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1.  Differences in the Association between Serum Leptin Levels and Body Mass Index in Black and White Women: A Report from the Southern Community Cohort Study 
Background/Aims
Leptin may be an important link between obesity and many high-burden diseases, including cancer and cardiovascular disease, but leptin levels and correlates in individuals of diverse racial backgrounds have not been well characterized despite racial differences in incidence and mortality patterns for many obesity-related diseases.
Methods
In a cross-sectional study of 915 white and 892 black women enrolled in the Southern Community Cohort Study (age 40–79 years, half postmenopausal), serum leptin levels were compared between the race groups and across categories of body mass index (BMI). Potential correlates of leptin were assessed via race-stratified linear regression models.
Results
Blacks had higher unadjusted leptin levels than whites (geometric mean 22.4 vs. 19.0 ng/ml; p < 0.0001). Leptin increased with increasing BMI, and racial differences in leptin were most pronounced in women with BMI ≥25. Significant correlates of leptin included BMI, age, alcohol consumption, cigarette smoking, diabetes (both races) and fat consumption (black women only). Leptin remained higher in black women (22.7 vs. 18.8 ng/ml) after adjustment for these factors.
Conclusions
Persistent racial differences in leptin concentrations exist after adjustment for BMI and other factors. Leptin assessment may be informative in future studies that investigate racial differences in the development of obesity-related diseases.
doi:10.1159/000336180
PMCID: PMC3710998  PMID: 22353927
Leptin; Body mass index; Race; Adipokines
2.  Complementary Foods and Flavor Experiences: Setting the Foundation 
Annals of Nutrition & Metabolism  2012;60(Suppl 2):40-50.
Increased fruit and vegetable consumption early in life may lead to life-long intake of fruits and vegetables, which in turn may be beneficial for weight control and other health outcomes in later life. Although health officials worldwide recommend delaying solid foods until 6 months of age, younger infants often receive solid food, which may affect later obesity rates. The timing of introduction to solid foods is important both nutritionally and developmentally and may affect acceptance of foods both in infancy and later in life. Infants can clearly discriminate the flavors of different fruits and vegetables. Repeated flavor experiences promote the willingness to eat a variety of foods: infants will consume more of foods that have a familiar flavor and are more accepting of novel flavors if they have experience with flavor variety. Many flavors that the mother either ingests or inhales are transmitted to her milk and/or amniotic fluid. Mothers can help the transition from a diet exclusively of milk or formula to a mixed diet by providing the infant familiar flavors in both milk or formula and solid foods. Exposure to a variety of flavors during and between meals appears to facilitate acceptance of novel foods. Providing novelty in the context of a familiar food might prove to be an optimal combination to progressively accustom infants to a diversity of novel foods. When repeatedly exposing infants to flavors of some vegetables that have bitter tastes, mothers should focus not on infants' facial expressions but on their willingness to eat the food and should continue to provide repeated opportunities to taste the food. Introducing children repeatedly to individual as well as a variety of fruits and vegetables, both within and between meals, might help them be more accepting of fruits and vegetables, which is difficult to enhance beyond toddlerhood.
doi:10.1159/000335337
PMCID: PMC3363345  PMID: 22555188
Breastfeeding; Complementary feeding; First-food acceptance; Flavor variety; Health outcomes; Infant nutrition; Taste
3.  Determinants of Vitamin D Status among Overweight and Obese Puerto Rican Adults 
Background/Aims
Low vitamin D status is highly prevalent worldwide, and the major determinants are sun exposure and vitamin D intake. We aimed to measure vitamin D status in a sample of overweight/obese adults in Puerto Rico, an area with plenty of sun exposure, and relate it to vitamin D intake, sun exposure and body composition.
Methods
Serum 25(OH)D levels (liquid chromatography-tandem mass spectrometry), body weight and fat (bioimpedance), vitamin D intake and sun exposure (questionnaires) were assessed. Analysis included age-adjusted correlations and multivariate regression.
Results
In 98 subjects (66% females; 40–65 years), median serum 25(OH)D levels were 30.7 ng/ml (25–75th percentile 25.0–37.3); 55% had levels >30 ng/ml, 31% had levels between 20 and 30 ng/ml and 14% had levels <20 ng/ml. Total vitamin D intake was 180 IU/day (45–615), and the sun exposure score was 22 (17–27). After adjusting for gender, 25(OH)D levels were significantly correlated with vitamin D intake (r = 0.24, p = 0.018), the sum of sun exposure and vitamin D intake indices (r = 0.34, p = 0.001) and percent body fat (r = −0.25, p = 0.01). After adjusting for age, gender and percent body fat, the sum of sun exposure and vitamin D intake indices remained statistically associated with 25(OH)D levels (β = 1.5, p < 0.01).
Conclusions
In this group of overweight and obese individuals, 25(OH)D was significantly related to vitamin D intake, sun exposure and vitamin D intake indices and percent body fat.
doi:10.1159/000335282
PMCID: PMC3567879  PMID: 22222318
Vitamin D status; Overweight; Obesity; Puerto Ricans; Hispanics
4.  Metabolic Programming in the Immediate Postnatal Life 
Annals of Nutrition & Metabolism  2011;58(Suppl 2):18-28.
The metabolic programming effects of nutritional modifications in the immediate postnatal life are increasingly recognized to independently contribute to the development of metabolic syndrome in later life. Adjustment of litter size in rodents has been used to induce either under- or overnourishment in the immediate postnatal life of the offspring. While undernourishment led to growth retardation in the offspring, overnourishment produced increased body weight gains, hyperinsulinemia and hyperleptinemia. Overnourishment during the suckling period induced several adaptations in the energy circuitry in the hypothalamus of the offspring predisposing them for the onset of obesity later in life. Another approach for a nutritional modification in the immediate postnatal period is the artificial rearing of newborn rat pups on a high-carbohydrate (HC) milk formula without changes in the total calorie availability. Hyperinsulinemia, immediately evident in the HC pups, persisted in the post-weaning period even after withdrawal of the HC milk. Significant alterations in pancreatic islets supported chronic hyperinsulinemia in the HC rats. Alterations in the gene expression of hypothalamic neuropeptides predisposing to hyperphagia were evident during the period of the HC dietary modification. The persistence of these hypothalamic adaptations supported the obese phenotype in adult HC rats. A transgenerational effect gave rise to the development of chronic hyperinsulinemia and adult-onset obesity in the offspring of the HC female rats. Other studies have shown that lactation by a diabetic, obese or malnourished mother resulted in predisposition for the onset of metabolic disorders in the offspring. These observations from animal studies on the metabolic programming effects due to altered nutritional experiences in the immediate postnatal life strongly suggest that altered feeding practices for infants (formula feeding and early introduction of infant foods) could contribute to the rising incidence of overweight/obesity in children and adults.
doi:10.1159/000328040
PMCID: PMC3190171  PMID: 21846978
Hyperinsulinemia; Hyperphagia; Hypothalamic energy homeostasis; Increased carbohydrate intake; Nutritional experiences; Obesity; Overnourishment; Suckling period
5.  Effect of Consumption of Dried California Mission Figs on Lipid Concentrations 
Annals of Nutrition & Metabolism  2011;58(3):232-238.
Background
Figs are a rich source of soluble fiber. We evaluated the effect of consuming dried California Mission figs on serum lipids in hyperlipidemic adults.
Methods
In a crossover trial men and women aged 30–75 years with elevated low-density lipoprotein cholesterol (100–189 mg/dl) were randomized to add dried California Mission figs (120 g/day) to their usual diet for 5 weeks or eat their usual diet for 5 weeks, then crossed over to the other condition for another 5 weeks. Six 24-hour dietary recalls were obtained.
Results
Low- and high-density lipoprotein cholesterol and triglyceride concentrations did not differ between usual and figs-added diets (Bonferroni-corrected p > 0.017), while total cholesterol tended to increase with fig consumption (p = 0.02). Total cholesterol increased in participants (n = 41) randomized to usual followed by figs-added diet (p = 0.01), but remained unchanged in subjects (n = 42) who started with figs-added followed by usual diet (p = 0.4). During the figs-added diet, soluble fiber intake was 12.6 ± 3.7 versus 8.2 ± 4.1 g/day in the usual diet (p < 0.0001). Sugar intake increased from 23.4 ± 6.5 to 32.2 ± 6.3% of kcal in the figs-added diet (p < 0.0001). Body weight did not change (p = 0.08).
Conclusions
Daily consumption of figs did not reduce low-density lipoprotein cholesterol. Triglyceride concentrations were not significantly changed despite an increase in sugar intake.
doi:10.1159/000330112
PMCID: PMC3169356  PMID: 21811062
Figs; Dietary fiber; Hypercholesterolemia; Dietary intake; Lipids
6.  Passive Smoke Exposure and Circulating Carotenoids in the CARDIA Study 
Annals of Nutrition & Metabolism  2010;56(2):113-118.
Background/Aims
Our objective was to assess associations between passive smoke exposure in various venues and serum carotenoid concentrations.
Methods
CARDIA is an ongoing longitudinal study of the risk factors for subclinical and clinical cardiovascular disease. At baseline in 1985/1986, serum carotenoids were assayed and passive smoke exposure inside and outside of the home and diet were assessed by self-report. Our analytic sample consisted of 2,633 black and white non-smoking adults aged 18–30 years.
Results
Greater total passive smoke exposure was associated with lower levels of the sum of the three provitamin A carotenoids, α-carotene, β-carotene, and β-cryptoxanthin (–0.048 nmol/l per hour of passive smoke exposure, p = 0.001), unassociated with lutein/zeaxanthin, and associated with higher levels of lycopene (0.027 nmol/l per hour of passive smoke exposure, p = 0.010) after adjustment for demographics, diet, lipid profile, and supplement use. Exposure in both home and non-home spaces was also associated with lower levels of the provitamin A carotenoid index.
Conclusion
Cross-sectionally, in 1985/86, passive smoke exposure in various venues was associated with reduced levels of provitamin A serum carotenoids.
doi:10.1159/000277662
PMCID: PMC2842165  PMID: 20110671
Carotenoids; Micronutrients; Occupational health; Passive smoking; Smoke exposure; Tobacco smoke pollution
7.  Higher Fish Consumption in Pregnancy May Confer Protection against the Harmful Effect of Prenatal Exposure to Fine Particulate Matter 
Annals of Nutrition & Metabolism  2010;56(2):119-126.
Background/Aim
The objective of this study was to assess a hypothesized beneficial effect of fish consumption during the last trimester of pregnancy on adverse birth outcomes resulting from prenatal exposure to fine air particulate matter.
Methods
The cohort consisted of 481 nonsmoking women with singleton pregnancies, of 18–35 years of age, who gave birth at term. All recruited women were asked about their usual diet over the period of pregnancy. Measurements of particulate matter less than 2.5 μm in size (PM2.5) were carried out by personal air monitoring over 48 h during the second trimester of pregnancy. The effect of PM2.5 and fish intake during gestation on the birth weight of the babies was estimated from multivariable linear regression models, which beside the main independent variables considered a set of potential confounding factors such as the size of the mother (height, prepregnancy weight), maternal education, parity, the gender of the child, gestational age and the season of birth.
Results
The study showed that the adjusted birth weight was significantly lower in newborns whose mothers were exposed to particulate matter greater than 46.3 μg/m3 (β coefficient = −97.02, p = 0.032). Regression analysis stratified by the level of maternal fish consumption (in tertiles) showed that the deficit in birth weight amounted to 133.26 g (p = 0.052) in newborns whose mothers reported low fish intake (<91 g/week). The birth weight deficit in newborns whose mothers reported medium (91–205 g/week) or higher fish intake (>205 g/week) was insignificant. The interaction term between PM2.5 and fish intake levels was also insignificant (β = −107,35, p = 0.215). Neither gestational age nor birth weight correlated with maternal fish consumption.
Conclusions
The results suggest that a higher consumption of fish by women during pregnancy may reduce the risk of adverse effects of prenatal exposure to toxicants and highlight the fact that a full assessment of adverse birth outcomes resulting from prenatal exposure to ambient hazards should consider maternal nutrition during pregnancy.
doi:10.1159/000275918
PMCID: PMC2842166  PMID: 20134157
Air pollutants; Prenatal exposure; Fish consumption; Birth size; Cohort study
8.  Evaluation of the Effect of Four Fibers on Laxation, Gastrointestinal Tolerance and Serum Markers in Healthy Humans 
Background
Average dietary fiber intake in the United States is roughly half of the recommended amount. As new dietary fiber products are introduced to increase fiber intake, it is critical to evaluate the physiological effects of such fibers. Aims: This study examined the effect of 4 fibers derived from maize or tapioca on fecal chemistry, gastrointestinal (GI) symptoms and serum markers of chronic disease.
Methods
Twenty healthy subjects completed the single-blind crossover study in which 12 g/day of fiber (pullulan, Promitor™ Resistant Starch, soluble fiber dextrin or Promitor Soluble Corn Fiber) or placebo (maltodextrin) were consumed for 14 days followed by a 21-day washout. GI symptom surveys were completed (days 3 and 14), stools were collected (days 11–14), diet was recorded (days 12–14) and fasting blood samples were obtained (day 15).
Results
The 4 test fibers were well tolerated, with mild to moderate GI symptoms. Total short-chain fatty acid (SCFA) concentrations did not differ among the treatments. Fecal pH and individual SCFAs were affected by some treatments. Stool weight and serum markers of chronic disease did not change with these treatments.
Conclusion
Increasing fiber intake by 12 g/day was well tolerated and may have a positive impact on colon health due to fermentation.
doi:10.1159/000275962
PMCID: PMC2853587  PMID: 20090313
Pullulan; Resistant starch; Short-chain fatty acids; Gas production; Cholesterol; Ghrelin
9.  Early-Life Predictors of Higher Body Mass Index in Healthy Children 
Background/Aims
Childhood obesity tracks into adulthood, and may increase diabetes and cardiovascular disease risk in adulthood. Prospective analyses may better define the pathways between early life factors and greater childhood body mass index (BMI), a measure of obesity.
Methods
The Diabetes Autoimmunity Study in the Young (DAISY) prospectively follows children from birth that are at increased genetic risk for type 1 diabetes. We examined longitudinal data for 1,178 DAISY subjects (mean age at last follow-up: 6.59 years (range: 2.0–11.5 years). Birth size and diabetes exposure in utero were collected in the enrollment interview. Infant diet information was collected via interviews throughout infancy. Infant weight gain and childhood BMI were measured at clinic visits.
Results
Female gender, diabetes exposure in utero, larger size for gestational age, shorter breastfeeding duration, and more rapid infant weight gain predicted higher childhood BMI. Formal mediation analysis suggests the effect of shorter breastfeeding duration on childhood BMI may be mediated by more rapid infant weight gain. Also, the effect of diabetes exposure in utero on childhood BMI may be mediated by larger size for gestational age.
Conclusion
We identified strong interrelationships between early life factors and childhood BMI. Understanding these pathways may aid childhood obesity prevention efforts.
doi:10.1159/000261899
PMCID: PMC2855270  PMID: 19940472
Breastfeeding duration; Infant weight gain; Diabetes exposure in utero; Birth size; Mediator
10.  Association of a Common G6PC2 Variant with Fasting Plasma Glucose Levels in Non-Diabetic Individuals 
Background/Aims
Fasting plasma glucose (FPG) levels correlate with cardiovascular disease and mortality in both diabetic and non-diabetic subjects. G6PC2 encodes a pancreatic islet-specific glucose-6-phosphatase-related protein and G6pc2-null mice were reported to exhibit decreased blood glucose levels. Two recent genome-wide association studies have implicated a role for G6PC2 in regulation of FPGlevels in the general European population and reported the strongest association with the rs560887 SNP. The purpose of this study was to replicate this association in our independent epidemiological samples.
Methods
DNA samples from non-Hispanic white Americans (NHWs; n = 623), Hispanic Americans (n = 410) and black Africans (n = 787) were genotyped for rs560887 using TaqMan allelic discrimination.
Results
While no minor allele A of rs560887 was observed among blacks, its frequency was 33% in NHWs and 17.5% in Hispanics. The rs560887 minor allele was associated with reduced FPG levels in non-diabetic NHWs (p = 0.002 under an additive model). A similar trend of association was observed in non-diabetic Hispanics (p = 0.076 under a dominant model), which was more pronounced in normoglycemic subjects (p = 0.036).
Conclusions
Our results independently confirm the robust association of G6PC2/rs560887 with FPG levels in non-diabetic NHWs. The observed evidence for association in Hispanics warrants further studies in larger samples.
doi:10.1159/000268019
PMCID: PMC2855271  PMID: 20029179
Blood glucose; Plasma glucose; Fasting plasma glucose; G6PC2; Single nucleotide polymorphism; Polymorphism; rs560887
11.  Exercise Training and Dietary Glycemic Load May Have Synergistic Effects on Insulin Resistance in Older Obese Adults 
Annals of Nutrition & Metabolism  2009;55(4):326-333.
Background/Aims
The aim of this study was to assess the combined effects of exercise and dietary glycemic load on insulin resistance in older obese adults.
Methods
Eleven men and women (62 ± 2 years; 97.6 ± 4.8 kg; body mass index 33.2 ± 2.0) participated in a 12-week supervised exercise program, 5 days/week, for about 1 h/day, at 80–85% of maximum heart rate. Dietary glycemic load was calculated from dietary intake records. Insulin resistance was determined using the euglycemic (5.0 mM) hyperinsulinemic (40 mU/m2/min) clamp.
Results
The intervention improved insulin sensitivity (2.37 ± 0.37 to 3.28 ± 0.52 mg/kg/min, p < 0.004), increased VO2max (p < 0.009), and decreased body weight (p < 0.009). Despite similar caloric intakes (1,816 ± 128 vs. 1,610 ± 100 kcal/day), dietary glycemic load trended towards a decrease during the study (140 ± 10 g before, vs. 115 ± 8 g during, p < 0.04). The change in insulin sensitivity correlated with the change in glycemic load (r = 0.84, p < 0.009). Four subjects reduced their glycemic load by 61 ± 8%, and had significantly greater increases in insulin sensitivity (78 ± 11 vs. 23 ± 8%, p < 0.003), and decreases in body weight (p < 0.004) and plasma triglycerides (p < 0.04) compared to the rest of the group.
Conclusion
The data suggest that combining a low-glycemic diet with exercise may provide an alternative and more effective treatment for insulin resistance in older obese adults.
doi:10.1159/000248991
PMCID: PMC2853590  PMID: 19844089
Diabetes; Obesity; Aging; Insulin sensitivity; Physical activity; Glycemic index
12.  Influence of Early Nutritional Components on the Development of Murine Autoimmune Diabetes 
Annals of Nutrition & Metabolism  2009;54(3):208-217.
Background/Aims
Infant diet is suggested to modify autoimmune diabetes risk. The aim of this study was to determine whether infant food components affect diabetes development in the nonobese autoimmune diabetes (NOD) mouse.
Methods
A basal low-diabetogenic diet was identified by feeding litter-matched female NOD mice standardized diets with and without casein and wheat proteins after weaning. In subsequent trials, basal diet with supplements of wheat (5, 10 and 30%), gluten, wheat globulin/albumin, corn (5%), potato (5%), apple (5%) or carrot (5%) was fed to litter-matched female NOD mice after weaning. Mice were followed for diabetes development and insulin autoantibodies.
Results
A casein- and wheat-free diet was associated with the lowest rate of diabetes development (37% by age 25 weeks). Increased diabetes rates were observed when the basal diet was supplemented with 5% wheat (71% by age 25 weeks; p = 0.023) and 5% corn (57% by age 25 weeks; p = 0.05). Increasing wheat concentrations returned diabetes development to that in basal diet-fed mice. Other food supplements had no or minimal effects on diabetes development.
Conclusions
Early supplementation of a basal low-diabetogenic diet with low concentrations of the cereals wheat or corn is associated with a moderate increase in the rate of diabetes. Removal of cereals, however, does not abrogate diabetes development in NOD mice.
doi:10.1159/000220416
PMCID: PMC2814014  PMID: 19478481
Type 1 diabetes; Autoimmunity; NOD mice; Diet; Prevention; Gluten; Casein
13.  Dietary Supplements Contribute Substantially to the Total Nutrient Intake in Pregnant Norwegian Women 
Annals of Nutrition & Metabolism  2008;52(4):272-280.
Background
Use of dietary supplements during pregnancy may give an important contribution to nutrient intake, and for nutrients like folate and vitamin D supplements are recommended. Our objective was to study use and contribution of dietary supplement to nutrient intake among women participating in the Norwegian Mother and Child Cohort Study (MoBa).
Methods
This study is based on 40,108 women participating in MoBa which is conducted by the Norwegian Institute of Public Health. The women had filled inversion 2 of the food frequency questionnaire in MoBa between February 2002 and February 2005.
Results
81% reported use of one or more dietary supplements. The most commonly used category was cod liver oil/fish oil supplements (59%) followed by singular folic acid supplements (36%) and multivitamin/multimineral supplements (31%). The nutrient contribution of the dietary supplements varied from 65% for folate and vitamin D to 1% for potassium among supplement users. The dietary intake of vitamin D, folate, iodine and iron did not reach the Nordic Recommendations for pregnant women.
Conclusions
Use of supplements improved the intake of folate, iron and vitamin D, but not sufficiently to reach the recommended amounts.
doi:10.1159/000146274
PMCID: PMC2813797  PMID: 18645244
Dietary supplements; Pregnancy; Nutrient intake; Multivitamins; Minerals; Fatty acids; Vitamin D; Folate; Iodine
14.  Supplementation with 200 mg/Day Docosahexaenoic Acid from Mid-Pregnancy through Lactation Improves the Docosahexaenoic Acid Status of Mothers with a Habitually Low Fish Intake and of Their Infants 
Annals of Nutrition & Metabolism  2008;52(2):157-166.
Background/Aims
The supply of docosahexaenoic acid (DHA, 22:6ω–3), important for fetal/infant neurodevelopment, depends on the maternal fatty acid (FA) status, which may be marginal in central Europe. Therefore, we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids (RBC%), and in breast milk FA (%).
Methods
At 21 weeks’ gestation, 144 women were enrolled into a randomised, double-blind clinical trial receiving daily: (1) a basic vitamin-mineral supplement (Vit/Min group), (2) Vit/Min plus 4.5 g fructo-oligosaccharide (FOS group), or (3) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA (DHA-FOS group). FAs were determined by capillary gas-liquid chromatography.
Results
While maternal RBC-DHA% at enrolment was not different, at 37 weeks gestation, and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group. The breast milk DHA% was twice as high in the DHA-FOS group (0.50%) than in the two others (0.25 %) (p < 0.001), and the ratio ARA/DHA in the DHA-FOS group was 1.0 ± 0.43, in the others 2.1 ± 0.43 (p < 0.001). The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher, and correlated significantly with maternal RBC-DHA% before and 3 months after delivery.
Conclusions
In central Europe, a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants.
doi:10.1159/000129651
PMCID: PMC2790529  PMID: 18446020
Supplements; Docosahexaenoic acid; Pregnancy; Lactation; Concentration; Erythrocytes; Breast milk

Results 1-14 (14)