Maternal inflammatory, lipid and metabolic markers and associations with birth and breastfeeding outcomes.

Background: Conditions in utero influence intrauterine and postnatal infant growth and a few studies indicate that maternal inflammation and insulin resistance might affect birth and breastfeeding outcomes. Furthermore, hormones in human milk (HM) may influence infant appetite-regulation and thereby milk intake, but the associations are less understood. Objective: (1) To investigate associations between maternal inflammatory, lipid and metabolic markers and birth and breastfeeding outcomes, and (2) to assess predictors of maternal inflammatory, lipid and metabolic markers in pregnancy. Methods: Seventy-one mother-infant dyads participating in the Mothers, Infants and Lactation Quality (MILQ) study were included in the present study. Fasting blood samples were collected around 28th gestational week, and HM samples at three time points from 1.0 to 8.5 months, where milk intake was assessed using 24-h test weighing. Maternal plasma inflammatory, lipid and metabolic markers included high-sensitive C-reactive protein (hs-CRP), tumor-necrosis factor-α (TNFα), interferon-γ (IFNγ), Interleukin (IL)-6, IL-8, high-, low-, and very-low-density lipoprotein (HDL, LDL, VLDL), total-cholesterol, triglycerides, leptin, adiponectin, insulin, C-peptide, the homeostasis model assessment of insulin resistance (HOMA-IR) and glucose concentration at t = 120 min following an oral glucose tolerance test. Of these, TNFα, IFNγ, IL-6, IL-8, leptin, adiponectin and insulin were also measured in HM samples. Results: HDL in pregnancy was inversely associated with gestational age (GA) at birth and GA-adjusted birthweight z-score, whereas triglycerides and glucose (t = 120) were positively associated with GA-adjusted birthweight z-score. Higher hs-CRP, VLDL and triglycerides were associated with a higher placental weight. Furthermore, higher HDL, insulin, leptin and HOMA-IR were associated with longer duration of exclusive breastfeeding (EBF). Higher pre-pregnancy BMI was the main predictor of higher levels of hs-CRP, log-TNFα, leptin, insulin, C-peptide, and HOMA-IR. Conclusion: Maternal lipid and metabolic markers influenced birthweight z-score and placental weight as well as duration of EBF. Furthermore, pre-pregnancy BMI and maternal age predicted levels of several inflammatory and metabolic markers during pregnancy. Our findings indicate that maternal lipid and metabolic profiles in pregnancy may influence fetal growth and breastfeeding, possibly explained by overweight and/or higher placental weight. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT03254329.

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.

Early Nutrition and Its Effect on Growth, Body Composition, and Later Obesity.

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Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes.

Background: Appetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants' milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad. Objective: We aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively. Materials and methods: Maternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations. Results: A positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to < 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (p interaction < 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes. Conclusion: Our main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition. Clinical trials registry number: NCT03254329.

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.