Gestational Diabetes Mellitus: Heterogeneity of Maternal Age, Weight, Insulin Secretion, HLA Antigens, and Islet Cell Antibodies and the Impact of Maternal Metabolism on Pancreatic B-Cell and Somatic Development in the Offspring

Abstract

We have examined gravida with gestational diabetes mellitus (GDM), as defined by the National Diabetes Data Group (Diabetes 1979; 28:1039), for phenotypic and genotypic heterogeneity. Fasting plasma glucose (FPG) at diagnosis was used for further stratification of GDM according to putative metabolic severity into class A1 (FPG less than 105 mg/dl [N = 129]), class A2 (FPG 105-129 mg/dl [N = 47]), and class B1 (FPG greater than or equal to 130 mg/dl [N = 23]). All GDM classes tended to be older and heavier than consecutive gravida with documented normal glucose tolerance (controls, N = 148). Subdivision into "lean" and "obese" indicated that plasma immunoreactive insulin (IRI) was greater after overnight fast in the obese of all groups except B1. However, absolute increases in IRI above fasting levels in response to glucose during OGTT were significantly enhanced by obesity only in class A2 gravida. Adjustment for the effects of age and weight by covariate analysis indicated that the IRI response to glycemic stimulation is usually attenuated in all forms of GDM. Mean values for increases in IRI above fasting values during the first 15 min and IRI increments relative to the increases in plasma glucose throughout the 180-min OGTT were below control values in all GDM groups and progressively so, i.e., A1 less than A2 less than B1. The absolute insulinopenia was not invariable; a small number of gravida from all GDM groups displayed well-preserved IRI responses to oral glucose. Genotypic evaluation of the GDM population disclosed an increased occurrence of "markers" known to be associated with type I diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Genotypic and phenotypic differences between Arabian and Scandinavian women with gestational diabetes mellitus

“…This may, however, represent an over correction, as the HLA genotypes tested are in strong linkage disequilibrium [45] and thereby do not represent independent observations. A report showed a two-fold increase in the frequency of HLA-DR3 and -DR4 antigens in GDM compared with the controls matched for race, and the increase was statistically significant in black women from the Unit- ed States [22]. Another study found no significant difference in the frequency distribution of HLA-DQB1, -DQA1 and -DRB1 alleles between Caucasian GDM and control women from Germany [46].…”

“…Increased frequencies of HLA-risk antigens and high prevalence of ICA, insulinoma-associated antigen 2 (IA-2) and GAD antibodies have also been reported in women with GDM [22,23].…”

The type 1 diabetes protective HLA DQB1*0602 allele is less frequent in gestational diabetes mellitus

“…HLA genes of the MHC have been related to GDM in several studies. Some have demonstrated a positive association between GDM and HLA class II alleles [2], while others have not [3]. If GDM is to be properly classified, it is necessary to genetically characterise it and make distinctions from other types of diabetes.…”

Correlation of serum biomarkers in prediction of gestational diabetes mellitus

“…3 Khan et al in his study concluded that maternal age, BMI, previous history of gestational diabetes and family history of diabetes are the high-risk factors of GDM. 4 This association of increasing age with GDM might be due to the declining beta cell function and insulin sensitivity.…”