Diabetes Mellitus in Pregnancy and Periconceptional Genetic Counseling

ABSTRACT

Gestational diabetes constitutes 90% of all pregnant diabetic patients, whereas insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes melli-tus (NIDDM) together account for the remaining 10%. Diabetes is considered a heterogeneous disease with a continuous spectrum between IDDM and NIDDM. It is believed that gestational diabetes is also a heterogeneous disorder representing, at least in part, patients who are destined to develop in later life either IDDM or NIDDM. Studies in identical twins have shown clear-cut differences in the genetic inheritance of IDDM and NIDDM. Nearly 100% of identical twins were found to be concordant for NIDDM; whereas in IDDM the concordance rate ranges between 20 and 50%. This concordant pattern indicates a higher genetic contribution in NIDDM than IDDM. Furthermore, IDDM is an HLA-linked disorder, and NIDDM is not. The exact mechanism of inheritance of IDDM and NIDDM is not known; therefore the information used in genetic counseling is based on empirical risk estimates. Recent information demonstrates that IDDM is transmitted less frequently to the offspring of diabetic mothers than diabetic fathers (1.3% versus 6%). The estimated risk of recurrence of IDDM to offsprings with one already affected sibling and unaffected parents is 5 to 6%. Additionally, the empirical risk of NIDDM first-degree relatives developing diabetes is much higher than the observed in IDDM relatives, 15% for first-degree relatives and 60 to 75% when both parents have NIDDM. In the present report, current developments in the genetics of diabetes will be reviewed and pertinent information for genetic counseling of pregnant diabetic patients will be discussed.