529 GENETICS AND NATURAL HISTORY OF MATURITY ONSET DIABETES OF THE YOUNG

Abstract

Families with a 3 generation of a mild autosomal dominant form of diabetes mellitus (MODY) were HLA typed at the A and B loci. In family A, 6/6 affected members shared the same haplo type (A1,B8). In family B, 4/5 affected members had haplotype A29,B7. In family C, 1/2 affected members had haplotype A1,B8. With one exception, family members who lack these particular haplotypes do not develop MODY. This indicates a possible linkage between the genes in the HLA region and the gene(s) coding for susceptibility to MODY. Several affected members in family A have been followed with serial oral glucose tolerance tests (OGTT). Suring childhood, the fasting plasma glucose is high and the glucose peak during the OGTT is elevated and delayed. Simultaneous plasma insulin levels are quantitatively normal, but inappropriately low in relation to the elevated plasma glucose. During adolescence, deterioration in the OGTT often occurs; affected individuals fail to produce the physiologic increase in insulin output expected at this age. Treatment with tolbutamide displaces the OGTT curve downwards, but does not alter its shape. These individuals may at times be placed on insulin. Since the mode of inheritance and the prognosis appear to be entirely different from that of insulin dependent juvenile onset diabetes (JOD), it is important to distinguish children with MODY from those with classical JOD when planning studies of etiology or of assessments of therapy.