Bougnères P. F. Cyclosporin A suppresses insulin autoantibodies and heterologous insulin antibodies in type I diabetic children. Diabetes. 1988 Aug;37(8):1049–1052. doi: 10.2337/diab.37.8.1049. [DOI] [PubMed] [Google Scholar]
  12. Castaño L., Eisenbarth G. S. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol. 1990;8:647–679. doi: 10.1146/annurev.iy.08.040190.003243. [DOI] [PubMed] [Google Scholar]
  13. Cerasi E., Luft R. "What is inherited--what is added" hypothesis for the pathogenesis of diabetes mellitus. Diabetes. 1967 Sep;16(9):615–627. doi: 10.2337/diab.16.9.615. [DOI] [PubMed] [Google Scholar]
  14. Cutfield W. S., Bergman R. N., Menon R. K., Sperling M. A. The modified minimal model: application to measurement of insulin sensitivity in children. J Clin Endocrinol Metab. 1990 Jun;70(6):1644–1650. doi: 10.1210/jcem-70-6-1644. [DOI] [PubMed] [Google Scholar]
  15. Fontbonne A., Papoz L., Eschwege E. Drug sales data and prevalence of diabetes in France. Rev Epidemiol Sante Publique. 1986;34(2):100–105. [PubMed] [Google Scholar]
  16. Ginsberg-Fellner F., Dobersen M. J., Witt M. E., Rayfield E. J., Rubinstein P., Notkins A. L. HLA antigens, cytoplasmic islet cell antibodies, and carbohydrate tolerance in families of children with insulin-dependent diabetes mellitus. Diabetes. 1982 Apr;31(4 Pt 1):292–298. doi: 10.2337/diab.31.4.292. [DOI] [PubMed] [Google Scholar]
  17. Hartling S. G., Lindgren F., Dahlqvist G., Persson B., Binder C. Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity. Diabetes. 1989 Oct;38(10):1271–1274. doi: 10.2337/diab.38.10.1271. [DOI] [PubMed] [Google Scholar]
  18. Johnston C., Raghu P., McCulloch D. K., Beard J. C., Ward W. K., Klaff L. J., McKnight B., Bergman R. N., Palmer J. P. Beta-cell function and insulin sensitivity in nondiabetic HLA-identical siblings of insulin-dependent diabetics. Diabetes. 1987 Jul;36(7):829–837. doi: 10.2337/diab.36.7.829. [DOI] [PubMed] [Google Scholar]
  19. Julier C., Hyer R. N., Davies J., Merlin F., Soularue P., Briant L., Cathelineau G., Deschamps I., Rotter J. I., Froguel P. Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature. 1991 Nov 14;354(6349):155–159. doi: 10.1038/354155a0. [DOI] [PubMed] [Google Scholar]
  20. Karjalainen J., Salmela P., Ilonen J., Surcel H. M., Knip M. A comparison of childhood and adult type I diabetes mellitus. N Engl J Med. 1989 Apr 6;320(14):881–886. doi: 10.1056/NEJM198904063201401. [DOI] [PubMed] [Google Scholar]
  21. LaPorte R. E., Fishbein H. A., Drash A. L., Kuller L. H., Schneider B. B., Orchard T. J., Wagener D. K. The Pittsburgh insulin-dependent diabetes mellitus (IDDM) registry. The incidence of insulin-dependent diabetes mellitus in Allegheny County, Pennsylvania (1965-1976). Diabetes. 1981 Apr;30(4):279–284. doi: 10.2337/diab.30.4.279. [DOI] [PubMed] [Google Scholar]
  22. Levy-Marchal C., Papoz L., de Beaufort C., Doutreix J., Froment V., Voirin J., Collignon A., Garros B., Schleret Y., Czernichow P. Incidence of juvenile type 1 (insulin-dependent) diabetes mellitus in France. Diabetologia. 1990 Aug;33(8):465–469. doi: 10.1007/BF00405107. [DOI] [PubMed] [Google Scholar]
  23. Lindgren F., Dahlquist G., Efendic S., Möller E., Persson B., Thalme B., Olsson M. L. Glucose-induced insulin response and insulin sensitivity is not related to HLA-type but to age in young siblings of type 1 (insulin-dependent) diabetic patients. Diabetologia. 1987 Sep;30(9):727–732. doi: 10.1007/BF00296997. [DOI] [PubMed] [Google Scholar]
  24. McCulloch D. K., Klaff L. J., Kahn S. E., Schoenfeld S. L., Greenbaum C. J., Mauseth R. S., Benson E. A., Nepom G. T., Shewey L., Palmer J. P. Nonprogression of subclinical beta-cell dysfunction among first-degree relatives of IDDM patients. 5-yr follow-up of the Seattle Family Study. Diabetes. 1990 May;39(5):549–556. doi: 10.2337/diab.39.5.549. [DOI] [PubMed] [Google Scholar]
  25. Orchard T. J., Wagener D. K., Rabin B. S., LaPorte R. E., Cavender D., Kuller L. H., Drash A. L., Becker D. J. Glucose tolerance in siblings of type 1 diabetic patients: relationship to HLA status. Diabetologia. 1986 Jan;29(1):39–45. doi: 10.1007/BF02427279. [DOI] [PubMed] [Google Scholar]
  26. Rich S. S., Panter S. S., Goetz F. C., Hedlund B., Barbosa J. Shared genetic susceptibility of type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus: contributions of HLA and haptoglobin. Diabetologia. 1991 May;34(5):350–355. doi: 10.1007/BF00405008. [DOI] [PubMed] [Google Scholar]
  27. Riley W. J., Maclaren N. K., Krischer J., Spillar R. P., Silverstein J. H., Schatz D. A., Schwartz S., Malone J., Shah S., Vadheim C. A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. N Engl J Med. 1990 Oct 25;323(17):1167–1172. doi: 10.1056/NEJM199010253231704. [DOI] [PubMed] [Google Scholar]
  28. Rosenbloom A. L., Bianchi R., Chin F. T. Screening for glucose intolerance in siblings of children with diabetes. Metabolism. 1973 Feb;22(2):351–354. doi: 10.1016/0026-0495(73)90187-x. [DOI] [PubMed] [Google Scholar]
  29. Sidhu M., Crook D., Godsland I. F., Walton C., Wynn V., Oliver M. F. Inverse relationship between serum Lp(a) levels and first-phase insulin secretion. Diabetes. 1992 Oct;41(10):1341–1345. doi: 10.2337/diab.41.10.1341. [DOI] [PubMed] [Google Scholar]
  30. Simpson R. G., Benedetti A., Grodsky G. M., Karam J. H., Forsham P. H. Early phase of insulin release. Diabetes. 1968 Nov;17(11):684–692. doi: 10.2337/diab.17.11.684. [DOI] [PubMed] [Google Scholar]
  31. Smith C. P., Williams A. J., Thomas J. M., Archibald H. R., Algar V. D., Bottazzo G. F., Gale E. A., Savage M. O. The pattern of basal and stimulated insulin responses to intravenous glucose in first degree relatives of type 1 (insulin-dependent) diabetic children and unrelated adults aged 5 to 50 years. Diabetologia. 1988 Jul;31(7):430–434. doi: 10.1007/BF00271587. [DOI] [PubMed] [Google Scholar]
  32. Srikanta S., Ganda O. P., Rabizadeh A., Soeldner J. S., Eisenbarth G. S. First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion. N Engl J Med. 1985 Aug 22;313(8):461–464. doi: 10.1056/NEJM198508223130801. [DOI] [PubMed] [Google Scholar]
  33. Tarn A. C., Thomas J. M., Dean B. M., Ingram D., Schwarz G., Bottazzo G. F., Gale E. A. Predicting insulin-dependent diabetes. Lancet. 1988 Apr 16;1(8590):845–850. doi: 10.1016/s0140-6736(88)91601-7. [DOI] [PubMed] [Google Scholar]
  34. Thomson G., Robinson W. P., Kuhner M. K., Joe S., MacDonald M. J., Gottschall J. L., Barbosa J., Rich S. S., Bertrams J., Baur M. P. Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus. Am J Hum Genet. 1988 Dec;43(6):799–816. [PMC free article] [PubMed] [Google Scholar]
  35. Todd J. A., Bain S. C. A practical approach to identification of susceptibility genes for IDDM. Diabetes. 1992 Sep;41(9):1029–1034. doi: 10.2337/diab.41.9.1029. [DOI] [PubMed] [Google Scholar]
  36. Ziegler A. G., Herskowitz R. D., Jackson R. A., Soeldner J. S., Eisenbarth G. S. Predicting type I diabetes. Diabetes Care. 1990 Jul;13(7):762–765. doi: 10.2337/diacare.13.7.762. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES