Adaptive thermogenesis, at the level of resting energy expenditure, after diet alone or diet plus bariatric surgery.

OBJECTIVE: The objective of this study was to compare the magnitude of adaptive thermogenesis (AT), at the level of resting energy expenditure (REE), after a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy, as well as to investigate the association between AT and changes in appetite. METHODS: A total of 44 participants with severe obesity underwent 10 weeks of a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy. Body weight and composition, REE, subjective appetite feelings, and plasma concentrations of gastrointestinal hormones were measured at baseline and week 11. AT, at the level of REE, was defined as a significantly lower measured versus predicted (using a regression model with baseline data) REE. RESULTS: Participants lost 18.4 ± 3.9 kg of body weight and experienced AT, at the level of REE (-121 ± 188 kcal/day; p < 0.001), with no differences among groups. The larger the AT, at the level of REE, the greater the reduction in fasting ghrelin concentrations and the smaller the reduction in feelings of hunger and desire to eat in the postprandial state. CONCLUSIONS: Weight-loss modality does not seem to modulate the magnitude of AT, at the level of REE. The greater the AT, at the level of REE, the greater the drive to eat following weight loss.

Interaction effect of systemic inflammation and modifiable rheumatoid cachexia risk factors on resting energy expenditure in patients with rheumatoid arthritis.

Background: In rheumatoid cachexia (RC), high resting energy expenditure (REE) is associated with loss of muscle mass driven by proinflammatory cytokines. The objectives of this study were to investigate parameters associated with RC, and the interaction between systemic inflammation and modifiable risk factors for RC on REE. Methods: Thirty-five rheumatoid arthritis (RA) and nineteen non-RA controls comparable in age, sex, race and BMI underwent measures of REE by indirect calorimetry. Clinical, dietary, body composition and physical function data were collected. Homeostasis model assessment for insulin resistance (HOMA-IR) and serum interleukin-6 (IL-6) were used as parameters of IR and systemic inflammation, respectively. Regression models tested association between REE and dependent variables, including pre-specified interaction tests involving HOMA-IR and IL-6 and dietary intake of protein per weight (PPW) and IL-6. Results: RA subjects were mostly women (94%) and had a median age of 54 years (50.5, 70) and BMI of 30.5 kg/m2 (26.1, 36.9). We observed a significant interaction effect between PPW and serum IL-6 on REE among RA subjects in the multiple regression model among RA. The upper tertile of PPW demonstrated a significant negative correlation between REE and IL-6 (ß=-19.97, 95% CI [-35.41, -4.54], p=0.01). The lower tertile of PPW demonstrated a significant positive correlation between REE and IL-6 (ß=42.24, 95% CI [4.25, 80.23], p=0.03). Conclusions: While IR can lead to muscle catabolism, IR was not significantly associated with REE in RA individuals. Higher dietary protein intake could attenuate the effect of systemic inflammation on REE in RA patients.

Changes in Ghrelin and Glucagon following a Low Glycemic Load Diet in Women with PCOS.

CONTEXT: Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin. OBJECTIVE: To test the hypothesis that following a 4-week, eucaloric low vs high GL diet habituation, a low vs high GL meal will increase glucagon and decrease ghrelin to reflect greater satiety and improve self-reported fullness. METHODS: Secondary analysis of a randomized crossover trial. PARTICIPANTS: Thirty women diagnosed with PCOS. INTERVENTION: Participants were provided low (41:19:40% energy from carbohydrate:protein:fat) and high (55:18:27) GL diets for 8 weeks each. At each diet midpoint, a solid meal test was administered to examine postprandial ghrelin, glucagon, glucose, insulin, and self-reported appetite scores. RESULTS: After 4 weeks, fasting glucagon was greater with the low vs high GL diet (P = .035), and higher fasting glucagon was associated with lesser feelings of hunger (P = .009). Significant diet effects indicate 4-hour glucagon was higher (P < .001) and ghrelin was lower (P = .009) after the low vs high GL meal. A trending time × diet interaction (P = .077) indicates feelings of fullness were greater in the early postprandial phase after the high GL meal, but no differences were observed the late postprandial phase. CONCLUSION: These findings suggest after low GL diet habituation, a low GL meal reduces ghrelin and increases glucagon in women with PCOS. Further research is needed to determine the influence of diet composition on ad libitum intake in women with PCOS.

A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: A Randomized, Controlled Trial.

Ketogenic diets (KDs) are emerging as effective therapies for several chronic diseases, including cancer. However, concerns regarding safety and adherence may prevent clinicians from prescribing KDs. We hypothesized that a KD does not negatively affect blood lipid profile compared to a lower-fat diet in ovarian and endometrial cancer patients, and that KD subjects would demonstrate acceptable adherence. Subjects were randomized to either a KD (70% fat, 25% protein, 5% carbohydrate), or the American Cancer Society diet (ACS; high-fiber and lower-fat). Blood lipids and ketones were measured at baseline and after 12 weeks of the assigned intervention. Adherence measures included urinary ketones in the KD and 4 days' diet records. Diet records were also examined to identify general patterns of consumption. Differences between the diets on blood lipids and dietary intake were assessed with Analysis of covariance and independent t-tests. Correlation analyses were used to estimate associations between dietary intake and serum analytes. At 12 weeks, there were no significant differences between diet groups in blood lipids, after adjusting for baseline values and weight loss. Adherence among KD subjects ranged from 57% to 80%. These findings suggest that KDs may be a safe and achievable component of treatment for some cancer patients.

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.

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.

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

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 ß-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 ß-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 ß-hydroxybutyrate may reflect a metabolic environment inhospitable to cancer proliferation. This trial was registered at www.clinicaltrials.gov as NCT03171506.

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.

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.

Effects of acute hyperinsulinemia on skeletal muscle mitochondrial function, reactive oxygen species production, and metabolism in premenopausal women.

BACKGROUND: Acute metabolic demands that promote excessive and/or prolonged reactive oxygen species production may stimulate changes in mitochondrial oxidative capacity. PURPOSE: To assess changes in skeletal muscle H2O2 production, mitochondrial function, and expression of genes at the mRNA and protein levels regulating energy metabolism and mitochondrial dynamics following a hyperinsulinemic-euglycemic clamp in a cohort of 11 healthy premenopausal women. METHODS: Skeletal muscle biopsies of the vastus lateralis were taken at baseline and immediately following the conclusion of a hyperinsulinemic-euglycemic clamp. Mitochondrial production of H2O2 was quantified fluorometrically and mitochondrial oxidation supported by pyruvate, malate, and succinate (PMS) or palmitoyl carnitine and malate (PCM) was measured by high-resolution respirometry in permeabilized muscle fiber bundles. mRNA and protein levels were assessed by real time PCR and Western blotting. RESULTS: H2O2 emission increased following the clamp (P<0.05). Coupled respiration (State 3) supported by PMS and the respiratory control ratio (index of mitochondrial coupling) for both PMS and PCM were lower following the clamp (P<0.05). IRS1 mRNA decreased, whereas PGC1α and GLUT4 mRNA increased following the clamp (P≤0.05). PGC1α, IRS1, and phosphorylated AKT protein levels were higher after the clamp compared to baseline (P<0.05). CONCLUSIONS: This study demonstrated that acute hyperinsulinemia induced H2O2 production and a concurrent decrease in coupling of mitochondrial respiration with ATP production in a cohort of healthy premenopausal women. Future studies should determine if this uncoupling ameliorates peripheral oxidative damage, and if this mechanism is impaired in diseases associated with chronic oxidative stress.

The impact of the Standard American Diet in rats: Effects on behavior, physiology and recovery from inflammatory injury.

BACKGROUND AND AIMS: Obesity is a significant health concern in the Western world and the presence of comorbid conditions suggests an interaction. The overlapping distributions of chronic pain populations and obesity suggests that an interaction may exist. Poor quality diet (high carbohydrates, saturated fats, omega-6 polyunsaturated fatty acids) can lead to increased adiposity which can activate immune cells independent of the activating effect of the diet components themselves. This dual action can contribute to chronic inflammation that may alter susceptibility to chronic pain and prolong recovery from injury. However, traditional examinations of diet focus on high-fat diets that often contain a single source of fat, that is not reflective of an American diet. Thus, we examined the impact of a novel human-relevant (high-carbohydrate) American diet on measures of pain and inflammation in rats, as well as the effect on recovery and immune cell activation. METHODS: We developed a novel, human-relevant Standard American Diet (SAD) to better model the kilocalorie levels and nutrient sources in an American population. Male and female rats were fed the SAD over the course of 20 weeks prior to persistent inflammatory pain induction with Complete Freund's Adjuvant (CFA). Mechanical and thermal sensitivity were measured weekly. Spontaneous pain, open field locomotion and blood glucose levels were measured during diet consumption. Body composition was assessed at 20 weeks. Following full recovery from CFA-induced hypersensitivity, blood was analyzed for inflammatory mediators and spinal cords were immunohistochemically processed for microglial markers. RESULTS: Chronic consumption of the SAD increased fat mass, decreased lean mass and reduce bone mineral density. SAD-fed rats had increased leptin levels and pro-inflammatory cytokines in peripheral blood serum. Following CFA administration, mechanical sensitivity was assessed and recovery was delayed significantly in SAD-fed animals. Sex differences in the impact of the SAD were also observed. The SAD increased body weight and common T-cell related inflammatory mediators in female, but not male, animals. In males, the SAD had a greater effect on bone mineral density and body composition. Long-term consumption of the SAD resulted in elevated microglial staining in the dorsal horn of the spinal cord, but no sex differences were observed. CONCLUSIONS: We demonstrate the negative effects of an American diet on physiology, behavior and recovery from injury. SAD consumption elevated pro-inflammatory mediators and increased microglial activation in the spinal cord. While there were sex differences in weight gain and inflammation, both sexes showed prolonged recovery from injury. IMPLICATIONS: These data suggest that poor quality diet may increase susceptibility to chronic pain due to persistent peripheral and central immune system activation. Furthermore, consumption of a diet that is high in carbohydrates and omega-6 polyunsaturated fatty acid is likely to lead to protracted recovery following trauma or surgical procedures. These data suggest that recovery of a number of patients eating a poor quality diet may be expedited with a change in diet to one that is healthier.

Childhood Maltreatment Is an Independent Risk Factor for Prediabetic Disturbances in Glucose Regulation.

AIMS: Childhood maltreatment (CM) is shown to be associated with obesity and depression. However, the relationship of CM to prediabetic state is much less studied. We tested the hypothesis that CM increases the risk for prediabetic state due to glucose intolerance, reduced insulin sensitivity, and beta cell function. METHODS: Oral glucose tolerance test (OGTT)-derived metabolic parameters of glucose tolerance, insulin sensitivity, and beta cell function were measured in 121 participants aged 19-60 years. CM exposure was measured using the Childhood Trauma Questionnaire. Blood samples were collected to measure the inflammatory factors. RESULTS: After controlling for age, race, gender, education, and depression, about 15% higher glucose area under the OGTT curve was observed in the CM group. CM individuals also exhibited impaired insulin sensitivity manifested by the Matsuda index and homeostasis model assessment of insulin resistance, which were correlated with CM severity after adjusting for depression. CM group showed approximately 50% lower disposition index. C-reactive protein and tumor necrosis factor-α levels were greater in the CM group vs. the non-CM group, and both were correlated with CM severity (r = 0.21, 0.23, respectively, both p < 0.05). Multiple regression analyses revealed that CM contributed to reduced insulin sensitivity and lower disposition index independent of depression and visceral fat mass. CONCLUSION: These data suggest an important relationship between CM and increased risk for prediabetic state due to glucose intolerance, impaired insulin sensitivity, and beta cell function. Our findings indicate that CM appears to be an independent risk factor for developing prediabetes.

Peri-muscular adipose tissue may play a unique role in determining insulin sensitivity/resistance in women with polycystic ovary syndrome.

STUDY QUESTION: Do the determinants of insulin sensitivity/resistance differ in women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Peri-muscular thigh adipose tissue is uniquely associated with insulin sensitivity/resistance in women with PCOS, whereas adiponectin and thigh subcutaneous adipose are the main correlates of insulin sensitivity/resistance in women without PCOS. WHAT IS KNOWN ALREADY: In subject populations without PCOS, insulin sensitivity/resistance is determined by body fat distribution and circulating concentrations of hormones and pro-inflammatory mediators. Specifically, visceral (intra-abdominal) adipose tissue mass is adversely associated with insulin sensitivity, whereas thigh subcutaneous adipose appears protective against metabolic disease. Adiponectin is an insulin-sensitizing hormone produced by healthy subcutaneous adipose that may mediate the protective effect of thigh subcutaneous adipose. Testosterone, which is elevated in PCOS, may have an adverse effect on insulin sensitivity/resistance. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 30 women with PCOS and 38 women without PCOS; data were collected between 2007 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were group-matched for obesity, as reflected in BMI (Mean ± SD; PCOS: 31.8 ± 6.0 kg/m2; without PCOS: 31.5 ± 5.0 kg/m2). The whole-body insulin sensitivity index (WBISI) was assessed using a mixed-meal tolerance test; Homeostasis Model Assessment-Insulin resistance (HOMA-IR) was determined from fasting insulin and glucose values. Adipose tissue distribution was determined by computed tomography (CT) scan. Partial correlation analysis, adjusting for total fat mass, was used to identify correlates of WBISI and HOMA-IR within each group of women from measures of body composition, body fat distribution, reproductive-endocrine hormones and adipokines/cytokines. Stepwise multiple linear regression analysis was used to identify the variables that best predicted WBISI and HOMA-IR. MAIN RESULTS AND THE ROLE OF CHANCE: Among women with PCOS, both WBISI and HOMA-IR were best predicted by peri-muscular adipose tissue cross-sectional area. Among women without PCOS, both WBISI and HOMA-IR were best predicted by adiponectin and thigh subcutaneous adipose tissue. LIMITATIONS, REASONS FOR CAUTION: Small sample size, group matching for BMI and age, and the use of surrogate measures of insulin sensitivity/resistance. WIDER IMPLICATIONS OF THE FINDINGS: Because insulin resistance is the root cause of obesity and comorbidities in PCOS, determining its cause could lead to potential therapies. Present results suggest that peri-muscular adipose tissue may play a unique role in determining insulin sensitivity/resistance in women with PCOS. Interventions such as restriction of dietary carbohydrates that have been shown to selectively reduce fatty infiltration of skeletal muscle may decrease the risk for type 2 diabetes in women with PCOS. STUDY FUNDING/COMPETING INTERESTS: The study was supported by National Institutes of Health grants R01HD054960, R01DK67538, P30DK56336, P60DK079626, M014RR00032 and UL1RR025777. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT00726908.

A lower-carbohydrate, higher-fat diet reduces abdominal and intermuscular fat and increases insulin sensitivity in adults at risk of type 2 diabetes.

BACKGROUND: Obesity, particularly visceral and ectopic adiposity, increases the risk of type 2 diabetes. OBJECTIVE: The aim of this study was to determine if restriction of dietary carbohydrate is beneficial for body composition and metabolic health. METHODS: Two studies were conducted. In the first, 69 overweight/obese men and women, 53% of whom were European American (EA) and 47% of whom were African American (AA), were provided with 1 of 2 diets (lower-fat diet: 55%, 18%, and 27% of energy from carbohydrate, protein, and fat, respectively; lower-carbohydrate diet: 43%, 18%, and 39%, respectively) for 8 wk at a eucaloric level and 8 wk at a hypocaloric level. In the second study, 30 women with polycystic ovary syndrome (PCOS) were provided with 2 diets (lower-fat diet: 55%, 18%, and 27% of energy from carbohydrate, protein, and fat, respectively; lower-carbohydrate diet: 41%, 19%, and 40%, respectively) at a eucaloric level for 8 wk in a random-order crossover design. RESULTS: As previously reported, among overweight/obese adults, after the eucaloric phase, participants who consumed the lower-carbohydrate vs. the lower-fat diet lost more intra-abdominal adipose tissue (IAAT) (11 ± 3% vs. 1 ± 3%; P < 0.05). After weight loss, participants who consumed the lower-carbohydrate diet had 4.4% less total fat mass. Original to this report, across the entire 16-wk study, AAs lost more fat mass with a lower-carbohydrate diet (6.2 vs. 2.9 kg; P < 0.01), whereas EAs showed no difference between diets. As previously reported, among women with PCOS, the lower-carbohydrate arm showed decreased fasting insulin (-2.8 µIU/mL; P < 0.001) and fasting glucose (-4.7 mg/dL; P < 0.01) and increased insulin sensitivity (1.06 arbitrary units; P < 0.05) and "dynamic" ß-cell response (96.1 · 10(9); P < 0.001). In the lower-carbohydrate arm, women lost both IAAT (-4.8 cm(2); P < 0.01) and intermuscular fat (-1.2 cm(2); P < 0.01). In the lower-fat arm, women lost lean mass (-0.6 kg; P < 0.05). Original to this report, after the lower-carbohydrate arm, the change in IAAT was positively associated with the change in tumor necrosis factor α (P < 0.05). CONCLUSION: A modest reduction in dietary carbohydrate has beneficial effects on body composition, fat distribution, and glucose metabolism. This trial was registered at clinicaltrials.gov as NCT00726908 and NCT01028989.

Effects of a eucaloric reduced-carbohydrate diet on body composition and fat distribution in women with PCOS.

OBJECTIVE: To determine if consumption of a reduced-carbohydrate (CHO) diet would result in preferential loss of adipose tissue under eucaloric conditions, and whether changes in adiposity were associated with changes in postprandial insulin concentration. METHODS: In a crossover-diet intervention, 30 women with PCOS consumed a reduced-CHO diet (41:19:40% energy from CHO:protein:fat) for 8 weeks and a standard diet (55:18:27) for 8 weeks. Body composition by DXA and fat distribution by CT were assessed at baseline and following each diet phase. Insulin AUC was obtained from a solid meal test (SMT) during each diet phase. RESULTS: Participants lost 3.7% and 2.2% total fat following the reduced-CHO diet and STD diet, resp. (p<0.05 for difference between diets). The reduced-CHO diet induced a decrease in subcutaneous-abdominal, intra-abdominal, and thigh-intermuscular adipose tissue (-7.1%, -4.6%, and -11.5%, resp.), and the STD diet induced a decrease in total lean mass. Loss of fat mass following the reduced CHO diet arm was associated with lower insulin AUC (p<0.05) during the SMT. CONCLUSIONS: In women with PCOS, consumption of a diet lower in CHO resulted in preferential loss of fat mass from metabolically harmful adipose depots, whereas a diet high in CHO appeared to promote repartitioning of lean mass to fat mass.

Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS.

OBJECTIVE: Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects ß-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. DESIGN: In a crossover design, two diets ('Standard,' STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. PATIENTS: Thirty women with PCOS. MEASUREMENTS: ß-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. RESULTS: Paired t-test indicated that the lower-CHO diet induced significant decreases in basal ß-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic ('first-phase') ß-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol-to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). CONCLUSIONS: In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone.

Favorite foods of older adults living in the Black Belt Region of the United States. Influences of ethnicity, gender, and education.

The purpose of this study was to examine food preferences of older adults living in the Black Belt Region of the Southeastern United States and the extent to which food preferences vary according to ethnicity, gender, and educational level. 270 older adults who were receiving home health services were interviewed in their home and were queried regarding their favorite foods. Descriptive statistics were used to characterize the sample. Chi-square analysis or one-way analyses of variance was used, where appropriate, in bivariate analyses, and logistic regression models were used in multivariate analyses. A total of 1,857 favorite foods were reported (mean per person=6.88). The top ten favorite foods reported included: (1) chicken (of any kind), (2) collard greens, (3) cornbread, (4) green or string beans, (5) fish (fried catfish is implied), (6) turnip greens, (7) potatoes, (8) apples, (9) tomatoes, fried chicken, and eggs tied, and (10) steak and ice cream tied. African Americans and those with lower levels of education were more likely to report traditional Southern foods among their favorite foods and had a more limited repertoire of favorite foods. Findings have implications for understanding health disparities that may be associated with diet and development of culturally-appropriate nutrition interventions.

Intra-abdominal adipose tissue is independently associated with sex-hormone binding globulin in premenopausal women.

Lower serum concentrations of sex-hormone binding globulin (SHBG) are associated with increased risk for several obesity-related diseases in women including hormone-sensitive cancers, type 2 diabetes, metabolic syndrome, and cardiovascular disease. Previous investigations have reported that body composition, specifically central obesity, and/or higher insulin concentrations are key factors associated with lower SHBG in overweight and obese women; however, these studies were limited by their cross-sectional design. We hypothesized that intra-abdominal adipose tissue (IAAT), a fat depot linked with an abnormal metabolic profile, is inversely and independently associated with SHBG. Therefore, we determined the longitudinal associations among SHBG, insulin, and IAAT in 107 premenopausal women enrolled in a weight loss study. Overweight (BMI 27-30 kg/m(2)) women were weight reduced until BMI of ≤ 24 was achieved. Body composition and IAAT were measured at baseline and after weight loss with dual-energy X-ray absorptiometry and computed tomography, respectively. Serum concentrations of insulin and SHBG were determined. Paired t-test showed that insulin and IAAT decreased significantly and SHBG increased significantly following weight loss (P < 0.0001 for all). Simple correlations from baseline showed no association with insulin and SHBG (r = -0.142, P = 0.143) and a significant inverse association between IAAT and SHBG (r = -0.43, P < 0.0001). Repeated measures mixed-model showed that after adjusting for age and time (weight loss), IAAT was significantly inversely associated with SHBG (P = 0.0002) and there was no association with insulin and SHBG (P = 0.180). We conclude that SHBG concentrations are influenced by IAAT and not insulin in premenopausal women.

Markers of inflammation and fat distribution following weight loss in African-American and white women.

Changes in markers of inflammation (MOI) and fat distribution with weight loss between African-American (AA) and white (W) women have yet to be characterized. The purpose of this study was to examine potential ethnic differences in MOI and regional fat distribution with weight loss, and identify the associations between these markers and changes in regional fat distribution with weight loss among AA and W women. Subjects were 126 healthy, premenopausal women, BMI 27-30 kg/m(2). They were placed on a weight-loss intervention consisting of diet and/or exercise until a BMI <25 was achieved. Fat distribution was measured with computed tomography, and body composition with dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor-α (TNF-α), soluble TNF receptor-I (sTNFR-I), sTNFR-II, C-reactive protein (CRP), and interleukin-6 (IL-6) were assessed. All MOI and adiposity measures significantly decreased with weight loss. Significant ethnic differences with weight loss were observed for fat mass, body fat, intra-abdominal adipose tissue (IAAT), sTNFR-I, and sTNFR-II. Mixed-model analysis indicated that adjusting for change in IAAT explained ethnic differences in change in TNF-α and the decrease in TNF-α with weight loss, while total fat mass only explained the decrease in sTNFR-I and sTNFR-II with weight loss. In conclusion, all MOI decreased following weight loss among W, whereas only IL-6 and CRP decreased following weight loss in AA. The most distinct phenotypic difference observed was a greater impact of weight loss on TNF-α in W compared to AA, which was directly associated with IAAT in W.

Longitudinal associations of the endocrine environment on fat partitioning in postmenopausal women.

Among postmenopausal women, declining estrogen may facilitate fat partitioning from the periphery to the intra-abdominal space. Furthermore, it has been suggested that excess androgens contribute to a central fat distribution pattern in women. The objective of this longitudinal study was to identify independent associations of the hormone milieu with fat distribution in postmenopausal women. Fifty-three healthy postmenopausal women, either using or not using hormone replacement therapy (HRT) were evaluated at baseline and 2 years. The main outcomes were intra-abdominal adipose tissue (IAAT), subcutaneous abdominal adipose tissue, and total thigh fat analyzed by computed tomography scanning and leg fat and total body fat mass measured by dual-energy X-ray absorptiometry. Serum estradiol, estrone, estrone sulfate, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate), sex hormone-binding globulin (SHBG), and cortisol were assessed. On average, in all women combined, IAAT increased by 10% (10.5 cm(2)) over 2 years (P < 0.05). Among HRT users, estradiol was inversely associated with, and estrone was positively associated with, 2-year gain in IAAT. Among HRT nonusers, free testosterone was inversely associated with, and SHBG was positively associated with, 2-year gain in IAAT. These results suggest that in postmenopausal women using HRT, greater circulating estradiol may play an integral role in limiting lipid deposition to the intra-abdominal cavity, a depot associated with metabolically detrimental attributes. However, a high proportion of weak estrogens may promote fat partitioning to the intra-abdominal cavity over time. Furthermore, among postmenopausal women not using HRT, greater circulating free testosterone may limit IAAT accrual.

Reduced mitogenicity of sera following weight loss in premenopausal women.

We investigated whether serum from normal weight women is less mitogenic and more apoptotic than sera from the same women in the overweight state. Sera from premenopausal women, age (mean ± SEE) 34.6 ± 0.53 years, who were randomized to caloric restriction (CR) (n = 13), CR + aerobic exercise (AE) (n = 14), or CR + resistance training (RT) (n = 20) were used to culture endometrial cancer cells. Phases of the cell cycle were determined, and proliferating cell nuclear antigen (PCNA) positivity was used to assess proliferation and apoptosis was assessed by determining cleaved caspase-3 and poly-ADP-ribose polymerase (PARP). Analyses showed that overall, cells grown in sera from the weight-reduced state had significantly more cells in G0/G1 and significantly fewer cells in the S and G2/M phases of the cell cycle than cells grown in sera from the overweight state. PCNA staining confirmed that cells grown in sera from the weight-reduced state had fewer proliferating cells. Cleaved caspase-3 and PARP were not different in cells grown in sera from the weight-reduced state compared to the overweight state. We conclude that weight loss with or without exercise could lower the risk for cancer through changes in serum that result in reduced cellular mitogenicity.

Relationship of intramyocellular lipid to insulin sensitivity may differ with ethnicity in healthy girls and women.

The prevalence of type 2 diabetes is greater among African Americans (AA) vs. European Americans (EA), independent of obesity and lifestyle. We tested the hypothesis that intramyocellular lipid (IMCL) or extramycellular lipid (EMCL) would be associated with insulin sensitivity among healthy young women, and that the associations would differ with ethnic background. We also explored the hypothesis that adipokines and estradiol would be associated with muscle lipid content. Participants were 57 healthy, normoglycemic, women and girls mean age 26 (±10) years; mean BMI 27.3 (±4.8) kg/m²; 32 AA, 25 EA. Soleus IMCL and EMCL were assessed with ¹H magnetic resonance spectroscopy (MRS); insulin sensitivity with an insulin-modified frequently sampled intravenous glucose tolerance test and minimal modeling; body composition with dual-energy X-ray absorptiometry; and intra-abdominal adipose tissue (IAAT) with computed tomography. Adiponectin, leptin, and estradiol were assessed in fasting sera. Analyses indicated that EMCL, but not IMCL, was greater in AA vs. EA (2.55 ± 0.16 vs. 1.98 ± 0.18 arbitrary units, respectively, P < 0.05; adjusted for total body fat). IMCL was associated with insulin sensitivity in EA (r = -0.54, P < 0.05, adjusted for total fat, IAAT, and age), but not AA (r = 0.16, P = 0.424). IMCL was inversely associated with adiponectin (r = -0.31, P < 0.05, adjusted for ethnicity, age, total fat, and IAAT). In conclusion, IMCL was a significant determinant of insulin sensitivity among healthy, young, EA but not AA women. Further research is needed to determine whether the component lipids of IMCL (e.g., diacylglycerol (DAG) or ceramide) are associated with insulin sensitivity in an ethnicity specific manner.