Biomedical subjects

David B Allison

Publications and source records attributed to David B Allison.

At least 73 records · Page 4Linked to original sources

PubMed2004

Dual-energy x-ray absorptiometry-measured lean soft tissue mass: differing relation to body cell mass across the adult life span.

Lean soft tissue (LST) measured by dual-energy X-ray absorptiometry (DEXA) is used as a metabolic measure in aging research despite evidence of extracellular fluid expansion and a corresponding reduction in body cell mass (BCM) in older participants. We investigated the hypothesis that the fraction of LST as BCM is smaller with greater age. Men and women (n = 2043) had DEXA and 40K-counting for body potassium and BCM measured on the same day. Both BCM and LST were lower with greater age but the relative lowering was larger for BCM. A multiple linear regression model was fitted with BCM/LST as the dependent variable, and age, sex, and interaction terms as independent variables. Men had a mean BCM/LST greater (p < .001) than women; quadratic and cubic age terms were also significant or approached significance. Thus, the fraction of LST as BCM is smaller in older adults, a finding that has implications for the interpretation of DEXA results.

Absorptiometry, Photon↗

PubMed2004

Metabolic and behavioral characteristics of metabolically obese but normal-weight women.

A unique subset of individuals termed metabolically obese but normal weight (MONW) has been identified. These young women are potentially at increased risk for development of the metabolic syndrome despite their young age and normal body mass index. We seek to determine metabolic and behavioral factors that could potentially distinguish MONW women from young women with a normal metabolic profile.Ninety-six women were classified as MONW (n = 12) or non-MONW (n = 84) based on a cut point of insulin sensitivity (as estimated by the homeostasis model assessment). Potentially distinguishing phenotypes between groups measured included serum lipids, ghrelin, leptin, adiponectin, body composition and body fat distribution, resting and physical activity energy expenditure, peak oxygen uptake, dietary intake, dietary behavior, and family history and lifestyle variables. Despite a similar body mass index between groups, MONW women showed higher percent body fat, lower fat-free mass, lower physical activity energy expenditure, and lower peak oxygen uptake than non-MONW women. Plasma cholesterol level was higher in MONW women, whereas no differences were noted for other blood lipids, ghrelin, leptin, adiponectin, and resting energy expenditure. MONW women had lower dietary restraint scores than non-MONW women, but no differences were noted in disinhibition, hunger, and dietary intake. Stepwise regression analysis performed on all subjects showed that 33.5% of the unique variance of the homeostasis model assessment was explained with the variables of percentage of body fat (17.1%), level of dietary restraint (10.4%), and age (6%). Both metabolic and dietary behavioral variables contribute to the deleterious metabolic profile of MONW women. They display lower insulin sensitivity due potentially to a cluster of sedentary behavior patterns that contribute to their higher adiposity. Furthermore, cognitive attitudes toward food (i.e. dietary restraint) and concomitant lifestyle behaviors may play a role in regulating insulin sensitivity in MONW women.

Adiponectin↗

PubMed2004

Characterization of epistasis influencing complex spontaneous obesity in the BSB model.

There is growing awareness that complex interactions among multiple genes and environmental factors play an important role in controlling obesity traits. The BSB mouse, which is produced by the backcross of (lean C57BL/6J x lean Mus spretus) x C57BL/6J, provides an excellent model of epistatic obesity. To evaluate potential epistatic interactions among six chromosomal regions previously determined to influence obesity phenotypes, we performed novel Bayesian analyses on the basis of both epistatic and nonepistatic models for four obesity traits: percentage of body fat, adiposity index, total fat mass, and body weight, and also for plasma total cholesterol. The epistatic analysis detected at least one more QTL than the nonepistatic analysis did for all obesity traits. These obesity traits were variously influenced by QTL on chromosomes 2, 7, 12, 15, and 16. Interaction between genes on chromosomes 2 and 12 was present for all obesity traits, accounting for 3-4.8% of the phenotypic variation. Chromosome 12 was found to have weak main effects on all obesity traits. Several different epistatic interactions were also detected for percentage of body fat, adiposity index, and total fat mass. Chromosomes 6 and 12 have not only main effects but also strong epistatic effects on plasma total cholesterol. Our results emphasize the importance of modeling epistasis for discovery of obesity genes.

Adipose Tissue↗

PubMed2004

Applications of Bayesian statistical methods in microarray data analysis.

Microarray technology allows one to measure gene expression levels simultaneously on the whole-genome scale. The rapid progress generates both a great wealth of information and challenges in making inferences from such massive data sets. Bayesian statistical modeling offers an alternative approach to frequentist methodologies, and has several features that make these methods advantageous for the analysis of microarray data. These include the incorporation of prior information, flexible exploration of arbitrarily complex hypotheses, easy inclusion of nuisance parameters, and relatively well developed methods to handle missing data. Recent developments in Bayesian methodology generated a variety of techniques for the identification of differentially expressed genes, finding genes with similar expression profiles, and uncovering underlying gene regulatory networks. Bayesian methods will undoubtedly become more common in the future because of their great utility in microarray analysis.

Bayes Theorem↗

PubMed2004

Rimonabant Sanofi-Synthélabo.

Rimonabant, an antagonist of central cannabinoid type 1 (CB1) receptors, is being developed by Sanofi-Synthélabo for the potential treatment of obesity and as a potential smoking cessation agent. Phase III trials were initiated for obesity in August 2001 and were ongoing in September 2003. By September 2002, the compound had entered phase III trials for smoking cessation, and these trials were ongoing in September 2003.

Animals↗

PubMed2003

Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction.

We investigated the influences of short-term and lifespan-prolonging long-term caloric restriction (LCR) on gene expression in white adipose tissue (WAT). Over 11,000 genes were examined using high-density oligonucleotide microarrays in four groups of 10- to 11-month-old male C57Bl6 mice that were either fasted for 18 h before death (F), subjected to short-term caloric restriction for 23 days (SCR), or LCR for 9 months and compared with nonfasted control (CO) mice. Only a few transcripts of F and SCR were differentially expressed compared with CO mice. In contrast, 345 transcripts of 6,266 genes found to be expressed in WAT were altered significantly by LCR. The expression of several genes encoding proteins involved in energy metabolism was increased by LCR. Further, many of the shifts in gene expression after LCR are known to occur during adipocyte differentiation. Selected LCR-associated alterations of gene expression were supported by quantitative reverse transcriptase-polymerase chain reaction, histology, and histochemical examinations. Our data provide new insights on the metabolic state associated with aging retardation by LCR.

Adipose Tissue↗

PubMed2003

Results of soy-based meal replacement formula on weight, anthropometry, serum lipids & blood pressure during a 40-week clinical weight loss trial.

BACKGROUND: To evaluate the intermediate-term health outcomes associated with a soy-based meal replacement, and to compare the weight loss efficacy of two distinct patterns of caloric restriction. METHODS: Ninety overweight/obese (28 < BMI < or = 41 kg/m2) adults received a single session of dietary counseling and were randomized to either 12 weeks at 1200 kcal/day, 16 weeks at 1500 kcal/d and 12 weeks at 1800 kcal/d (i.e., the 12/15/18 diet group), or 28 weeks at 1500 kcal/d and 12 weeks at 1800 kcal/d (i.e., the 15/18 diet group). Weight, body fat, waist circumference, blood pressure and serum lipid concentrations were measured at 4-week intervals throughout the 40-week trial. RESULTS: Subjects in both treatments showed statistically significant improvements in outcomes. A regression model for weight change suggests that subjects with larger baseline weights tended to lose more weight and subjects in the 12/15/18 group tended to experience, on average, an additional 0.9 kg of weight loss compared with subjects in the 15/18 group. CONCLUSION: Both treatments using the soy-based meal replacement program were associated with significant and comparable weight loss and improvements on selected health variables.

Clinical Trial↗

PubMed2003

"Are we there yet?": Deciding when one has demonstrated specific genetic causation in complex diseases and quantitative traits.

Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, "Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it." We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what "causation" means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called "causative."

Cystic Fibrosis↗

PubMed2003

Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys.

The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the one-compartment (1CMM) and the two-compartment (2CMM) minimal models were used to analyze stable isotope-labeled intravenous glucose tolerance test (IVGTT) data from year 10 of a study of the effect of dietary restriction (DR) in male rhesus monkeys. Adult monkeys were energy restricted (R; n = 12) on a semipurified diet to approximately 70% of control (C) intake (ad libitum-fed monkeys; n = 12). Under ketamine anesthesia, fasting insulin levels were greater among C monkeys. Insulin sensitivity estimates from all models were greater in R than C monkeys, whereas glucose effectiveness estimates were not consistently greater in R monkeys. Fasting plasma glucose as well as hepatic glucose production and clearance rates did not differ between groups. Body fat, in part, statistically mediated the effect of DR to enhance insulin sensitivity indexes. Precision of estimation and intermodel relationships among insulin sensitivity and glucose effectiveness estimates were in the ranges of those reported previously for humans and dogs, suggesting that the models may provide valid estimates for rhesus monkeys as well. The observed insulin sensitivity indexes from all models, elevated among R vs. C monkeys, may be explained, at least in part, by the difference in body fat content between these groups after chronic DR.

Adipose Tissue↗

PubMed2003

Hierarchical linear models for the development of growth curves: an example with body mass index in overweight/obese adults.

When data are available on multiple individuals measured at multiple time points that may vary in number or inter-measurement interval, hierarchical linear models (HLM) may be an ideal option. The present paper offers an applied tutorial on the use of HLM for developing growth curves depicting natural changes over time. We illustrate these methods with an example of body mass index (BMI; kg/m(2)) among overweight and obese adults. We modelled among-person variation in BMI growth curves as a function of subjects' baseline characteristics. Specifically, growth curves were modelled with two-level observations, where the first level was each time point of measurement within each individual and the second level was each individual. Four longitudinal databases with measured weight and height met the inclusion criteria and were pooled for analysis: the Framingham Heart Study (FHS); the Multiple Risk Factor Intervention Trial (MRFIT); the National Health and Nutritional Examination Survey I (NHANES-I) and its follow-up study; and the Tecumseh Mortality Follow-up Study (TMFS). Results indicated that significant quadratic patterns of the BMI growth trajectory depend primarily upon a combination of age and baseline BMI. Specifically, BMI tends to increase with time for younger people with relatively moderate obesity (25 BMI <30) but decrease for older people regardless of degree of obesity. The gradients of these changes are inversely related to baseline BMI and do not substantially depend on gender.

Adult↗

PubMed2003

Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism.

Several theoretical studies have suggested that large samples of randomly ascertained siblings can be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. Here, we report a genetic linkage scan using extremely discordant and concordant sibling pairs, selected from 34,580 sibling pairs in the southwest of England who completed a personality questionnaire. We performed a genomewide scan for quantitative-trait loci (QTLs) that influence variation in the personality trait of neuroticism, or emotional stability, and we established genomewide empirical significance thresholds by simulation. The maximum pointwise P values, expressed as the negative logarithm (base 10), were found on 1q (3.95), 4q (3.84), 7p (3.90), 12q (4.74), and 13q (3.81). These five loci met or exceeded the 5% genomewide significance threshold of 3.8 (negative logarithm of the P value). QTLs on chromosomes 1, 12, and 13 are likely to be female specific. One locus, on chromosome 1, is syntenic with that reported from QTL mapping of rodent emotionality, an animal model of neuroticism, suggesting that some animal and human QTLs influencing emotional stability may be homologous.

Adult↗

PubMed2003

Years of life lost due to obesity.

CONTEXT: Public health officials and organizations have disseminated health messages regarding the dangers of obesity, but these have not produced the desired effect. OBJECTIVE: To estimate the expected number of years of life lost (YLL) due to overweight and obesity across the life span of an adult. DESIGN, SETTING, AND SUBJECTS: Data from the (1) US Life Tables (1999); (2) Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994); and (3) First National Health and Nutrition Epidemiologic Follow-up Study (NHANES I and II; 1971-1992) and NHANES II Mortality Study (1976-1992) were used to derive YLL estimates for adults aged 18 to 85 years. Body mass index (BMI) integer-defined categories were used (ie, <17; 17 to <18; 18 to <19; 20 to <21; 21 to 45; or > or =45). A BMI of 24 was used as the reference category. MAIN OUTCOME MEASURE: The difference between the number of years of life expected if an individual were obese vs not obese, which was designated YLL. RESULTS: Marked race and sex differences were observed in estimated YLL. Among whites, a J- or U-shaped association was found between overweight or obesity and YLL. The optimal BMI (associated with the least YLL or greatest longevity) is approximately 23 to 25 for whites and 23 to 30 for blacks. For any given degree of overweight, younger adults generally had greater YLL than did older adults. The maximum YLL for white men aged 20 to 30 years with a severe level of obesity (BMI >45) is 13 and is 8 for white women. For men, this could represent a 22% reduction in expected remaining life span. Among black men and black women older than 60 years, overweight and moderate obesity were generally not associated with an increased YLL and only severe obesity resulted in YLL. However, blacks at younger ages with severe levels of obesity had a maximum YLL of 20 for men and 5 for women. CONCLUSION: Obesity appears to lessen life expectancy markedly, especially among younger adults.

Adult↗

PubMed2003

Maternal-child feeding patterns and child body weight: findings from a population-based sample.

BACKGROUND: Certain mother-child feeding patterns (MCFPs) may promote childhood obesity and/or disordered eating. OBJECTIVES: To assess the demographic correlates of MCFPs and to test whether differences in MCFPs are associated with child body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) z scores in a population-based study. DESIGN: A secondary analysis of the National Longitudinal Survey of Youth main and child cohorts was conducted on more than 1000 Hispanic, African American, and non-Hispanic/non-African American children, aged 3 to 6 years. The MCFPs were measured by means of 3 interview questions probing mother-allotted child food choice, child compliance during meals, and child obedience during meals. RESULTS: Mothers of non-Hispanic/non-African American children allotted greater food choice than mothers of African American or Hispanic children. Maternal BMI and other demographic measures were unrelated to MCFPs. The lowest levels of mother-allotted child food choice and child eating compliance were associated with reduced child BMI, with mean BMI z scores of -0.36 and -0.41, respectively. Effect sizes were small, however, and MCFPs did not discriminate children who were overweight or at risk for being overweight from children who were not (P>.05). CONCLUSIONS: Feeding strategies providing the least child food choice were associated with reduced child BMI. However, MCFPs did not relate to child overweight status.

Analysis of Variance↗

PubMed2003

Treatment and prevention of obesity: what works, what doesn't work, and what might work.

We provide a very broad conceptual overview of some of the issues involved in the treatment and prevention of obesity. Data suggest that clinicians have some ability to promote positive changes with obesity treatment. The environment, though important in influencing one's degree of adiposity, has largely transient effects that do not tend to carry over from one time to substantially later times. In contrast, the genetic influences on body mass index at any one time do tend to carry over to later times. This information influences the types of approaches that are and are not likely to be successful in terms of preventing obesity or reducing obesity on a population level. A second issue concerns the composition of weight lost. Conditional on fat loss, weight loss has been associated with an increased mortality rate (MR) whereas, conditional upon weight loss, fat loss has been associated with a decreased MR. This suggests that we should seek treatments that maximize the proportion of weight lost as fat. Third, the efficacy of current treatments is far below patients' expectations and desires. We need both to increase the efficacy of our treatments dramatically and help patients adjust their expectations so that they can take satisfaction in smaller weight losses. Perhaps, with continued efforts at enhancing treatments, we will see incremental advances in the treatment and prevention of obesity.

Animals↗

PubMed2003

Strain variation in the response of body temperature to dietary restriction.

Dietary restriction (DR, also referred to as calorie restriction, energy restriction, and food restriction) retards senescence and increases longevity in mammals. DR also lowers mean body temperature (T(b)), and thus mean T(b) might be useful as a covariate of DR-induced life extension. Indeed, lower T(b) could itself underlie some of the beneficial life-extension effects that occur during DR. To assess the relationship between lower T(b) during DR and life extension, we asked whether significant strain variation exists in the T(b) response of mice being fed 60% ad libitum (AL). Individually-housed, female mice from 28 strains, representing a genealogically diverse sample of the classical inbred strains, were directly compared. The mean T(b)s in response to DR exhibited highly significant strain variation, ranging from 1.5 degrees C below normal to a phenomenal 5 degrees C below normal. This variation was not explained by differences in loss of thermoregulation, AL adiposity, sensitivity to a nonadaptive hypothermia, motor activity, thermal arousal, absolute food intake, or efficacy of nutrient extraction. The variation in strain mean T(b) was also present in the absence of torpor. This strain variation could be used to critically test whether lower T(b) is a covariate of life extension during DR.

Adipose Tissue↗

PubMed2003

Nizatidine for prevention of weight gain with olanzapine: a double-blind placebo-controlled trial.

Weight gain is associated with treatment with olanzapine and other psychotropic agents. Nizatidine, a histamine H-2 receptor antagonist, has been proposed to have weight-reducing effects. This double-blind trial evaluated the efficacy of nizatidine in limiting weight gain in patients with schizophrenia and related disorders who were treated with olanzapine for up to 16 weeks. After an initial screening period, 175 patients were randomized to receive olanzapine (5-20 mg) with either placebo or nizatidine (150 mg b.i.d. or 300 mg b.i.d.). Significantly less weight gain was observed on average at weeks 3 and 4 with olanzapine+nizatidine 300 mg b.i.d. (P<0.05) compared to olanzapine+placebo, but the difference was not statistically significant at 16 weeks. Nizatidine was well-tolerated and did not adversely affect clinical outcomes. Nizatidine 300 mg b.i.d. may have an early transient effect in limiting the weight gain, but this potential early effect appeared to be diminished or eliminated by 16 weeks.

Adolescent↗

PubMed2003

Associations of body mass index and anthropometric indicators of fat mass and fat free mass with all-cause mortality among women in the first and second National Health and Nutrition Examination Surveys follow-up studies.

PURPOSE: This study tests whether fat mass (FM) and fat free mass (FFM) have opposite associations with mortality in a nationally representative sample of females. METHODS: Data on 13,369 female participants from National Health and Nutrition Examination Surveys (NHANES) I and II (aged 25 to 75 years) were analyzed. Mean follow-up time was 16.1 years. Ninety-seven percent of the participants with 3020 deaths were successfully followed. Subscapular and triceps skinfolds thickness were used as a FM indicator (FMI). Upper arm circumference was used as a FFM indicator (FFMI). Cox regression tested the relationships of BMI, FM and FFM with all-cause mortality adjusting for various socio-demographic variables. RESULTS: BMI had a U-shaped relationship with mortality with a nadir of approximately 27 kg/m(2). When FFMI was added to the model, the relationship between BMI and mortality became more monotonic increasing. FMI showed a significant negative relationship with mortality. CONCLUSIONS: Contrary to expectations, both FFMI and FMI had negative relationships with mortality. These results differ from patterns previously observed in males and may reflect sex differences in fat distribution. Research using superior measures of body fat amount and distribution may resolve these discrepancies.

Adult↗

PubMed2003

Association of African genetic admixture with resting metabolic rate and obesity among women.

OBJECTIVE: To investigate the role of genetic admixture in explaining phenotypic variation in obesity-related traits in a sample of African-American women (n = 145) and to determine significant associations between obesity traits and admixture genetic markers. RESEARCH METHODS AND PROCEDURES: Associations between genetic admixture and BMI, resting metabolic rate, fat mass, fat-free mass, and bone mineral density were tested using linear regression considering the estimation of admixture by 1) a maximum-likelihood approach (MLA) and 2) a Bayesian analysis. RESULTS: Both the conservative MLA and the Bayesian approach support an association between African genetic admixture and BMI. Evidence for the associations of African genetic admixture with fat mass and fat-free mass was supported by the Bayesian analysis; the MLA supported an association with bone mineral density. When the individual ancestry informative markers that were used to estimate admixture were tested for associations with BMI, significant associations were identified in chromosomes 1, 11, and 12. DISCUSSION: These results provide evidence supporting the application of admixture mapping methods to the identification of genes that result in higher levels of obesity among African-American women. Further research is needed to replicate and further explore these findings.

Apolipoprotein A-I↗