The effect of traditional diet on glucose homoeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: a randomised crossover study.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (-0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

Sagittal abdominal diameter and waist circumference appear to be equally good as identifiers of cardiometabolic risk.

BACKGROUND AND AIMS: Body mass index (BMI) and waist circumference (WC) are commonly used markers of cardiometabolic risk. However, sagittal abdominal diameter (SAD) has been proposed as a possibly more sensitive marker of intra-abdominal obesity. We investigated differences in how SAD, WC, and BMI were correlated with cardiometabolic risk markers. METHODS AND RESULTS: This cross-sectional study investigated anthropometric and metabolic baseline measurements of individuals from six trials. Multiple linear regression and (partial) correlation coefficients were used to investigate associations between SAD, WC, and BMI and cardiometabolic risk markers, including components of the metabolic syndrome as well as insulin resistance, blood lipids, and lowgrade inflammation. In total 1516 mostly overweight or obese individuals were included in the study. SAD was significantly more correlated with TG than WC for all studies, and overall increase in correlation was 0.05 (95% CI (0.02; 0.08). SAD was significantly more correlated with the markers TG and DBP 0.11 (95% CI (0.08, 0.14)) and 0.04 (95% CI (0.006, 0.07), respectively compared to BMI across all or most studies. CONCLUSION: This study showed that no single anthropometric indicator was consistently more strongly correlated across all markers of cardiometabolic risk. However, SAD was significantly more strongly correlated with TG than WC and significantly more strongly correlated with DBP and TG than BMI.

Effects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: In observational studies, higher S-25-hydroxyvitamin D [S-25(OH)D] has been associated with a more favorable cardiometabolic profile in childhood, but results may be confounded. We examined effects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents. METHODS: We systematically searched relevant databases for randomized controlled trials (RCTs) examining effects of vitamin D supplementation compared to placebo or a lower dose of vitamin D on blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), glycated hemoglobin, cholesterol [total, high-density, and low-density lipoprotein (LDL-C)], triglycerides, or blood pressure. We conducted random-effects meta-analyses of weighted mean differences in all participants and in subgroups of overweight/obese versus normal weight participants with or without baseline S-25(OH)D < 50 nmol/L. We also explored associations between responses in S-25(OH)D and outcomes by meta-regression. RESULTS: Fourteen RCTs with a total of 1088 participants aged 4-19 years were included. In the meta-analysis, vitamin D supplementation increased S-25(OH)D by 27 nmol/L [95% CI 16; 37] (P < 0.0001) and increased LDL-C by 0.11 mmol/L [0.02; 0.20] (P = 0.02) without any subgroup differences and a generally low to moderate heterogeneity. Vitamin D supplementation had no other effects. However, in the meta-regression analysis, HOMA-IR decreased by 0.51 points [- 0.97; - 0.04] per 10 nmol/L increase in the endpoint S-25(OH)D among overweight/obese participants (P = 0.04). CONCLUSIONS: These results do not support the use of vitamin D supplementation for improving cardiometabolic health in childhood. Indicated beneficial effects on insulin resistance in those with obesity could be investigated further, while unfavorable effects on LDL-C may be a concern.

Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.

OBJECTIVE: To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN: 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS: 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION: Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER: NCT01731366; Results.

Intake and sources of gluten in 20- to 75-year-old Danish adults: a national dietary survey.

PURPOSE: Celiac disease, an immunological response triggered by gluten, affects ~1 % of the Western population. Information concerning gluten intake in the general population is scarce. We determined intake of gluten from wheat, barley, rye and oat in the Danish National Survey of Diet and Physical Activity 2005-2008. The study population comprised a random cross-sectional sample of 1494 adults 20-75 years, selected from the Danish Civil Registration System. METHODS: Protein content in wheat, rye, barley and oat was determined from the National Danish Food Composition Table and multiplied with the amount of cereal used in recipes. Amount of gluten was calculated as amount of cereal protein ×0.80 for wheat and oat, ×0.65 for rye and ×0.50 for barley. Dietary intake was recorded daily during seven consecutive days in pre-coded food diaries with open-answer possibilities. RESULTS: Mean total gluten intake was 10.4 ± 4.4 g/day (10th-90th percentiles; 5.4-16.2 g/day), in men 12.0 ± 4.6 g/day and 9.0 ± 3.4 g/day in women. It was higher among men than among women in all age groups (20-75 years; P < 0.0001); however, this difference was eliminated when adjusting for energy intake. Intake of different gluten sources tended to be higher in men than in women with the exception of gluten from barley. Total gluten intake decreased with increasing age (P < 0.0001) as did gluten intake from wheat (P < 0.0001), whereas intake of gluten from rye (P < 0.0001) and barley (P = 0.001) increased with increasing age, also when adjusted for energy intake or body weight. CONCLUSION: This study presents representative population-based data on gluten intake in Danish adults. Total gluten intake decreased with increasing age.

A high-throughput method for liquid chromatography-tandem mass spectrometry determination of plasma alkylresorcinols, biomarkers of whole grain wheat and rye intake.

Plasma alkylresorcinols are increasingly analyzed in cohort studies to improve estimates of whole grain intake and their relationship with disease incidence. Current methods require large volumes of solvent (>10 ml/sample) and have relatively low daily sample throughput. We tested five different supported extraction methods for extracting alkylresorcinols from plasma and improved a normal-phase liquid chromatography coupled to a tandem mass spectrometer method to reduce sample analysis time. The method was validated and compared with gas chromatography-mass spectrometry analysis. Sample preparation with HybridSPE supported extraction was most effective for alkylresorcinol extraction, with recoveries of 77-82% from 100 µl of plasma. The use of 96-well plates allowed extraction of 160 samples per day. Using a 5-cm NH2 column and heptane reduced run times to 3 min. The new method had a limit of detection and limit of quantification equivalent to 1.1-1.8 nmol/L and 3.5-6.1 nmol/L plasma, respectively, for the different alkylresorcinol homologues. Accuracy was 93-105%, and intra- and inter-batch precision values were 4-18% across different plasma concentrations. This method makes it possible to quantify plasma alkylresorcinols in 100 µl of plasma at a rate of at least 160 samples per day without the need for large volumes of organic solvents.

Food Reward after a Traditional Inuit or a Westernised Diet in an Inuit Population in Greenland.

The food availability and dietary behaviours in Greenland have changed with increasing Westernisation. Food reward is an important driver of food choice and intake, which has not previously been explored in the Arctic population. The aim of this study was to explore differences in food reward after a four-week intervention period with a traditional Inuit diet (TID) or Westernised diet (WD) in Inuit populations in Northern and Western Greenland. This cross-sectional analysis included 44 adults (n = 20 after TID and n = 24 after WD). We assessed the food reward components, explicit liking and implicit wanting, using the Leeds Food Preference Questionnaire under standardised conditions 60 min after drinking a glucose drink as part of an oral glucose tolerance test after four weeks following a TID or WD. The food intake was assessed using food frequency questionnaires. The intervention groups differed only in implicit wanting for high-fat sweet foods, with higher implicit wanting among the participants following TID compared to WD. Both groups had lower explicit liking and implicit wanting for sweet relative to savoury foods and for high-fat relative to low-fat foods. This exploratory study can guide future studies in Inuit populations to include measures of food reward to better understand food intake in the Arctic.

The role of a traditional and western diet on glucose homeostasis in Greenlandic Inuit carriers and non-carriers of type 2 diabetes variant in the TBC1D4 gene: A protocol for a randomized clinical trial.

INTRODUCTION: The lifestyle of Inuit in Greenland and worldwide is undergoing a transition from a fisher-hunter to a westernized society and meanwhile the prevalence of type-2 diabetes (T2D) has increased dramatically. Studies have shown that a common nonsense p.Arg684Ter variant in TBC1D4, which is frequent in Greenland, confers genetic susceptibility towards high risk of T2D. The aim of the study is to investigate whether a traditional marine diet, with high fat and low carbohydrate, will improve glycemic control in Greenland Inuit compared to a western diet. Moreover, we want to examine if the response is more pronounced in carriers of the p.Arg684Ter variant. MATERIALS AND METHODS: We will conduct a randomized, clinical cross-over trial with two dietary intervention periods of four weeks duration. The diet intervention comprise provision of >20E% and instruction for the remaining part of the diet. We expect to include 30 homozygous carriers and 30 homozygous non-carriers of the p.Arg684Ter variant, aged 18-80 years, across three Greenlandic towns. The primary outcome is plasma (p)-glucose 2 h post an oral glucose tolerance test and we aim to have 80% power, at α = 0.05, to detect a difference of 1.1 mmol/L. We will also include supporting measures of glucose homeostasis, assess other markers of the metabolic syndrome and perform metabolome and microbiome profiling. The statistical analysis will be performed as complete case analyses using linear mixed models. ETHICS AND DISSEMINATION: The study received approval by the Ethics Committee of Greenland (KVUG 2018-26) and will be disseminated via international peer-reviewed journal articles and conferences. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier no. NCT04011904.

Maternal milk microbiota and oligosaccharides contribute to the infant gut microbiota assembly.

Breastfeeding protects against diseases, with potential mechanisms driving this being human milk oligosaccharides (HMOs) and the seeding of milk-associated bacteria in the infant gut. In a cohort of 34 mother-infant dyads we analyzed the microbiota and HMO profiles in breast milk samples and infant's feces. The microbiota in foremilk and hindmilk samples of breast milk was compositionally similar, however hindmilk had higher bacterial load and absolute abundance of oral-associated bacteria, but a lower absolute abundance of skin-associated Staphylococcus spp. The microbial communities within both milk and infant's feces changed significantly over the lactation period. On average 33% and 23% of the bacterial taxa detected in infant's feces were shared with the corresponding mother's milk at 5 and 9 months of age, respectively, with Streptococcus, Veillonella and Bifidobacterium spp. among the most frequently shared. The predominant HMOs in feces associated with the infant's fecal microbiota, and the dominating infant species B. longum ssp. infantis and B. bifidum correlated inversely with HMOs. Our results show that breast milk microbiota changes over time and within a feeding session, likely due to transfer of infant oral bacteria during breastfeeding and suggest that milk-associated bacteria and HMOs direct the assembly of the infant gut microbiota.

Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation, Which Associates With Body Composition in the Offspring.

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring's lean mass and early growth.

The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial.

BACKGROUND: Protein supplementation alone or combined with resistance training has been proposed to be effective in counteracting age-related losses of muscle mass and strength. OBJECTIVES: To investigate the effect of protein supplementation alone or combined with light-intensity or heavy-load resistance exercise on muscle size, strength, and function in older adults. METHODS: In a 1-y randomized controlled trial, 208 healthy older adults (>65 y) were randomly assigned to 1 of 5 interventions: 1) carbohydrate supplementation (CARB); 2) collagen protein supplementation (COLL); 3) whey protein supplementation (WHEY); 4) light-intensity resistance training 3-5 times/wk with whey protein supplementation (LITW); and 5) heavy resistance training 3 times weekly with whey protein supplementation (HRTW). Protein supplements contained 20 g protein + 10 g carbohydrate, whereas CARB contained 30 g of carbohydrates. All intervention groups received the supplement twice daily. The primary outcome was change in the quadriceps cross-sectional area (qCSA). Secondary outcomes included measures of lower extremity strength and power, functional capabilities, and body composition. RESULTS: There were 184 participants who completed the study. COLL and WHEY did not affect any measured parameter compared to CARB. Compared to WHEY, HRTW improved the qCSA size (between-group difference, +1.68 cm2; 95% CI, +0.41 to +2.95 cm2; P = 0.03), as well as dynamic (+18.4 Nm; 95% CI, +10.1 to +26.6 Nm; P < 10-4) and isometric knee extensor strength (+23.9 Nm; 95% CI, +14.2 to +33.6 Nm; P < 10-5). LITW did not improve the qCSA size, but increased dynamic knee extensor strength compared to WHEY (+13.7 Nm; 95% CI, +5.3 and +22.1 Nm; P = 0.01). CONCLUSIONS: Recommending protein supplementation as a stand-alone intervention for healthy older individuals seems ineffective in improving muscle mass and strength. Only HRTW was effective in both preserving muscle mass and increasing strength. Thus, we recommend that future studies investigate strategies to increase long-term compliance to heavy resistance exercise in healthy older adults. This trial was registered at clinicaltrials.gov as NCT02034760.

Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut.

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum. We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+ T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3). Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.

Breastmilk Lipids and Oligosaccharides Influence Branched Short-Chain Fatty Acid Concentrations in Infants with Excessive Weight Gain.

SCOPE: The aim is to identify breastmilk components associated with fecal concentration of SCFAs and to investigate whether they differ between infants with high weight gain (HW) and normal weight gain (NW). METHODS AND RESULTS: Breastmilk and fecal samples are collected from mother-infant dyads with HW (n = 11) and NW (n = 15) at 5 and 9 months of age. Breastmilk is profiled on ultra-performance LC-quadrupole TOF-MS platform. Fecal SCFAs are quantified using an isotope-labeled chemical derivatization method. Human milk oligosaccharides (HMOs) are quantified using HPLC after fluorescent derivatization. Lower levels of α-linolenic acid, oleic acid, 3-oxohexadecanoic acid, LPE (P-16:0), LPC (16:0), LPC (18:0), PC (36:2) in breastmilk from mothers from the HW-group at 5 months of age is found. Fecal SCFA concentrations are increased during the transition period from breastfeeding to complementary feeding. Fecal butyrate concentration is higher in the NW-group at 9 months of age. Fecal branched SCFAs are positively associated with breastmilk phospholipid levels, free-fatty acid levels, HMO-diversity, sialylated-HMOs, 6'-sialyllactose, and disialyl-lacto-N-hexaose. CONCLUSION: Fecal branched SCFA concentrations seem to be affected by breastmilk lipid and HMO composition. These differences in breastmilk metabolites may partially explain the excessive weight gain in early life.

Daily Protein and Energy Intake Are Not Associated with Muscle Mass and Physical Function in Healthy Older Individuals-A Cross-Sectional Study.

Dietary protein has a pivotal role in muscle mass maintenance with advancing age. However, an optimal dose and distribution of protein intake across the day as well as the interaction with energy intake for the maintenance of muscle mass and physical function in healthy older adults remain to be fully elucidated. The purpose of this study was to examine the association between muscle mass, strength, and physical function, and the total amount and distribution of protein and energy intake across the day in healthy older individuals. The research question was addressed in a cross-sectional study including 184 Danish men and woman (age: 70.2 ± 3.9 years, body mass: 74.9 ± 12.1 kg, Body Mass Index (BMI): 25.4 ± 3.7 kg/m2) where a 3-day dietary registration, muscle mass, strength, and functional measurements were collected. We found that neither daily total protein intake nor distribution throughout the day were associated with muscle mass, strength, or physical function. Consequently, we do not provide an incentive for healthy older Danish individuals who already adhere to the current internationally accepted recommended dietary protein intake (0.83 g/kg/day) to change dietary protein intake or its distribution pattern throughout the day.

Intestinal Enterococcus abundance correlates inversely with excessive weight gain and increased plasma leptin in breastfed infants.

Epidemiological evidence indicates that breastfeeding provides protection against development of overweight/obesity. Nonetheless, a small subgroup of infants undergo excessive weight gain during exclusive breastfeeding, a phenomenon that remains unexplained. Breast milk contains both gut-seeding microbes and substrates for microbial growth in the gut of infants, and a large body of evidence suggests a role for gut microbes in host metabolism. Based on the recently established SKOT III cohort, we investigated the role of the infant gut microbiota in excessive infant weight gain during breastfeeding, including 30 exclusively breastfed infants, 13 of which exhibited excessive weight gain and 17 controls which exhibited normal weight gain during infancy. Infants undergoing excessive weight gain during breastfeeding had a reduced abundance of gut Enterococcus as compared with that observed in the controls. Within the complete cohort, Enterococcus abundance correlated inversely with age/gender-adjusted body-weight, body-mass index and waist circumference, body fat and levels of plasma leptin. The reduced abundance of Enterococcus in infants with excessive weight gain was coupled to a lower content of Enterococcus in breast milk samples of their mothers than seen for mothers in the control group. Together, this suggests that lack of breast milk-derived gut-seeding Enterococci may contribute to excessive weight gain in breastfed infants.

Data integration for prediction of weight loss in randomized controlled dietary trials.

Diet is an important component in weight management strategies, but heterogeneous responses to the same diet make it difficult to foresee individual weight-loss outcomes. Omics-based technologies now allow for analysis of multiple factors for weight loss prediction at the individual level. Here, we classify weight loss responders (N = 106) and non-responders (N = 97) of overweight non-diabetic middle-aged Danes to two earlier reported dietary trials over 8 weeks. Random forest models integrated gut microbiome, host genetics, urine metabolome, measures of physiology and anthropometrics measured prior to any dietary intervention to identify individual predisposing features of weight loss in combination with diet. The most predictive models for weight loss included features of diet, gut bacterial species and urine metabolites (ROC-AUC: 0.84-0.88) compared to a diet-only model (ROC-AUC: 0.62). A model ensemble integrating multi-omics identified 64% of the non-responders with 80% confidence. Such models will be useful to assist in selecting appropriate weight management strategies, as individual predisposition to diet response varies.

Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials.

Background: Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes. Objective: The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes. Design: We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine. Results: When compared with placebo, folate supplementation lowered fasting insulin (WMD: -13.47 pmol/L; 95% CI: -21.41, -5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: -0.57 units; 95% CI: -0.76, -0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (ß = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (ß = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16). Conclusion: Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.

Development of a Mobility Diet Score (MDS) and Associations With Bone Mineral Density and Muscle Function in Older Adults.

Introduction: Reduced bone mineral density (BMD) and muscle function is associated with increased risk of multiple health related issues. Diet may play a role in sustaining BMD and muscle function throughout old age, but much is still to be learned with regards to which specific food groups and dietary patterns that are important for such outcomes. The aim of the current study was to identify food groups important for both BMD and muscle function. Methods: A narrative review was performed on studies published on dietary patterns and their association with BMD and muscle function, respectively. Based on these findings, two dietary indices were constructed characterizing food groups associated with BMD and muscle function, respectively. Associations between adherence to these indices and BMD and muscle function were then investigated in a population of older community-dwelling Danes. Food groups found to be associated with both BMD and muscle function in our study population were suggested for inclusion into a common dietary index named the Mobility Diet Score. Results: In contrast to previous studies, adherence to a dietary index based on foods previously linked to BMD could not be established as important for BMD in our study population of 184 older individuals (53.3% men). We found that adhering to a dietary index characterized by higher intakes of whole grains, dairy products, fish, legumes, nuts, fruit, and vegetables is associated with faster 400 m walking speeds and an increased number of chair stands measured over a 30 s time period. Since no food group could be established as important for both BMD and muscle function in our study population, a Mobility Diet Score could not be established. However, based on our narrative review, the food groups commonly associated with improved BMD and muscle function are similar. Conclusion: Adherence to a dietary index characterized by high intakes of whole grains, dairy products, fish, legumes, nuts, fruit, and vegetables was not found to be associated with BMD in a group of community-dwelling older Danes. However, our results indicate that the adherence to such foods could be important in sustaining physical function in older individuals.

Breastfeeding, Breast Milk Composition, and Growth Outcomes.

Breastfed infants have a growth pattern that is different from formula-fed infants, which is regarded as the optimal growth pattern. Breastfed infants increase more in weight, length, and BMI during the first 2-3 months of life and then have a slower growth velocity up to 12 months. They also have a higher accumulation of fat during early infancy. Breastfed infants have lower levels of circulating IGF-I and insulin, which could be part of the explanation of their growth pattern. Many studies and meta-analyses have examined the association between breastfeeding and later obesity. Most find a moderate reduction in the risk of later obesity, but it has been argued that this could be biased due to residual confounding and reverse causation. From studies in low- and middle-income countries randomizing women to breastfeeding promotion, there was only little effect on early growth. Recent studies have found associations between breast milk composition (total fat, protein, human milk oligosaccharides, adiponectin, leptin, and insulin) and growth. However, the studies are few, and the results are inconsistent. More studies, including studies of maternal factors influencing breast milk composition, are needed to better understand how breastfeeding influences current and later growth and thereby short- and long-term health.

Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women.

Background: Diet is frequently associated with both the development and prevention of type 2 diabetes (T2D), but there is a lack of objective tools for assessing the relation between diet and T2D. Biomarkers of dietary intake are unconfounded by recall and reporting bias, and using multiple dietary biomarkers could help strengthen the link between a healthy diet and the prevention of T2D.Objective: The objective of this study was to explore how diet is related to glucose tolerance status (GTS) and to future development of T2D irrespective of common T2D and cardiovascular disease risk factors by using multiple dietary biomarkers.Design: Dietary biomarkers were measured in plasma from 64-y-old Swedish women with different GTS [normal glucose tolerance (NGT; n = 190), impaired glucose tolerance (IGT; n = 209), and diabetes (n = 230)]. The same subjects were followed up after 5 y to determine changes in glucose tolerance (n = 167 for NGT, n = 174 for IGT, and n = 159 for diabetes). ANCOVA and logistic regression were used to explore baseline data for associations between dietary biomarkers, GTS, and new T2D cases at follow-up (n = 69).Results: Of the 10 dietary biomarkers analyzed, ß-alanine (beef) (P-raw < 0.001), alkylresorcinols C17 and C19 (whole-grain wheat and rye) (P-raw = 0.003 and 0.011), eicosapentaenoic acid (fish) (P-raw = 0.041), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (fish) (P-raw = 0.002), linoleic acid (P-raw < 0.001), oleic acid (P-raw = 0.003), and α-tocopherol (margarine and vegetable oil) (P-raw < 0.001) were associated with GTS, and CMPF (fish) (OR: 0.72; 95% CI: 0.56, 0.93; P-raw = 0.013) and α-tocopherol (OR: 0.71; 95% CI: 0.51, 0.98; P-raw = 0.041) were inversely associated with future T2D development.Conclusions: Several circulating dietary biomarkers were strongly associated with GTS after correction for known T2D risk factors, underlining the role of diet in the development and prevention of T2D. To our knowledge, this study is the first to use multiple dietary biomarkers to investigate the link between diet and disease risk.