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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Duration of Catheter Use in Patients with Diabetes Using Continuous Subcutaneous Insulin Infusion: A Review.

Increasing proportions of patients with diabetes use continuous subcutaneous insulin infusion (CSII) therapy mostly due to its clinical efficacy and flexibility for insulin dosing and adjustments. Some challenges are nevertheless associated with this technology. A key and underlooked component of CSII technical difficulties is the subcutaneous catheter used to infuse insulin. Several adverse events (AEs) have been experienced by patients in relation to catheters, such as blockage, kinking, and insertion site reactions, including irritation, infections, lipohypertrophies etc., all of which could compromise the metabolic control. With the objective of minimizing these AEs, recommendations for changing catheters every 2-3 days have historically been provided by manufacturers based on reports derived from small studies and anecdotal data. The aim of this review was to provide an updated analysis of current recommendations and patients' practices in relation to frequency of catheter change. Our main findings are: (1) adequately designed and powered studies investigating optimal catheter wearing time are still lacking; (2) increasing catheter wearing time is generally associated with increased frequency of catheter AEs; (3) however, interpatient variability is large, with some individuals needing to change their catheters every 2-3 days, whereas others probably being able to keep them in place for longer periods without problems. Further research is thus warranted to provide more solid and evidence-based recommendations while exploring personalized approaches at the same time. Increasing catheter wear life without significant side effects is an important goal to simplify CSII therapy and reduce its associated costs and burdens.

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.