Lynn P. Lowe

Hyperglycemia and adverse pregnancy outcomes

BACKGROUND It is controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes. METHODS A total of 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter (5.8 mmol per liter) or less and the 2-hour plasma glucose level was 200 mg per deciliter (11.1 mmol per liter) or less. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia. RESULTS For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight above the 90th percentile, the odds ratios were 1.38 (95% confidence interval [CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker. CONCLUSIONS Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels.

International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy

In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort. The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …

International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy: Response to Weinert

In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort. The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …

The Hyperglycemia and Adverse Pregnancy Outcome Study: Associations of GDM and obesity with pregnancy outcomes

OBJECTIVE To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes. RESULTS Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m2), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93–2.47), for obesity alone 1.73 (1.50–2.00), and for both GDM and obesity 3.62 (3.04–4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women). CONCLUSIONS Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: Associations with Neonatal Anthropometrics

OBJECTIVE—To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS—Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the babys sex. RESULTS—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. CONCLUSIONS—These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth.

Frequency of Gestational Diabetes Mellitus at Collaborating Centers Based on IADPSG Consensus Panel–Recommended Criteria The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

OBJECTIVE To report frequencies of gestational diabetes mellitus (GDM) among the 15 centers that participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study using the new International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. RESEARCH DESIGN AND METHODS All participants underwent a 75-g oral glucose tolerance test between 24 and 32 weeks’ gestation. GDM was retrospectively classified using the IADPSG criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations equal to or greater than threshold values of 5.1, 10.0, or 8.5 mmol/L, respectively). RESULTS Overall frequency of GDM was 17.8% (range 9.3–25.5%). There was substantial center-to-center variation in which glucose measures met diagnostic thresholds. CONCLUSIONS Although the new diagnostic criteria for GDM apply globally, center-to-center differences occur in GDM frequency and relative diagnostic importance of fasting, 1-h, and 2-h glucose levels. This may impact strategies used for the diagnosis of GDM.

Diabetes, Asymptomatic Hyperglycemia, and 22-Year Mortality in Black and White Men: The Chicago Heart Association Detection Project in Industry Study

OBJECTIVE To assess relationships of diabetes and asymptomatic hyperglycemia at baseline to the risk of cardiovascular disease (CVD) and all-cause (ALL) mortality in employed, white and black middle-aged men. RESEARCH DESIGN AND METHODS A prospective cohort study of 11,554 white men and 666 black men between the ages 35 and 64 from 1967 to 1973 was conducted using data from the Chicago Heart Association (CHA) Detection Project in Industry 22-year mortality follow-up. cox proportional hazards models, adjusted fro age and other CVD risk factors, were used to estimate the relative risk (RR) and the 95% CI of mortality associated with baseline glycemic status. RESULTS Age-adjusted baseline prevalence of clinical diabetes was similar in white (3.7%) and black (4.3%) men; asymptomatic hyperglycemia (glucose post–50-g load ≥ 11.1 mmol/l) was present in 11.1% of whites and 7.8% of blacks. After controlling for age, lifestyle, and other CVD risk factors, mortality risk was increased among white men with clinical diabetes (CVD: RR 2.51, CI 2.08−3.02; ALL: RR 1.88, CI 1.63−2.17) and asymptomatic hyperglycemia (CVD: RR 1.18, CI 1.01−1.37; ALL: RR 1.24, CI 1.11−1.37), compared with men with postload glucose < 8.9 mmol/l. Risks were similarly, though nonsignificantly (owing to low statistical power), increased among black men with clinical diabetes (CVD: RR 1.60, CI 0.60−4.29; ALL: RR 1.78, CI 0.97−3.25) and asymptomatic hyperglycemia (CVD: RR 1.29, CI 0.61−2.72; ALL: RR 1.37, CI 0.85−2.20). CONCLUSIONS Asymptomatic hyperglycemia and clinical diabetes appear to confer increased mortality risk in both white and black men. In addition, mortality risk is increased with increased severity of glycemia. These findings indicate the importance of applying efforts to reduce risk factors and prevent diabetes in both blacks and whites.

Benefit of a favorable cardiovascular risk-factor profile in middle age with respect to medicare costs

BACKGROUND People without major risk factors for cardiovascular disease in middle age live longer than those with unfavorable risk-factor profiles. It is not known whether such low-risk status also results in lower expenditures for medical care at older ages. We used data from the Chicago Heart Association Detection Project in Industry to assess the relation of a low risk of cardiovascular disease in middle age to Medicare expenditures later in life. METHODS We studied 7039 men and 6757 women who were 40 to 64 years of age when surveyed between 1967 and 1973 and who survived to have at least two years of Medicare coverage in 1984 through 1994. Men and women classified as being at low risk for cardiovascular disease were those who had the following characteristics at the time they were initially surveyed: serum cholesterol level, <200 mg per deciliter (5.2 mmol per liter); blood pressure, < or =120/80 mm Hg; no current smoking; an absence of electrocardiographic abnormalities; no history of diabetes; and no history of myocardial infarction. We compared Medicare costs for the 279 men (4.0 percent) and 298 women (4.4 percent) who had this low-risk profile with those for the rest of the study group, who were not at low risk. Health Care Financing Administration charges for services to Medicare beneficiaries were used to estimate average annual health care costs (total costs, those for cardiovascular diseases, and those for cancer). RESULTS Average annual health care charges were much lower for persons at low risk - the total charges for the men at low risk were less than two thirds of the charges for the men not at low risk (

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus

1,615 less); for the women at low risk, the charges were less than one half of those for the women not at low risk (

Prevalence and Correlates of Coronary Calcification in Black and White Young Adults The Coronary Artery Risk Development in Young Adults (CARDIA) Study

1,885 less). Charges related to cardiovascular disease were lower for the low-risk groups of men and women than for those not at low risk (by