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1.  Do improvements in dietary behaviour contribute to cardiovascular risk factor reduction over and above cardio-protective medication in newly diagnosed diabetes patients? 
European journal of clinical nutrition  2014;68(10):1113-1118.
Background/objectives
A healthy diet is an integral component of successful diabetes management. However, the comparative importance of adopting a healthy diet for cardiovascular risk factor reduction over and above medication use among newly diagnosed diabetes patients remains unclear.
Subjects/Methods
We computed a dietary score consistent with American Diabetes Association and Diabetes UK recommendations in 574 newly diagnosed diabetes patients by summing standardised values for the intake of total energy, saturated fat, sodium, fibre and plasma vitamin C. In linear regression analyses, stratified by cardio-protective medication use (yes/no), we quantified the comparative longitudinal associations of baseline diet and change in diet over 1-year with change in blood pressure, HbA1c and lipids.
Results
Baseline diet was generally not predictive of change in cardiovascular risk factor levels at 1-year. In contrast, dietary change over 1-year among patients prescribed and not prescribed cardio-protective medication after baseline was associated with comparative (p-interaction all ≥0.95) reductions in diastolic blood pressure (−2.38 vs. −2.93 mmHg, respectively) and triglycerides (−0.31 vs. −0.21 mmol/l, respectively), independent of potential confounding factors and change from baseline to follow-up in physical activity and smoking status.
Conclusions
Modest dietary change over the first year following diagnosis of diabetes was associated with reductions in blood pressure and triglycerides, over and above the effects of cardio-protective medication. Our findings support the notion that dietary change should be viewed as an integral component of successful diabetes self-management, irrespective of medication use.
doi:10.1038/ejcn.2014.79
PMCID: PMC4306328  PMID: 24801371
Diabetes Mellitus, Type 2; Diet; Medication; Cardiovascular risk; Prevention
2.  [No title available] 
PMCID: PMC4293521  PMID: 20700137
3.  Relationships of neophobia and pickiness with dietary variety, dietary quality and diabetes management adherence in youth with type 1 diabetes 
BACKGROUND/OBJECTIVES
Neophobia, pickiness and diet variety are associated with diet quality and health outcomes in young children. Limited research has examined these associations among youth with type 1 diabetes (T1D), a population at risk for poor health outcomes when dietary quality is inadequate.
SUBJECTS/METHODS
Youth (n = 252, age 13.2±2.8 years, 92% white, diabetes duration 6.3±3.4 years) with T1D and their parents completed 3-day youth diet records; parents completed questionnaires regarding youth neophobia, pickiness and diabetes management adherence. Medical records provided biomedical data. Dietary quality indicators included Nutrient-Rich Foods Index 9.3 (NRF9.3), Healthy Eating Index-2005 (HEI-2005), Whole Plant Food Density (WPFD) and key single nutrients. Dietary variety was operationalized as a count of 20 recommended food groups consumed. Relationships of dietary quality and diabetes management adherence with neophobia, pickiness and dietary variety as independent variables were examined using multiple linear regression analyses adjusted for total energy intake, age, height and weight.
RESULTS
In multiple linear regression analyses, NRF9.3 and HEI-2005 were each inversely associated with neophobia and pickiness, and positively associated with dietary variety. WPF and potassium were each positively associated and saturated fat was inversely associated with dietary variety. However, in models simultaneously including neophobia, pickiness and dietary variety as independent correlates of dietary quality, only relationships with dietary variety remained significant. Diabetes management adherence was negatively associated with both neophobia and pickiness and positively associated with dietary variety.
CONCLUSIONS
Findings suggest that increasing dietary variety may contribute toward improved dietary quality among youth with T1D, despite potentially adverse influences of neophobia and pickiness.
doi:10.1038/ejcn.2013.239
PMCID: PMC4165343  PMID: 24253761
dietary variety; dietary quality; neophobia; pickiness; type 1 diabetes; youth
4.  Maternal perception of causes and consequences of sibling differences in eating behaviour 
European journal of clinical nutrition  2010;64(11):1316-1322.
Objective
To explore mothers’ perceptions of differences between their children in the eating behaviour domain.
Methods
Twelve semi-structured interviews were carried out with mothers who had at least two children aged between 6 and 15 years, to discuss feeding experiences, particularly around healthy eating. Interviews were recorded and transcribed verbatim and analysed using Framework Analysis.
Results
Mothers frequently identified differences in appetite and food preferences between their children, which they attributed largely to genetic factors. These sibling differences meant that although feeding goals might be common, the pathways to the goals varied depending on each child’s appetitive characteristics. The overall pattern was one of flexible responsiveness to each child. In contrast to perceptions of their own children’s eating behaviours, feeding difficulties in other families were usually attributed to lack of parental control.
Conclusion
The feeding relationship is complex and interactive, resulting in parents modulating their feeding strategies to match each child’s eating behaviour. Guidance to parents on healthy feeding needs to acknowledge the nuanced and interactive nature of feeding practices.
doi:10.1038/ejcn.2010.159
PMCID: PMC4273081  PMID: 20717131
sibling; eating behaviour; feeding; parents; qualitative
5.  Pharmacokinetics of daily versus monthly vitamin D3 supplementation in non-lactating women 
This study compared serum cholecalciferol and 25-hydroxyvitamin D [25(OH)D] concentrations over four weeks in healthy, non-pregnant, non-lactating females aged 18-40 years, who were randomized to oral cholecalciferol 5,000 international units (IU) daily for 28 days or a single dose of 150,000 IU. The study was conducted in Rochester, MN in March and April of 2010. We found no difference in mean 25(OH)D between treatment groups on study day 0 or day 28 (p = 0.14 and 0.28, respectively). The daily group had 11 more days of detectable serum cholecalciferol than the single-dose group (p < 0.001). There was no difference observed in cholecalciferol area under the curve (AUC28) between groups (p = 0.49). However, The single dose group had a significantly greater mean 25(OH)D AUC28 compared with the daily group (p < 0.001).
doi:10.1038/ejcn.2013.278
PMCID: PMC4266550  PMID: 24424073
nutrition; women; metabolism; Vitamin D; pharmacokinetics
6.  Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition – the EPIC-InterAct study 
Background
Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including 8 countries with large geographical variation.
Methods
Using a case-cohort design, 11,245 incident cases of type 2 diabetes and a representative subcohort (N=15,798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. 24-h diet recall data from a subsample (N=2347) were used to calibrate habitual intake data derived from dietary questionnaires.
Results
Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95 % CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22), (ptrend=0.17). No associations were observed in a sex-specific analysis. The overall pooled effect [HR (95% CI)] using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 μg/day dietary vitamin D.
Conclusion
This observational study does not support an association between higher dietary vitamin D intake and type-2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.
doi:10.1038/ejcn.2013.235
PMCID: PMC4234029  PMID: 24253760
vitamin D; type-2 diabetes; dietary intake; observational study; EPIC
7.  Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: a two-year randomized trial 
Background/Objectives
Short-term studies have suggested beneficial effects of a Palaeolithic-type diet (PD) on body weight and metabolic balance. We now report long-term effects in obese postmenopausal women of a PD on anthropometric measurements and metabolic balance, in comparison with a diet according to the Nordic Nutrition Recommendations (NNR).
Subjects/Methods
Seventy obese postmenopausal women (mean age 60 years, body mass index 33 kg/m2) were assigned to an ad libitum PD or NNR diet in a 2-year randomized controlled trial. The primary outcome was change in fat mass as measured by dual energy X-ray absorptiometry.
Results
Both groups significantly decreased total fat mass at 6 months (−6.5 and −2.6 kg) and 24 months (−4.6 and −2.9 kg), with a more pronounced fat loss in the PD group at 6 months (P<0.001), but not at 24 months (P=0.095). Waist circumference and sagittal diameter also decreased in both groups, with a more pronounced decrease in the PD group at 6 months (−11.1 vs. −5.8 cm, P=0.001 and −3.7 vs. −2.0 cm, P<0.001, respectively). Triglyceride levels decreased significantly more at 6 and 24 months in the PD group versus the NNR group (P<0.001 and P=0.004). Nitrogen excretion did not differ between groups.
Conclusions
A PD has greater beneficial effects versus an NNR diet regarding fat mass, abdominal obesity and triglyceride levels in obese postmenopausal women; effects not fully sustained for anthropometric measurements at 24 months. Adherence to protein intake was poor in the PD group. The long-term consequences of these changes remain to be studied.
doi:10.1038/ejcn.2013.290
PMCID: PMC4216932  PMID: 24473459
adipose tissue; diet; insulin resistance; postmenopausal; weight
8.  Non-nutritive sweeteners: no class effect on the glycemic or appetite responses to ingested glucose 
There is considerable interest in whether non-nutritive sweeteners are sensed in the gastrointestinal tract to modulate appetitive or absorptive responses to ingested carbohydrate. We determined the effect of a panel of non-nutritive sweeteners, aspartame, saccharin and acesulfame-K, delivered in doses that would be consumed in normal usage. Each was given in combination with glucose, assessing their effect on glycemic responses and appetite in ten healthy human subjects. There was no additional effect of aspartame or saccharin on the blood glucose response to oral glucose at any time point, although acesulfame-K exerted a small effect. However, none had an effect on perceptions of hunger or fullness. We conclude that there is no consistent evidence that non-nutrient sweeteners, when acutely consumed with glucose in dietetically relevant doses, have a class effect in modulating blood glucose in healthy human subjects. However, acesulfame-K may require further exploration.
doi:10.1038/ejcn.2014.19
PMCID: PMC4012981  PMID: 24595225
Non-nutritive sweeteners; glucose; glucose metabolism; appetite
9.  Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic-Hunter-Gatherer-type diets 
Background
Formulas developed to estimate diet-dependent net acid excretion (NAE) generally agree with measured values for typical Western diets. Whether they can also appropriately predict NAE for "Paleolithic-type" (Paleo) diets – which contain very high amounts of fruits and vegetables (F&V) and concurrent high amounts of protein is unknown. Here we compare measured NAEs with established NAE-estimates in subjects with Type 2 diabetes (T2D).
Methods
Thirteen subjects with well controlled T2D were randomized to either a Paleo or American Diabetes Association (ADA) diet for 14 days. 24-hour urine collections were performed at baseline and end of the diet period, and analyzed for titratable acid, bicarbonate, and ammonium to calculate measured NAE. Three formulas for estimating NAE from dietary intake were used; two (NAE_diet R or L) that include dietary mineral intake and sulfate- and organic acid (OA) production, and one that is empirically-derived (NAE_diet F) only considering potassium and protein intake.
Results
Measured NAE on the Paleo diet was significantly lower than on the ADA diet (+31±22 vs. 112±52 mEq/day, p=0.002). Although all formula estimates showed similar and reasonable correlations (r=0.52–0.76) with measured NAE, each one underestimated measured values. The formula with the best correlation did not contain an estimate of dietary organic acid production.
Conclusions
Paleo diets are lower in NAE than typical Western diets. However, commonly used formulas clearly underestimate NAE, especially for diets with very high F&V (as the Paleo diet), and in subjects with T2D. This may be due to an inappropriate estimation of proton loads stemming from OAs, underlining the necessity for improved measures of OA-related proton sources.
doi:10.1038/ejcn.2013.124
PMCID: PMC4209958  PMID: 23859996
net acid excretion; Paleolithic diet; organic acids; type 2 diabetes
10.  Dietary Magnesium Intake is Inversely Associated with Serum C-reactive Protein Levels: Meta-analysis and Systematic Review 
Objectives
To quantitatively summarize the association of dietary magnesium (Mg) intake with serum C-reactive protein (CRP) levels in the general population.
Methods
Observational and experimental studies through February 2013 were reviewed in PubMed and EMBASE. Additional information was retrieved through Google or hand search of related reference lists. The main outcome is either adjusted geometric mean of CRP or odds ratio (OR) of having serum CRP≥3 mg/L. Meta-regression was used to determine the linear association of dietary Mg intake and adjusted geometric means of CRP levels. A fixed-effects model was used to pool ORs of interest, comparing those in the lowest with those in the highest group of dietary Mg intake.
Results
A dataset derived from seven cross-sectional studies including 32,918 participants was quantitatively assessed. A weighted inverse association between Mg intake and serum CRP levels was observed[β coefficient: −0.0028; 95% CI, −0.0043 to −0.0013; P for trend=0.001] from four cross-sectional studies. The pooled OR (95%CI) of having CRP≥3 mg/L was 1.49(1.18 to 1.89) comparing the lowest to the highest group of Mg intake from three studies with data available. Qualitative assessment among five intervention studies also showed a potential beneficial effect of Mg intake on serum CRP levels.
Conclusion
This meta-analysis and systematic review indicate that dietary Mg intake is significantly and inversely associated with serum CRP levels. The potential beneficial effect of Mg intake on chronic diseases may be, at least in part, explained by inhibiting inflammation.
doi:10.1038/ejcn.2014.7
PMCID: PMC3975661  PMID: 24518747
magnesium; inflammation; C-reactive protein; meta-analysis; systematic review
11.  Outcomes of Percutaneous Endoscopic Gastrostomy in Hospitalized Patients at a Tertiary Care Hospital in Turkey 
BACKGROUND / OBJECTIVES
The aim of this study was to perform a retrospective analysis characterizing patients receiving tube feeding following percutaneous endoscopic gastrostomy ( PEG) tube placement between 2004 and 2012 at Erciyes University Hospital in Turkey.
METHODS
Patients above the age of 18 years, who required long term enteral tube feeding were studied. All PEGs were performed using the pull-through technique by one experienced endoscopist Demographic, clinical outcomes, and PEG-related complication data were collected.
RESULTS
Of the 128 subjects studied, 91 were male (71%) and 37 were female (29%). The mean age of this patient population was 54±19 years. The most common reason for PEG tube insertion was inability to consume oral diet due to complications of cerebrovascular disease (CVD; 27%), while cerebral hypoxia, occuring after non-neurological medical disorders, was the second most common indication (23%). A total of 70 patients (55%) had chronic comorbidities, with hypertension the most common (20%). The most common procedure related complication was insertion site bleeding, which occurred in 4 % of patients. Long term complications, during one year were insertion site cellulitis, gastric contents leakage, and peristomal ulceration occurred in 14%, 5%, and 0.5% of patients, respectively. There were no PEG insertion-related mortalities; one-year mortality was unrelated to the indication for PEG tube insertion.
CONCLUSIONS
PEG tube insertion was a safe method to provide enteral access for nutrition support in this hospitalized patient population.
doi:10.1038/ejcn.2014.11
PMCID: PMC3975672  PMID: 24518749
PEG; gastrostomy; enteral nutrition; tube feeding; Turkey
12.  Serum concentrations of cholesterol, apolipoprotein A-I, and apolipoprotein B in a total of 1 694 meat-eaters, fish-eaters, vegetarians, and vegans 
BACKGROUND
The objective of this study was to describe serum lipid concentrations, including apolipoproteins A-I and B, in different diet groups.
METHODS
A cross-sectional analysis of a sample of 424 meat-eaters, 425 fish-eaters, 423 vegetarians, and 422 vegans, matched on sex and age, from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford cohort. Serum concentrations of total, and HDL cholesterol, as well as apolipoproteins A-I and B were measured, and serum non-HDL cholesterol was calculated.
RESULTS
Vegans had the lowest BMI, and the highest and lowest intakes of polyunsaturated and saturated fat, respectively. After adjustment for age, alcohol and physical activity, compared to meat-eaters, fish-eaters and vegetarians, serum concentrations of total and non-HDL cholesterol, and apolipoprotein B were significantly lower in vegans. Serum apolipoprotein A-I concentrations did not differ between the diet groups. In males, the mean serum total cholesterol concentration was 0.87 nmol/L lower in vegans than in meat-eaters; after further adjustment for BMI this difference was 0.76 nmol/L. In females, the difference in total cholesterol between these two groups was 0.60 nmol/L, and after further adjustment for BMI was 0.55 nmol/L.
CONCLUSIONS
In this study, which included a large number of vegans, serum total cholesterol and apolipoprotein B concentrations were lower in vegans compared to meat-eaters, fish-eaters and vegetarians. A small proportion of the observed differences in serum lipid concentrations was explained by differences in BMI, but a large proportion is most likely due to diet.
doi:10.1038/ejcn.2013.248
PMCID: PMC3916209  PMID: 24346473
lipids; cholesterol; apolipoproteins; vegetarian diet; vegan diet
13.  Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices 
Objectives
Uridine abrogates mitochondrial toxicities of nucleoside reverse transcriptase inhibitor in adipocyte cell culture. We aim to study the effect of uridine supplementation on human adipocyte mitochondrial DNA (mtDNA) levels in subjects with human immunodeficiency (HIV) lipoatrophy.
Methods
Sixteen patients with lipoatrophy on stavudine-containing antiretroviral therapy were enrolled, and received NucleomaxX, a dietary supplement with a high bioavailability of uridine (36 g TID every other day for 16 weeks). Patients were then followed off-uridine for another 16 weeks. Highly active antiretroviral therapy remained unchanged during the trial.
Results
Fourteen patients completed the study. Two subjects dropped out before week 4 for study-unrelated reasons. No adverse events were noted throughout the study. HIV-1 RNA, CD4 counts, liver enzymes and hemoglobin remained unchanged. Body mass index, lactate, lipids, insulin and homeostasis model assessment of insulin resistance were unaltered. Fat and peripheral blood and mononuclear cell mtDNA levels did not correlate with each other and exhibited no changes throughout the study. Lipoatrophy scores by patients and physician improved significantly at weeks 16 and 32 compared to study entry.
Conclusion
In this pilot study, NucleomaxX was safe, well tolerated without apparent deleterious effect on HIV indices. In contrast to in vitro data, NucleomaxX did not lead to changes in fat or blood mtDNA levels.
doi:10.1038/sj.ejcn.1602793
PMCID: PMC4105300  PMID: 17538545
mitochondria; uridine; lipoatrophy; lipodystrophy; mitochondrial DNA
14.  Ethnicity, plasma phospholipid fatty acid composition and inflammatory/endothelial activation biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA) 
BACKGROUND/OBJECTIVES
It has been recognized that certain long-chain polyunsaturated fatty acids (LC-PUFAs) are involved in inflammation and its resolution. It has also been shown that ethnicity may be a factor in affecting systemic inflammation, and limited evidence suggests it may influence plasma LC-PUFA composition. Given the links among these three factors, we aim to determine ethnicity-based differences in plasma LC-PUFA composition among White, Black, Hispanic and Chinese participants, and whether such differences contribute to variations in markers of inflammation and endothelial activation in a sub-cohort of the Multi-Ethnic Study of Atherosclerosis (MESA).
SUBJECTS/METHODS
Plasma phospholipid LC-PUFAs levels (%) were determined in 2848 MESA participants using gas chromatography-flame ionization detection. Enzyme immunoassays determined inflammatory markers levels for high-sensitivity C-reactive protein (n =2848), interleukin-6 (n =2796), soluble tumor necrosis factor-α receptor type 1 (n =998), and endothelial activation markers soluble intercellular adhesion molecule-1 (n =1192) and soluble E-selectin (n =998).
The modifying influence of ethnicity was tested by linear regression analysis.
RESULTS
Chinese adults were found to have the highest mean levels of plasma eicosapentaenoic acid (EPA, 1.24%) and docosahexaenoic acid (DHA, 4.95%), and the lowest mean levels of γ-linolenic (0.10%), dihomo-γ-linolenic (DGLA, 2.96%) and arachidonic (10.72%) acids compared with the other ethnicities (all P≤0.01). In contrast, Hispanics had the lowest mean levels of plasma EPA (0.70%) and DHA (3.49%), and the highest levels of DGLA (3.59%; all P≤0.01). Significant differences in EPA and DHA among ethnicities were attenuated following adjustment for dietary non-fried fish and fish oil supplementation. Ethnicity did not modify the associations of LC-PUFAs with markers of inflammation or endothelial activation (all Pinteraction>0.05).
CONCLUSIONS
The absence of a modifying effect of ethnicity indicates that the putative benefits of LC-PUFAs with respect to inflammation are pan-ethnic. Future longitudinal studies may elucidate the origin(s) of ethnicity-based differences in LC-PUFA composition and whether certain patterns, that is, high plasma levels of DGLA and low levels of EPA/DHA, contribute to inflammation-associated health outcomes.
doi:10.1038/ejcn.2011.215
PMCID: PMC4096912  PMID: 22215136
race; endothelial activation; inflammation; fatty acid; omega-3; omega-6
15.  Isotopic estimates of sugar intake are related to chronic disease risk factors but not obesity in an Alaska Native (Yup’ik) study population 
Background
Sugar intake may be causally associated with chronic disease risk, either directly or by contributing to obesity. However, evidence from observational studies is mixed, in part due to the error and bias inherent in self-reported measures of sugar intake. Objective biomarkers may clarify the relationship between sugar intake and chronic disease risk. We have recently validated a biomarker of sugar intake in an Alaska Native (Yup’ik) study population that incorporates red blood cell carbon and nitrogen isotope ratios in a predictive model.
Objective
This study tested associations of isotopic estimates of sugar intake with BMI, waist circumference (WC), and a broad array of other physiological and biochemical measures of chronic disease risk in Yup’ik people.
Subjects/Methods
In a cross-sectional sample of 1076 Yup’ik people, multiple linear regression was used to examine associations of sugar intake with BMI, WC and other chronic disease risk factors.
Results
Isotopic estimates of sugar intake were not associated with BMI (P = 0.50) or WC (P = 0.85). They were positively associated with blood pressure, triglycerides, and leptin, and inversely associated with total-, HDL- and LDL-cholesterol and adiponectin.
Conclusions
Isotopic estimates of sugar intake were not associated with obesity, but were adversely associated with other chronic disease risk factors in this Yup’ik study population. This first use of stable isotope markers of sugar intake may influence recommendations for sugar intake by Yup’ik people; however, longitudinal studies are required to understand associations with chronic disease incidence.
doi:10.1038/ejcn.2013.230
PMCID: PMC3947290  PMID: 24219893
Isotopes; carbon; Isotopes; nitrogen; Chronic disease; Risk factors; Caloric sweeteners
16.  Vitamin D and type 2 diabetes: a systematic review 
Background/Objectives
Vitamin D may modify the risk of type 2 diabetes mellitus. The aim of this review was to examine the association between vitamin D status and incident type 2 diabetes, and the effect of vitamin D supplementation on glycemic outcomes.
Methods
We performed a systematic review of English-language studies using MEDLINE through February 2011. Longitudinal cohort studies reporting associations between vitamin D status and incident type 2 diabetes, and randomized controlled trials (RCTs) of vitamin D supplementation, were included. Study characteristics and results were extracted, and study quality was assessed.
Results
A total of 8 observational cohort studies and 11 RCTs were included. In meta-analyses of observational studies, vitamin D intake > 500 international units (IU)/day decreased the risk of type 2 diabetes by 13% compared with vitamin D intake < 200 IU/day. Individuals with the highest vitamin D status (> 25 ng/ml) had a 43% lower risk of developing type 2 diabetes (95% confidence interval 24, 57%) compared with those in the lowest group (< 14 ng/ml). In post hoc analyses from eight trials among participants with normal glucose tolerance at baseline and in three small underpowered (n = 32–62) trials of patients with established type 2 diabetes, there was no effect of vitamin D supplementation on glycemic outcomes. In two trials among patients with baseline glucose intolerance, vitamin D supplementation improved insulin resistance.
Conclusions
Vitamin D may play a role in type 2 diabetes; however, to better define the role of vitamin D in the development and progression of type 2 diabetes, high-quality observational studies and RCTs that measure blood 25-hydroxyvitamin D concentration and clinically relevant glycemic outcomes are needed.
doi:10.1038/ejcn.2011.118
PMCID: PMC4066381  PMID: 21731035
vitamin D; type 2 diabetes mellitus; systematic review; meta-analysis
17.  Resting energy expenditure and adiposity accretion among children with Down syndrome: a three year prospective study 
European journal of clinical nutrition  2013;67(10):1087-1091.
Background
Children with Down syndrome (DS) have a higher prevalence of obesity than other children. Whether this increased risk for obesity is due to a lower resting energy expenditure (REE) is controversial. Our study assessed whether 1) the REE of children with DS adjusted for fat free mass (FFM) was lower than that of sibling controls and 2) the changes in fat mass (FM) over three years were associated with FFM-adjusted baseline REE.
Methods
This study used cross-sectional and prospective cohort designs. Four annual measurement visits were conducted with 28 children with DS and 35 sibling controls aged 3–10y. REE and serum thyroxine (T4) were measured at baseline. Anthropometry, skinfold thicknesses measures, and, in a subsample, dual energy x-ray absorptiometry (DXA) were used at each visit to calculate FM.
Results
Children with DS had significantly lower REE adjusted for FFM (−78 kcal/day, 95% CI: −133 to −27, p=0.003). The difference remained significant after adjustment for FM, sex, and African ancestry (−49 kcal/day, 95% CI: −94 to −4, p=0.03). In the longitudinal analysis, the baseline REE adjusted for baseline FFM was not predictive of FM accretion over time (p=0.8).
Conclusion
Children with DS have lower REE than sibling controls, but REE was not associated with changes in FM over time. The results suggest that the lower REE of children with DS does not explain their increased risk for obesity.
doi:10.1038/ejcn.2013.137
PMCID: PMC3790863  PMID: 23900244
obesity; fat free mass; fat mass
18.  Effect of a dairy and calcium rich diet on weight loss and appetite during energy restriction in overweight and obese adults: a randomized trial 
Background/Objectives
A diet rich in dairy and calcium (Ca) has been variably associated with improvements in body composition and decreased risk of type 2 diabetes. Our objective was to determine if a dietary pattern high in dairy and Ca improves weight loss and subjective appetite to a greater extent than a low dairy/Ca diet during energy restriction in overweight and obese adults with metabolic syndrome.
Subjects/Methods
49 participants were randomized to one of two treatment groups: CONTROL [low dairy, ~700 mg/day Ca, −500 kcal/d] or DAIRY/CA [high dairy, ~1400 mg/day Ca, −500 kcal/d] for 12wk. Body composition, subjective ratings of appetite, food intake, plasma satiety hormones, glycemic response and inflammatory cytokines were measured.
Results
CONTROL (−2.2±0.5 kg) and DAIRY/CA (−3.3±0.6 kg) had similar weight loss. Based on self-reported energy intake, the percent of expected weight loss achieved was higher with DAIRY/CA (82.1±19.4%) than CONTROL (32.2±7.7%)(P=0.03). Subjects in the DAIRY/CA group reported feeling more satisfied (P=0.01) and had lower dietary fat intake (P=0.02) over 12wk compared to CONTROL. Compared to CONTROL, DAIRY/CA had higher plasma levels of peptide tyrosine tyrosine (PYY, P=0.01) during the meal tolerance test at wk12. Monocyte chemoattractant protein-1 was reduced at 30 min with DAIRY/CA compared to CONTROL (P=0.04).
Conclusions
In conclusion, a dairy and Ca rich diet was not associated with greater weight loss than control. Modest increases in plasma PYY concentrations with increased dairy/Ca intake, however, may contribute to enhanced sensations of satisfaction and reduced dietary fat intake during energy restriction. Registered Trial: ClinicalTrials.gov (NCT00564551).
doi:10.1038/ejcn.2013.52
PMCID: PMC3948984  PMID: 23462943 CAMSID: cams4035
Calcium; dairy; peptide YY; clinical trial; satiety
19.  Prediction of Fat-Free Mass Using Bioelectrical Impedance Analysis in Young Adults from Five Populations of African Origin 
Background/Objectives
Bio-electrical impedance analysis (BIA) is used in population and clinical studies as a technique for estimating body composition. Because of significant underrepresentation in existing literature, we sought to develop and validate predictive equation(s) for BIA for studies in populations of African origin.
Subjects/Methods
Among five cohorts of the Modeling the Epidemiologic Transition Study (METS), height, weight, waist circumference and body composition, using isotope dilution, were measured in 362 adults, ages 25 to 45 with mean BMIs ranging from 24 to 32. BIA measures of resistance and reactance were measured using tetrapolar placement of electrodes and the same model of analyzer across sites (BIA 101Q, RJL Systems). Multiple linear regression analysis was used to develop equations for predicting FFM, as measured by isotope dilution; covariates included sex, age, waist, reactance and height2/resistance, along with dummy variables for each site. Developed equations were then tested in a validation sample; FFM predicted by previously published equations were tested in the total sample.
Results
A site-combined equation and site-specific equations were developed. The mean differences between FFM (reference) and FFM predicted by the study-derived equations were between 0.4–0.6 kg (i.e. 1% difference between actual and predicted FFM) and the measured and predicted values were highly correlated. The site-combined equation performed slightly better than the site-specific equations and the previously published equations.
Conclusions
Relatively small differences exist between BIA equations to estimate FFM, whether study-derived or published equations, although the site-combined equation performed slightly better than other. The study-derived equations provide an important tool for research in these understudied populations.
doi:10.1038/ejcn.2013.123
PMCID: PMC3766444  PMID: 23881006
predictive equation; body composition; epidemiology
20.  Inulin Increases Short-Term Markers for Colonic Fermentation similarly in Healthy and Hyperinsulinemic Humans 
European journal of clinical nutrition  2011;65(12):1279-1286.
Background/Objectives
Colonic fermentation of dietary fibre produces short-chain fatty-acids (SCFA) acetate, propionate and butyrate, which may protect against type 2 diabetes by reducing serum free-fatty acids (FFA). Since hyperinsulinemia is associated with insulin resistance and increased diabetes risk, the main objective was to compare markers of colonic fermentation after acute inulin ingestion in subjects with normal (< 40pmol/L, NI) and high (≥ 40pmol/L, HI) plasma-insulin.
Subjects/Methods
Overnight fasted NI (n = 9) and HI (n = 9) subjects were studied for 4 h on 2 separate days after consuming 300 ml drinks containing 75 g glucose (Glucose) or 75 g glucose plus 24 g inulin (Inulin) using a randomized, single-blind, cross-over design.
Results
Inulin elicited a higher breath hydrogen and methane AUC but the increases in SCFA responses were not statistically significant. Overall mean serum-acetate over the 4 h study period was higher in NI than HI subjects (44.3±6.9 vs 22.5±3.7 μmol/L, p = 0.001). The rate of rebound of FFA was reduced by Inulin, with FFA at 4hr being less after Inulin than Glucose, regardless of insulin status (0.310±0.028 vs 0.432±0.042 mEq/L, p = 0.008).
Conclusions
This suggests that inulin increases short-term markers for colonic fermentation but a longer study period may be necessary to observe differences in SCFA production. The reason for the lower serum-acetate in HI is unclear but may be due to reduced absorption, increased clearance or decreased endogenous production. This suggests the need to compare acetate kinetics in normal and hyperinsulinemic subjects.
doi:10.1038/ejcn.2011.116
PMCID: PMC3937120  PMID: 21712835 CAMSID: cams4024
Colonic fermentation; short chain fatty acids; acetate; inulin; hyperinsulinemia; free fatty acids
21.  Intravenous Acetate Elicits a Greater Free Fatty Acid Rebound in Normal than Hyperinsulinaemic Humans 
Background/Objectives
Colonic fermentation of dietary fiber may improve insulin sensitivity via the metabolic effects of short chain fatty acids (SCFA) in reducing free fatty acids (FFA). The main objectives of this study were to compare peripheral uptake of acetate (AC) in participants with normal (< 40pmol/L, NI) and high (≥ 40pmol/L, HI) plasma-insulin and the ability of AC to reduce FFA in both groups.
Subject/Methods
Overnight fasted NI (n = 9) and HI (n = 9) participants were given an intravenous (IV) infusion of 140 mmol/L sodium acetate at 3 different rates over 90 minutes. The total amount of AC infused was 51.85 mmols.
Results
Acetate clearance in NI participants was not significantly different than that in HI participants (2.11 ± 0.23 vs 2.09 ± 0.24 ml/min). FFA fell in both groups, but rebounded to a greater extent in NI than HI participants (time × group interaction, P = 0.001). Significant correlations between insulin resistance (IR) indices (HOMA-IR, Matsuda and Insulinogenic Index) vs FFA rebound during IV AC infusion were also observed.
Conclusions
These findings suggest that AC uptake is similar in both groups. Participants with lower plasma insulin and lower IR indices had a greater FFA rebound. These results support the hypothesis that increasing AC concentrations in the systemic circulation may reduce lipolysis and plasma FFA concentrations and thus improve insulin sensitivity. More in-depth studies are needed to look at the effects of SCFA on FFA metabolism in insulin resistant participants.
doi:10.1038/ejcn.2012.98
PMCID: PMC3937122  PMID: 22828730 CAMSID: cams4033
Humans; acetate; FFA; insulin sensitivity
22.  Measuring energy expenditure in clinical populations: rewards and challenges 
The measurement of energy expenditure (EE) is recommended as an important component of comprehensive clinical nutrition assessments in patients with altered metabolic states, who failed to respond to nutrition support and with critical illness that require individualized nutrition support. There is evidence that EE is variable in patients with metabolic diseases, such as chronic renal disease, cirrhosis, HIV, cancer cachexia, cystic fibrosis and patients under intensive care. By using appropriate techniques and interpretations of basal or resting EE, clinicians can facilitate the adequate nutrition support with minimum negative impacts from under- or overfeeding in these patients. This review is based on our current understanding of the different components of EE and the techniques to measure them, and to re-examine advances and challenges to determine energy needs in clinical populations with more focuses on the obese, pediatric and elderly patients. In addition, technological advances have expanded the choices of market-available equipments for assessing EE, which also bring specific challenges and rewards in selecting the right equipment with specific performance criteria. Lastly, analytical considerations of interpreting the results of EE in the context of changing body composition are presented and discussed.
doi:10.1038/ejcn.2013.38
PMCID: PMC3928639  PMID: 23443826
basal metabolic rate; indirect calorimetry; oxygen consumption; obesity; children; elderly
23.  European ancestry and resting metabolic rate in older African Americans 
Background/Objectives
Resting metabolic rate (RMR) contributes 60–80% of total energy expenditure and is consistently lower in populations of African descent compared with populations of European populations. Determination of European ancestry (EA) through SNP analysis would provide an initial step for identifying genetic associations that contribute to low RMR. We sought to evaluate the association between RMR and EA in African Americans.
Subjects/Methods
RMR was measured by indirect calorimetry in 141 African American men and women (aged 74.7 ± 3.0 years) enrolled in a substudy of the Health, Aging and Body Composition Study. Ancestry informative markers were used to estimate individual percent EA. Multivariate regression was used to assess the association between RMR and EA after adjustments for soft tissue fat-free mass (STFFM), fat mass, age, study site, physical activity level and sex.
Results
Mean EA was 23.8 ± 16% (range: 0.1% to 70.7%) and there were no differences by sex. Following adjustments, each percent EA was associated with a 1.6 kcal/day (95% Confidence interval: 0.42, 2.7 kcal/day) higher RMR (p = 0.008). This equates to a 160 kcal/day lower RMR in a population of completely African ancestry with one of completely European ancestry. Additional adjustment for trunk STFFM that partially accounts for high-metabolic rate organs did not affect this association.
Conclusions
European ancestry in African Americans is strongly associated with higher RMR. The data suggest that population differences in RMR may be due to genetic variants.
doi:10.1038/ejcn.2011.22
PMCID: PMC3915864  PMID: 21468093
Admixture; energy metabolism; body composition; genetic mapping
24.  Single nucleotide polymorphisms in uracil-processing genes, intake of one-carbon nutrients and breast cancer risk 
Background/Objectives
The misincorporation of uracil into DNA leads to genomic instability. In a prior study, some of us identified four common SNPs in uracil-processing genes (rs2029166 and rs7296239 in SMUG1, rs34259 in UNG, and rs4775748 in DUT) that were associated with significantly altered levels of uracil in human DNA. We investigated whether any of these SNPs are associated with an altered risk of developing breast cancer and if one-carbon nutrients intake can modify their effects.
Subjects/Methods
We genotyped the four SNPs in 1,077 cases of incident breast cancer and 1,910 age and race-matched controls in the Western New York Exposures and Breast Cancer (WEB) Study and examined associations with breast cancer risk and interactions with intake of folate, vitamins B6 and B12.
Results
After adjustment for known risk factors for breast cancer, there was increased risk of breast cancer among postmenopausal women who were heterozygous for either of the SMUG1 SNPs (OR 1.29, 95% CI 1.07–1.56) and (1.29, 1.07–1.55). Among premenopausal women, increased risk associated with the SMUG1 rs2029166 genotype was limited to those with low folate intake. There were no other interactions with vitamins B6 or B12 intake.
Conclusions
Our study suggests that the four selected SNPs are not robust determinants of breast cancer risk, but that the two SNPs in SMUG1 might modestly alter the risk of breast cancer. However, the increase in risk among heterozygotes in the two SNPs in SMUG1, which is thought to be the most active glycosylase in vivo, raises the possibility that subtle ‘heterosis’ effects on cancer risk might be produced by these SNPs.
doi:10.1038/ejcn.2011.29
PMCID: PMC3902360  PMID: 21427733
Uracil-Processing Genes; Single nucleotide polymorphisms; Breast cancer
25.  Family and infant characteristics associated with timing of core and non-core food introduction in early childhood 
Objective
To identify family and infant characteristics associated with timing of introduction of two food types: core foods (nutrient-dense) and non-core foods (nutrient-poor) in a population-based sample of mothers and infants.
Method
Participants were 1861 mothers and infants from the Gemini twin birth cohort (one child per family). Family and infant characteristics were assessed when the infants were around 8 months old. Timing of introducing core and non-core foods was assessed at 8 and 15 months. As the distributions of timing were skewed, three similar-sized groups were created for each food type: earlier (core: 1–4 months; non-core: 3–8 months), average (core: 5 months; non-core: 9–10 months), and later introduction (core: 6–12 months; non-core: 11–18 months). Ordinal logistic regression was used to examine predictors of core and non-core food introduction, with bootstrapping to test for differences between the core and non-core models.
Results
Younger maternal age, lower education level, and higher maternal BMI were associated with earlier core and non-core food introduction. Not breastfeeding for at least 3 months and higher birth weight were specifically associated with earlier introduction of core foods. Having older children was specifically associated with earlier introduction of non-core foods.
Conclusion
There are similarities and differences in the characteristics associated with earlier introduction of core and non-core foods. Successful interventions may require a combination of approaches to target both food types.
doi:10.1038/ejcn.2013.63
PMCID: PMC3674911  PMID: 23486509
Infant feeding; core foods; non-core foods

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