Association of glucose metabolism and blood pressure during pregnancy with subsequent maternal blood pressure.

The goal of this study was to examine associations of measures of maternal glucose metabolism and blood pressure during pregnancy with blood pressure at follow-up in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Follow-Up Study included 4747 women who had a 75-g oral glucose tolerance test (OGTT) at ~28 weeks' gestation. Of these, 4572 women who did not have chronic hypertension during their pregnancy or other excluding factors, had blood pressure evaluation 10-14 years after the birth of their HAPO child. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (SBP ≥ 140 and/or DBP ≥ 90 or treatment for hypertension) at follow-up. Blood pressure during pregnancy was associated with all blood pressure outcomes at follow-up independent of glucose and insulin sensitivity during pregnancy. The sum of glucose z-scores was associated with blood pressure outcomes at follow-up but associations were attenuated in models that included pregnancy blood pressure measures. Associations with SBP were significant in adjusted models, while associations with DBP and hypertension were not. Insulin sensitivity during pregnancy was associated with all blood pressure outcomes at follow-up, and although attenuated after adjustments, remained statistically significant (hypertension OR 0.79, 95%CI 0.68-0.92; SBP beta -0.91, 95% CI -1.34 to -0.49; DBP beta -0.50, 95% CI -0.81 to -0.19). In conclusion, maternal glucose values at the pregnancy OGTT were not independently associated with maternal blood pressure outcomes 10-14 years postpartum; however, insulin sensitivity during pregnancy was associated independently of blood pressure, BMI, and other covariates measured during pregnancy.

The chromosome 3q25 locus associated with fetal adiposity is not associated with childhood adiposity.

Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), ß=0.026 and P=4.8 × 10(-4), ß=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; ß =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; ß=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.

Maternal testosterone levels are associated with C-peptide levels in the Mexican American subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort.

Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resistance and sex hormone levels, we examined the associations of sex hormone-binding globulin (SHBG) and testosterone with measures of glycemia and insulinemia in a healthy pregnant population. We measured fasting serum SHBG and testosterone levels in 215 Hispanic mothers of Mexican ancestry from the HAPO Study cohort and tested for associations between SHBG and testosterone levels and maternal plasma glucose and C-peptide. After adjusting for confounding variables, serum total testosterone (TT) was positively associated with fasting C-peptide (0.18 µg/l higher for TT higher by 1 SD, p=0.001) and 1-h C-peptide (0.79 µg/l higher for TT higher by 1 SD, p<0.001). Free testosterone (FT) was also positively associated with fasting C-peptide (0.19 µg/l higher for FT higher by 1 SD, p<0.001), and 1-h C-peptide (0.83 µg/l higher for FT higher by 1 SD, p<0.001). Although these findings are from a single cohort, this study provides evidence for an association between testosterone and C-peptide during pregnancy in a nondiabetic Hispanic obstetric population.

The role of the polycystic ovary syndrome susceptibility locus D19S884 allele 8 in maternal glycemia and fetal size.

CONTEXT: The high incidence of insulin resistance, type 2 diabetes, and metabolic syndrome in Western societies and their impact on quality of life emphasize the importance of identifying underlying susceptibility loci for metabolic diseases. The polycystic ovary syndrome (PCOS) susceptibility locus D19S884 allele 8 (A8) is associated with measures of insulin resistance, beta-cell dysfunction, and other metabolic phenotypes in PCOS families. We now investigate the role of D19S884 A8 in pregnancy. OBJECTIVE: Using the multiethnic Hyperglycemia and Adverse Pregnancy Outcome cohort, we assessed the associations of D19S884 A8 with measures of maternal glycemia and fetal size. DESIGN: We tested for association of maternal D19S884 A8 with maternal outcomes (fasting, 1-h, and 2-h plasma glucose, and fasting and 1-h C-peptide from an oral glucose tolerance test) and fetal and maternal D19S884 A8 with fetal outcomes (birth weight, length, head circumference, sum of skin folds, fat mass, cord C-peptide, and 2-h neonatal plasma glucose). SUBJECTS: We analyzed 4424 Caucasian mothers and 3347 offspring of northern European ancestry, 1957 Thai mothers and 2089 offspring from Bangkok, 1208 Afro-Caribbean mothers and 1209 offspring from Barbados, and 774 Hispanic mothers and 762 offspring from Bellflower, California. RESULTS: After adjusting for confounding variables and multiple testing, neither maternal nor fetal D19S884 A8 showed significant evidence for association with any of the outcomes tested. CONCLUSIONS: The PCOS susceptibility locus, D19S884 A8, is not a major factor contributing to glycemia during pregnancy or fetal size in a general obstetric population.

Prevalence and correlates of coronary calcification in black and white young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Whereas cardiovascular risk factor levels are substantially different in black and white Americans, the relative rates of cardiovascular disease in the 2 groups are not always consistent with these differences. To compare the prevalence of coronary calcification, an indicator of coronary atherosclerosis, in young adult blacks and whites, we performed electron-beam computed tomography of the heart in 443 men and women aged 28 to 40 years recruited from a population-based cohort. The presence of calcium, defined as at least 1 focus of at least 2.05 mm(2) in area and >130 Hounsfield units in density within the coronary arteries, was identified in 16.1% of black men, 11.8% of black women, 17.1% of white men, and 4.6% of white women (P=0.04 for comparison across groups). Coronary calcium was associated with age and male sex, and after adjustment for age, race, and sex, coronary calcium was positively associated with body mass index, weight, systolic blood pressure, total cholesterol, low density lipoprotein cholesterol, triglycerides, and fasting insulin and negatively associated with education (all P<0.05). Independent risk factors included male sex, body mass index, and low density lipoprotein cholesterol. Race was not significantly associated with coronary calcium in men or women, before or after adjustment for risk factors. Coronary calcification is associated with increased levels of cardiovascular risk factors in young adults, and its prevalence is not significantly different in blacks and whites.

Impact of major cardiovascular disease risk factors, particularly in combination, on 22-year mortality in women and men.

BACKGROUND: The appropriateness of current cardiovascular disease (CVD) risk factor guidelines in women continues to be debated. OBJECTIVE: To present new data on the appropriateness of current CVD risk factor guidelines, for women and men, from long-term follow-up of a large population sample. METHODS: Cardiovascular disease risk factor status according to current clinical guidelines and long-term impact on mortality were determined in 8686 women and 10503 men aged 40 to 64 years at baseline from the Chicago Heart Association Detection Project in Industry; average follow-up was 22 years. RESULTS: At baseline, only 6.6% of women and 4.8% of men had desirable levels for all 3 major risk factors (cholesterol level, <5.20 mmol/L [<200 mg/dL]; systolic and diastolic blood pressure, <120 and <80 mm Hg, respectively; and nonsmoking). With control for age, race, and other risk factors, each major risk factor considered separately was associated with increased risk of death for women and men. In analyses of combinations of major risk factors, risk increased with number of risk factors. Relative risks (RRs) associated with any 2 or all 3 risk factors were similar: for coronary heart disease mortality in women, RR= 5.72 (95% confidence interval [CI], 2.35-13.93), and in men, RR = 5.51 (95% CI, 3.10-9.77); for CVD mortality in women, RR = 4.54 (95% CI, 2.33-8.84), and in men, RR = 4.12 (95% CI, 2.56-6.37); and for all-cause mortality in women, RR = 2.34 (95% CI, 1.73-3.15), and in men, RR = 3.20 (95% CI, 2.47-4.14). Absolute excess risks were high in women and men with any 2 or all 3 major risk factors. CONCLUSIONS: Combinations of major CVD risk factors place women and men at high relative, absolute, and absolute excess risk of coronary heart disease, CVD, and all-cause mortality. These findings support the value of (1) measurement of major CVD risk factors, especially in combination, for assessing long-term mortality risk and (2) current advice to match treatment intensity to the level of CVD risk in both women and men.

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 ($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 ($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 $979 and $556, respectively), and charges related to cancer were also lower (by $134 and $189). CONCLUSIONS: People with favorable cardiovascular risk profiles in middle age had lower average annual Medicare charges in older age. Having optimal status with respect to major cardiovascular risk factors may result not only in greater longevity but also in lower health care costs.

Epidemiology of alcohol use in a group of older American Indians.

PURPOSE: This study describes alcohol use in a group of older American Indians and the associations with demographic and health status characteristics, by gender. METHODS: Alcohol use was examined in a cross-sectional, population-based study of 161 American Indians, aged 45-76 years (a substudy of the Strong Heart Study). Alcohol use was measured by a questionnaire administered during a personal interview. Information about demographic characteristics and health status was ascertained from interviews and abstraction of medical records. RESULTS: A higher proportion of men than women had used alcohol heavily (71% vs. 28%). Men were more likely than women to drink currently (46% vs. 18%), to binge (26% vs. 5%), and to screen positive for alcoholism (77% vs. 43%). Among current drinkers, > 30% had diabetes, and the average score on the Short Michigan Alcoholism Screening Test (SMAST) was in the alcoholic range. Heavy drinking was associated with more symptoms of depression in women (P < 0.05) and fewer in men (P < 0.05). Alcoholism was positively associated with a history of heavy drinking in both men (P < 0.05) and women (P < 0.001). CONCLUSIONS: Alcohol use was common and varied by gender. Alcohol use also varied according to other sociodemographic and health status characteristics. Since many older American Indians with chronic illness are currently drinking, this age group may require enhanced alcohol control programs.

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 > or = 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.

Type II diabetes and cognitive function. A population-based study of Native Americans.

OBJECTIVE: To explore the relationship between type II diabetes and cognitive function in older Native Americans and to assess the effects of other selected risk factors for cognitive dysfunction on this relationship. RESEARCH DESIGN AND METHODS: Cognitive function was assessed in 80 diabetic and 81 nondiabetic Native Americans who were 45-76 years of age in a cross-sectional population-based sub-study of the Strong Heart Study. Thirteen cognitive function tests were administered during a personal interview. Information about six other risk factors for cognitive dysfunction, including depressive symptoms, physical function, alcoholism, current alcohol use, hypertension, and myocardial infarction, was ascertained from interviews and from abstraction of medical records. RESULTS: Diabetes was associated with impairment on only two tests of cognitive function: verbal fluency (P = 0.004) and similarities (P = 0.010). Depressive symptoms were related to verbal fluency (P = 0.004), but did not explain the diabetes-related difference in performance. The effects of hypertension, depressive symptoms, and current alcohol use explained the diabetes-related performance difference on similarities. Cognitive function was not related to metabolic control (HbA1c level). CONCLUSIONS: We found little evidence that type II diabetes in this population of Native Americans is associated with decrement in cognitive function. Some of the cognitive impairment previously attributed to diabetes may be related, at least in part, to the influence of other risk factors. This should be considered in the design of future studies in other populations.