Showing papers by "Barbara A. Gower published in 2018"

A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer.

Abstract: Background The glycolytic nature of cancer cells presents a potential treatment target that may be addressed by a ketogenic diet (KD). Objective We hypothesized that a KD would improve body composition and lower serum insulin and insulin-like growth factor-I (IGF-I) in women with ovarian or endometrial cancer. Methods In this randomized controlled trial, women with ovarian or endometrial cancer [age: ≥19 y; body mass index (kg/m2): ≥18.5] were randomly assigned to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS; high-fiber, low-fat). Body composition (DXA) and fasting serum insulin, IGF-I, and β-hydroxybutyrate were obtained at baseline and at 12 wk; urinary ketones were also measured throughout the intervention. We assessed differences between the diets with ANCOVA and independent t tests. We used correlation analyses to estimate associations between changes in serum analytes and body composition. Results After 12 wk, the KD (compared with ACS) group had lower adjusted total (35.3 compared with 38.0 kg, P < 0.05) and android (3.0 compared with 3.3 kg, P < 0.05) fat mass. Percentage of change in visceral fat was greater in the KD group (compared with the ACS group; -21.2% compared with -4.6%, P < 0.05). Adjusted total lean mass did not differ between the groups. The KD (compared with ACS) group had lower adjusted fasting serum insulin (7.6 compared with 11.2 µU/mL, P < 0.01). There was a significant inverse association between the changes in serum β-hydroxybutyrate and IGF-I concentrations (r = -0.57; P < 0.0001). Conclusions In women with ovarian or endometrial cancer, a KD results in selective loss of fat mass and retention of lean mass. Visceral fat mass and fasting serum insulin also are reduced by the KD, perhaps owing to enhanced insulin sensitivity. Elevated serum β-hydroxybutyrate may reflect a metabolic environment inhospitable to cancer proliferation. This trial was registered at www.clinicaltrials.gov as NCT03171506.

Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized, Controlled Trial.

Abstract: Ketogenic diets (KDs) are gaining attention as a potential adjuvant therapy for cancer, but data are limited for KDs’ effects on quality of life. We hypothesized that the KD would (1) improve mental and physical function, including energy levels, (2) reduce hunger, and (3) diminish sweet and starchy food cravings in women with ovarian or endometrial cancer. Participants were randomized to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS: high-fiber, lower-fat). Questionnaires were administered at baseline and after 12 weeks on the assigned diet to assess changes in mental and physical health, perceived energy, appetite, and food cravings. We assessed both between-group differences and within-group changes using ANCOVA and paired t-tests, respectively. After 12 weeks, there was a significant between-group difference in adjusted physical function scores (p < 0.05), and KD participants not receiving chemotherapy reported a significant within-group reduction in fatigue (p < 0.05). There were no significant between-group differences in mental function, hunger, or appetite. There was a significant between-group difference in adjusted cravings for starchy foods and fast food fats at 12 weeks (p < 0.05 for both), with the KD group demonstrating less frequent cravings than the ACS. In conclusion, in women with ovarian or endometrial cancer, a KD does not negatively affect quality of life and in fact may improve physical function, increase energy, and diminish specific food cravings. This trial was registered at ClinicalTrials.gov as NCT03171506.

Comparison of segmental body composition estimated by bioelectrical impedance analysis and dual-energy X-ray absorptiometry.

Abstract: Summary Background & aims Segmental body composition may be an important indicator of health and nutritional status in conditions where variations in fat and lean mass are frequently isolated to a particular body segment (e.g. paralysis, sarcopenia). Until recently, segment-specific body composition could only be assessed using invasive and expensive methods such as dual-energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), or computed tomography (CT). Bioelectrical impedance analysis (BIA) may be a rapid, inexpensive alternative for assessing segmental composition, but it has not been fully validated for this purpose. The purpose of this study was to compare segmental estimates of lean and fat mass using BIA versus a criterion standard of DXA. Methods A cross-sectional pilot study was conducted in n = 30 healthy adults. Outcome measures included total mass, fat mass and lean mass of arm, leg and trunk. Pearson correlation coefficients (r) and paired-samples t-tests (t) were used to assess relationships between each outcome as measured by BIA and DXA. Results Although the methods were strongly correlated for all measures, (r > .87 for all segments) BIA routinely overestimated lean mass for arm and trunk (mean difference arm: 0.97 kg, p = .008; trunk: 5.58 kg, p Conclusions Significant discrepancies were noted between DXA and BIA in all body segments. Further research is needed to refine BIA methods for segmental composition estimates in heterogeneous samples and disease-specific populations before this methods can be used reliably in a clinical setting.

Dissection of hepatic versus extra-hepatic insulin clearance: Ethnic differences in childhood.

Abstract: AIMS Adult African American (AA) women have one third of the hepatic insulin clearance of European American (EA) women. This lower hepatic (but not extra-hepatic) insulin clearance in AA individuals is associated with higher plasma insulin concentrations. This study aims to understand whether impairment of hepatic insulin clearance is seen in AA individuals since childhood, possibly suggesting that genetic/epigenetic factors, rather than lifestyle only, contribute to this. MATERIALS AND METHODS A total of 203 children (105 male and 98 female (55 AA, 88 EA and 60 Hispanic American [HA]; ages, 7-13 years; mean BMI, 19 kg/m2 )) underwent the frequently applied intravenous glucose tolerance test (FSIGT) at the University of Alabama at Birmingham, General Clinical Research Center and Department of Nutrition Sciences. Glucose, insulin and C-peptide levels were measured and hepatic and extra-hepatic insulin clearances were calculated using mathematical modelling. RESULTS Fractional hepatic insulin extraction (FEL ) was lower in AA than in EA children (mean (SD), 19% (20%) vs 33% (20%); P = 0.0007). Adjusting for age, Tanner stage and body fat, FEL was lower in AA than in EA children (P = 0.0012), and there was a slight sex-related difference (FEL, 24% (10%) vs 29% (10%) in boys vs girls; P = 0.04). Extra-hepatic insulin clearance did not differ with ethnicity (27 (12), 21 (12) and 24 (28) mL/kg/min for AA, HA and EA children, respectively; P > 0.05). CONCLUSIONS At a young age, FEL is lower in AAs than in EAs, which does not rule out genetic/epigenetic factors. These differences are related to hyperinsulinaemia and, over time, could possibly contribute to metabolic disorders in AA individuals.

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: Results from a prospective cohort study

Abstract: No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC-specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23-4.25), total sugar (HR: 3.03; 95% CI: 1.12-3.68), glycemic load (HR: 2.10; 95% CI: 1.15-3.83) and simple carbohydrates (HR 2.26; 95% CI 1.19-4.32) were associated with significantly increased risk of all-cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45; 95% CI: 1.23-4.25) and total sugar (HR 3.03; 95% CI 1.12-3.68) were associated with increased risk of HNSCC-specific mortality. In post-treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01-0.69) and all-cause mortality (HR 0.27; 95% CI 0.07-0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted.

A method for measuring human body composition using digital images

Abstract: Background/Objectives Body mass index (BMI) is a proxy for obesity that is commonly used in spite of its limitation in estimating body fatness. Trained observers with repeated exposure to different body types can estimate body fat (BF) of individuals compared to criterion methods with reasonable accuracy. The purpose of this study was to develop and validate a computer algorithm to provide a valid estimate %BF using digital photographs. Subjects/Methods Our sample included 97 children and 226 adults (age in years: 11.3±3.3; 38.1±11.6, respectively). Measured height and weight were used (BMI in kg/m2: 20.4±4.4; 28.7±6.6 for children and adults, respectively). Dual x-ray absorptiometry (DXA) was the criterion method. Body volume (BVPHOTO) and body shape (BSPHOTO) were derived from two digital images. Final support vector regression (SVR) models were trained using age, sex, race, BMI for % BFNOPHOTO, plus BVPHOTO and BSPHOTO for %BFPHOTO. Separate validation models were used to evaluate the learning algorithm in children and adults. The differences in correlations between %BFDXA, %BFNOPHOTO and %BFPHOTO were tested using the Fisher’s Z-score transformation. Results Mean BFDXA and BFPHOTO were 27.0%±9.2 vs. 26.7%± 7.4 in children and 32.9± 10.4% vs. 32.8%±9.3 in adults. SVR models produced %BFPHOTO values strongly correlated with %BFDXA. Our final model produced correlations of rDP = 0.80 and rDP = 0.87 in children and adults, respectively for %BFPHOTO vs. %BFDXA. The correlation between %BFNOPHOTO and %BFDXA was moderate, yet statistically significant in both children rDB = 0.70; p <0.0001 and adults rDB = 0.86; p<0.0001. However, the correlations for rDP were statistically higher than rDB (%BFDXA vs. %BFNOPHOTO) in both children and adults (children: Z = 5.95, p<0.001; adults: Z = 3.27, p<0.0001). Conclusions Our photographic method produced valid estimates of BF in both children and adults. Further research is needed to create norms for subgroups by sex, race/ethnicity, and mobility status.

A High-Fat Compared with a High-Carbohydrate Breakfast Enhances 24-Hour Fat Oxidation in Older Adults.

Abstract: Background The ability to oxidize fat is associated with a lower risk of chronic metabolic disease. Preclinical data in mice showed that a high-fat "breakfast" increased 24-h fat oxidation relative to a high-carbohydrate breakfast. Objectives The objectives of this study were to determine whether the timing of macronutrient intake in humans affects daily fuel utilization and to examine associations between fuel utilization and metabolic indexes. Methods Participants were 29 healthy sedentary men and women (aged 55-75 y) with a body mass index (kg/m2) between 25 and 35. Participants were randomly assigned to receive either a high-fat breakfast (FB; 35% carbohydrate, 20% protein, 45% fat; n = 13) or a high-carbohydrate breakfast (CB; 60% carbohydrate, 20% protein, 20% fat; n = 16) for 4 wk while consuming a "neutral" lunch and dinner. Twenty-four-hour and postprandial respiratory quotients (RQs) were measured by whole-room indirect calorimetry. Insulin and glucose measures including insulin sensitivity were determined by an oral-glucose-tolerance test. Measures were taken at baseline and after the 4-wk intervention. Group-by-time interactions were determined by 2-factor repeated-measures mixed-model ANOVA. Pearson's correlation analyses were used to determine associations of 24-h RQs with metabolic measures after the intervention. Results There was a significant group-by-time interaction for change in the 24-h RQ [FB (mean ± SD): 0.88 ± 0.02 to 0.86 ± 0.02; CB: 0.88 ± 0.02 for both; P < 0.05], breakfast RQ (FB: 0.88 ± 0.03 to 0.86 ± 0.03; CB: 0.89 ± 0.02 to 0.90 ± 0.02; P < 0.01), and lunch RQ (FB: 0.089 ± 0.03 to 0.85 ± 0.03; CB: 0.89 ± 0.03 for both; P < 0.01). In the CB group at follow-up, 24-h RQ was positively associated with fasting glucose (r = 0.66, P < 0.05), glucose area under the curve (AUC) (r = 0.51, P < 0.05), and insulin AUC (r = 0.52, P < 0.05) and inversely associated with insulin sensitivity (r = -0.51, P < 0.05). Conclusions The macronutrient composition of breakfast affects substrate utilization throughout the day in older adults. The consumption of a high-fat, lower-carbohydrate breakfast may reduce the risk of metabolic disease. This trial was registered at www.clinicaltrials.gov as NCT03164200.

Associations of neonatal adiponectin and leptin with growth and body composition in African American infants

Abstract: BACKGROUND Cord blood adiponectin and leptin concentrations are associated with birth weight and adiposity. Birth size and rate of infant weight gain are associated with future obesity risk. However, it is unclear whether biomarkers reflecting the intrauterine environment are predictive of infant prospective body composition change. OBJECTIVES To examine whether cord blood adiponectin and leptin are predictive of neonatal adiposity and fat mass (FM) accrual to 3 months of age. METHODS Participants (n = 36) were healthy African American infants. Leptin and adiponectin concentrations were measured in umbilical cord blood. At 2 weeks and 3 months, infant body composition was assessed via air displacement plethysmography. Weight-for-length z-scores (WLZ) were calculated using World Health Organization standards. Multiple linear regression was used to examine associations of cord blood adiponectin and leptin with birth WLZ; WLZ, FM and fat-free mass at 2 weeks, and the conditional change in these variables from 2 weeks to 3 months (body composition at 3 months adjusted for body composition at 2 weeks). RESULTS Adiponectin was positively associated with FM at 2 weeks (r = 0.45, P < 0.01), but inversely associated with conditional FM change from 2 weeks to 3 months of age (r = -0.38, P < 0.05). Leptin was not significantly associated with infant body composition. CONCLUSIONS Adiponectin may be a marker for FM accrual in African American infants, a relatively understudied population with a high long-term obesity risk. Mechanistic studies are needed to determine whether adiponectin directly influences infant growth or is simply a maker reflective of other ongoing biological changes after birth.

The ketogenic diet as a non-pharmacological treatment for HIV-associated neurocognitive disorder: A descriptive analysis.

Abstract: Mitochondrial dysfunction is associated with abnormal glucose metabolism, inflammation and greater oxidative stress in the brain, each of which may contribute uniquely and perhaps synergistically to HIV-Associated Neurocognitive Disorders (HAND) risk. The ketogenic (i.e., low carbohydrate) diet provides the brain with a highly efficient mitochondrial fuel and is associated with improved cognitive performance in older adults with impaired neurocognitive functioning secondary to ageing, Alzheimer's, and Parkinson's disease; however, whether these cognitive gains are generalizable to older adults with HAND is unknown. Thus, the process and cognitive outcomes of the first participant randomized to the intervention and to the control group were investigated in this case-comparison study. To our knowledge, this is first report to establish the plausibility of the ketogenic diet as a treatment for HAND.

Balanced high fat diet reduces cardiovascular risk in obese women although changes in adipose tissue, lipoproteins, and insulin resistance differ by race

Abstract: Background We previously reported that consuming a balanced high fat diet (BHFD) wherein total saturated fat was reduced and total unsaturated fat increased by proportionately balancing the type of fat (1/3 saturated, 1/3 monounsaturated, 1/3 polyunsaturated) led to significant improvements in inflammatory burden, blood pressure, and vascular function in obese premenopausal European American (EA) and African American (AA) women. Objective Here we compared changes in adipose tissue, lipoproteins, insulin resistance, and cardiovascular risk between EA and AA women. Methods Dietary intakes, plasma fatty acids, lipids, apolipoproteins, lipoproteins, HOMA-IR and ASCVD risk was measured in 144 women who consumed BHFD for 16 weeks. Generalized linear modeling was performed while controlling for change in body weight. Results EA women had greater reductions in visceral adipose tissue. Only EA women had significant reductions in fasting insulin levels (↓24.8%) and HOMA-IR (↓29%) scores. In EA women, the most significant improvements occurred in VLDL particle size (↑), apolipoprotein B levels (↑), serum TG (↓), number of plasma LDL particles (↓), and serum LDL-cholesterol (↓). In AA women, significant improvements occurred in HDL particle size (↑), number of large HDL particles (↑), and apolipoprotein AI levels (↑). Consequently, both groups had improved ASCVD risk scores (↓5.5%). Conclusions Consuming the balanced high fat diet led to significant reduction in cardiovascular risk factors in both groups. However, the pattern of response to BHFD differed with EA women responding more in components of the apolipoprotein B pathway versus AA women responding more in components of the apolipoprotein AI pathway.

The sliding set-point: how insulin and diet interact to explain the obesity epidemic (and how to fix it).

Abstract: Purpose of reviewThe current approach to weight loss (intentional energy deficit) is difficult to implement and sustain, and rarely leads to successful long-term weight loss maintenance. The aim of this article is to review recent literature on the role of insulin in obesity propensity, and by exten