Hapo trial diabetes

While a glucose tolerance test is commonly employed, glucose challenge dosages vary and diagnostic thre challenge is widely used throughout the sholds are myriad.

The 75 gram glucose roughout the world for diagnostic testing in the nonpregnant state. At the Third International Workshop-Conference on Gestational Diabetes in 1 a series of recommendations were made which included universal employment of the 75 gram glucose challenge during pregnancy.

Some sets of diagnostic criteria, such as those proposed by the World Health Organization, were simply based on criteria used in nonpregnant individuals, and did not take into account changes in carbohydrate metabolism brought about by the pregnant state.

The organizers advocated for international agreement on all aspects of diagnostic testing, and for the development of criteria based on pregnancy outcomes. Subsequently a group of investigators from the disciplines of obstetrics and gynecology, diabetology and neonatology, based in North America, Europe, Asia and the Middle East, met to plan a study to examine the relationship between maternal glucose and adverse neonatal outcomes.

A workshop sponsored by NICHD and NIDDK 3 supported the rationale behind this effort, concluding that carefully designed studies were critical in order to answer outstanding questions about the sensitivity, specificity and cost-effectiveness of efforts to diagnose and treat gestational diabetes to prevent adverse perinatal effects.

Another area of controversy surrounded the potential benefit, or lack of benefit, of screening a population for gestational diabetes and treating when the diagnosis was made. While there was little or no argument that type 1 and type 2 diabetes increase the risk of any number of adverse pregnancy outcomes, HAPO sought to determine the level of glucose intolerance during pregnancy, short of overt diabetes, that is associated with adverse outcomes.

The study design has been described in detail elsewhere. Each subject underwent a 75 gram, 2-hour oral glucose tolerance test at between 24 and 32 weeks gestation mean gestational age At the time of delivery, cord blood samples were obtained and analyzed at the Central Laboratory for glucose and for C-peptide. C-peptide was chosen as a marker for fetal insulin levels because, in the presence of hemolysis, it is much more stable than insulin in stored specimens.

Neonatal anthropometric measurements were collected within 72 hours of delivery. These consisted of weight, length, head circumference and skinfold thickness measured at the flank, subscapular and triceps areas.

Additional data were abstracted from maternal and neonatal medical records. A number of secondary outcomes were also considered.

Participants were enrolled between July and April Data were analyzed, blinded to test results, for 23, mother-newborn pairs.

The mean fasting plasma glucose value across all participants was At 1 and 2 hours after the 75 gram oral glucose challenge the means were The average gestational age at delivery was The one and two hour value categories were chosen to yield proportions of the population that were similar to those of the fasting plasma glucose categories.

As shown in figure 1 , the four primary outcomes were all related to each of the three glucose determinations in a continuous and graded manner. Clinical neonatal hypoglycemia, which occurred in only 2.

For example, the prevalence of cord C-peptide above the 90 th centile increased from 3. When logistic models were constructed to account for potential confounders such as location i.

Frequency of primary outcomes across the glucose categories. Reprinted, with permission, from the New England Journal of Medicine 9. The relationship between OGTT values and each of the four primary outcomes was also evaluated using glucose as a continuous variable, and correcting for the potential confounders described above.

As shown in table 1 these relationships were expressed as the odds ratio for a given outcome for each SD increase in glucose. The association between each of the OGTT values and each of the primary outcomes remained significant with the exception of that between both fasting plasma glucose and 2 hour plasma glucose with clinical neonatal hypoglycemia. A number of secondary outcomes were also evaluated.

Preterm delivery was associated with the one and two hour glucose values, but not with fasting plasma glucose. One of the most critical observations of the HAPO Study was that the associations of various adverse outcomes with OGTT results were continuous, and no clear inflection points could be identified.

It was clear that the results of HAPO were applicable to all the involved field centers since the associations did not vary significantly across field centers, even though the prevalence of adverse outcomes differed among them.

Thus the HAPO results should be applicable globally to develop outcome based criteria for classifying glucose metabolism in pregnancy.

The HAPO investigators did not make specific recommendations for diagnostic criteria. Because there were not obvious inflection points in the associations, and because it was important that any recommended diagnostic criteria be accepted internationally, a committee of experts was convened to develop a consensus regarding appropriate diagnostic criteria. There were presentations of data from HAPO and other studies, and discussion of these data by the delegates from approximately 40 different countries.

This was followed by caucuses of the various groups who were present. A smaller steering committee and writing group was appointed. The delegates agreed that the choice of thresholds would have to be somewhat arbitrary since inflection points in these continuous and graded relationships were not apparent. The group decided that the various adverse outcomes were not equally important in devising diagnostic thresholds, and that some outcomes such as macrosomia and cesarean section were inter-related.

The outcomes of large for gestational age, and fat or hyperinsulinemic babies comprise the primary basis for the recommended diagnostic criteria.

It would have simplified matters if a single glucose determination, such as fasting plasma glucose, would be sufficient for the diagnosis, so as to preclude the need for a full OGTT. Therefore, the relative independent contributions of the fasting, 1-hour and 2-hour glucose values were considered. As described below, each of the three samples contributed at least partially independently as a predictor of adverse pregnancy outcome, and the group decided to recommend the full 2-hour 75 gram oral glucose tolerance test, leaving open the possibility that a particular professional organization might opt to eliminate one or more of the three tests, thereby reducing the sensitivity of the process but also decreasing the cost and inconvenience.

The mean glucose value at each of the three time points was chosen as the reference value, against which proposed thresholds would be compared. Thresholds which yielded odds ratios of 1. Setting thresholds at an odds ratio of 1. Using an odds ratio of 1. The thresholds recommended represent odds ratios of 1. It may be stated that the IADPSG recommendations are based on pregnancy outcomes, but do not take into account the predictive values for maternal well-being or long term neonatal outcomes.

Glucose tolerance is assessed by a 75 g 2-h OGTT at weeks' gestation. Sociodemographic and health history data are collected via questionnaire and medical record abstraction. Maternal blood is obtained for measurement of serum C-peptide and hemoglobin A1c HbA 1C , cord blood for serum C-peptide and plasma glucose, and a capillary specimen is taken between 1 and 2 h following delivery for neonatal plasma glucose.

Neonatal anthropometrics are obtained, and follow-up data are collected at weeks post-delivery. Abstract Objective: The objective of the Hyperglycemia and Adverse Pregnancy Outcome HAPO Study is to clarify unanswered questions on associations of maternal glycemia, less severe than overt diabetes mellitus, with risks of adverse pregnancy outcome.