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1.  Varenicline in smokers with diabetes: A pooled analysis of 15 randomized, placebo‐controlled studies of varenicline 
Stopping smoking deserves high priority in preventing complications of diabetes; however, only sparse data are available regarding the efficacy of pharmacotherapy in smokers with diabetes. We assessed the efficacy and safety of varenicline in smokers with diabetes who participated in 15 double‐blind, randomized, placebo‐controlled studies.
Materials and Methods
This retrospective pooled analysis included data from smokers of ≥10 cigarettes per day with diabetes. Participants received varenicline 1 mg b.i.d. or placebo for 12 weeks. We examined carbon monoxide‐confirmed continuous abstinence rates (CARs) for weeks 9–12, 9–24 and 9–52, and compared safety in participants with and without diabetes.
Of 6,771 participants, 323 had diabetes (varenicline n = 162; placebo n = 161). Week 9–12 CAR was higher with varenicline than placebo (43.8% vs 24.8%; odds ratio 2.36, 95% CI 1.47–3.79), as was week 9–24 CAR (27.5% vs 14.4%; odds ratio 2.25, 95% CI 1.27–4.00). Week 9–52 CAR was 18.4% for varenicline and 10.1% for placebo (odds ratio 2.00, 95% CI 0.90–4.49). The most commonly‐reported adverse events in participants with diabetes for varenicline vs placebo were: nausea (27.2% vs 8.1%); headache (9.3% vs 9.9%); and insomnia (8.6% vs 5.6%), incidences that were similar in participants without diabetes (29.6% vs 9.7%; 13.4% vs 10.9%; and 11.4% vs 7.1%, respectively). Weight gain in quitters with diabetes (1.7 kg) was similar to that of those without diabetes (2.1 kg).
Varenicline was an effective and well‐tolerated aid for smoking cessation in individuals with diabetes. Safety was comparable with participants without diabetes.
PMCID: PMC5217903  PMID: 27223809
Diabetes mellitus; Smoking; Varenicline
2.  Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies 
BMC Medicine  2016;14:207.
Although nut consumption has been associated with a reduced risk of cardiovascular disease and all-cause mortality, data on less common causes of death has not been systematically assessed. Previous reviews missed several studies and additional studies have since been published. We therefore conducted a systematic review and meta-analysis of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality.
PubMed and Embase were searched for prospective studies of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality in adult populations published up to July 19, 2016. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The burden of mortality attributable to low nut consumption was calculated for selected regions.
Twenty studies (29 publications) were included in the meta-analysis. The summary RRs per 28 grams/day increase in nut intake was for coronary heart disease, 0.71 (95% CI: 0.63–0.80, I2 = 47%, n = 11), stroke, 0.93 (95% CI: 0.83–1.05, I2 = 14%, n = 11), cardiovascular disease, 0.79 (95% CI: 0.70–0.88, I2 = 60%, n = 12), total cancer, 0.85 (95% CI: 0.76–0.94, I2 = 42%, n = 8), all-cause mortality, 0.78 (95% CI: 0.72–0.84, I2 = 66%, n = 15), and for mortality from respiratory disease, 0.48 (95% CI: 0.26–0.89, I2 = 61%, n = 3), diabetes, 0.61 (95% CI: 0.43–0.88, I2 = 0%, n = 4), neurodegenerative disease, 0.65 (95% CI: 0.40–1.08, I2 = 5.9%, n = 3), infectious disease, 0.25 (95% CI: 0.07–0.85, I2 = 54%, n = 2), and kidney disease, 0.27 (95% CI: 0.04–1.91, I2 = 61%, n = 2). The results were similar for tree nuts and peanuts. If the associations are causal, an estimated 4.4 million premature deaths in the America, Europe, Southeast Asia, and Western Pacific would be attributable to a nut intake below 20 grams per day in 2013.
Higher nut intake is associated with reduced risk of cardiovascular disease, total cancer and all-cause mortality, and mortality from respiratory disease, diabetes, and infections.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-016-0730-3) contains supplementary material, which is available to authorized users.
PMCID: PMC5137221  PMID: 27916000
Nuts; Peanuts; Cardiovascular disease; Cancer; All-cause mortality; Cause-specific mortality; Meta-analysis
3.  Physical activity and the risk of gestational diabetes mellitus: a systematic review and dose–response meta-analysis of epidemiological studies 
European Journal of Epidemiology  2016;31(10):967-997.
Physical activity has been inconsistently associated with risk of gestational diabetes mellitus in epidemiological studies, and questions remain about the strength and shape of the dose–response relationship between the two. We therefore conducted a systematic review and meta-analysis of cohort studies and randomized trials on physical activity and gestational diabetes mellitus. PubMed, Embase and Ovid databases were searched for cohort studies, and randomized controlled trials of physical activity and risk of gestational diabetes mellitus, up to August 5th 2015. Summary relative risks (RRs) were estimated using a random effects model. Twenty-five studies (26 publications) were included. For total physical activity the summary RR for high versus low activity was 0.62 (95 % CI 0.41–0.94, I2 = 0 %, n = 4) before pregnancy, and 0.66 (95 % CI 0.36–1.21, I2 = 0 %, n = 3) during pregnancy. For leisure-time physical activity the respective summary RRs for high versus low activity was 0.78 (95 % CI 0.61–1.00, I2 = 47 %, n = 8) before pregnancy, and it was 0.80 (95 % CI 0.64–1.00, I2 = 17 %, n = 17) during pregnancy. The summary RR for pre-pregnancy activity was 0.70 (95 % CI 0.49–1.01, I2 = 72.6 %, n = 3) per increment of 5 h/week and for activity during pregnancy was 0.98 (95 % CI 0.87–1.09, I2 = 0 %, n = 3) per 5 h/week. There was evidence of a nonlinear association between physical activity before pregnancy and the risk of gestational diabetes mellitus, pnonlinearity = 0.005, with a slightly steeper association at lower levels of activity although further reductions in risk were observed up to 10 h/week. There was also evidence of nonlinearity for physical activity in early pregnancy, pnonlinearity = 0.008, with no further reduction in risk above 8 h/week. There was some indication of inverse associations between walking (before and during pregnancy) and vigorous activity (before pregnancy) and the risk of gestational diabetes mellitus. This meta-analysis suggests that there is a significant inverse association between physical activity before pregnancy and in early pregnancy and the risk of gestational diabetes mellitus. Further studies are needed to clarify the association between specific types and intensities of activity and gestational diabetes mellitus.
Electronic supplementary material
The online version of this article (doi:10.1007/s10654-016-0176-0) contains supplementary material, which is available to authorized users.
PMCID: PMC5065594  PMID: 27485519
Physical activity; Exercise; Walking; Gestational diabetes; Abnormal glucose tolerance; Review; Meta-analysis
4.  Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies 
The BMJ  2016;353:i2716.
Objective To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality.
Data sources PubMed and Embase searched up to 3 April 2016.
Study selection Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality.
Data synthesis Summary relative risks and 95% confidence intervals calculated with a random effects model.
Results 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I2=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I2=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I2=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I2=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I2=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I2=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I2=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I2=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I2=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I2=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains.
Conclusions This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality.
PMCID: PMC4908315  PMID: 27301975
5.  Trans Fatty Acid Intake and Emotion Regulation 
Journal of health psychology  2015;20(6):785-793.
We examined whether there is a relationship between trans fatty acid (TFA) intakes and emotion regulation, mediated by positive or negative affect.
Archival data on 1699 men and 3293 women were used to measure TFA intake at baseline, positive and negative affect and emotion regulation at follow up.
Higher TFA intake related to subsequent difficulties with emotional awareness (p=.045), clarity (p=0.012) and regulation strategies (p=.009). Affect mediated these relationships. Lower TFA intake associated with increased positive and decreased negative affect which, in turn, associated with improved emotion regulation.
TFA intakes may be associated with subsequent ability to regulate emotions.
PMCID: PMC4607029  PMID: 26032795
Emotion regulation; emotion regulation; trans fatty acids; positive affect; negative affect
6.  BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants 
The BMJ  2016;353:i2156.
Objective To conduct a systematic review and meta-analysis of cohort studies of body mass index (BMI) and the risk of all cause mortality, and to clarify the shape and the nadir of the dose-response curve, and the influence on the results of confounding from smoking, weight loss associated with disease, and preclinical disease.
Data sources PubMed and Embase databases searched up to 23 September 2015.
Study selection Cohort studies that reported adjusted risk estimates for at least three categories of BMI in relation to all cause mortality.
Data synthesis Summary relative risks were calculated with random effects models. Non-linear associations were explored with fractional polynomial models.
Results 230 cohort studies (207 publications) were included. The analysis of never smokers included 53 cohort studies (44 risk estimates) with >738 144 deaths and >9 976 077 participants. The analysis of all participants included 228 cohort studies (198 risk estimates) with >3 744 722 deaths among 30 233 329 participants. The summary relative risk for a 5 unit increment in BMI was 1.18 (95% confidence interval 1.15 to 1.21; I2=95%, n=44) among never smokers, 1.21 (1.18 to 1.25; I2=93%, n=25) among healthy never smokers, 1.27 (1.21 to 1.33; I2=89%, n=11) among healthy never smokers with exclusion of early follow-up, and 1.05 (1.04 to 1.07; I2=97%, n=198) among all participants. There was a J shaped dose-response relation in never smokers (Pnon-linearity <0.001), and the lowest risk was observed at BMI 23-24 in never smokers, 22-23 in healthy never smokers, and 20-22 in studies of never smokers with ≥20 years’ follow-up. In contrast there was a U shaped association between BMI and mortality in analyses with a greater potential for bias including all participants, current, former, or ever smokers, and in studies with a short duration of follow-up (<5 years or <10 years), or with moderate study quality scores.
Conclusion Overweight and obesity is associated with increased risk of all cause mortality and the nadir of the curve was observed at BMI 23-24 among never smokers, 22-23 among healthy never smokers, and 20-22 with longer durations of follow-up. The increased risk of mortality observed in underweight people could at least partly be caused by residual confounding from prediagnostic disease. Lack of exclusion of ever smokers, people with prevalent and preclinical disease, and early follow-up could bias the results towards a more U shaped association.
PMCID: PMC4856854  PMID: 27146380
7.  Recommendations to improve smoking cessation outcomes from people with lung conditions who smoke 
ERJ Open Research  2016;2(2):00009-2016.
This study aimed to gain insight into the impact of lung conditions on smoking behaviour and smoking cessation, and identify recommendations for smoking cessation and professional-patient communications. The study was led by the European Lung Foundation in collaboration with the European Respiratory Society Task Force on “Statement on smoking cessation on COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit”.
A web-based observational cross-sectional questionnaire was developed from a patient-centered literature review. Topics covered were: cohort characteristics; perspectives on smoking cessation; interactions with healthcare professionals; and recommendations to improve cessation outcomes.
The questionnaire was disseminated via existing patient and professional networks and social media channels. The survey was available online for a period of 4 months in 16 languages. The data were analysed as a whole, not by country, with thematic analysis of the open responses.
Common characteristics were: male (54%); age 40–55 years (39%); 11–20 cigarettes a day (39%); smokes within 30 min of waking (61%); and has made 1–5 cessation attempts in the previous 12 months (54%). 59% had tried cessation treatments, but, of these, 55% had not found any treatments helpful.
Recommendations were: earlier intervention; discussion of the patient's smoking beliefs, behaviours and motivation; giving constructive advice; understanding addiction; informed decision-making; and treatment options. Areas for new and further research have been highlighted through exploring the smoking cessation perspectives and recommendations of people with lung conditions in Europe who smoke.
People across Europe with lung conditions and who smoke make recommendations to improve smoking cessation outcomes
PMCID: PMC5005168  PMID: 27730185
8.  Body mass index gain between ages 20-40 years and lifestyle characteristics of men at ages 40-60 years: The Adventist Health Study-2 
Obesity increases risk of premature disease, and may be associated with unfavorable lifestyle changes that add to risk. This study analyzed the association of midlife BMI change with current lifestyle patterns among multiethnic men.
Men aged 40-60 years (n=9864) retrospectively reported body weight between ages 20-40 years and current dietary, TV, physical activity and sleep practices in the Adventist Health Study II, a study of church-goers in the US and Canada. In multivariate logistic regression analysis, odds ratios for BMI gain were calculated for each lifestyle practice controlling for sociodemographic and other lifestyle factors and current BMI.
Men with median or higher BMI gain (2.79 kg/m2) between ages 20-40 years were more likely to consume a non-vegetarian diet, and engage in excessive TV watching and little physical activity and had a shorter sleep duration compared to men with BMI gain below the median (all p<0.001). In multivariate logistic analysis current BMI was significantly associated with all lifestyle factors in multivariate analyses (all p≤0.005). BMI gain was associated with lower odds of vegetarian diet (odds ratio [OR] 0.939; 95% confidence interval [CI] 0.921-0.957) and of physical activity ≥150 minutes/week (OR 0.979, 95% CI 0.960-0.999).
These findings imply that diet and less physical activity are associated with both gained and attained BMI, while inactivity (TV watching) and short sleep duration correlated only with attained BMI. Unhealthy lifestyle may add risk to that associated with BMI. Longitudinal and intervention studies are needed to infer causal relationships.
PMCID: PMC4250575  PMID: 25434910
obesity; diet; physical activity; sedentariness; sleep; men
9.  The Association of TV Watching to Sleep Problems in a Church-going Population 
Family & community health  2014;37(4):279-287.
Sensory stimuli/inactivity may affect sleep. Sleep problems are associated with multiple health problems. We assessed TV habits in the Adventist Health Study-2 at baseline and sleep problems in the Biopsychosocial Religion and Health Study 1–4 years later. After exclusions, 3,914 subjects split equally into TV watchers <2 hours/day or ≥2 hours/day. Watching TV ≥2 hours/day predicted problems falling asleep, middle of the night awakening and waking early with inability to sleep again in multiple logistic regression. Excess TV watching disturbed sleep induction and quality, though the relationship may be bidirectional. TV habits should be considered in individuals with sleep problems.
PMCID: PMC4607020  PMID: 25167068
Church-goers; lifestyle; sleep; TV watching
10.  Prevalence of hyperthyroidism according to type of vegetarian diet 
Public health nutrition  2014;18(8):1482-1487.
Vegetarian diets may be associated with low prevalence of autoimmune disease, as observed in rural sub-Saharan Africans. Graves’ disease, an autoimmune disorder, is the most common cause of hyperthyroidism. We studied prevalence of hyperthyroidism according to dietary pattern in a population with a high proportion of vegetarians.
Cross-sectional prevalence study. The association between diet and prevalence of hyperthyroidism was examined using multivariate logistic regression analyses controlling for sociodemographic characteristics and salt use.
The Adventist Health Study-2 conducted in the USA and Canada.
Church members (n 65 981) provided demographic, dietary, lifestyle and medical history data by questionnaire.
The prevalence of self-reported hyperthyroidism was 0·9 %. Male gender (OR=0·32; 95 % CI 0·26, 0·41) and moderate or high income (OR=0·67; 95 % CI 0·52, 0·88 and OR=0·73; 95 % CI 0·58, 0·91, respectively) protected against hyperthyroidism, while obesity and prevalent CVD were associated with increased risk (OR=1·25; 95 % CI 1·02, 1·54 and OR=1·92; 95 % CI 1·53, 2·42, respectively). Vegan, lacto-ovo and pesco vegetarian diets were associated with lower risk compared with omnivorous diets (OR=0·49; 95 % CI 0·33, OR=0·72, 0·65; 95 % CI 0·53, 0·81 and OR=0·74; 95 % CI 0·56, 1·00, respectively).
Exclusion of all animal foods was associated with half the prevalence of hyperthyroidism compared with omnivorous diets. Lacto-ovo and pesco vegetarian diets were associated with intermediate protection. Further study of potential mechanisms is warranted.
PMCID: PMC4377303  PMID: 25263477
Diet; Vegetarianism; Vegan; Thyroid
11.  Bidirectional longitudinal study of type 2 diabetes and depression symptoms in black and white church going adults 
There is a need to longitudinally examine depression and DM2 relationship in a population that values positive health behaviors. The aim of this study was to prospectively investigate the bidirectional relationship between depression and DM2.
A cohort sample of 4,746 Black (28.4%) and White (71.6%) Seventh-day Adventist adults who participated in the Biopsychosocial Religion and Health Study (BRHS) completed a short form of the Center for Epidemiologic Studies Depression Scale (CES-D) 11 along with self-report of lifetime physician diagnosis of type 2 diabetes (DM2) and treatment of DM2 and/or depression in the last 12 months in 2006–7 and 2010–11. Hierarchical logistic regression analyses were completed to predict risk for future disease while controlling for demographic and health related variables.
While there were no direct effects of depression on later DM2, there was an indirect effect mediated by BMI (effect = 0.13; 95% CIs [0.08, 0.20]) even after controlling for demographic variables as covariates using Hayes’ PROCESS macro mediation analysis. Similarly, there was also only an indirect effect of DM2 on later depression mediated by BMI (effect = 0.13; 95% CIs [0.05, 0.22]) after controlling for demographic variables.
The results highlight BMI as a risk factor for both DM2 and depression. The negative consequences of having higher BMI in conjunction at baseline with another disease can increase the risk for other chronic disease even in a span of 2.04 – 5.74 years, the length of study interval.
PMCID: PMC4404000  PMID: 25897418
Type 2 diabetes; Depression; Bidirectional; Black; Adventist
12.  Estimating the Impact of Smoking Cessation During Pregnancy: The San Bernardino County Experience 
Journal of community health  2013;38(5):838-846.
We examined the relation between maternal smoking and adverse infant outcomes [low birth weight (LBW), and preterm birth (PTB)] during 2007–2008 in San Bernardino County, California—the largest county in the contiguous United States which has one of the highest rates of infant mortality in California. Using birth certificate data, we identified 1,430 mothers in 2007 and 1,355 in 2008 who smoked during pregnancy. We assessed the effect of never smoking and smoking cessation during pregnancy relative to smoking during pregnancy for the 1,843/1,798 LBW, and 3,480/3,238 PTB’s recorded for 2007/2008, respectively. To describe the effect of quitting smoking during pregnancy, we calculated the exposure impact number for smoking during pregnancy. Major findings are: (1) relative to smoking during pregnancy, significantly lower risk of LBW among never smoking mothers [OR, year: 0.56, 2007; 0.54, 2008] and for smoking cessation during pregnancy [0.57, 2007; 0.72, 2008]; (2) relative to smoking during pregnancy, significantly lower risk of PTB was found for never smoking mothers [0.68, 2007; 0.68, 2008] and for smoking cessation during pregnancy [0.69, 2007; 0.69, 2008]; (3) an exposure impact assessment indicating each LBW or PTB outcome in the county could have been prevented either by at least 35 mothers quitting smoking during pregnancy or by 25 mothers being never smokers during pre-pregnancy. Our findings identify an important burden of adverse infant outcomes due to maternal smoking in San Bernardino County that can be effectively decreased by maternal smoking cessation.
PMCID: PMC4227584  PMID: 23553684
San Bernardino County; Maternal tobacco use; Smoking cessation during pregnancy; Exposure impact number
13.  Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease 
Circulation  2010;121(2):221-229.
Smoking cessation is a key component of secondary cardiovascular disease prevention. Varenicline, a partial α4β2 nicotinic acetylcholine receptor agonist, is effective for smoking cessation in healthy smokers, but its efficacy and safety in smokers with cardiovascular disease are unknown.
Methods and Results
A multicenter, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease. Participants received varenicline (1 mg twice daily) or placebo, along with smoking-cessation counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was carbon monoxide–confirmed continuous abstinence rate for weeks 9 through 12 (last 4 weeks of treatment). The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95% confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus 7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups did not differ significantly in cardiovascular mortality (0.3% versus 0.6%; difference, −0.3%; 95% CI, −1.3 to 0.7), all-cause mortality (0.6% versus 1.4%; difference, −0.8%; 95% CI, −2.3 to 0.6), cardiovascular events (7.1% versus 5.7%; difference, 1.4%; 95% CI, −2.3 to 5.0), or serious adverse events (6.5% and 6.0%; difference, 0.5%; 95% CI, −3.1 to 4.1). As a result of adverse events, 9.6% of varenicline and 4.3% of placebo participants discontinued study drug.
Varenicline is effective for smoking cessation in smokers with cardiovascular disease. It was well tolerated and did not increase cardiovascular events or mortality; however, trial size and duration limit definitive conclusions about safety.
Clinical Trial Registration Information
URL: Unique identifier: NCT00282984
PMCID: PMC4096941  PMID: 20048210
cardiovascular diseases; cerebrovascular disorders; peripheral vascular diseases; smoking; trials
14.  Associations Between Temperament at Age 1.5 Years and Obesogenic Diet at Ages 3 and 7 Years 
To investigate whether temperament in 1.5-year-olds predicts their consumption of potentially obesogenic foods and drinks at ages 3 and 7 years.
Participants were 6 997 mothers and infants from the Norwegian Mother and Child Cohort Study. Questionnaires were collected during pregnancy, at birth, and at child ages 6 months and 1.5, 3, and 7 years. Predictor variables: children’s temperament at age 1.5 (internalizing, externalizing, surgent) and mothers’ negative affectivity. Outcome variables: children’s consumption of sweet foods, sweet drinks, and fruits/vegetables at ages 3 and 7 (dichotomized at the 85th percentile).
Controlling for covariates, internalizing 1.5-year-olds (anxious, dependent) were 77% and 63% more likely to consume sweet drinks daily at ages 3 and 7, respectively; they were 55% and 43% more likely to consume sweet foods daily at ages 3 and 7, respectively. Externalizing 1.5-year-olds (hyperactive, aggressive) were 34% more likely to consume sweet drinks daily at age 7, 39% and 44% more likely to consume sweet foods daily at ages 3 and 7, respectively, and they were 47% and 33% less likely to consume fruits/vegetables daily at ages 3 and 7, respectively. Surgent 1.5-year-olds (active, sociable) were 197% and 78% more likely to consume two portions of fruits/vegetables daily at ages 3 and 7, respectively. The association of maternal negative affectivity was limited to the child’s consumption of sweet foods at 3 and 7 years.
Early child temperament is a risk factor for obesogenic diet in later childhood. Mechanisms explaining this association need to be explored.
PMCID: PMC3492946  PMID: 23117597
child; temperament; obesity; diet; eating
15.  Vegan Diets and Hypothyroidism 
Nutrients  2013;5(11):4642-4652.
Diets eliminating animal products have rarely been associated with hypothyroidism but may protect against autoimmune disease. Thus, we investigated whether risk of hypothyroidism was associated with vegetarian compared to omnivorous dietary patterns. The Adventist Health Study-2 was conducted among church members in North America who provided data in a self-administered questionnaire. Hypothyroidism was queried at baseline in 2002 and at follow-up to 2008. Diet was examined as a determinant of prevalent (n = 4237 of 65,981 [6.4%]) and incident cases (1184 of 41,212 [2.9%]) in multivariate logistic regression models, controlled for demographics and salt use. In the prevalence study, in addition to demographic characterstics, overweight and obesity increased the odds (OR 1.32, 95% CI: 1.22–1.42 and 1.78, 95% CI: 1.64–1.93, respectively). Vegan versus omnivorous diets tended to be associated with reduced risk (OR 0.89, 95% CI: 0.78–1.01, not statistically significant) while a lacto-ovo diet was associated with increased risk (OR 1.09, 95% CI: 1.01–1.18). In the incidence study, female gender, white ethnicity, higher education and BMI were predictors of hypothyroidism. Following a vegan diet tended to be protective (OR 0.78, 95% CI: 0.59–1.03, not statistically significant). In conclusion, a vegan diet tended to be associated with lower, not higher, risk of hypothyroid disease.
PMCID: PMC3847753  PMID: 24264226
vegan; hypothyroidism; diet; prevalence; incidence
16.  The effect of non-exercise activity thermogenesis on subjects with metabolic syndrome – a proof of concept study in Qatar 
Qatar Medical Journal  2013;2013(1):12-18.
Metabolic syndrome is a cluster of metabolic abnormalities that increases the risk of cardiovascular disease and type 2 diabetes. Total human energy expenditure is divided into three major components; resting metabolic rate, thermic effect of food, and activity thermogenesis which is divided into exercise and non exercise activity thermogenesis (NEAT). In this study, NEAT was used as a lifestyle intervention on subjects with metabolic syndrome. 200 eligible patients from the Diabetes and Endocrinology Department at Hamad Medical Hospital in Doha, Qatar were assigned to an intervention (n = 100) or control (n = 100) group and followed for one year. The intervention group was advised to practice NEAT enhancing activities, while the control group was not advised about NEAT. Measurements of waist circumference, weight, BMI, blood pressure, glucose and lipid profile were assessed at baseline, six months and 1 year.
After 1 year 52 intervention and 55 control subjects completed the study. The results revealed no statistically significant differences in metabolic syndrome components between the two randomized groups. The amount of recommended NEAT activity appears to have been too small to influence study outcomes. Future studies in similar populations may need to consider the high dropout rate, and use of incentives or other interventions to increase compliance and retention.
PMCID: PMC3991052  PMID: 25003052
17.  Intake of Mediterranean foods associated with positive affect and low negative affect 
Journal of psychosomatic research  2012;74(2):142-148.
To examine associations between consumption of foods typical of Mediterranean versus Western diets with positive and negative affect. Nutrients influence mental states yet few studies have examined whether foods protective or deleterious for cardiovascular disease affect mood.
Participants were 9255 Adventist church attendees in North America who completed a validated food frequency questionnaire in 2002–6. Scores for affect were obtained from the Positive and Negative Affect Schedule questionnaire in 2006–7. Multiple linear regression models controlled for age, gender, ethnicity, BMI, education, sleep, sleep squared (to account for high or low amounts), exercise, total caloric intake, alcohol and time between the questionnaires.
Intake of vegetables (β=0.124 [95% CI 0.101, 0.147]), fruit (β=0.066 [95% CI 0.046, 0.085]), olive oil (β=0.070 [95% CI 0.029, 0.111]), nuts (β=0.054 [95% CI 0.026, 0.082]), and legumes (β=0.055 [95% CI 0.032, 0.077]) were associated with positive affect while sweets/desserts (β=−0.066 [95% CI −0.086, −0.046]), soda (β=−0.025 [95% CI −0.037, −0.013]) and fast food frequency (β=−0.046 [95% CI −0.062, −0.030]) were inversely associated with positive affect. Intake of sweets/desserts (β=0.058 [95% CI 0.037, 0.078]) and fast food frequency (β=0.052 [95% CI 0.036, 0.068]) were associated with negative affect while intake of vegetables (β=−0.076 [95% CI −0.099, −0.052]), fruit (β=−0.033 [95% CI −0.053, −0.014]) and nuts (β=−0.088 [95% CI −0.116, −0.060]) were inversely associated with negative affect. Gender interacted with red meat intake (P<.001) and fast food frequency (P<.001) such that these foods were associated with negative affect in females only.
Foods typical of Mediterranean diets were associated with positive affect as well as lower negative affect while Western foods were associated with low positive affect in general and negative affect in women.
PMCID: PMC3790574  PMID: 23332529
Affect; Dietary behaviors; Mediterranean; Mental health; Western
18.  Validation of Recall of Body Weight over a 26 year Period in Cohort Members of Adventist Health Study 2 
Annals of epidemiology  2012;22(10):744-746.
PMCID: PMC3459141  PMID: 22863312
Recall Bias; Correlation Coefficient; Overweight; Elderly; Body Mass Index
19.  Health related quality of life after gastric bypass or intensive lifestyle intervention: a controlled clinical study 
There is little robust evidence relating to changes in health related quality of life (HRQL) in morbidly obese patients following a multidisciplinary non-surgical weight loss program or laparoscopic Roux-en-Y Gastric Bypass (RYGB). The aim of the present study was to describe and compare changes in five dimensions of HRQL in morbidly obese subjects. In addition, we wanted to assess the clinical relevance of the changes in HRQL between and within these two groups after one year. We hypothesized that RYGB would be associated with larger improvements in HRQL than a part residential intensive lifestyle-intervention program (ILI) with morbidly obese subjects.
A total of 139 morbidly obese patients chose treatment with RYGB (n=76) or ILI (n=63). The ILI comprised four stays (seven weeks) at a specialized rehabilitation center over one year. The daily schedule was divided between physical activity, psychosocially-oriented interventions, and motivational approaches. No special diet or weight-loss drugs were prescribed. The participants completed three HRQL-questionnaires before treatment and 1 year thereafter. Both linear regression and ANCOVA were used to analyze differences between weight loss and treatment for five dimensions of HRQL (physical, mental, emotional, symptoms and symptom distress) controlling for baseline HRQL, age, age of onset of obesity, BMI, and physical activity. Clinical relevance was assessed by effect size (ES) where ES<.49 was considered small, between .50-.79 as moderate, and ES>.80 as large.
The adjusted between group mean difference (95% CI) was 8.6 (4.6,12.6) points (ES=.83) for the physical dimension, 5.4 (1.5–9.3) points (ES=.50) for the mental dimension, 25.2 (15.0–35.4) points (ES=1.06) for the emotional dimension, 8.7 (1.8–15.4) points (ES=.37) for the measured symptom distress, and 2.5 for (.6,4.5) fewer symptoms (ES=.56), all in favor of RYGB. Within-group changes in HRQOL in the RYGB group were large for all dimensions of HRQL. Within the ILI group, changes in the emotional dimension, symptom reduction and symptom distress were moderate. Linear regression analyses of weight loss on HRQL change showed a standardized beta-coefficient of –.430 (p<.001) on the physical dimension, –.288 (p=.004) on the mental dimension, –.432 (p<.001) on the emotional dimension, .287 (p=.008) on number of symptoms, and .274 (p=.009) on reduction of symptom pressure.
Morbidly obese participants undergoing RYGB and ILI had improved HRQL after 1 year. The weaker response of ILI on HRQL, compared to RYGB, may be explained by the difference in weight loss following the two treatments.
Trial registration
Clinical number NCT00273104
PMCID: PMC3599616  PMID: 23406190
Quality of life; Bariatric surgery; Lifestyle modification
20.  Determinants of Inflammatory Markers in a Bi-ethnic Population 
Ethnicity & disease  2011;21(2):142-149.
Inflammation is a common pathophysiological pathway for a number of chronic diseases, and is strongly influenced by sociodemographic factors and lifestyle. Less is known about factors that may influence the inflammatory response in individuals of distinct ethnic backgrounds. Therefore, this study examined the relationship between ethnicity and blood levels of inflammatory markers in a sample of non-smoking church-goers.
In a cross-sectional investigation, 508 men and women (>35 years old, 62% White, 38% Black) participated in the Biopsy-chosocial Religion and Health substudy of the Adventist Health Study 2. The contribution of socioeconomic status (education level and difficulty meeting expenses for basic needs) and health covariates (exercise, vegetarian or other type of diet, body mass index, and presence of inflammatory conditions) toward serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was assessed with linear regression models. Levels of interleukin-10 (IL-10), an anti-inflammatory marker, were also assessed.
Blacks showed higher levels of CRP and IL-6 than Whites. Controlling for socio-demographic and health variables attenuated the ethnic difference in CRP while IL-6 levels remained higher in Blacks than in Whites (β=.118; 95% confidence interval=.014–.206; P=.025). Ethnic differences in IL-10 and TNF-α were not found. Vegetarian diet was associated with lower CRP levels while exercise frequency was associated with higher IL-10 levels.
Higher susceptibility of Blacks to inflammatory diseases may reflect higher IL-6, which could be important in assessing health disparities among Blacks and Whites. Vegetarian diet and exercise may counteract effects of disparities.
PMCID: PMC3427005  PMID: 21749016
Inflammatory Markers; Ethnicity; Health Behavior; Adventists
21.  Effect of Consumption of Dried California Mission Figs on Lipid Concentrations 
Annals of Nutrition & Metabolism  2011;58(3):232-238.
Figs are a rich source of soluble fiber. We evaluated the effect of consuming dried California Mission figs on serum lipids in hyperlipidemic adults.
In a crossover trial men and women aged 30–75 years with elevated low-density lipoprotein cholesterol (100–189 mg/dl) were randomized to add dried California Mission figs (120 g/day) to their usual diet for 5 weeks or eat their usual diet for 5 weeks, then crossed over to the other condition for another 5 weeks. Six 24-hour dietary recalls were obtained.
Low- and high-density lipoprotein cholesterol and triglyceride concentrations did not differ between usual and figs-added diets (Bonferroni-corrected p > 0.017), while total cholesterol tended to increase with fig consumption (p = 0.02). Total cholesterol increased in participants (n = 41) randomized to usual followed by figs-added diet (p = 0.01), but remained unchanged in subjects (n = 42) who started with figs-added followed by usual diet (p = 0.4). During the figs-added diet, soluble fiber intake was 12.6 ± 3.7 versus 8.2 ± 4.1 g/day in the usual diet (p < 0.0001). Sugar intake increased from 23.4 ± 6.5 to 32.2 ± 6.3% of kcal in the figs-added diet (p < 0.0001). Body weight did not change (p = 0.08).
Daily consumption of figs did not reduce low-density lipoprotein cholesterol. Triglyceride concentrations were not significantly changed despite an increase in sugar intake.
PMCID: PMC3169356  PMID: 21811062
Figs; Dietary fiber; Hypercholesterolemia; Dietary intake; Lipids
22.  Infant Temperament is Associated with Potentially Obesogenic Diet at 18 Months 
This study investigated whether infants’ temperament at 18 months is associated with the feeding of foods and drinks that may increase the risk for later obesity.
This was a cross-sectional study of mothers and infants (N = 40,266) participating in the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Data were collected by questionnaire. Predictor variables were: infants’ temperament at 18 months (internalizing, externalizing, and surgency/extraversion), and mothers’ negative affectivity. Outcomes variables were feeding of sweet foods, sweet drinks, and night-time caloric drinks at 18 months (all dichotomized). Confounders were child’s gender, weight-for-height at 18 months, breastfeeding, and mother’s level of education.
After controlling for confounders, infant temperament dimensions at 18 months were significantly associated with mothers’ feeding of potentially obesogenic foods and drinks independent of mothers’ negative affectivity. Infants who were more internalizing were more likely to be given sweet foods (OR 1.47, CI 1.32–1.65), sweet drinks (OR 1.76, CI 1.56–1.98), and drinks at night (OR 2.91, CI 2.54–3.33); infants who were more externalizing were more likely to be given sweet food (OR 1.53, CI 1.40–1.67) and sweet drinks (OR 1.22, CI 1.11–1.34); and infants who were more surgent were more likely to be given drinks at night (OR1.66, CI 1.42–1.92).
The association between infant temperament and maternal feeding patterns suggests early mechanisms for later obesity that should be investigated in future studies.
PMCID: PMC3128685  PMID: 20854098
infant temperament; sweet foods; sweet drinks; night-time caloric drinks
23.  Reduction in BMI z-score and improvement in cardiometabolic risk factors in obese children and adolescents. The Oslo Adiposity Intervention Study - a hospital/public health nurse combined treatment  
BMC Pediatrics  2011;11:47.
Weight loss and increased physical fitness are established approaches to reduce cardiovascular risk factors. We studied the reduction in BMI z-score associated with improvement in cardiometabolic risk factors in overweight and obese children and adolescents treated with a combined hospital/public health nurse model. We also examined how aerobic fitness influenced the results.
From 2004-2007, 307 overweight and obese children and adolescents aged 7-17 years were referred to an outpatient hospital pediatrics clinic and evaluated by a multidisciplinary team. Together with family members, they were counseled regarding diet and physical activity at biannual clinic visits. Visits with the public health nurse at local schools or at maternal and child health centres were scheduled between the hospital consultations. Fasting blood samples were taken at baseline and after one year, and aerobic fitness (VO2peak) was measured. In the analyses, 230 subjects completing one year of follow-up by December 2008 were divided into four groups according to changes in BMI z-score: Group 1: decrease in BMI z-score≥0.23, Group 2: decrease in BMI z-score≥0.1-< 0.23, Group 3: decrease in/stable BMI z-score≥0.0-< 0.1, Group 4: increase in BMI z-score (>0.00-0.55).
230 participants were included in the analyses (75%). Mean (SD) BMI z-score was reduced from 2.18 (0.30) to 2.05 (0.39) (p < 0.001) in the group as a whole. After adjustment for BMI z-score, waist circumference and gender, the three groups with reduced BMI z-score had a significantly greater reduction in HOMA-IR, insulin, total cholesterol, LDL cholesterol and total/HDL cholesterol ratio than the group with increased BMI z-score. Adding change in aerobic fitness to the model had little influence on the results. Even a very small reduction in BMI z-score (group 3) was associated with significantly lower insulin, total cholesterol, LDL and total/HDL cholesterol ratio. The group with the largest reduction in BMI z-score had improvements in HOMA-IR and aerobic fitness as well. An increase in BMI z-score was associated with worsening of C-peptide and total/HDL cholesterol ratio.
Even a modest reduction in BMI z-score after one year of combined hospital/and public health nurse intervention was associated with improvement in several cardiovascular risk factors.
PMCID: PMC3121603  PMID: 21619652
24.  Orlistat after initial dietary/behavioural treatment: changes in body weight and dietary maintenance in subjects with sleep related breathing disorders 
Nutrition Journal  2011;10:21.
Sleep related breathing disorders (SRBD) are associated with increased morbidity and mortality and weight loss is recommended to overweight or obese patients with SRBD. However, maintenance of weight loss is difficult to achieve and strategies for weight loss maintenance is needed. Orlistat is a pharmacological agent that reduces the intestinal absorption of fat and may favour long-term weight maintenance.
To examine the change in body weight and dietary intake during a 1-year treatment with orlistat after an initial weight loss in obese subjects with SRBD. Furthermore, to explore the dietary determinants of weight maintenance during treatment with orlistat.
Men and women with SRBD aged 32-62 years (n = 63) participated in a 3-month dietary intervention to increase intake of vegetables and fruit. After an initial weight loss of 3.4 kg they achieved a mean body mass index of 34.3 ± 4.7 kg/m2. Subsequently they were treated with orlistat for 1 year. During this year, dietary and behavioural interventions to attain weight loss were provided in the course of 14 group sessions. Dietary intake, energy density and food choices were assessed with a food frequency questionnaire before and after orlistat treatment.
With orlistat, body weight decreased by a mean of 3.5 kg (95% CI 1.5, 5.5). The dietary E% from saturated fat, intake of fatty dairy products and energy density increased after 1 year while intakes of oils, fish and vegetables decreased (all P < 0.05). After multivariate adjustments, weight loss was associated with E% protein (R2adj = 0.19 [95% CI 0.10, 0.46]), and inversely associated with E% saturated fat (R2adj = 0.20 [95% CI 0.12, 0.47]) and fatty dairy products (R2adj = 0.23 [95% CI 0.12, 0.49]).
Orlistat induced further weight loss, but dietary compliance declined with time. Increasing dietary protein and restricting saturated fat and fatty dairy products may facilitate weight loss with orlistat.
PMCID: PMC3060836  PMID: 21385420
25.  Impacting obesity and glycemic control using a culturally-sensitive diabetes education program in Hispanic patients with type 2 diabetes 
Diabetes mellitus and obesity are prevalent in the Hispanic community. This group has not benefited greatly from diabetes interventions due to cultural, language and financial constraints. We designed a prospective cohort study to determine the clinical impact on adiposity and glycemic control in Hispanics with type 2 diabetes.
Research design and methods
The program conducted in Spanish by a multidisciplinary team of health care providers focused on improving glycemic control and complications through cultural lifestyle changes. Outcomes were changes in glycemic control by fasting insulin, glucose and HbA1c, body composition and selected adipokines, adiponectin, leptin and ghrelin. Body composition was measured by dual energy x-ray absorptiometry. Changes from baseline at three months were compared using paired t-tests and with Spearman’s correlations.
Glycemic control improved by HbA1c (7.9% ± 2.0% vs 7.1% ± 1.7%; P = <0.001), and fasting glucose (166.4 ± 66.0 mg/dl vs 143.2 ± 57.9 mg/dl; P = 0.003). Body weight (81.3 ± 17.9 kg vs 80.3 ± 18.0 kg; P = 0.002), waist circumference (101.6 ± 13.4 cm vs 99.1 ± 12.7 cm; P = 0.015), and truncal fat (16.5 ± 5.7 kg vs 15.9 ± 5.6 kg; P = 0.001) decreased. Only leptin (19.6 ± 15.0 ng/ml vs 16.3 ± 12.7 ng/ml; P = 0.002) was reduced and related to change in body weight (r = 0.392; P = 0.022).
Our program significantly improved glycemic control and decreased obesity in diabetic Hispanic subjects. The early benefits on glycemic control may be related to reductions in leptin through loss of adipose tissue. Success in impacting diabetes and related complications can occur in a culturally focused and multidisciplinary context.
PMCID: PMC3036541  PMID: 21318090
glycemic control; obesity; leptin; culture

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