Associations of prenatal exposure to impaired glucose tolerance with eating in the absence of hunger in early adolescence.

OBJECTIVE: Exposure to impaired gestational glucose tolerance has been shown to have sex-specific associations with offspring obesity risk, perhaps by affecting the development of appetite regulation. We examined the extent to which prenatal exposure to impaired glucose tolerance was associated with eating in the absence of hunger (EAH) in early adolescent offspring, and in turn, whether EAH was cross-sectionally associated with body composition. METHODS: We included data from 1097 adolescents participating in Project Viva, a pre-birth longitudinal cohort. We obtained the results of two-stage prenatal glycemic screening (50 g glucose challenge test, followed if abnormal by 100 g oral glucose tolerance test) at 26-28 weeks of gestation, and categorized mothers as having normal glucose tolerance, isolated hyperglycemia (IH, n = 92, 8.4%), impaired glucose tolerance (IGT, n = 36, 3.3%), or gestational diabetes mellitus (GDM, n = 52, 4.7%). At a median age of 13 years, offspring reported on two modified items of the Eating in the Absence of Hunger in Children and Adolescents questionnaire, we measured height and weight, and performed dual X-ray absorptiometry scans to assess fat and fat-free mass. We used multivariable linear regression analyses adjusted for sociodemographic and prenatal covariates, including maternal pre-pregnancy BMI. RESULTS: On a ten-point scale, the mean (SD) EAH score was 4.4 points (SD = 1.5) in boys and 4.4 (SD = 1.4) in girls. In girls, prenatal exposure to both IH and IGT was associated with more EAH compared with normal glucose tolerance (e.g., for IH: 0.56 points, 95% CI: 0.17, 0.96), whereas in boys, prenatal exposure to IGT was associated with less EAH (-0.81 points, 95% CI: -1.41, -0.21). We did not observe an association between exposure to GDM and EAH, nor did we observe associations between EAH and body composition in early adolescence. CONCLUSIONS: These findings suggest sex-specific associations of exposure to impaired gestational glucose tolerance with offspring EAH in early adolescence.

Early-Life Exposures and Risk of Diabetes Mellitus and Obesity.

PURPOSE OF REVIEW: Type 2 diabetes is a growing concern worldwide with increasing incidence in youth. Development of preventive strategies in earlier stages of life is crucial. We aimed to examine epidemiological evidence of early-life exposures and their associations with childhood and later risk of obesity and diabetes, and to discuss potential mechanisms. RECENT FINDINGS: Parental obesity and diabetes in the preconception period may influence offspring's obesity risk via epigenetic mechanisms influencing gametogenesis and early development that could have significant transgenerational effects. A more comprehensive understanding of these effects is needed to identify possible avenues for interventions in both fathers and mothers to be. In addition, current evidence suggests that growth and body weight trajectories in infancy and childhood are useful indicators of later obesity and type 2 diabetes. Moreover, the composition and variations in the microbiome in early life are associated with long-term health and could mediate associations between several early-life exposures and later risk of diseases. Altogether, the epidemiological evidence supports the need for preconception and early-life interventions to reduce the obesity and diabetes burden in later life.

The challenges of achieving postprandial glucose control using closed-loop systems in patients with type 1 diabetes.

For patients with type 1 diabetes, closed-loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared with conventional therapy. Yet, reducing glucose excursion and simplification of prandial insulin doses remain a challenge. The objective of this literature review is to examine current meal-time strategies in the context of automated delivery systems in adults and children with type 1 diabetes. Current challenges and considerations for post-meal glucose control will also be discussed. Despite promising results with meal detection, the fully automated CLS has yet failed to provide comparable glucose control to CLS with carbohydrate-matched bolus in the post-meal period. The latter strategy has been efficient in controlling post-meal glucose using different algorithms and in various settings, but at the cost of a meal carbohydrate counting burden for patients. Further improvements in meal detection algorithms or simplified meal-priming boluses may represent interesting avenues. The greatest challenges remain in regards to the pharmacokinetic and dynamic profiles of available rapid insulins as well as sensor accuracy and lag-time. New and upcoming faster acting insulins could provide important benefits. Multi-hormone CLS (eg, dual-hormone combining insulin with glucagon or pramlintide) and adjunctive therapy (eg, GLP-1 and SGLT2 inhibitors) also represent promising options. Meal glucose control with the artificial pancreas remains an important challenge for which the optimal strategy is still to be determined.

Impact of macronutrient content of meals on postprandial glucose control in the context of closed-loop insulin delivery: A randomized cross-over study.

The aim of this randomized four-way cross-over study was to examine the effect of added protein and/or fat in standard meals with a fixed carbohydrate content on postprandial glucose control with closed-loop insulin delivery in adults with type 1 diabetes. Participants (n = 15) consumed breakfast meals with a fixed carbohydrate content (75 ± 1 g) and added protein and/or fat (35 ± 2 g): (1) carbohydrate-only (standard), (2) high protein (HP), (3) high fat (HF) and (4) high fat + protein (HFHP). The closed-loop insulin delivery algorithm generated insulin bolus and infusion rates. The addition of fat, protein or both did not impact 5-hour post-meal sensor glucose area under the curve (AUC) (main outcome), mean sensor glucose or glycaemic peak as compared with a standard meal (P > 0.05). However, time to glycaemic peak was delayed by 40 minutes (P = 0.03) and 5-hour post-meal basal insulin requirements were 39% higher (P = 0.04) with an HFHP meal compared with a standard meal. In conclusion, in the context of closed-loop insulin delivery, protein and/or fat meal content affects the timing of postprandial glycaemic peak, insulin requirements and late glycaemic excursion, without impacting overall 5-hour AUC.

Dietary behaviors throughout childhood are associated with adiposity and estimated insulin resistance in early adolescence: a longitudinal study.

BACKGROUND: Despite the growing prevalence of excess weight and prediabetes in children, the contributing role of dietary behaviors throughout childhood remains poorly understood. We examined longitudinal associations of dietary behaviors throughout childhood with adiposity and estimated insulin resistance (HOMA-IR) in adolescence. METHODS: Among 995 children from Project Viva, a pre-birth cohort, we examined associations of child dietary behaviors (frequency of eating breakfast, fast food, family dinner, and eating meals while watching television) reported annually throughout childhood (from ages 4 to 11 years) with body mass index z-score (BMI-z; n = 991), waist circumference (WC; n = 995), DXA overall and central adiposity measurements (n = 721), and HOMA-IR (n = 579) in early adolescence (13.2 ± 0.9 years old). We used mixed effects models adjusted for potential confounders. RESULTS: Eating breakfast daily throughout childhood was associated with lower BMI-z and DXA-measured overall and central adiposity in boys and girls (e.g. for whole-body fat %: ß - 1.43% [95% CI: -2.42, - 0.45] and - 1.47% [- 2.25, - 0.68]), and with lower HOMA-IR in boys (% difference - 15.6% [- 22.7, - 7.9]). Daily family dinner and eating fast food less than once per week throughout childhood were both associated with lower BMI-z and adiposity in girls (for BMI-z: ß - 0.17 units [- 0.24, - 0.11] and ß - 0.09 units [- 0.17, - 0.02]) and lower insulin resistance in boys (% difference - 7.3% [- 12.4,- 1.8] and - 7.6% [- 13.2, - 1.7]). Finally, eating meals while watching television < 1/week throughout childhood was associated with lower adolescent adiposity (e.g. WC: - 1.55 cm [- 2.39, - 0.71]) and HOMA-IR (% difference: - 10.7% [- 15.8, - 5.2]) in boys. CONCLUSION: Healthful dietary behaviors throughout childhood are associated with less adiposity and lower estimated insulin resistance in early adolescence. TRIAL REGISTRATION: NCT02820402.

Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use.

The role of glucagon in the pathophysiology of diabetes has long been recognized, although its approved clinical use has so far been limited to the emergency treatment of severe hypoglycaemia. A novel use of glucagon as intermittent mini-boluses is proposed in the dual-hormone version (insulin and glucagon) of the external artificial pancreas. Short-term studies suggest that the incorporation of glucagon into artificial pancreas systems has the potential to further decrease hypoglycaemic risk and improve overall glucose control; however, the potential long-term safety and benefits also need to be investigated given the recognized systemic effects of glucagon. In the present report, we review the available animal and human data on the physiological functions of glucagon, as well as its pharmacological use, according to dosing and duration (acute and chronic). Along with its main role in hepatic glucose metabolism, glucagon affects the cardiovascular, renal, pulmonary and gastrointestinal systems. It has a potential role in weight reduction through its central satiety function and its role in increasing energy expenditure. Most of the pharmacological studies investigating the effects of glucagon have used doses exceeding 1 mg, in contrast to the mini-boluses used in the artificial pancreas. The available data are reassuring but comprehensive human studies using small but chronic glucagon doses that are close to the physiological ranges are lacking. We propose a list of variables that could be monitored during long-term trials of the artificial pancreas. Such trials should address the questions about the risk-benefit ratio of chronic glucagon use.

Lifestyle and cardiometabolic risk in adults with type 1 diabetes: a review.

Over the past decades, there has been a major upward shift in the prevalence of cardiometabolic risk (CMR) factors (central obesity, insulin resistance, hypertension and dyslipidemia) in patients with type 1 diabetes, which could have either an additive or a synergistic effect on risk for cardiovascular disease. These metabolic changes are occurring in parallel to the worldwide obesity epidemic and the widespread use of intensive insulin therapy. Poor lifestyle habits (poor diet quality, sedentary behaviours and smoking) are known to be driving factors for increased CMR factors in the general population. The objective of this review is to explore the lifestyle habits of adults with type 1 diabetes and its potential association with CMR factors. Evidence suggests that adherence to dietary guidelines is low in subjects with type 1 diabetes with a high prevalence of patients consuming an atherogenic diet. Sedentary habits are also more prevalent than in the general population, possibly because of the additional contribution of exercise-induced hypoglycemic fear. Moreover, the prevalence of smokers is still significant in the population with type 1 diabetes. All of these behaviours could trigger a cascade of metabolic anomalies that may contribute to increased CMR factors in patients with type 1 diabetes. The intensification of insulin treatment leading to new daily challenges (e.g. carbohydrates counting, increase of hypoglycemia) could contribute to the adoption of poor lifestyle habits. Preventive measures, such as identification of patients at high risk and promotion of lifestyle changes, should be encouraged. The most appropriate therapeutic measures remain to be established.

Construct validity and reliability of a French-Canadian translation of the eating in the absence of hunger questionnaire for children and adolescents.

Eating in the absence of hunger (EAH) has been associated with overweight and obesity during childhood. The gold standard to assess this behavior is a laboratory-based protocol, but a questionnaire to assess EAH more efficiently in children and adolescents has been developed and validated in English. We assessed construct validity (structural and convergent validity) and reliability (internal consistency and temporal stability) of a French translation of the EAH Questionnaire for Children and Adolescents among French-Canadian youths. We recruited participants in Montreal (Canada) aged 7-15 years old, who completed the questionnaire and provided anthropometric data. We asked participants to complete the questionnaire a second time ~4 weeks later. The questionnaire consists of 14 questions and 3 subscales that assess EAH due to negative affect, fatigue/boredom and external cues. We performed an exploratory factor analysis to test the factor structure and we calculated Cronbach alpha coefficients and intra-class correlations to assess internal consistency and temporal stability, respectively. We assessed associations between EAH and BMI z-score using Pearson correlations. We included 196 participants (50% girls; mean (SD) 11.9 (2.3) years old) for the first completion and 153 for the second completion. The exploratory factor analysis generated the same 3 subscales as the original questionnaire: negative affect (α=0.86; ICC=0.78), fatigue/boredom (α=0.75; ICC=0.70), and external cues (α=0.68; ICC=0.68). Participant's BMI z-scores were positively associated with the average scores from the negative affect subscale (r=0.19; ρ=0.009). Our results suggest that this questionnaire had an adequate construct validity, internal consistency, and temporal stability.

Use of glycated hemoglobin and waist circumference for diabetic screening in women with a history of gestational diabetes.

OBJECTIVE: Although their risk of type 2 diabetes is markedly increased, women with prior gestational diabetes mellitus (GDM) do not receive appropriate testing following their pregnancy. Identifying a less burdensome testing method might increase postpartum testing rates. Our objective was to examine the adequacy of glycated hemoglobin (A1C) and waist circumference (WC) measurements to detect impaired glucose metabolism among women with prior GDM. METHODS: The analysis included 178 women who had GDM between 2003 and 2010. WC and A1C were measured, and a 75g 2h-OGTT was performed. Pre-diabetes was defined as a fasting plasma glucose (FPG) ≥ 5.6 and < 7.0 mmol/L or a 2-hour plasma glucose (2h-PG) ≥ 7.8 and < 11.0 mmol/L, and type 2 diabetes was defined as a FPG ≥ 7.0 mmol/L and/or a 2h-PG ≥ 11.1 mmol/L. Sensitivity and specificity analyses were performed. RESULTS: The mean age of subjects was 36.4 ± 4.8 years, and testing occurred at a mean 3.5 ± 1.9 years following delivery. Combining A1C ≥ 5.7% and WC ≥ 88 cm to detect pre-diabetes had a sensitivity of 76% and specificity of 62%, and to detect type 2 diabetes it had a sensitivity of 91% and specificity of 34%. Compared with women who had A1C and WC within the normal range, women with A1C ≥ 5.7% and WC ≥ 88 cm were more likely to have type 2 diabetes (OR 4.4; 95% CI 2.0 to 9.9). CONCLUSION: These analyses suggest that the combination of A1C and WC could represent a sensitive test for pre-diabetes and type 2 diabetes in the years following a pregnancy complicated by GDM. Further validation of this testing method is required.

Objectif : Bien que leur risque de présenter un diabète de type 2 connaisse une hausse considérable, les femmes ayant déjà connu un diabète sucré gestationnel (DSG) ne bénéficient pas de services de dépistage adéquats à la suite de leur grossesse. L'identification d'une méthode de dépistage moins lourde pourrait accroître les taux de dépistage postpartum. Nous avions pour objectif d'examiner le caractère adéquat des mesures du taux d'hémoglobine glyquée (A1C) et du tour de taille (TT) pour ce qui est de la détection de l'altération du métabolisme du glucose chez les femmes ayant déjà connu un DSG. Méthodes : L'analyse portait sur 178 femmes ayant connu un DSG entre 2003 et 2010. Le TT et le taux d'A1C ont été mesurés, et une épreuve d'hyperglycémie provoquée par voie orale (75 g, 2 h) a été menée. Le prédiabète a été défini comme étant une glycémie à jeun (GJ) ≥ 5,6 et < 7,0 mmol/l ou une glycémie à 2 heures (G-2 h) ≥ 7,8 et < 11,0 mmol/l, tandis que le diabète de type 2 a été défini comme étant une GJ ≥ 7,0 mmol/l et/ou une G-2 h ≥ 11,1 mmol/l. Des analyses de sensibilité et de spécificité ont été menées. Résultats : L'âge moyen des sujets était de 36,4 ± 4,8 ans et le dépistage s'est déroulé, en moyenne, 3,5 ± 1,9 ans à la suite de l'accouchement. La combinaison d'un taux de A1C ≥ 5,7 % et d'un TT ≥ 88 cm pour détecter le prédiabète comptait une sensibilité de 76 % et une spécificité de 62 %; pour ce qui est de la détection du diabète de type 2, cette combinaison comptait une sensibilité de 91 % et une spécificité de 34 %. Par comparaison avec les femmes qui présentaient un taux d'A1C et un TT se situant dans la plage normale, les femmes qui présentaient un taux d'A1C ≥ 5,7 % et un TT ≥ 88 cm étaient plus susceptibles de connaître un diabète de type 2 (RC, 4,4; IC à 95 %, 2,0 - 9,9). Conclusion : Ces analyses semblent indiquer que la combinaison du taux d'A1C et de la mesure du TT pourrait constituer un test sensible pour le dépistage du prédiabète et du diabète de type 2 au cours des années qui suivent une grossesse ayant été compliquée par la présence d'un DSG. La tenue d'autres études permettant de valider cette méthode de dépistage s'avère requise.

Are Complementary Feeding Practices Aligned with Current Recommendations? A Narrative Review.

The complementary feeding introduction period (introduction of solid foods alongside breastmilk or formula) is defining in children's health; however, it appears that many parents do not follow complementary feeding guidelines. Our aim was to describe current parental feeding practices during complementary feeding in relation to current recommendations and explore determinants of adherence to guidelines. We included any relevant studies published within the last decade in French or English and summarized findings by recommendation category. The timing of complementary food introduction varied widely across and within continents (earlier in North America and often delayed in Asia). The introduction of allergenic foods tended to be delayed globally. Although some parents now begin complementary feeding with solid foods (i.e., baby-led weaning), delayed introduction of lumpy textures was still prevalent in the United States and in Europe. The consumption of iron-rich foods was predominantly low in Africa. Added sugars were globally introduced early, especially in America. Evidence for the prevalence of responsive feeding practices among parents is unclear due to the small number of studies. Determinants of complementary feeding practices included parental characteristics, such as age, education, socio-economic status, and race/ethnicity. Interventions aiming to increase adherence to complementary feeding guidelines must account for parental characteristics.

Non-severe hypoglycemia in type 1 diabetes: a randomized crossover trial comparing two quantities of oral carbohydrates at different insulin-induced hypoglycemia ranges.

Aims: Non-severe hypoglycemia (NS-H) is challenging for people living with type 1 diabetes (PWT1D) and often results from relative iatrogenic hyper-insulinemia. Current guidelines recommend a one-size-fits-all approach of 15-20 g of simple carbohydrates (CHO) every 15 min regardless of the triggering conditions of the NS-H event. We aimed to test different amounts of CHO to treat insulin-induced NS-H at various glucose ranges. Methods: This is a randomized, four-way, crossover study involving PWT1D, testing NS-H treatment outcomes with 16 g vs. 32 g CHO at two plasma glucose (PG) ranges: A: 3.0-3.5 mmol/L and B: <3.0 mmol/L. Across all study arms, participants consumed an additional 16 g of CHO if PG was still <3.0 mmol/L at 15 min and <4.0 mmol/L at 45 min post-initial treatment. Subcutaneous insulin was used in a fasting state to induce NS-H. Participants had frequent venous sampling of PG, insulin, and glucagon levels. Results: Participants (n = 32; 56% female participants) had a mean (SD) age of 46.1 (17.1) years, had HbA1c at 54.0 (6.8 mmol/mol) [7.1% (0.9%)], and had a diabetes duration of 27.5 (17.0) years; 56% were insulin pump users. We compared NS-H correction parameters between 16 g and 32 g of CHO for range A, 3.0-3.5 mmol/L (n = 32), and range B, <3.0 mmol/L (n = 29). Change in PG at 15 min for A: 0.1 (0.8) mmol/L vs. 0.6 (0.9) mmol/L, p = 0.02; and for B: 0.8 (0.9) mmol/L vs. 0.8 (1.0) mmol/L, p = 1.0. Percentage of participants with corrected episodes at 15 min: (A) 19% vs. 47%, p = 0.09; (B) 21% vs. 24%, p = 1.0. A second treatment was necessary in (A) 50% vs. 15% of participants, p = 0.001; (B) 45% vs. 34% of participants, p = 0.37. No statistically significant differences in insulin and glucagon parameters were observed. Conclusions: NS-H, in the context of hyper-insulinemia, is difficult to treat in PWT1D. Initial consumption of 32 g of CHO revealed some advantages at the 3.0-3.5 mmol/L range. This was not reproduced at lower PG ranges since participants needed additional CHO regardless of the amount of initial consumption. Clinical trial registration: ClinicalTrials.gov, identifier NCT03489967.

Precision gestational diabetes treatment: a systematic review and meta-analyses.

BACKGROUND: Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus. METHODS: We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions. RESULTS: There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis. CONCLUSIONS: Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies.

Gestational diabetes (GDM) is high blood sugar first detected during pregnancy. Normalizing blood sugar levels quickly is important to avoid pregnancy complications. Many women achieve this with lifestyle changes, such as to diet, but some need to inject insulin or take tablets. We did two thorough reviews of existing research to see if we could predict which women need medication. Firstly we looked for ways to identify the characteristics of women who benefit most from changing their lifestyles to treat GDM, but found very limited research on this topic. We secondly searched for characteristics that help identify women who need medication to treat GDM. We found some useful characteristics that are obtained during routine pregnancy care. Further studies are needed to test if additional information could provide even better information about how we could make GDM treatment more tailored for individuals during pregnancy.

Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Factors Associated with Eating in the Absence of Hunger among Children and Adolescents: A Systematic Review.

Eating in the absence of hunger (EAH) has been extensively studied over the past two decades and has been associated with excess body weight and the development of obesity. However, determinants of EAH remain uncertain. This systematic review aims to identify individual, familial, and environmental factors associated with EAH among children and adolescents. We included studies with a measure of EAH in participants aged 3-17 years old and including ≥1 factor associated with EAH. Our search identified 1494 articles. Of these, we included 81 studies: 53 cross-sectional, 19 longitudinal and nine intervention studies. In childhood (≤12 years old), EAH increases with age, it is greater in boys compared to girls, and it is positively associated with adiposity. Moreover, EAH development seems to be influenced by genetics. In adolescence, the number of studies is limited; yet, studies show that EAH slightly increases or remains stable with age, is not clearly different between sexes, and findings for overweight or obesity are less consistent across studies in adolescence. For familial factors, parental restrictive feeding practices are positively associated with EAH during childhood, mostly for girls. Studies assessing environmental factors are lacking and robust longitudinal studies spanning from early childhood to adolescence are needed.

Estimated causal effects of complementary feeding behaviors on early childhood diet quality in a US cohort.

BACKGROUND: Complementary feeding (CF) provides an opportunity to shape children's future dietary habits, setting the foundation for good nutrition and health. OBJECTIVES: We estimated effects of 3 CF behaviors on early childhood diet quality using inverse probability (IP) weighting of marginal structural models (MSMs). METHODS: Among 1041 children from the Boston-area Project Viva cohort, we estimated effects on the mean Youth Healthy Eating Index (YHEI) score in early childhood of 1) delayed (≥12 mo) compared with early (<12 mo) introduction of sweets and fruit juice; 2) continued compared with ceased offering of initially refused foods; and 3) early (<12 mo) compared with late (≥12 mo) introduction of flavor/texture variety. Mothers reported CF behaviors at 1 y and completed FFQs for children in early childhood (median age: 3.1 y). We estimated average treatment effects (ATEs) using IP weighting of MSMs to adjust for both confounding and selection bias due to censored outcomes and examined effect modification by child sex and breastfeeding compared with formula feeding at 6 mo. RESULTS: Twelve percent of mothers delayed introducing sweets/fruit juice, 93% continued offering initially refused foods, and 32% introduced flavor/texture variety early. The mean ± SD YHEI score was 52.8 ± 9.2 points. In adjusted models, we estimated a higher mean YHEI score with delayed (compared with early) sweets and fruit juice among breastfeeding children (ATE: 4.5 points; 95% CI: 1.0, 7.4 points), as well as with continued (compared with ceased) offering of refused foods among females (ATE: 5.4 points; 95% CI: 0.8, 9.1 points). The ATE for early (compared with late) flavor/texture variety was 1.7 points (95% CI: 0.3, 3.2 points) overall and stronger (2.8 points; 95% CI: 0.7, 5.1 points) among the formula-fed group. CONCLUSIONS: Delayed introduction of sweets/juice, continued offering of refused foods, and early flavor/texture variety may all result in higher childhood diet quality. Effects may depend on child sex and infant breastfeeding status.

Patterns of Complementary Feeding Behaviors Predict Diet Quality in Early Childhood.

Infancy is a time of plasticity in development of taste preference. Complementary feeding (CF) may be a "sensitive period" for learning new taste preferences and establishing healthy dietary behaviors that may track later in life. Among 1162 children in the U.S. prospective cohort study Project Viva, we aimed to identify patterns of CF behaviors around 1 year and examine associations with diet quality in early childhood (median age 3.1y). We identified patterns of CF using latent class analysis (LCA) and examined later diet quality based on scores on the Youth Healthy Eating Index (YHEI). We identified four distinct CF patterns (latent classes). Later YHEI scores were highest in the class characterized by "breast milk and delayed sweets and fruit juice" and lowest in the "picky eaters" class. The classes defined as "late flavor introduction and delayed sweets" and "early flavor introduction and more fruit juice" had similar, moderate scores. Our results suggest that CF patterns that increase food acceptance and discourage the innate preference for sweetness may have persistent influences on diet quality.

Associations of Early Parental Concerns and Feeding Behaviors with Child's Diet Quality through Mid-Childhood.

Parental feeding practices have been associated with children's dietary intakes, yet the directionality of these associations remains unclear. Among 1172 mother-child pairs from Project Viva, we aimed to examine associations of parental concerns and feeding behaviors at 2 years (behaviors dichotomized as yes vs. no), with diet quality (Youth Healthy Eating Index; YHEI) in early (mean 3.2, SD 0.3 years; n = 1076) and mid-childhood (mean 7.8, SD 0.7 years; n = 993). We used multivariable linear regression models adjusted for sociodemographic characteristics, parental body mass index (BMI), maternal diet quality in pregnancy, and child's BMI z-score and diet quality at 2 years. Early parental concerns about their child becoming overweight (15%) was associated with lower YHEI (ß -1.54 points; 95%CI -2.75, -0.33; fully adjusted model) in early childhood. Early parental concerns about their child becoming underweight (7%) was associated with lower YHEI (-2.19 points; -4.31, -0.07) in early childhood, but the association was attenuated after adjustment for child's BMI z-score and diet quality at 2 years. We did not find associations of parental restrictive feeding (8%) and parental pressure to eat (47%) with child's YHEI through mid-childhood. In conclusion, we found no evidence that early parental concerns and feeding behaviors independently contribute to child's diet quality through childhood.

Early life exposure to green space and insulin resistance: An assessment from infancy to early adolescence.

BACKGROUND: Recent studies suggest that greater exposure to natural vegetation, or "green space" is associated with lower diabetes risk, possibly through increasing physical activity. However, there is limited research on green space and insulin resistance in youth. We hypothesized greater green space at early-life sensitive time periods would be associated with lower insulin resistance in youth. METHODS: We used data from Project Viva (N = 460), a pre-birth cohort study that recruited pregnant women in eastern Massachusetts, 1999-2002, and followed offspring into adolescence. We defined residential green space exposure at infancy (median age - 1.1 years), early childhood (3.2 years), mid-childhood (7.7 years), and early adolescence (12.8 years), using 30 m resolution Landsat satellite imagery to estimate the Normalized Difference Vegetation Index [NDVI]. Our main outcome was early adolescence estimated insulin resistance (HOMA-IR). We used multiple imputation to account for missing data and multiple linear regression models adjusted for age, sex, race/ethnicity, parental education, household income, and neighborhood median household income. RESULTS: The highest green space tertile had the highest percentage of white participants (85%), college-educated mothers (87%) and fathers (85%), and households with income higher than US$70,000 (86%). Unadjusted models showed that participants living in the highest green space tertile at infancy had a 0.15 unit lower HOMA-IR (95% CI: -0.23, -0.06) in early adolescence, than those living in the lowest tertile. However, in adjusted models, we did not observe evidence of associations between green space from infancy to early adolescence and HOMA-IR in early adolescence, although some point estimates were in the hypothesized direction. For example, participants in the highest green space tertile in infancy had 0.03 units lower HOMA-IR (95%CI: -0.14, 0.08) than those living in the lowest tertile. CONCLUSIONS: Exposure to green space at early life sensitive time periods was not associated with HOMA-IR in youth. Early-life longitudinal studies across diverse populations are needed to confirm or refute our results.

Timing of Complementary Feeding Introduction and Adiposity Throughout Childhood.

OBJECTIVES: To examine associations of the timing of complementary feeding (CF) introduction with adiposity throughout childhood. METHODS: We studied 1013 children from Project Viva. Our exposure was CF introduction, categorized as <4 months (19%), 4 to <6 months (68%; reference group), and ≥6 months of age (14%). Our outcomes included adiposity measures in midchildhood (mean: 7.9 years; SD 0.8; n = 896) and early adolescence (mean: 13.2 years; SD 0.9; n = 850). We used linear regression models adjusted for potential confounders and ran separate models for infants who were breastfed at least partly for ≥4 months (categorized as breastfed; 69%) and infants who were never breastfed or stopped breastfeeding at <4 months (categorized as formula fed; 31%). RESULTS: CF initiated at <4 months was associated with higher adiposity in midchildhood in breastfed children; associations persisted into adolescence for waist circumference, truncal fat mass, and the sum of subscapular and triceps skinfolds (eg, waist circumference: confounder-adjusted ß 2.97 [95% confidence interval (CI) 0.47 to 5.47] cm). The effect estimates were larger in formula-fed children, with more associations persisting into adolescence (eg, waist circumference: adjusted ß 3.42 [95% CI 0.12 to 6.71] cm). CF initiated at ≥6 months was associated with a higher subscapular/triceps skinfold ratio in midchildhood and adolescence (adjusted ß 0.13 [95% CI 0.02 to 0.25]) in formula-fed children. CONCLUSIONS: We found associations of early CF introduction with higher adiposity measurements in breastfed and formula-fed children and associations of late introduction of CF with higher adiposity in formula-fed children.

Mid-Pregnancy Fructosamine Measurement-Predictive Value for Gestational Diabetes and Association with Postpartum Glycemic Indices.

Screening for gestational diabetes mellitus (GDM) during pregnancy is cumbersome. Measurement of plasma fructosamine may help simplify the first step of detecting GDM. We aimed to assess the predictive value of mid-pregnancy fructosamine for GDM, and its association with postpartum glycemic indices. Among 1488 women from Project Viva (mean ± SD: 32.1 ± 5.0 years old; pre-pregnancy body mass index 24.7 ± 5.3 kg/m²), we measured second trimester fructosamine and assessed gestational glucose tolerance with a 50 g glucose challenge test (GCT) followed, if abnormal, by a 100 g oral glucose tolerance test (OGTT). Approximately 3 years postpartum (median 3.2 years; SD 0.4 years), we measured maternal glycated hemoglobin (n = 450) and estimated insulin resistance (HOMA-IR; n = 132) from fasting blood samples. Higher glucose levels 1 h post 50 g GCT were associated with higher fructosamine levels (Pearson's r = 0.06; p = 0.02). However, fructosamine ≥222 µmol/L (median) had a sensitivity of 54.8% and specificity of 48.6% to detect GDM (area under the receiver operating characteristic curve = 0.52); other fructosamine thresholds did not show better predictive characteristics. Fructosamine was also weakly associated with 3-year postpartum glycated hemoglobin (per 1 SD increment: adjusted ß = 0.03 95% CI [0.00, 0.05] %) and HOMA-IR (per 1 SD increment: adjusted % difference 15.7, 95% CI [3.7, 29.0] %). Second trimester fructosamine is a poor predictor of gestational glucose tolerance and postpartum glycemic indices.