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Biomedical subjects

D B Allison

Publications and source records attributed to D B Allison.

At least 127 records · Page 7Linked to original sources

Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes.

OBJECTIVE: To examine the effect of a single high oral dose of the novel noncaloric sweetener sucralose on short-term glucose homeostasis in patients with IDDM or NIDDM. RESEARCH DESIGN AND METHODS: A total of 13 IDDM and 13 NIDDM patients with glycosylated hemoglobin levels < 10% completed this double-blind cross-over study. After an overnight fast, patients were administered opaque capsules containing either 1,000 mg sucralose or cellulose placebo, followed by a standardized 360-kcal liquid breakfast. Plasma glucose and serum C-peptide levels were measured over the next 4 h. RESULTS: Regardless of the type of diabetes, areas under the curves for changes of plasma glucose and serum C-peptide levels after sucralose administration were not significantly different from those after placebo. During test meals with sucralose, one episode of symptomatic hypoglycemia occurred in each of three IDDM patients, but these episodes were not considered the result of sucralose administration. CONCLUSIONS: The present results support the conclusion that sucralose consumption does not adversely affect short-term blood glucose control in patients with diabetes.

Administration, Oral↗

On estimating the minima of BMI-mortality curves.

OBJECTIVE: To identify the 'optimal' BMI, that is, the BMI associated with minimal mortality, researchers frequently fit a quadratic function to data and identify the nadir of the BMI-mortality curve. However, Waaler (1984)8 has argued that this approach systematically overestimates the optimal BMI because the true curve might not be quadratic. The purpose of this study was to test this proposition. DESIGN: We simulated 25 decidedly nonquadratic curves in which the true minimum corresponded to a BMI of 24. RESULTS: When fitting a quadratic model to this data and solving for the nadir of the curve, the estimated optimal BMI was 21.14 (SD = 0.586). CONCLUSIONS: It is concluded that there is no way of knowing a priori whether the BMI associated with minimum mortality will systematically overestimate, underestimate, or estimate in an unbiased manner the true optimal BMI when the true model underlying the data is not known.

Body Mass Index↗

The heritability of body mass index among an international sample of monozygotic twins reared apart.

BACKGROUND: Published heritability estimates (h2) for body mass index (BMI) range from as low as 0.05 to as high as 0.90. The purpose of this paper is to introduce new data to help narrow the range of plausible estimates. SUBJECTS: Subjects were 53 pairs (23 M; 30 F) of monozygotic twins reared apart (MZAs), whose mean BMI was 24.2 (SD = 4.7). BMI's were transformed to approximate normality via the Box-Cox transformation. Twin paris came from the Finnish Twin Cohort (17 pairs), a data base of Japanese twins (10 pairs) and published case histories of primarily American twins (26 pairs). RESULTS: The h2 for MZAs is given by the correlation among the twin pairs. For the transformed data, the zero-order correlation of twins' BMIs was 0.79 for all twins, 0.63 for the Finnish twins, 0.73 for the Japanese twins and 0.85 for the 'archival' twins. When modeled with regression to control for relevant covariates, the estimate of h2 is either 0.50 or 0.70, depending on one's definition. The semipartial r was 0.50, suggesting that 50% of the total variance in BMI appears to the genetic in origin after controlling the covariates. The partial r was 0.70, suggesting that 70% of the variance in BMI that is not accounted for by the covariates can be attributed to genetic variation. Separation age had a small positive correlation with absolute intra-pair difference in BMI, suggesting that these estimates of h2 are not biased upwards due to early shared environment. CONCLUSIONS: Findings are consistent with past studies of MZAs and suggest that h2 estimates between 0.50 and 0.70 are reasonable. Implications of this finding are discussed.

Adult↗

The use of discordant sibling pairs for finding genetic loci linked to obesity: practical considerations.

BACKGROUND: Currently there is substantial interest in finding genetic loci linked to human obesity. However, the complexity of the genetic architecture for human body fatness and body weight make this a very challenging task. Recently, several authors have proposed the use of discordant sibling pairs to improve the power to detect linkage for obesity and other continuously distributed complex phenotypes. The use of discordant siblings pairs can markedly increase the power of statistical analyses to detect linkage. However, the use of discordant sibling pairs also presents several practical concerns. These include both the difficulty and cost of locating markedly discordant sibling pairs and the possibility that when such pairs are located, they may in fact be only half-siblings due to non-paternity. In this paper, I consider both of these issues. RESULTS: Quantitative estimates of the probability of finding pairs of a given degree of discordance are presented based on the assumption of a normal distribution as well as on actual data. Quantitative estimates of the odds of selecting pairs that are actually half siblings as opposed to full siblings are also presented for different degrees of discordance. Finally, percentile scores for BMI are tabulated as these are necessary for researchers to implement certain sibling selection strategies.

Adult↗

Publication bias in obesity treatment trials?

OBJECTIVE: The present investigation examined the extent of publication bias (namely the tendency to publish significant findings and file away non-significant findings) within the obesity treatment literature. DESIGN: Quantitative literature synthesis of four published meta-analyses from the obesity treatment literature. Interventions in these studies included pharmacological, educational, child, and couples treatments. METHODS: To assess publication bias, several regression procedures (for example weighted least-squares, random-effects multi-level modeling, and robust regression methods) were used to regress effect sizes onto their standard errors, or proxies thereof, within each of the four meta-analysis. A significant positive beta weight in these analyses signified publication bias. RESULTS: There was evidence for publication bias within two of the four published meta-analyses, such that reviews of published studies were likely to overestimate clinical efficacy. The lack of evidence for publication bias within the two other meta-analyses might have been due to insufficient statistical power rather than the absence of selection bias. CONCLUSIONS: As in other disciplines, publication bias appears to exist in the obesity treatment literature. Suggestions are offered for managing publication bias once identified or reducing its likelihood in the first place.

Bias↗

Risch's lambda values for human obesity.

OBJECTIVE: Risch's lambda statistic (lambda R) is related to the heritability of traits and can be useful in several contexts, including the conduct of power analyses to determine sample size for gene mapping studies. However, values of lambda R have not been presented for human obesity. DESIGN AND RESULTS: Using both analytic and empirical approaches, the present study calculates estimates of lambda R. Examples are provided to illustrate the use of these estimates for determining sample size for genetic mapping studies.

Adolescent↗

Genetic, environmental, and phenotypic links between body mass index and blood pressure among women.

Greater relative weight is associated with higher blood pressure, but the reasons are unknown. The inability of current technology to induce sustained weight loss among overweight persons precludes experimental tests of whether this association is causal. We evaluated the degree to which the covariation between body mass index (BMI; kg/m2) and blood pressure (BP) among women is due to pleiotropic genetic factors, environmental factors, or phenotypic causation. The sample included 75 monozygotic (MZ) and 39 dizygotic (DZ) pairs of adult female twins. "BP" was calculated as the unit-weighted mean of systolic and diastolic. Data were analyzed through structural equation modeling. A model was specified stipulating that additive genetic effects (A) and unique environmental effects (E) each contributed to the covariance between BMI and BP, thus allowing for both pleiotropic and unique environmental influences on the covariance between BMI and BP. Dropping the pleiotropic influences significantly worsened the model (chi 2 = 4.62, df = 1, P = .032), suggesting significant pleiotropic effects. Dropping the environmental influences on the cross-phenotype covariance did not significantly worsen the model (chi 2 = 1.42, df = 1, P = .233). This indicates no significant effect of the environment on the covariance between BMI and BP. Finally, a model of phenotypic causation in which BMI directly influenced BP was fitted. This model provided the best single parameter explanation of the BP-BMI covariation. These data suggest that, among women, regardless of the source of variation, changes in BMI should lead to long-standing changes in BP.

Adult↗

When is it worth measuring a covariate in a randomized clinical trial?

In a randomized clinical trial, an experimenter can increase statistical power by including a covariate (e.g., a pretest). This will generally reduce the total number of participants needed to achieve a specified level of power. However, it will also increase the cost per participant. Thus, the question arises, "When do the savings incurred by needing fewer participants exceed the costs incurred by measuring each participant on the covariate?" A simple closed form expression is derived that applied researchers can use in the design phase of studies to answer this question.

Adult↗

The calorie: myth, measurement, and reality.

Few dietary components are surrounded by more misinformation and myths than the calorie. This confusion can be attributed in part to a lack of accurate and practical methods for assessing energy intake and thus requirements in humans over periods extending beyond several days. The availability of modern respiratory-chamber indirect calorimetry systems and results from human studies with doubly labeled water are now helping to clarify uncertainties surrounding energy requirements. We describe studies of patients with endogenous obesity as an example of how these research methods are resolving long-standing questions regarding energy requirements. The results of these investigations reveal some of the flaws in estimating energy requirements by self-report methods. Advances in accurately measuring energy expenditure are making important contributions to the study of human energy requirements and are providing new and important research opportunities.

Calorimetry↗

Behaviour problems in Angelman syndrome.

Angelman syndrome (AS) is a genetic disorder that is associated with a deletion on chromosome 15, and is characterized by abnormalities or impairments in neurological, motor and intellectual functioning. While behaviour problems have been reported in clients with AS, relatively little is known about their developmental course and outcome. In this study, data on the nature and prevalence of behaviour problems among clients with AS were gathered from two sources: (1) a review of published case reports; and (2) parent responses to a survey of behaviour problems in a small (n = 11) sample of children with AS. Data from both sources showed that behaviour problems were present in males and females of all ages, and included language deficits, excessive laughter, hyperactivity, short attention span, problems with eating and sleeping, aggression, noncompliance, mouthing of objects, tantrums, and repetitive and stereotyped behaviour. Identification and treatment of severe behaviour problems in clients with AS may improve their adaptive functioning.

Adolescent↗

The use of areas under curves in diabetes research.

Recently, several articles appearing in the diabetes literature have suggested that many investigators are unclear about a number of issues involving the use of areas under the curve (AUCs). This prompted us to reconsider issues in the calculation, use, meaning, and presentation of AUCs. We discuss five issues: 1) What is a curve and an area? 2) How should one graphically present a group's curve? 3) How should one calculate AUCs? 4) Should one subtract baseline values from outcome values before calculating AUCs? And 5) are AUCs the best way to combine multiple readings into a single index?

Analysis of Variance↗

Is the intra-uterine period really a critical period for the development of adiposity?

OBJECTIVE: The intra-uterine environment may be a critical period for the development of adiposity. Alternatively, most of the co-variance of relative weight from birth to adulthood may be genetic in origin. This study tested whether birth weight 'tracks' into adulthood, independent of genetic factors. DESIGN: Observational twin study. Birth weights and gestational ages from birth records of 8040 twins from the Minnesota Twin Registry including 699 monozygotic (MZ) male pairs, 609 dizygotic (DZ) male pairs, 939 MZ female pairs, 880 DZ female pairs, and 893 opposite sex DZ pairs ages (yrs) 28 to 52 (Mean = 40.3; s.d. = 6.2) were compared to self-reported adult height and weight. RESULTS: The correlation of birth weight with adult height was 0.236, with adult weight 0.188, and with adult body mass index 0.078 (all P-values < 0.0005). To test if this tracking was independent of genetic influences, we analyzed intra-pair differences for MZ twins. If differences in birth weight between members of a MZ twin pair correlate with adult relative weight, this association cannot be attributed to genetic influences. The correlation of intra-pair differences in birth weight with intra-pair differences in adult height was 0.316 (P < 0.0005), with adult weight 0.136 (P < 0.0005), and with adult BMI 0.026 (P = 0.331). Results were unchanged when multivariate regression modeling was employed. CONCLUSION: These data suggest that the intra-uterine environmental influences on birth weight have an enduring impact on adult height but not on adult relative weight. This suggests that the intra-uterine period is a critical period for the development of height but not for adiposity.

Adipose Tissue↗

Low spinal and pelvic bone mineral density among individuals with Down syndrome.

The bone mineral density of 15 adults with Down syndrome was compared to 25 control subjects without Down syndrome. Bone mineral density was measured by dual x-ray absorptiometry with a Lunar DPX scanner. Arm, leg, pelvic, and spine bone mineral density was tested. Analysis of covariance was conducted for each variable; Down syndrome was the independent variable, and the covariates were height, lean body mass, fat mass, age, and gender. No significant group differences were found for arm or leg bone mineral density. Individuals with Down syndrome had significantly lower pelvic and spinal bone mineral density. Before adjustment for covariates, percentage difference between group means for spine was 14.5% and for pelvis, 11.6%. Adjusted percentage was 11.1% and 13.9%, respectively. Suggestions for further research were made.

Adult↗

Issues relating to normalization of body fat content in men and women.

OBJECTIVE: Body mass index (BMI), % body fat, and the fat:lean ratio are ratios frequently used as obesity indices. Ratios are based on an assumption that the regression between the numerator (e.g. fat mass) and the denominator (e.g. body mass) has a zero-intercept. As shown in the companion paper, non-zero intercepts cause several problems when ratios are used to adjust data and analysis of covariance (ANCOVA) is frequently the preferred statistical tool. The purpose of this paper is to examine whether BMI, % body fat and the fat:lean ratio meet the necessary criteria for suitable obesity indices using gender comparisons as an example. RESULTS: In 720 healthy men and women, BMI was higher in men (24.9 +/- 3.3 vs 23.4 +/- 3.2 kg/m2, P < 0.001), but fat mass, % fat and the fat:lean ratio were higher in women (14.8 +/- 8.4 vs 19.1 +/- 8.1 kg fat; 18.6 +/- 8.7 vs 29.9 +/- 9.7% body fat; 0.24 +/- 0.14 vs 0.46 +/- 0.20 for the fat:lean ratio; P < 0.001). Body mass (BM) was correlated with height2 in men (r = 0.40) and women (r = 0.36) with equivalent regression slopes (17.1 +/- 1.9 vs 15.6 +/- 2.3 kg per m2 in women), but the intercepts were different from zero (24.1 kg in men, 20.7 kg in women). When BM was adjusted for height2 using ANCOVA, men remained significantly heavier than women (74.4 +/- 11.0 vs 68.8 +/- 11.6 kg; P < 0.001). Fat mass (FM) was significantly correlated with BM in males (r = 0.64) and females (r = 0.78) but the regression slopes were different (0.49 +/- 0.03 vs 0.71 +/- 0.03 kg of fat per kg body mass in females; P < 0.05) and the intercepts were different from zero (-23.2 +/- 2.2 kg in males; -24.8 +/- 2.1 kg in females). FM adjusted for BM was significantly higher in women (11.7 vs 25.6 kg). FM was inversely correlated with fat free mass (FFM) in males (r = -0.17) and females (r = -0.20), with similar regression slopes (-0.16 +/- 0.05 vs -0.26 +/- 0.08 kg of FM per kg of FFM in women) and the intercepts were significantly different from zero (24.8 +/- 3.0 kg in males; 30.7 +/- 3.6 kg in females). When FM was adjusted for FFM, there was no significant difference between men (16.3 kg) and women (17.0 kg). CONCLUSIONS: It is concluded that: (a) the presence of significant intercepts does not support the use of ratios as obesity indices and regression based models should be considered; and, (b) the direction and magnitude of the difference in obesity index between men and women changes with different normalization approaches.

Adolescent↗

Statistical considerations regarding the use of ratios to adjust data.

OBJECTIVE: The use of ratios to adjust data (i.e. 'index' variables) is common in obesity and related research. The rationale for the use of ratios often seems to be the desire to control or eliminate the influence of the variable in the denominator. The purpose of this paper is to gain a greater appreciation of the statistical assumptions underlying ratios and their impact on data interpretation. RESULTS: We demonstrate the limitations of the indiscriminant use of ratios to adjust data. Specifically, we show that: (1) given linearity, a zero intercept between the numerator and denominator are necessary and sufficient conditions for a ratio to remove the confounding effects of the denominator; (2) seemingly minor departures from a zero intercept can have major consequences on the ratio's ability to control for the denominator; (3) the ratio of two normally distributed variables cannot be normally distributed, and this may violate the assumptions of subsequent parametric statistical analyses; (4) the use of ratios affects the error distribution of the data which may also violate the assumptions of subsequent parametric statistical analyses; (5) the use of ratios cannot easily take nonlinear effects between the numerator and denominator into account; (6) the use of ratios can introduce spurious correlations among the ratios and other variables; (7) the use of ratios can create interpretive difficulties. We also clarify that the mean of ratios is not necessarily equivalent to the ratio of the means of the numerator and denominator. Finally, we present and discuss formulae for the reliability of ratios and residuals. CONCLUSION: Because of the above issues, we question the indiscriminant use of ratios and advocate that investigators consider regression-based approaches as alternatives.

Body Constitution↗

A randomised placebo-controlled clinical trial of an acupressure device for weight loss.

OBJECTIVE: To provide a randomized placebo-controlled trial to determine the efficacy of an auricular acupressure device. DESIGN: Subjects were randomly assigned to either treatment or placebo. The treatment group received the acupressure device and were instructed to use the device in their dominant ear. The placebo group received an acupressure device for their wrist. Participants were followed for 12 weeks. SETTING: Outpatient core of the New York Obesity Research Center. SUBJECTS: 96 obese adult volunteers, 80 females and 16 males, between 19 and 70 years of age. MEASUREMENTS: Weight, body fat, and blood pressure measured every two weeks. RESULTS: All subjects combined lost, on average, 0.96 kg. There was no significant difference between the two groups on weight loss (mean wt loss = 1.28 [s.d. = 2.74] kg for treatment and 0.63 [s.d. = 3.26] kg for placebo) regardless of whether all subjects were examined or only the most compliant subjects were examined. Similarly, there were no significant differences between the two groups regarding fat loss or blood pressure reduction. CONCLUSION: The acupressure device appears to be a safe device (did not cause any harmful side effects). However, it did not promote significantly greater weight or fat loss, or declines in blood pressure than placebo.

Acupressure↗