First versus repeat treatment with a lifestyle intervention program: attendance and weight loss outcomes.

OBJECTIVE: Following unblinding of the Diabetes Prevention Program (DPP) results, a 16-session lifestyle intervention program was offered to all study participants, including those who had initially been randomized to lifestyle treatment. This study compares the effects of the lifestyle program between participants who had previous exposure and those who had not. DESIGN: A 16-session behavioral intervention was conducted in groups at each of the 27 DPP sites during a transitional (bridge) period from the DPP trial to the DPP Outcomes Study (DPPOS). Session participation for this 6-month behavioral weight loss program was confirmed by originally randomized treatment groups. SUBJECTS AND MEASUREMENTS: Independently assessed weight measurements were available within a 7-month period before and after the program for 2808 ethnically diverse participants. RESULTS: Participants from the lifestyle group in the DPP were the least likely to attend a repeat offering of a 16-session behavioral weight loss program conducted in groups. Weight loss during the transitional lifestyle program was strongly related to the duration of attendance in the three groups that were participating in the program for the first time (metformin, placebo and troglitazone), but not related to amount of earlier weight loss. CONCLUSION: Individuals who were naive to the behavioral program lost a greater amount of weight and this was strongly related to their degree of participation. A second exposure to a behavioral weight loss program resulted in unsatisfactory low attendance rates and weight loss.

Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies.

Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.

Sex differences in insulin levels in older adults and the effect of body size, estrogen replacement therapy, and glucose tolerance status. The Rancho Bernardo Study, 1984-1987.

OBJECTIVE--To determine if insulin levels vary with sex, independent of estrogen replacement therapy (ERT), differences in body mass index (BMI), waist-to-hip ratio (WHR), and glycemia. RESEARCH DESIGN AND METHODS--In a population-based study of older adults, insulin levels were measured before and after a standardized oral glucose tolerance test in 673 men and 849 women, all free of known diabetes. RESULTS--Age-adjusted fasting insulin levels were highest in men, intermediate in women not taking estrogen, and lowest in estrogen-treated women (P < 0.01). Differences between men and women not taking estrogen disappeared after adjusting for age and BMI, but not glycemia; estrogen-treated women had significantly lower fasting insulin levels than did men (P < 0.01) and women not taking estrogen (P < 0.01). The association of estrogen use with lower fasting insulin levels persisted after adjusting for age and WHR (P < 0.001) and was stronger among women with abnormal glucose tolerance. Age-adjusted postchallenge insulin levels were higher in women than in men (P < 0.01). The sex difference persisted after adjusting for age and BMI or glycemia. Postchallenge insulin levels did not vary by ERT. CONCLUSIONS--Men have higher fasting insulin levels than do women, whether or not the women are using ERT. Differences between men and untreated women are explained by differences in BMI, but estrogen users have lower fasting insulin levels independent of BMI. Postchallenge insulin levels are higher in women than men and are independent of ERT, BMI, and glycemia. Clinical trials in women are needed to determine whether ERT can improve insulin and glucose metabolism.

The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up.

CONTEXT: Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women with a history of GDM. OBJECTIVE: The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study. DESIGN: This was a randomized controlled clinical trial with an observational follow-up. SETTING: The study was conducted at 27 clinical centers. PARTICIPANTS: Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study. The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry. INTERVENTIONS: Interventions included placebo, ILS, or metformin. OUTCOMES MEASURE: Outcomes measure was diabetes mellitus. RESULTS: Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes. CONCLUSIONS: Women with a history of GDM are at an increased risk of developing diabetes. In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study, both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period. Among women without a history of GDM, lifestyle but not metformin reduced progression to diabetes.

Low bioavailable testosterone levels predict future height loss in postmenopausal women.

The objective of this study was to examine the relation of endogenous sex hormones to subsequent height loss in postmenopausal women, in whom height loss is usually a surrogate for osteoporotic vertebral fractures. This was a prospective, community-based study. The site chosen was Rancho Bernardo, an upper middle class community in Southern California. A total of 170 postmenopausal women participated, aged 55-80 years. None of them were taking exogenous estrogen between 1972 and 1974. Plasma was obtained for sex hormone and sex hormone-binding globulin (SHBG) assays. Estradiol/SHBG and testosterone/SHBG ratios were used to estimate biologically available hormone levels; bioavailable (non-SHBG-bound) testosterone was measured directly in 60 women. Height loss was based on height measurements taken 16 years apart. Height loss was strongly correlated with age (p = 0.001). These women lost an average 0.22 cm/year in height. Neither estrone nor estradiol levels were significantly and independently related to height loss. Both estimated bioavailable testosterone (testosterone/SHBG ratio) and measured bioavailable testosterone levels predicted future height loss (p = 0.02 and 0.08, respectively) independent of age, obesity, cigarette smoking, alcohol intake, and use of thiazides and estrogen. We conclude that bioavailable testosterone is an independent predictor of height loss in elderly postmenopausal women. The reduced height loss is compatible with a direct effect of testosterone on bone mineral density or bone remodeling.

Sex differences in bone mineral density in 1653 men and women in the sixth through tenth decades of life: the Rancho Bernardo Study.

This cross-sectional population-based study examined the effect of age and sex on bone mineral density (BMD) in the elderly. BMD was measured at the spine and hip using dual-energy x-ray absorptiometry and at midshaft and ultradistal radius using single-photon absorptiometry in 672 men and 981 women aged 50-98 years. In both sexes, mean BMD levels decreased significantly with age at all sites except the male spine. In linear regression models, the slope of loss was significantly greater in women than in men at all sites except the ultradistal radius. The slope was steeper at most sites in women aged 50-59 years than in older women, 60-98 years. In both age groups, mean age-adjusted BMD levels were lower at all sites in women who were past or never users of replacement estrogen than in women who were current estrogen users. Current estrogen users generally had lower slopes of loss with age than never or past estrogen users; however, few of these differences were statistically significant. We conclude that BMD levels decrease in old age in both sexes. Continued bone loss in old age raises the possibility that intervention to retard further loss may still be warranted in the elderly.

Family history of osteoporosis and bone mineral density at the axial skeleton: the Rancho Bernardo Study.

To determine whether a family history of osteoporosis identifies individuals with low bone mineral density (BMD), we studied 1477 white elderly (aged 60-89 years), noninstitutionalized ambulatory men (n = 600) and women (n = 877) from the Rancho Bernardo, California cohort. Family history data on biologic parents and full sisters were obtained by questionnaire. BMD of the lumbar spine and hip was measured using dual-energy x-ray absorptiometry. After adjustment for age, body mass index, history of cigarette smoking, thiazide use, and estrogen use, men and women with a family history of osteoporosis had lower BMD than those with a negative family history. In men, a positive family history was associated with lower BMD at the hip (p = 0.01), whereas in women a significant association was observed for the spine (p = 0.02). BMD decreased in a stepwise fashion with an increasing number of family members with a history of osteoporosis. Analysis of the effect of parental history of osteoporosis on BMD showed a significant relation between paternal (but not maternal) history and lumbar spine BMD in both sexes and a significant relation between maternal (but not paternal) history and hip BMD only in men. The relative risk of having categoric osteopenia was highest in those whose fathers had a history of osteoporosis (RR 2.16, 95% CI = 1.38-3.37). A similar association was found for subjects with fractures. These results were not explained by differential awareness of family history in individuals with known osteoporosis, because the prevalence of family history was unrelated to personal history of osteoporosis in men and only weakly related in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased meal frequency associated with decreased cholesterol concentrations; Rancho Bernardo, CA, 1984-1987.

The hypothesis that meal frequency is associated with plasma cholesterol was tested in a population-based sample of 2034 white men and women aged 50-89 y. Total, low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol and triglycerides were measured after a 12-h fast in a Lipid Research Clinic laboratory and meal frequency was obtained by questionnaire. The age-adjusted total cholesterol concentrations for men and women reporting greater than or equal to 4 meals/d averaged 0.23 mmol/L lower than for those who reported 1-2 meals/d (P = 0.01). Similarly, LDL concentrations were lower in those reporting higher meal frequency (0.16 mmol/L, P = 0.06). These associations persisted after adjustment for smoking, alcohol, waist-to-hip ratio, systolic blood pressure, body mass index, and dietary nutrients. These results suggest that cholesterol reductions might be achieved by modest increases in meal frequency without an increase in caloric intake.

Is birth order associated with adult mortality?

The objective of this study was to determine whether birth order is associated with total or cause-specific adult mortality and whether the association differed by sex, was confounded by age, number of siblings, or socioeconomic status, or was mediated by personality, education, or health behaviors. Teachers throughout California identified intellectually gifted children as part of a prospective study begun in the 1920s by Lewis Terman. Information on birth order was available on 1162 subjects (85% of cohort) who have since been followed for over 70 years. Cox proportional hazards models indicated that birth order was not associated with adult all-cause, cardiovascular, or cancer mortality. Among women, middle children were more likely than oldest children to die from causes of death other than cardiovascular disease or cancer, although the numbers in this category were small. This study did not provide evidence that birth order is associated with adult mortality in this highly intelligent, middle-class cohort.

Albumin levels as a predictor of mortality in the healthy elderly.

Serum albumin levels probably predict subsequent mortality in the elderly, but it is not clear whether this is independent of disease. A 3 year prospective study of 2342 healthy non-institutionalized men and women aged 50-89 years old, residing in Rancho Bernardo, California, confirmed the following findings. Serum albumin levels decreased with increasing age in both men and women, and this association was independent of health status. In addition, for every standard deviation decrease in albumin, the relative odds of dying was 1.24 (p = 0.04), after adjusting for age, sex and lifestyle factors such as smoking, exercise and alcohol consumption. Separating the study sample into those who did and did not report disease at baseline did not appreciably alter these findings. Most of the albumin levels of the older adults (70-89) fall within the normal and narrow range of the younger adults (50-69), nevertheless, albumin levels predict outcome independent of known disease. The albumin-early mortality association suggests that serum albumin levels are a predictor for subclinical disease in the healthy elderly.

A prospective study of dehydroepiandrosterone sulfate and cognitive function in an older population: the Rancho Bernardo Study.

OBJECTIVE: To determine whether low plasma dehydroepiandrosterone sulfate (DHEAS) levels predict poor cognitive function in the elderly. DESIGN: A prospective, population-based study with periodic clinical evaluations and 100% follow-up for vital status. SETTING: Rancho Bernardo, California PATIENTS: 270 men and 167 women (80% of surviving, local, age-eligible subjects) from the Rancho Bernardo cohort who had plasma obtained for DHEAS assays in 1972 to 1974 and screening for dementia in 1988 to 1991. MEASUREMENTS: DHEAS levels were measured by radioimmunoassay. There were five interviewer-administered standard screening tests of cognitive function: Mini-Mental Status Examination, Buschke selective reminding test, Trails B, category fluency, and Heaton Visual Reproduction test. RESULTS: DHEAS levels were higher in men than women and decreased with age in both sexes. There were no significant differences in age-adjusted DHEAS levels in the percent of men or women with categorically impaired performance on any test. When analyzed as a continuous variable, DHEAS levels were significantly correlated with only one test, the Bushke, and only in women. Low baseline DHEAS levels were not associated with any mention of dementia on death certificates or with non-participation of survivors. Low levels of DHEAS predicted mortality in men more than in women such that men were more likely to have died before cognitive function testing than women. CONCLUSION: The single DHEAS-memory association, restricted to women, is most likely to be spurious, consequent to multiple comparisons. We cannot exclude a true effect of low DHEAS, restricted to women and reflecting their better survival than men.

Weight loss precedes dementia in community-dwelling older adults.

OBJECTIVE: To determine whether the weight loss associated with Alzheimer's disease precedes or follows the dementia. DESIGN: Older community-dwelling men (n = 134) and women (n = 165) were followed for 20 years before they were diagnosed as cognitively intact or demented. A repeated measures analysis was used to compare weight change in those who developed Alzheimer's Disease (AD) with those who remained cognitively intact. MEASUREMENTS: Weight was measured at three clinic visits between 1972-74, 1984-87, and 1990-93. Participants were classified as having probable or possible AD or being cognitively intact at the 1990-93 evaluation. Diagnoses were made by two neurologists and a neuropsychometrist, based on neuropsychological tests and physical examination, using NINCDS-ADRDA criteria. RESULTS: There were 36 men and 24 women diagnosed with probable or possible AD; they were considered to have mild to moderate dementia based on their test scores and community-dwelling status. Those who developed dementia were older than those diagnosed as cognitively intact. In age-adjusted analyses, both men and women who were later diagnosed with AD had a significant decrease in weight after the baseline visit (P < .001 and P < .003, respectively), but there was no significant weight loss in the men and women who remained cognitively intact. These differences were not explained by lifestyle, depression, or other illness. CONCLUSION: Weight loss precedes mild to moderate dementia; early weight loss is, therefore, unlikely to be a consequence of AD patients being unable or unwilling to eat.

Factors associated with health behavior change among residents 50 to 96 years of age in Rancho Bernardo, California.

Alterations in personal health habits can prevent disease and reduce morbidity and mortality. We examined the association between self-reported healthy behavioral change and age, sex chronic disease, plasma cholesterol, and body mass index in an older Caucasian population in southern California. Overall, about two thirds of respondents reported decreased dietary salt or fat intake over the last 15 years, whereas one third reported increased frequency of exercise. Women were more likely than men to report increasing exercise, changing diet, or reading self-help materials. Individuals 50-69 years of age reported more positive health behavior changes than those 70 years and older. Those with diabetes and hypertension were more likely to decrease salt intake, but less likely to increase exercise than those without disease. Hypertensive and diabetic men, but not women, were also more likely to change their diet or read self-help materials than their peers without disease. The presence of risk factors for cardiovascular disease, such as obesity, elevated serum cholesterol, diabetes, and hypertension, were generally associated with positive alterations in diet and inversely related to increasing exercise.

DES awareness and exposure: the 1994 California Behavioral Risk Factor Survey.

INTRODUCTION: Diethylstilbestrol (DES), a drug used in millions of pregnancies between 1938 and 1971, is the first known human transplacental carcinogen. DES is also associated with other serious health problems for those exposed to it either in utero or while pregnant; however, many men and women are unaware of their exposure or how to protect their health. This first population-based study of DES awareness is part of the National Cancer Instututes's National DES Education Program. METHODS: In 1994, 2,077 women and 1,625 men 23 years of age and over responded to the California Behavioral Risk Factor Survey (BRFS). These subjects were either born during the years DES was in use (men and women 23-53 years old in 1994) or could have been pregnant during those years (women 39 years or older). RESULTS: Analyses weighted to the 1994 California age and ethnicity distribution indicate that only 43% of women and 22% of men had over heard of DES (P < .001). Although 44% of Caucasians had heard of DES, only 10% of Hispanics, 27% of African Americans, and 24% of other races had heard of DES. Within each group, women had heard of DES significantly more often than men. Only 17% of women and 5% of men had ever tried to confirm whether they were exposed to DES in utero, and 8% of women whether they were exposed while pregnant. CONCLUSIONS: Given the serious health consequences of DES exposure and available prevention strategies, this lack of awareness warrants an immediate educational effort.

Bed sharing and the sudden infant death syndrome.

OBJECTIVE: To determine whether infants who died of the sudden infant death syndrome routinely shared their parents' bed more commonly than control infants. DESIGN: Case-control study. SETTING: Southern California. SUBJECTS: 200 white, African-American, Latin American, and Asian infants who died and 200 living controls, matched by birth hospital, date of birth, sex, and race. MAIN OUTCOME MEASURES: Routine bedding (for example, crib, cradle), day and night time sleeping arrangement (for example, alone or sharing a bed); for cases only, sleeping arrangement at death. Differences in bed sharing practices among races. RESULTS: Of the infants who died of the syndrome, 45 (22.4%) were sharing a bed. Daytime bed sharing was more common in African-American (P < 0.001) and Latin American families (P < 0.001) than in white families. The overall adjusted odds ratio for the syndrome and routine bed sharing in the daytime was 1.38 (95% confidence interval 0.59 to 3.22) and for night was 1.21 (0.59 to 2.48). These odds ratios were adjusted for routine sleep position, passive smoking, breast feeding, intercom use, infant birth weight, medical conditions at birth, and maternal age and education. There was no interaction between bed sharing and passive smoking or alcohol use by either parent. CONCLUSIONS: Although there was a significant difference between bed sharing among African-American and Latin American parents compared with white parents, there was no significant relation between routine bed sharing and the sudden infant death syndrome.

Obesity and preference-weighted quality of life of ethnically diverse middle school children: the HEALTHY study.

To date, studies examining the relation between body mass index percentile (BMI%) categories and health-related quality of life (QOL) measurements have not reported preference-weighted scores among ethnically diverse children. We report the associations between BMI% categories and preference-weighted scores among a large cohort of ethnically diverse sixth grade children who participated in the HEALTHY school-based type 2 diabetes risk factor prevention study. Health Utility Index 2 (HUI2) and Health Utility Index 3 (HUI3) and the feeling thermometer (FT) were the preference-weighted QOL instruments used to measure student's preference scores. Of 6358 consented students, 4979 (78.3%) had complete QOL, height, weight, and covariate data. Mean (SD) preference scores were 0.846 (0.160), 0.796 (0.237), and 0.806 (0.161) for the HUI2, HUI3, and FT, respectively. After adjusting for age, sex, blood glucose and insulin, Tanner stage, race/ethnicity, family history of diabetes, and educational attainment, children with severe obesity (>99%) had significantly lower preference scores compared to normal weight on all three instruments (HUI2 P = 0.013; HUI3 P = 0.025; and FT P < 0.001). Obese and severe obese categories were significantly associated with lower HUI2 functional ratings in the mobility domain and with lower HUI3 functional ratings in the speech domain.

Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy.

AIM: To determine whether there is an association between complement factor H (CFH) or LOC387715 genotypes and response to treatment with photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). METHODS: Sixty-nine patients being treated for neovascular AMD with PDT were genotyped for the CFH Y402H and LOC387715 A69S polymorphisms by allele-specific digestion of PCR products. AMD phenotypes were characterized by clinical examination, fundus photography, and fluorescein angiography. RESULTS: Adjusting for age, pre-PDT visual acuity (VA), and lesion type, mean VA after PDT was significantly worse for the CFH TT genotype than for the TC or CC genotypes (P=0.05). Post-PDT VA was significantly worse for the CFH TT genotype in the subgroup of patients with predominantly classic choroidal neovascular lesions (P=0.04), but not for the patients with occult lesions (P=0.22). For the LOC387715 A69S variant, there was no significant difference among the genotypes in response to PDT therapy. CONCLUSIONS: The CFH Y402H variant was associated with a response to PDT treatment in this study. Patients with the CFH TT genotype fared significantly worse with PDT than did those with the CFH TC and CC genotypes, suggesting a potential relationship between CFH genotype and response to PDT.

Relation between body size and bone mineral density in elderly men and women.

This cross-sectional study of the Rancho Bernardo, California, cohort examines the relation between bone mineral density and eight measures of body size (total weight, body mass index, waist-hip ratio, lean mass, fat mass, percentage fat mass, and current and maximum adult height) measured between 1988 and 1991 in 1,492 ambulatory white adults aged 55-84 years. Lean mass, fat mass, and percentage fat mass were measured by bioelectric impedance. Bone mineral density was measured at the hip and lumbar spine with dual-energy x-ray absorptiometry and at the midshaft and ultradistal radius with single photon absorptiometry. In multiple linear regression models adjusted for age, smoking, exercise, alcohol, thiazide use, and estrogen use (in women), total weight was the most consistent marker of bone mineral density overall. In this cohort, all measures of body size were associated with bone mineral density in both sexes and were better markers of bone mineral density in the weight-bearing sites than in the non-weight-bearing sites, implying a mechanical effect of weight on bone mineral density.

Poisson regression with a surrogate X: an analysis of vitamin A and Indonesian children's mortality.

"A Poisson regression model with a surrogate X variable is proposed to help to assess the efficacy of vitamin A in reducing child mortality in Indonesia. In a recent community trial, the mortality rate in villages receiving vitamin A supplementation was 35% less than in control villages. However, at base-line, control villages were found to have slightly higher rates of xerophthalmia, an ocular disease caused by vitamin A deficiency. It was therefore desirable to adjust the mortality comparison for base-line vitamin A levels as indicated by xerophthalmia prevalence. This paper presents a parametric errors-in-X regression model developed for this purpose. Likelihood methods for fitting and inference are discussed. The model is illustrated on the Indonesian data set."

A prospective study of dehydroepiandrosterone sulfate (DHEAS) and bone mineral density in older men and women.

The purpose of this study was to prospectively examine the relation of dehydroepiandrosterone sulfate (DHEAS) to bone mineral density in a community-based sample of 260 men and 162 women who were residents of Rancho Bernardo, California. DHEAS levels had been measured in plasma obtained in 1972-1974 when the men were 50-74 years of age and the women were 55-74. In 1988-1991, bone mineral density was measured at the lumbar spine and hip using dual x-ray absorptiometry, and at the mid-radius and ultradistal radius using single photon absorptiometry. Among men, there was a significant decrease in DHEAS levels and bone mineral density at the hip, ultradistal radius, and midshaft radius with increasing age. However, for both men and women, there was no significant association of DHEAS levels with bone mineral density at any site, both before and after adjustment for age, obesity, cigarette smoking, and use of antihypertensive medications. These data do not support the hypothesis of DHEAS having a causal role in senile osteoporosis.