Search

Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio = 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio = 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions.

A variety of methods are available for estimating genetic admixture proportions in populations; however, few investigators have conducted detailed comparisons using empirical data. The authors characterized admixture proportions among self-identified African Americans (n = 535) and Latinos (n = 412) living in the San Francisco Bay Area who participated in a lung cancer case-control study (1998–2003). Individual estimates of genetic ancestry based on 184 informative markers were obtained from a Bayesian approach and 2 maximum likelihood approaches and were compared using descriptive statistics, Pearson correlation coefficients, and Bland-Altman plots. Case-control differences in individual admixture proportions were assessed using 2-sample t tests and logistic regression analysis. Results indicated that Bayesian and frequentist approaches to estimating admixture provide similar estimates and inferences. No difference was observed in admixture proportions between African-American cases and controls, but Latino cases and controls significantly differed according to Amerindian and European genetic ancestry. Differences in admixture proportions between Latino cases and controls were not unexpected, since cases were more likely to have been born in the United States. Genetic admixture proportions provide a quantitative measure of ancestry differences among Latinos that can be used in analyses of genetic risk factors.

The objective of this study was to examine the associations between dietary patterns and the risk of Barrett’s esophagus, a precursor to esophageal adenocarcinoma. The authors conducted a case-control study within the Kaiser Permanente Northern California population between 2002 and 2005. Patients with a new diagnosis of Barrett’s esophagus (n = 296 cases) were matched to persons with gastroesophageal reflux disease (n = 308) without Barrett’s esophagus and to population controls (n = 309). Dietary information was obtained from a validated, 110-item food frequency questionnaire. A principal component analysis was used to identify major dietary patterns. Two major dietary patterns were “Western” (high in fast food and meat) and “health-conscious” (high in fruits, vegetables, and nonfried fish). When cases and population controls were compared, strong adherence to the health-conscious dietary pattern was inversely associated with Barrett’s esophagus (odds ratio = 0.35, 95% confidence interval: 0.20, 0.64; fourth vs. first quartile comparison). In contrast, data suggested an adverse effect of the Western dietary pattern on the risk of Barrett’s esophagus, although no dose-effect relation was found. Results suggest strong associations between a diet rich in fruits and vegetables and the risk of Barrett’s esophagus.

From 1996 to 2001, the authors undertook a case-control study of 192 pelvis fracture cases (men and women) and 2,402 controls aged � 45 years at five Kaiser Permanente medical centers in Northern California. Most information on potential risk factors was obtained by means of an interviewer-administered questionnaire. Number of fractures since age 45 years and a maternal history of hip fracture were associated with increased risks. Several factors thought to protect against loss of bone mass, including recent use of menopausal hormone therapy (adjusted odds ratio (OR) ¼ 0.55, 95% confidence interval (CI): 0.33, 0.91) and high body mass index (weight (kg)/height (m) 2 ; per 5-unit increase, adjusted OR ¼ 0.65, 95% CI: 0.52, 0.81), were associated with decreased risks, while cigarette smoking (adjusted OR ¼ 2.17, 95% CI: 1.34, 3.52) and hysterectomy (adjusted OR ¼ 1.75, 95% CI: 1.15, 2.66) were associated with increased risks. Various conditions related to propensity to fall were associated with increased risks. Most indicators of frailty, including use of walking aids and needing help with or being unable to perform various activities of daily living, conferred increased risks. Thus, low bone mass, frailty, and probably a propensity to fall appear to be associated with increased risk of pelvis fracture. accidental falls; aged; estrogen replacement therapy; fractures; frail elderly; osteoporosis; pelvis

Controversy exists regarding the extent to which age, menopausal status, and/or lifestyle behaviors account for the increased weight, fat mass, and central adiposity experienced by midlife women. To address this question, the authors longitudinally examined the relations of aging, menopausal status, and physical activity to weight and waist circumference in 3,064 racially/ethnically diverse women aged 42-52 years at baseline who were participating in the Study of Women's Health Across the Nation (SWAN), an observational study of the menopausal transition. Over 3 years of follow-up (1996-1997 to 1999-2000), mean weight increased by 2.1 kg (standard deviation (SD), 4.8) or 3.0% (SD, 6.5) and mean waist circumference increased by 2.2 cm (SD, 5.4) or 2.8% (SD, 6.3). Change in menopausal status was not associated with weight gain or significantly associated with increases in waist circumference. A one-unit increase in reported level of sports/exercise (on a scale of 1-5) was longitudinally related to decreases of 0.32 kg in weight (p < 0.0001) and 0.10 cm in waist circumference (not significant). Similar inverse relations were observed for daily routine physical activity (biking and walking for transportation and less television viewing). These findings suggest that, although midlife women tend to experience increases in weight and waist circumference over time, maintaining or increasing participation in regular physical activity contributes to prevention or attenuation of those gains.

This case-control study of proximal humerus fracture included 448 incident female and male cases and 2,023 controls aged 45 years or older identified in five Northern California Kaiser Permanente Medical Centers in 1996-2001. Data were collected by using an interviewer-administered questionnaire. Some factors related to low bone mass, including number of fractures since age 45 years and low dietary calcium intake, were associated with increased risks of fracture, and factors thought to protect against bone loss, such as menopausal hormone therapy and calcium carbonate tablet use, were associated with reduced risks. Fall-related risk factors included previous falls, diabetes mellitus, and difficulty walking in dim light. Possible fall-related risk factors suggested for the first time in this study were seizure medication use (adjusted odds ratio (OR) = 2.80, 95% confidence interval (CI): 1.45, 5.42), depression (OR = 1.34, 95% CI: 0.98, 1.84), almost always using a hearing aid (OR = 1.92, 95% CI: 1.12, 3.31 vs. never prescribed), and left-handedness (OR = 2.36, 95% CI: 1.51, 3.68 vs. right-handedness). Difficulty with activities of daily living and lack of physical activity tended to be associated with increased risk. Prevention of falls among frail, osteoporotic persons would likely reduce the frequency of proximal humerus fracture.

This case-control study examined the relation of circumstances of falls and characteristics of fallers with risk of fractures at five sites among persons 45 years of age or older from five Kaiser Permanente Medical Centers in Northern California from 1996 to 2001. Included were distal forearm (n = 1,016), foot (n = 574), proximal humerus (n = 467), pelvis (n = 150), and shaft of the tibia/fibula (n = 141) cases who fell at the time of their fracture, and controls (n = 512) who reported falling in the year before the interview but did not fracture. Interviewers collected information by using a standardized questionnaire. Medium-/high-heeled shoes and shoes with a narrow heel increased the risk of all fractures, and slip-on shoes (adjusted odds ratio = 2.3, 95% confidence interval: 1.4, 4.0) and sandals (adjusted odds ratio = 3.1, 95% confidence interval: 1.5, 6.3) increased the risk of foot fractures. Falling from more than a standing height increased the risk of all fractures by two- to fivefold, while breaking the fall was associated with lower risks of all fractures except the distal forearm. Physical activity and hormone therapy were associated with lower risks of most fractures. These results suggest ways in which risks of fractures in older persons can be reduced.

This case-control study examines whether foot problems are risk factors of fractures of five sites among people aged 45 years or older at six Kaiser Permanente Medical Centers in northern California. From October 1996 to May 2001, interviewers collected information through a standardized questionnaire. Incident cases of distal forearm (n = 1,000), foot (n = 827), proximal humerus (n = 448), shaft of the tibia/fibula (n = 168), and pelvis (n = 172) fractures and 1,913 controls from the same medical centers were included. After adjustment for potential confounders and for each additional foot problem, the odds of a foot fracture increased by 8% (adjusted odds ratio = 1.08, 95% confidence interval: 1.03, 1.13). In contrast, each additional foot problem was associated with a reduction in the odds of a forearm fracture (adjusted odds ratio = 0.93, 95% confidence interval: 0.89, 0.98). In general, foot problems were not related to fractures of other sites, although diabetes, which may result in foot problems, increased the odds of a proximal humerus fracture (adjusted odds ratio = 1.65, 95% confidence interval: 1.20, 2.26). If these findings are supported by data from other studies, preventive measures to retard the development of foot problems could reduce the incidence of foot fractures.

The performances of two commonly used diet instruments, the Block and the Willett food frequency questionnaires, were compared with a longer, interviewer-administered diet history. Participants in a case-control study on diet and colon cancer were interviewed between 1990 and 1994 in northern California, Utah, and Minnesota by trained nutritionists using a validated diet history. Two separate subsamples of participants were asked to complete either the Block or the Willett questionnaire exactly 5 days after they completed the original diet history. Data were analyzed separately by subsample comparing either the Block or the Willett questionnaire with the original diet history by using means, correlations, quintile agreement, and odds ratios for the relation between several nutrients and colon cancer. The Block and the Willett questionnaires generally provided lower absolute intake estimates than did the original diet history; however, the Block questionnaire underestimated more than did that by Willett. Both correlations and quintile agreement were slightly better for the Willett questionnaire than for that by Block when compared with the original diet history. In general, point estimates obtained from either the Block or the Willett questionnaire fell within the confidence intervals of the estimates of the odds ratios obtained from the original diet history, and no real difference in significance levels appeared. Although the Block and Willett questionnaires differed slightly from each other and from our original diet history in estimating absolute nutrients and ranking or classifying individuals, they were very similar in their ability to predict disease outcome.

Low protein diets are commonly prescribed for patients with idiopathic calcium nephrolithiasis, who account for > 80% of new diagnoses of kidney stones. This dietary advice is supported by metabolic studies and epidemiologic observational studies but has not been evaluated in a controlled trial. Using 1983-1985 data from three Northern California Kaiser Permanente Medical Centers, the authors randomly assigned 99 persons who had calcium oxalate stones for the first time to a low animal protein, high fiber diet that contained approximately 56-64 g daily of protein, 75 mg daily of purine (primarily from animal protein and legumes), one-fourth cup of wheat bran supplement, and fruits and vegetables. Intervention subjects were also instructed to drink six to eight glasses of liquid daily and to maintain adequate calcium intake from dairy products or calcium supplements. Control subjects were instructed only on fluid intake and adequate calcium intake. Both groups were followed regularly for up to 4.5 years with food frequency questionnaires, serum and urine chemistry analysis, and abdominal radiography; and they were urged to comply with dietary instructions. In the intervention group of 50 subjects, stones recurred in 12 (7.1 per 100 person-years) compared with two (1.2 per 100 person-years) in the control group; both groups received a mean of 3.4 person-years of follow-up (p = 0.006). After adjustment for possible confounding effects of age, sex, education, and baseline protein and fluid intake, the relative risk of a recurrent stone in the intervention group was 5.6 (95% confidence interval 1.2-26.1) compared with the control group. The authors conclude that advice to follow a low animal protein, high fiber, high fluid diet has no advantage over advice to increase fluid intake alone.

The authors conducted a case-control study to examine the benefit of digital-rectal examination in reducing mortality from distal rectal cancer. The Kaiser Permanente Medical Care Program provides prepaid medical services to approximately 30 percent of the residents in its northern California service area. Members of the program aged 45 years and over who were diagnosed with fatal cancer of the distal rectum during the period 1971-1986 and who died before 1988 as a result of their cancer (n = 172) and matched controls were selected for the study. Information on digital-rectal examinations received in the absence of recorded symptoms during the 10 years prior to the diagnosis date of the case was obtained from medical charts. Similar proportions of cases (20.9%) and controls (23.3%) had been screened during the year before the diagnosis of the case (adjusted odds ratio = 0.96, 95% confidence interval 0.56-1.7) and during longer intervals throughout the 10 years before the diagnosis date of the case. These results suggest no efficacy of digital-rectal examination for preventing mortality from rectal cancer, although a modest effect cannot be ruled out.

This study examined prepregnancy cardiometabolic risk factors and gestational diabetes mellitus (GDM) in subsequent pregnancies. The authors selected 1,164 women without diabetes before pregnancy who delivered 1,809 livebirths between 5 consecutive examinations from 1985 to 2006 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The authors measured prepregnancy cardiometabolic risk factors and performed multivariate repeated-measures logistic regression to compute the odds of GDM adjusted for race, age, parity, birth order, and other covariates. Impaired fasting glucose (100–125 vs. 15–20 and >20 vs. 50 mg/dL) before pregnancy were directly associated with GDM: The odds ratios = 4.74 (95% confidence interval (CI): 2.14, 10.51) for fasting glucose, 2.19 (95% CI: 1.15, 4.17) for middle insulin levels and 2.36 (95% CI: 1.20, 4.63) for highest insulin levels, and 3.07 (95% CI: 1.62, 5.84) for low levels of high-density lipoprotein cholesterol among women with a negative family history of diabetes; all P < 0.01. Among overweight women, 26.7% with 1 or more cardiometabolic risk factors developed GDM versus 7.4% with none. Metabolic impairment exists before GDM pregnancy in nondiabetic women. Interconceptual metabolic screening could be included in routine health assessments to identify high-risk women for GDM in a subsequent pregnancy and to potentially minimize fetal exposure to metabolic abnormalities that program future disease.

The incidence of surgically treated benign prostatic hypertrophy and of prostate cancer was examined to December 1987 in 14,897 men (2,175 blacks and 12,722 whites) who received multiphasic health checkups during 1971-1972 while members of the Kaiser Permanente Medical Care Program (San Francisco-Oakland, California). Prostate cancer incidence was higher in blacks than in whites for all age groups (age-adjusted relative risk (RR) = 1.8, 95% confidence interval (CI) 1.4-2.3). The incidence of benign prostatic hypertrophy was somewhat higher in blacks than in whites until age 65 years, after which it was higher in whites. In contrast to the risk of prostate cancer, the age-adjusted risk of benign prostatic hypertrophy was the same for blacks as for whites (RR = 1.0, 95% Cl 0.8-1.2).

Relations between physical activity and prospectively collected menstrual cycle characteristics were examined in two large cohorts. One cohort consisted of women employed in the semiconductor industry in 1989 who participated in a prospective study of reproductive outcomes (n = 367). The other consisted of women living in Tecumseh, Michigan, who completed both the 1992-1993 and 1993-1994 examinations for the Michigan Bone Health Study (n = 328). Mean cycle length, variability of cycle length, and mean bleed length were calculated from daily diaries (Semiconductor cohort) or monthly menstrual calendars (Michigan cohort) for a median of five and 11 cycles, respectively. Physical activity was assessed by self-report at baseline and expressed as metabolic equivalent-minutes per week. In the Semiconductor study, women also reported daily minutes of vigorous exercise in their diaries. In the Michigan cohort, total physical activity, total recreational physical activity, and vigorous recreational activity were positively associated with cycle length. The magnitude of these associations declined as body mass index increased. In the Semiconductor cohort, the minutes of daily vigorous exercise were positively associated with cycle length only in a repeated-measures analysis. These findings lend modest support to the hypothesis that moderate levels of physical activity can lengthen the menstrual cycle.

Multiple factors may determine insulin resistance and the insulin resistance syndrome. The contributions of genes and environment to the distribution of fasting insulin levels and to the associations of fasting insulin with elements of the syndrome were evaluated in the second examination of the Kaiser Permanente Women Twins Study (Oakland, California, 1989-1990). Subjects included 556 white women (165 monozygous twin pairs, 113 dizygous pairs; 455 women with normal glucose tolerance, 75 with impaired glucose tolerance, and 26 with non-insulin-dependent diabetes by World Health Organization criteria). The intraclass correlation coefficients for log fasting insulin for monozygous and dizygous twin pairs were 0.64 and 0.40, respectively. After adjustment for age, behavioral factors, and body mass index, the estimated classic heritability was 0.53 (p = 0.003). Commingling analysis of fasting insulin indicated the presence of four distributions (p < 0.001), consistent with at least one, and perhaps two, genes influencing this trait. In an unmatched multiple regression model among women from monozygous twin pairs only, log fasting insulin was independently associated with body mass index (p < 0.0001), waist/hip ratio (p = 0.02), and glucose intolerance (p = 0.04), but not with triglycerides, high density lipoprotein cholesterol, or hypertension. After removal of genetic influences by analysis of monozygous intrapair differences, only body mass index (p < 0.0001) remained independently related to fasting insulin. The authors conclude that, in addition to significant genetic influences on fasting insulin, environmental or behavioral factors (particularly nongenetic variation in obesity) are important determinants of fasting insulin and the insulin resistance syndrome.

The effect of bereavement on mortality among surviving spouses was examined in a cohort of 12,522 spouse pairs belonging to a prepaid health care plan in northern California. Both spouses were examined and completed a questionnaire between 1964 and 1973, and they were followed for mortality through 1987. Between 1964 and 1987, 1,453 men (12%) and 3,294 women (26%) were bereaved; 440 bereaved men (30%) and 510 women (15%) died during follow-up. Mortality following bereavement was significantly elevated in both men and women after adjusting for age, education, and other predictors of mortality in proportional hazards analyses. The highest relative risks (RRs) of mortality occurred 7-12 months following bereavement. Among women, the RR was 1.9 (95% confidence interval (CI) 1.35-2.71) 7-12 months after bereavement. Among men, the effect of bereavement interacted with prior health status as follows: In men with few health problems, the RR of mortality was 2.12 (95% CI 1.42-3.17); men with many health problems had a RR of 1.56 (95% CI 0.98-2.55) 7-12 months after bereavement. In both men and women, the RR declined after the first year of bereavement but remained above 1.0 for more than 2 years after bereavement. The addition of terms reflecting the influence of the other spouse's characteristics and behaviors did not alter the RR of mortality, indicating no effect of a shared unfavorable environment on mortality following bereavement.

Exploratory analyses were conducted in a nested case-control study of 1,031 incident cases of essential hypertension and 1,031 persistently normotensive controls from the Kaiser Permanente Multiphasic Health Checkup cohort in Northern California. Previous analyses have confirmed hypotheses that baseline weight, subsequent weight gain, alcohol consumption, parental history of hypertension, excessive use of salt, and centralized body fat distribution are predictive of developing hypertension. In the present study, pulmonary function tests, several serum chemistries, and heart rate were strongly predictive in univariate analyses. Adjusting for the risk factors mentioned above, forced vital capacity (p less than 0.001), serum uric acid (p = 0.003), serum cholesterol (p = 0.012), and heart rate (p = 0.014) remained independently predictive. Further adjustment for baseline blood pressure completely explained the association of heart rate with hypertension, and reduced the association with serum cholesterol to borderline significance. Forced vital capacity remained a strong, inverse predictor (odds ratio, fifth vs. first quintile = 0.22, 95% confidence interval (Cl) 0.11-0.46). Uric acid remained positively related to risk (odds ratio, fifth vs. first quintile = 2.19, 95% Cl 1.20-3.98). Although neither association is presently understood, both forced vital capacity and serum uric acid are closely linked to development of hypertension and may be markers of susceptibility or intermediate steps in pathways leading to hypertension.

Progression from normotension between 1964 and 1972 to essential hypertension by age 55 years was documented in 1,031 adult members of the Kaiser Permanente Medical Care Program (Northern California region) from computerized multiphasic health checkup records and medical record review. Each case was matched to a persistently normotensive control on age, sex, race, number, and dates of multiphasics. In 609 pairs with baseline measurements of subscapular and triceps skinfolds, mean interval from baseline to the case's first hypertensive multiphasic was 5.7 years, and mean age at onset of hypertension was 47 years. Baseline measures of body mass index, subscapular skinfold, and triceps skinfold were each predictive of development of hypertension (odds ratios 3.85, 3.75, and 2.29 respectively, comparing highest with lowest quintiles, p less than 0.0001 for each). When both skinfolds were included in the same model, subscapular skinfold was highly predictive and triceps skinfold was no longer related to risk. When the authors controlled for overall obesity (body mass index), subscapular skinfold remained highly predictive (p less than 0.0001). In 330 pairs who also had skinfold measurements at the hypertensive multiphasic, weight gain was a strong predictor of hypertension. Increase in subscapular skinfold conferred a small increase in risk in women only. The authors conclude that centrally deposited body fat increases risk for developing essential hypertension independent of the overall level of obesity, while peripherally deposited fat does not.