Leptin levels recover normally in healthy older adults after acute diet-induced weight loss.

OBJECTIVES: Involuntary weight loss affects 20% of community dwelling older adults. The underlying mechanism for this disorder is unknown. Objective is to determine if failure of older persons to regain weight is associated with elevated pro-inflammatory cytokine and leptin levels. DESIGN: Prospective diet intervention study. SETTING: University of Washington Medical Center from 2001-2005. PARTICIPANTS: Twenty-one younger (18-35 years old) and nineteen older (>or= 70 years old) men and women. INTERVENTION: Each subject was placed for two weeks on a weight-maintaining diet, followed in sequence by 2 weeks of 30% caloric restriction, then 4 weeks of ad libitum food intake. MEASUREMENTS: Plasma leptin levels, fasting serum pro-inflammatory cytokine levels, and peripheral blood mononuclear cell cytokine levels were measured. RESULTS: Leptin levels in the two cohorts decreased after caloric restriction and increased after ad-libitum food consumption resumed. Plasma TNF alpha levels were higher in older subjects compared to younger adults. However, there was no association between changes in TNF alpha levels and changes in AUC leptin. CONCLUSION: Leptin levels in healthy older individuals responded appropriately in a compensatory manner to changes in body weight. These data do not support a cytokine dependent elevation in leptin levels as being responsible for the failure of older adults to regain weight.

Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.

INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD. SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease. METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure. RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95% CI = 1.03, 1.76) in men and was 1.66 (95% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95% CI, 1.12- 1.98) and in women, was 2.21 (95% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men. CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.

Bias induced by self-reported smoking on periodontitis-systemic disease associations.

Non-causal associations between periodontitis and systemic diseases may be spuriously induced by smoking because of its strong relationship to both. The goal of this study was to evaluate whether adjustment for self-reported smoking removes tobacco-related confounding and eliminated such spurious confounding. Using NHANES III data, we evaluated associations between attachment loss and serum cotinine after adjustment by self-reported number of cigarettes smoked. Cotinine, a metabolite of nicotine, should not be related to attachment loss, if self-reported smoking captures the effect of tobacco on attachment levels. Adjustment for self-reported cigarette smoking did not completely remove the correlation between attachment loss and serum-cotinine level (r = 0.075, n= 1507, p = 0.003). Simulation studies indicated similar results for time-to-event data. These findings demonstrate the difficulty in distinguishing the effects of periodontitis from those of smoking with respect to a smoking-related outcome. Future studies should report results of analyses on separate subcohorts of never-smokers and smokers.

Randomized clinical trial of interceptive and comprehensive orthodontics.

Focusing public insurance programs on interceptive orthodontics (IO) may increase access for low-income children. This report presents outcomes from a randomized clinical trial (RCT) comparing IO with comprehensive orthodontics (CO) in Medicaid patients. One hundred seventy pre-adolescents with Medicaid-eligible malocclusions were randomized to IO (n = 86) followed by observation (OBS) or OBS followed by CO (n = 84). One hundred thirty-four completed the trial. Models at pre-treatment (baseline) and following ≤ 2 years of intervention and 2 years of OBS (48 mos) were scored by calibrated examiners using the Peer Assessment Rating (PAR) and Index of Complexity, Outcome and Need (ICON). Overall outcomes and clinically meaningful categorical ICON data on need/acceptability, complexity, and improvement were compared. At baseline, groups were balanced by age, gender, ethnicity, and PAR/ICON scores. Most were minorities. Most (77%) were rated as difficult-to-very difficult. Scores improved significantly for both groups, but CO more than IO (PAR, 18.6 [95%CI 15.1, 22.1] vs.10.1 [95%CI 6.7, 13.4]; ICON, 44.8 [95% CI 39.7, 49.9] vs. 35.2 [95%CI 29.7, 40.6], respectively). On average, IO is effective at reducing malocclusions in Medicaid patients, but less than CO. (ClinicalTrials.gov number CT00067379).

Circulating TNF alpha receptor levels identify older adults who fail to regain weight after acute weight loss.

OBJECTIVE: Some healthy older adults have difficulty regaining weight after acute weight loss, and the reason for this failure to regain weight is unknown. The objective of this study was to determine if elevated leptin or pro-inflammatory cytokine levels are associated with failure to regain weight over two years after an acute weight loss intervention. DESIGN: Two year prospective study after an acute weight loss intervention. SETTING: University of Washington Medical Center from 2001-2006. PARTICIPANTS: Nineteen older (≥ 70 years old) men and women. MEASUREMENTS: Body weights, health status questionnaire, body composition data, serum leptin, glucose, insulin, C- reactive protein and pro-inflammatory cytokine levels were measured every six months for two years. RESULTS: Five subjects out of 19 failed to regain weight after two years. The subjects who failed to regain weight after 2 years had higher circulating levels of tumor necrosis factor receptor particle 55 (TNFRp55) at baseline and at 6, 12, 18 and 24 months of follow up compared to subjects who regained weight after 2 years (P = 0.02 ). CONCLUSION: Five out of 19 older subjects had difficulty regaining weight for up to 2 years following an acute weight loss intervention, and their TNFRp55 levels were persistently higher than in subjects who regained weight. Greater TNF α action, as reflected by higher circulating levels of TNFRp55, could be contributing towards inability of some older persons to regain weight after acute weight loss.

Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria.

BACKGROUND: The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly. METHODS: We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria. FINDINGS: There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%). INTERPRETATION: The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.