Women with isolated fasting hyperglycemia in pregnancy are at a higher genetic risk for type 2 diabetes

Using genetic scores for fasting plasma glucose (FPG GS) and Type 2 diabetes (T2D GS), we investigated whether different diagnostic criteria for gestational diabetes (GDM) have different implications for genetic susceptibility to later T2D in women from the the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) and Atlantic Diabetes in Pregnancy (DIP) studies. To investigate different features of WHO (1999) and IADPSG (2010) criteria for diagnosing GDM, cases were divided into three subgroups: (i) FPG ≥5.1 mmol/L only, n=261; (ii) 2-hour glucose post 75 g oral glucose load ≥7.8 mmol/L only, n=305); and (iii) both FPG ≥5.1 mmol/L and 2-hour glucose ≥7.8 mmol/L, n=135. We compared the FPG and T2D genetic scores of these groups with controls (n=3,083). GDM as defined by fasting hyperglycemia was associated with a higher genetic score for both FPG and T2D, whether or not 2-hour glucose was also raised. GDM defined only by 2-hour hyperglycemia, was associated with a higher T2D GS, but not a higher FPG GS. The T2D GS was similar whether the fasting glucose alone, 2-hour glucose alone, or both fasting and 2-hour glucose were raised. Thus, the newest criteria identify women with a genetic predisposition to T2D who may not have been identified by previous criteria.