Elizabeth Rose Mayeda

Helicobacter pylori Infection Is Associated With an Increased Rate of Diabetes

OBJECTIVE Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes. RESEARCH DESIGN AND METHODS We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998–1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels. RESULTS Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10–6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection. CONCLUSIONS We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.

Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women

BACKGROUND This study was conducted to compare oral contraceptive (OC) pharmacokinetics (PK) in normal-weight [body mass index (BMI) 19.0-24.9] and obese (BMI 30.0-39.9) women. STUDY DESIGN During the third week of the third cycle of OC use, we admitted 15 normal-weight and 15 obese women for collection of 12 venous specimens over 24 h. Using radioimmunoassay techniques, we measured levels of ethinyl estradiol (EE) and levonorgestrel (LNG). During the same cycle, women underwent twice-weekly sonography to assess ovarian follicular development and blood draws to measure endogenous estradiol (E2) and progesterone levels. RESULTS Obese women had a lower area under the curve (AUC; 1077.2 vs. 1413.7 pg*h/mL) and lower maximum values (85.7 vs. 129.5 pg/mL) for EE than normal-weight women (p=.04 and <0.01, respectively); EE trough levels were similar between BMI groups. The similar, but smaller, differences in their LNG levels for AUC and maximum values (C(max)) were not statistically significant. While peak values differed somewhat, the LNG trough levels were similar for obese and normal-weight women (2.6 and 2.5 ng/mL, respectively). Women with greater EE AUC had smaller follicular diameters (p=.05) and lower E2 levels (p=.04). While follicular diameters tended to be larger among obese women, these differences were not statistically significant. CONCLUSION OC hormone peak levels are lower among obese women compared to normal-weight women, but their trough levels are similar. In this small study, the observed PK differences did not translate into more ovarian follicular activity among obese OC users.

Ovarian suppression in normal-weight and obese women during oral contraceptive use: a randomized controlled trial.

OBJECTIVE: To assess ovarian suppression during oral contraceptive pill (OCP) use among normal-weight and obese women using two OCP doses. METHODS: This was a prospective, double-blind, randomized trial of two 21-day monophasic OCP formulations (20-microgram ethinyl estradiol [E2],/100-microgram levonorgestrel compared with 30-microgram ethinyl E2/150-microgram levonorgestrel) among normal-weight (body mass index 19.0–24.9) and obese (body mass index 30.0–39.9) women with regular menses and normal ovarian ultrasonography. Participants underwent transvaginal ultrasonography and phlebotomy twice weekly for 4 weeks during the third or fourth OCP cycle. We assessed OCP compliance using serum levonorgestrel levels. Outcomes included follicular development, endogenous E2 levels, ovulation, and self-reported bleeding patterns. RESULTS: Two hundred twenty-six women enrolled. One hundred eighty-one participants completed the study; we retained 150 consistent OCP users in the main analysis (96 normal weight, 54 obese). Consistent users of either OCP dose had substantial suppression of follicular development; obesity and follicular development were not related. Among the consistent OCP users, 2.7% ovulated during the study cycle (3 of 96 normal-weight and 1 of 54 obese participants). Two ovulations occurred with each OCP formulation. Inconsistent OCP use or nonuse during the study cycle was associated with more ovulation (P<.001). Normal-weight and obese participants had similar follicular development, endogenous estradiol levels, Hoogland scores, and bleeding patterns. CONCLUSION: Normal-weight and obese participants who were consistent OCP users experienced substantial and comparable ovarian suppression during OCP use. Higher OCP failure rates among obese women reported elsewhere are thus unlikely to be attributable to physiological differences in OCP effect. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov; NCT00827632. LEVEL OF EVIDENCE: I

Predictors of noncompliance in an oral contraceptive clinical trial.

BACKGROUND This analysis was conducted to identify the participant characteristics associated with noncompliance in an oral contraceptive (OC) clinical trial. STUDY DESIGN We studied ovarian suppression among normal-weight and obese women during the use of levonorgestrel (LNG)-containing combination OCs. Participants underwent twice weekly phlebotomy during the study cycle and received up to

Inequalities in dementia incidence between six racial and ethnic groups over 14 years

360 for participation. Along with other study assays, we analyzed 903 specimens from 181 women to measure LNG to assess OC compliance. Consistently undetectable LNG levels indicated noncompliance. To evaluate predictors of OC noncompliance during this study, we compared the characteristics of compliant and noncompliant participants using multivariable logistic regression. We assigned each participant to a relative poverty level based on US census data; all other individual characteristics came directly from participant responses during the baseline interview. RESULTS One hundred eighty-one women completed the study; 31 were noncompliant (17%). In multivariable analyses, poverty level was the strongest predictor of noncompliance. Compared with those women in the quartile with the lowest level of residential poverty, other women were far more likely to be noncompliant, especially women in the quartile with the greatest prevalence of poverty (adjusted odds ratio, 8.4; 95% confidence interval, 1.5-46.1). Additional factors associated with noncompliance were education level less than a bachelors degree and Hispanic ethnicity. Other demographic and psychometric measures were not associated with compliance. CONCLUSIONS We found that noncompliance was strongly associated with residential poverty level, an indirect measure of individual income. In the United States, poverty is associated with female obesity, Hispanic ethnicity and low education, which were also associated here with noncompliance. Study compensation may motivate poor individuals to participate in clinical trials for income. Noncompliance in clinical trials, particularly differential noncompliance, jeopardizes study validity.

Type 2 Diabetes and 10-Year Risk of Dementia and Cognitive Impairment Among Older Mexican Americans

Reducing racial/ethnic disparities is a primary objective of the National Alzheimers Plan (NAPA), yet direct comparisons within large samples representing diversity of the United States are lacking.

Diabetes and cognition.

OBJECTIVE Type 2 diabetes has been linked with increased risk of dementia and cognitive impairment among older adults and with premature mortality in young and middle-aged adults. No studies have evaluated the association between diabetes and dementia among Mexican Americans, a population with a high burden of diabetes. We evaluated the association of diabetes with incidence of dementia and cognitive impairment without dementia (CIND) among older Mexican Americans while accounting for competing risk from death. RESEARCH DESIGN AND METHODS This study included 1,617 participants 60–98 years of age from the Sacramento Area Latino Study on Aging followed up to 10 years from 1998. We evaluated the association between diabetes and dementia/CIND with competing risk regression models. RESULTS Participants free of dementia/CIND at baseline (n = 1,617) were followed annually up to 10 years. There were 677 (41.9%) participants with diabetes, 159 (9.8%) incident dementia/CIND cases, and 361 (22.3%) deaths. Treated and untreated diabetes (hazard ratio 2.12 [95% CI 1.65–2.73] and 2.15 [1.58–2.95]) and dementia/CIND (2.48 [1.75–3.51]) were associated with an increased risk of death. In models adjusted for competing risk of death, those with treated and untreated diabetes had an increased risk of dementia/CIND (2.05 [1.41–2.97] and 1.55 [0.93–2.58]) compared with those without diabetes. CONCLUSIONS These findings provide evidence that the association between type 2 diabetes and dementia/CIND among Mexican Americans remains strong after accounting for competing risk of mortality. Treatments that modify risk of death among those with diabetes may change future dementia risk.

Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women.

Dementia is a major cause of disability and death among older adults. Those with type 2 diabetes (T2D) are 50-100% more likely to develop dementia than those without T2D, but it is unknown whether this association reflects a causal relationship. Proposed mechanisms through which T2D could cause dementia include the effects of insulin dysregulation and chronic hyperglycemia on features of Alzheimers disease and macrovascular and microvascular disorders in the brain. More research is needed to elucidate the link between T2D and dementia and identify strategies to maintain cognitive function among people with T2D.

Racial/ethnic differences in dementia risk among older type 2 diabetic patients: The diabetes and aging study

OBJECTIVE Many observational studies indicate higher oral contraceptive failure among obese women, but most clinical trials and physiologic studies do not support these differences. Limited data indicate higher failure rates among obese contraceptive patch users. Data regarding contraceptive vaginal ring performance in obese women are needed. STUDY DESIGN Twenty normal weight (body mass index [BMI] 19.0-24.9; median, 21.65) and 20 obese (BMI 30.0-39.9; median, 33.7) women enrolled in a prospective study of ethinyl estradiol (EE(2)) and etonorgestrel pharmacokinetics and of ovarian follicle development, endometrial thickness, and bleeding patterns, all measured biweekly during the second cycle of contraceptive vaginal ring use. RESULTS Thirty-seven women completed follow-up. Mean day 0-21 EE(2) concentrations were lower among obese vs normal weight women (15.0 vs 22.0 pg/mL, respectively, P = .004), whereas etonorgestrel concentrations were similar (1138 vs 1256 pg/mL, respectively, P = .39). Follicular development was minimal in both groups, with only 5 women achieving a maximum follicle diameter >13 mm at any time during 3 weeks follow-up (3 normal weight and 2 obese women); these women had serum progesterone levels <1.0. Obese women reported more bleeding or spotting than normal weight women (3.6 vs 1.4 days, respectively, P = .01). CONCLUSION Although obese women had lower EE(2) levels during contraceptive vaginal ring use, they had excellent suppression of ovarian follicle development, similar to normal weight women. This predicts that contraceptive vaginal ring effectiveness will be similar in women with a BMI up to 39.9. The lower serum EE(2) levels in the obese women may explain the greater reported bleeding or spotting days.

The Association of Blood Pressure and Mortality Differs by Self-reported Walking Speed in Older Latinos

OBJECTIVE Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients. RESEARCH DESIGN AND METHODS We identified 22,171 diabetic patients without preexisting dementia aged ≥60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control. RESULTS Dementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30–2.06) for Native Americans, 1.44 (1.24–1.67) for African Americans, 1.30 (1.15–1.47) for non-Hispanic whites, and 1.19 (1.02–1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results. CONCLUSIONS Among type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40–60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.