Offspring of mothers with pre-existing diabetes mellitus (DM) or gestational DM (GDM) have an increased risk of childhood obesity. GDM is also associated with an increased maternal risk of type 2 DM. What is not known is the risk of childhood obesity and metabolic disorders or maternal disorders of glucose metabolism along the continuum of maternal glucose to levels diagnostic of DM. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-up Study will recruit from the cohort of women and their offspring who participated in the HAPO Study to address these questions. Its hypothesis is hyperglycemia in pregnancy, less severe than overt DM, is independently associated with increased risk of adverse childhood and maternal outcomes 8-12 years later. HAPO, an observational study, examined glucose tolerance in a large, multi-national, racially diverse cohort of women in the 3rd trimester of gestation using a common protocol and data collection instruments, uniform training of personnel and a central laboratory. HAPO's hypothesis was hyperglycemia in pregnancy, less severe than overt diabetes, is independently associated with increased risk of adverse maternal and neonatal outcomes. Its results led a consensus panel to formulate new International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria for the diagnosis of GDM. In HAPO, higher levels of maternal glucose were independently associated with increased frequency of birthweight, cord serum C- peptide, and infant adiposity >90th percentile. In the offspring of diabetic mothers, these outcomes are risk factors for childhood obesity and metabolic disorders, but the nature of these associations and magnitude of risk associated with increasing levels of maternal glucose below those diagnostic of diabetes, including mothers with GDM based upon the new IADPSG criteria, are not known. A HAPO Follow-Up Study is uniquely positioned to address these important questions. Its General Aim is to obtain measures of adiposity, glucose, insulin sensitivity and secretion, lipids, inflammation and blood pressure (BP) in 7,000 HAPO mother-offspring (aged 8-12) pairs of multiple ethnic/race groups in 10 of the 15 HAPO field centers. The primary aims and hypotheses are: Primary Aim 1: To determine associations of maternal glucose levels during pregnancy with measures of adiposity in offspring. Hypothesis 1: Maternal glucose levels, including those newly classified as GDM, are positively and independently associated with measures of adiposity in offspring (obesity, overweight, percent fat). Primary Aim 2: Determine associations of maternal glucose levels during pregnancy and maternal metabolic disorders 8-12 years later. Hypothesis 2: Maternal glucose levels, including those newly classified as GDM, are positively and independently associated with later maternal risk of disorders of glucose metabolism (diabetes, impaired fasting glucose, impaired glucose tolerance). Secondary aims will examine associations of maternal glucose levels during pregnancy with glycemia and insulin sensitivity and secretion, lipids, BP and inflammation in the offspring and measures of cardiovascular risk in the mothers.
Children of mothers who had diabetes mellitus during pregnancy or were diagnosed with gestational diabetes (i.e., diabetes that develops during pregnancy) have an increased risk of being obese or overweight in childhood, but, whether this risk is also present for higher levels of blood sugar less than those diagnostic of diabetes is not known. This project will address this and other questions by following up on a prior study in which the impact of mothers'blood sugar levels in the 3rd trimester of pregnancy on the birth outcomes of mothers and babies was determined in a large, multinational, racially diverse cohort of women and used to establish new guidelines for the diagnosis of gestational diabetes. In this follow-up study, we will recruit 7,000 mother-child pairs from the original study to determine whether a mother's blood sugar levels during pregnancy, including those newly diagnostic of gestational diabetes, are associated with measures of fatness in children and a mother's risk of abnormal blood sugar levels 8-12 years following the pregnancy, which could impact recommendations for the treatment and follow-up of mothers'blood sugar levels during pregnancy.