Implicit or Unconscious Bias in Diabetes Care.

"Implicit bias," also called "unconscious bias," refers to associations outside of conscious awareness that adversely affect one's perception of a person or group. Awareness of implicit bias has been increasing in the realm of diabetes care. Here, the authors highlight several types of unconscious bias on the part of clinicians and patients, including biases based on race, ethnicity, and obesity. They discuss how these biases can negatively affect patient-centered clinical interactions and diabetes care delivery, and they recommend implementation of evidence-based interventions and other health system policy approaches to reduce the potential impact of such biases in health care settings.

The role of preproglucagon peptides in regulating ß-cell morphology and responses to streptozotocin-induced diabetes.

Insulin secretion from ß-cells is tightly regulated by local signaling from preproglucagon (Gcg) products from neighboring α-cells. Physiological paracrine signaling within the microenvironment of the ß-cell is altered after metabolic stress, such as high-fat diet or the ß-cell toxin, streptozotocin (STZ). Here, we examined the role and source of Gcg peptides in ß-cell function and in response to STZ-induced hyperglycemia. We used whole body Gcg null (GcgNull) mice and mice with Gcg expression either specifically within the pancreas (GcgΔPanc) or the intestine (GcgΔIntest). With lower doses of STZ exposure, insulin levels were greater and glucose levels were lower in GcgNull mice compared with wild-type mice. When Gcg was functional only in the intestine, plasma glucagon-like peptide-1 (GLP-1) levels were fully restored but these mice did not have any additional protection from STZ-induced diabetes. Pancreatic Gcg reactivation normalized the hyperglycemic response to STZ. In animals not treated with STZ, GcgNull mice had increased pancreas mass via both α- and ß-cell hyperplasia and reactivation of Gcg in the intestine normalized ß- but not α-cell mass, whereas pancreatic reactivation normalized both ß- and α-cell mass. GcgNull and GcgΔIntest mice maintained higher ß-cell mass after treatment with STZ compared with control and GcgΔPanc mice. Although in vivo insulin response to glucose was normal, global lack of Gcg impaired glucose-stimulated insulin secretion in isolated islets. Congenital replacement of Gcg either in the pancreas or intestine normalized glucose-stimulated insulin secretion. Interestingly, mice that had intestinal Gcg reactivated in adulthood had impaired insulin response to KCl. We surmise that the expansion of ß-cell mass in the GcgNull mice compensated for decreased individual ß-cell insulin secretion, which is sufficient to normalize glucose under physiological conditions and conferred some protection after STZ-induced diabetes.NEW & NOTEWORTHY We examined the role of Gcg on ß-cell function under normal and high glucose conditions. GcgNull mice had decreased glucose-stimulated insulin secretion, increased ß-cell mass, and partial protection against STZ-induced hyperglycemia. Expression of Gcg within the pancreas normalized these endpoints. Intestinal expression of Gcg only normalized ß-cell mass and glucose-stimulated insulin secretion. Increased ß-cell mass in GcgNull mice likely compensated for decreased insulin secretion normalizing physiological glucose levels and conferring some protection after STZ-induced diabetes.

Insulin Receptor-Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice.

Insulin receptor (IR) expression on the T cell surface can indicate an activated state; however, the IR is also chemotactic, enabling T cells with high IR expression to physically move toward insulin. In humans with type 1 diabetes (T1D) and the NOD mouse model, a T cell-mediated autoimmune destruction of insulin-producing pancreatic ß cells occurs. In previous work, when purified IR+ and IR- T cells were sorted from diabetic NOD mice and transferred into irradiated nondiabetic NOD mice, only those that received IR+ T cells developed insulitis and diabetes. In this study, peripheral blood samples from individuals with T1D (new onset to 14 y of duration), relatives at high-risk for T1D, defined by positivity for islet autoantibodies, and healthy controls were examined for frequency of IR+ T cells. High-risk individuals had significantly higher numbers of IR+ T cells as compared with those with T1D (p < 0.01) and controls (p < 0.001); however, the percentage of IR+ T cells in circulation did not differ significantly between T1D and control subjects. With the hypothesis that IR+ T cells traffic to the pancreas in T1D, we developed a (to our knowledge) novel mouse model exhibiting a FLAG-tagged mouse IR on T cells on the C57BL/6 background, which is not susceptible to developing T1D. Interestingly, these C57BL/6-CD3FLAGmIR/mfm mice showed evidence of increased IR+ T cell trafficking into the islets compared with C57BL/6 controls (p < 0.001). This transgenic animal model provides a (to our knowledge) novel platform for investigating the influence of IR expression on T cell trafficking and the development of insulitis.

Developing Priorities to Alleviate the Long-Term Impact of the COVID-19 Pandemic on Women Engaged in Diabetes Research, Education, and Care: A Concept Mapping Study.

Objective: The aim of this study was to develop priorities through stakeholder engagement to alleviate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the professional careers of women engaged in diabetes research, education, and care. Research Design and Methods: This study used concept mapping, a mixed-methods, multistep process, to generate a conceptual map of recommendations through the following steps: 1) identify stakeholders and develop the focus prompt, 2) generate ideas through brainstorming, 3) structure ideas through sorting and rating on priority and likelihood, 4) analyze the data and create a cluster map, and 5) interpret and use results. Results: Fifty-two participants completed the brainstorming phase, and 24 participated in sorting and rating. The final concept map included seven clusters. Those rated as highest priority were to ensure supportive workplace culture (µ = 4.43); promote practices to achieve gender parity in hiring, workload, and promotion (µ = 4.37); and increase funding opportunities and allow extensions (µ = 4.36). Conclusion: This study identified recommendations for institutions to better support women engaged in diabetes-related work to alleviate the long-term impact of the COVID-19 pandemic on their careers. Some areas were rated as high in priority and high in likelihood, such as ensuring a supportive workplace culture. In contrast, family-friendly benefits and policies were rated as high in priority but low in likelihood of being implemented; these may take more effort to address, including coordinated efforts within institutions (e.g., women's academic networks) and professional societies to promote standards and programs that advance gender equity in medicine.

Short Term Changes in Dietary Fat Content and Metformin Treatment During Lactation Impact Milk Composition and Mammary Gland Morphology.

Maternal health and diet can have important consequences for offspring nutrition and metabolic health. During lactation, signals are communicated from the mother to the infant through milk via macronutrients, hormones, and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring weaning. We found that lactational HFD increased maternal adipose tissue weight, mammary gland adipocyte size, and altered milk lipid composition causing a higher amount of omega-6 (n6) long chain fatty acids and lower omega-3 (n3). Offspring of HFD dams were heavier with more body fat during suckling. Metformin (Met) exposure decreased maternal blood glucose and several milk amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin than HFD, but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to rescue the offspring from the effects of a maternal HFD during lactation.

Maternal Dietary Intake of Total Fat, Saturated Fat, and Added Sugar Is Associated with Infant Adiposity and Weight Status at 6 mo of Age.

BACKGROUND: Whether current dietary guidelines are appropriate for pregnancy and lactation has not been well studied. Many women of reproductive age are not meeting recommendations for dietary components such as fat, added sugar, and fiber. OBJECTIVES: To assess associations between maternal dietary components during pregnancy and lactation and infant growth and adiposity at 6 mo of age. METHODS: Mother-infant dyads (n = 349) from the prospective, observational Mothers and Infants Linked for Healthy Growth study were included (100% fully breastfed for 1 mo; 75% to 6 mo). Daily intake of fat, fiber, and added sugar was obtained using the National Cancer Institute Diet History Questionnaire II during the third trimester of pregnancy and at 1 and 3 mo postpartum. Furthermore, intakes were categorized as meeting/exceeding 2015-2020 Dietary Guidelines for Americans. Multiple linear regression models adjusted for numerous potential confounders tested relations between dietary components and infant adiposity (via DXA) and growth parameters. Regression coefficients (ß) for continuous variables were expressed per SD to allow for comparison of effect sizes. RESULTS: Maternal intake of total fat and saturated fat was positively associated with infant percent body fat (%BF) (ß: 0.84 per SD, P = 0.04; ß: 0.96 per SD, P = 0.01, respectively). Added sugar intake was positively associated with infant weight-for-length z score (ß: 0.16 per SD, P = 0.02), and excessive added sugar intake was positively associated with %BF at 6 mo (ß: 0.75 per SD, P = 0.05). CONCLUSIONS: In a predominantly fully breastfeeding cohort of women, maternal intake of fat and added sugar during pregnancy and lactation were associated with small increases in infant adiposity and relative weight at 6 mo. Additional research is needed to determine if these relations persist later in infancy and if such elevations in adiposity are important for long-term obesity risk.

Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner.

We previously demonstrated that exposing mouse dams to metformin during gestation results in increased beta-cell mass at birth and increased beta-cell insulin secretion in adult male offspring. Given these favorable changes after a gestational maternal metformin exposure, we wanted to understand the long-term metabolic impact on offspring after exposing dams to metformin during the postnatal window. The newborn period provides a feasible clinical window for intervention and is important for beta-cell proliferation and metabolic tissue development. Using a C57BL/6 model, we administered metformin to dams from the day of birth to postnatal day 21. We monitored maternal health and offspring growth during the lactation window, as well as adult glucose homeostasis through in vivo testing. At necropsy we assessed pancreas and adipocyte morphology using histological and immunofluorescent staining techniques. We found that metformin exposure programmed male and female offspring to be leaner with a higher proportion of small adipocytes in the gonadal white adipose tissue (GWAT). Male, but not female, offspring had an improvement in glucose tolerance as young adults concordant with a mild increase in insulin secretion in response to glucose in vivo. These data demonstrate long-term metabolic programming of offspring associated with maternal exposure to metformin during lactation.

Maternal low-protein diet on the last week of pregnancy contributes to insulin resistance and ß-cell dysfunction in the mouse offspring.

Maternal low-protein diet (LP) throughout gestation affects pancreatic ß-cell fraction of the offspring at birth, thus increasing their susceptibility to metabolic dysfunction and type 2 diabetes in adulthood. The present study sought to strictly examine the effects of LP during the last week of gestation (LP12.5) alone as a developmental window for ß-cell programming and metabolic dysfunction in adulthood. Islet morphology analysis revealed normal ß-cell fraction in LP12.5 newborns. Normal glucose tolerance was observed in 6- to 8-wk-old male and female LP12.5 offspring. However, male LP12.5 offspring displayed glucose intolerance and reduced insulin sensitivity associated with ß-cell dysfunction with aging. High-fat diet exposure of metabolically normal 12-wk-old male LP12.5 induced glucose intolerance due to increased body weight, insulin resistance, and insufficient ß-cell mass adaptation despite higher insulin secretion. Assessment of epigenetic mechanisms through microRNAs (miRs) by a real-time PCR-based microarray in islets revealed elevation in miRs that regulate insulin secretion (miRs 342, 143), insulin resistance (miR143), and obesity (miR219). In the islets, overexpression of miR143 reduced insulin secretion in response to glucose. In contrast to the model of LP exposure throughout pregnancy, islet protein levels of mTOR and pancreatic and duodenal homeobox 1 were normal in LP12.5 islets. Collectively, these data suggest that LP diet during the last week of pregnancy is critical and sufficient to induce specific and distinct developmental programming effects of tissues that control glucose homeostasis, thus causing permanent changes in specific set of microRNAs that may contribute to the overall vulnerability of the offspring to obesity, insulin resistance, and type 2 diabetes.

Impact of maternal overweight and obesity on milk composition and infant growth.

Overweight and obesity (OW/OB) impact half of the pregnancies in the United States and can have negative consequences for offspring health. Studies are limited on human milk alterations in the context of maternal obesity. Alterations in milk are hypothesized to impact offspring development during the critical period of lactation. We aimed to evaluate the relationships between mothers with OW/OB (body mass index [BMI] ≥25 kg/m2 ), infant growth, and selected milk nutrients. We recruited mother-infant dyads with pre-pregnancy OW/OB and normal weight status. The primary study included 52 dyads with infant growth measures through 6 months. Thirty-two dyads provided milk at 2 weeks, which was analysed for macronutrients, long-chain fatty acids, and insulin. We used multivariable linear regression to examine the association of maternal weight status with infant growth, maternal weight status with milk components, and milk components with infant growth. Mothers with OW/OB had infants with higher weight-for-length (WFL) and BMI Z-scores at birth. Mothers with OW/OB had higher milk insulin and dihomo-gamma-linolenic, adrenic, and palmitic acids and reduced conjugated linoleic and oleic acids. N6 long-chain polyunsaturated fatty acid (LC-PUFA)-driven factor 1 was associated with higher WFL, lower length-for-age (LFA), and lower head circumference-for-age Z-scores change from 2 weeks to 2 months in human milk-fed infants, whereas N6 LC-PUFA-driven factor 5 was associated with lower LFA Z-score change. Human milk composition is associated with maternal pre-pregnancy weight status and composition may be a contributing factor to early infant growth trajectory.

Lactational programming of glucose homeostasis: a window of opportunity.

The window of lactation is a critical period during which nutritional and environmental exposures impact lifelong metabolic disease risk. Significant organ and tissue development, organ expansion and maturation of cellular functions occur during the lactation period, making this a vulnerable time during which transient insults can have lasting effects. This review will cover current literature on factors influencing lactational programming such as milk composition, maternal health status and environmental endocrine disruptors. The underlying mechanisms that have the potential to contribute to lactational programming of glucose homeostasis will also be addressed, as well as potential interventions to reduce offspring metabolic disease risk.

Metformin; a review of its history and future: from lilac to longevity.

Metformin is a widely prescribed medication that has been used to treat children with type 2 diabetes in the United States for the past 15 years. Metformin now has a variety of clinical applications in pediatrics, and its potential clinical uses continue to expand. In addition to reviewing the current understanding of its mechanisms of action including the newly discovered effects on the gastrointestinal tract, we will also discuss current clinical uses in pediatrics, including in type 1 diabetes. Finally, we examine the existing state of monitoring for metformin efficacy and side effects and discuss prospective future clinical uses.

Vitamin D status in youth with type 1 and type 2 diabetes enrolled in the Pediatric Diabetes Consortium (PDC) is not worse than in youth without diabetes.

OBJECTIVE: To describe vitamin D levels and prevalence of vitamin D sufficiency, insufficiency and deficiency in a large, ethnically/racially diverse population of youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) in comparison to national data and examine the associations between clinical/demographic factors and vitamin D levels. METHODS: 25-hydroxy vitamin D (25OHD) levels were measured in 215 youth with T1D and 326 youth with T2D enrolled in the Pediatric Diabetes Consortium (PDC). These levels were compared with those of youth of the same age without diabetes from the 2005-2006 NHANES Survey. RESULTS: Vitamin D deficiency (<21 ng/mL) was present in 36% of PDC participants, and insufficiency (21-29 ng/mL) was present in an additional 34%. About 36% of age-matched youth in the NHANES Survey were vitamin D deficient and an additional 41% were insufficient. Deficiency or insufficiency varied by race/ethnicity, being highest in African-Americans (86%), intermediate in Hispanics (77%), and lowest in non-Hispanic whites (47%). Lower 25OHD levels were observed in African-American and Hispanic youth, during fall and winter, and at sites in the northern United States (all p-values < 0.001). Youth with T2D had significantly lower 25OHD levels than youth with T1D (p < 0.001), but this difference was largely eliminated after adjusting for race/ethnicity and socio-economic status. CONCLUSIONS: Vitamin D deficiency/insufficiency is present in a substantial proportion of youth with diabetes, particularly minorities, but the prevalence appears similar to that in youth without diabetes. Further studies are needed to examine whether youth with diabetes would benefit from vitamin D supplementation.

C-peptide levels in pediatric type 2 diabetes in the Pediatric Diabetes Consortium T2D Clinic Registry.

OBJECTIVE: To describe C-peptide levels in a large cohort of children with type 2 diabetes T2D and examine associations with demographic and clinical factors. METHODS: The Pediatric Diabetes Consortium (PDC) T2D Registry has collected clinical and biologic data from youth with T2D cared for at eight US Pediatric Diabetes Centers. In this study, we assessed C-peptide levels in 331 youth with T2D (mean age, 16.1 ± 2.5 yr; median T2D duration, 2.4 yr). RESULTS: Median (interquartile range) for 90 fasted C-peptide measurements was 3.5 ng/mL (2.3-4.8 ng/mL) [1.2 nmol/L (0.8-1.6 nmol/L)] and for 241 random non-fasted C-peptide measurements were 4.2 ng/mL (2.6-7.0 ng/mL) [1.4 nmol/L (0.9-2.3 nmol/L)]. C-peptide levels were lower with insulin therapy (p < 0.001), lower body mass index (p < 0.001), hemoglobin A1c (HbA1c) ≥9% (p < 0.001), and T2D duration ≥ 6 yr (p = 0.04). Among those with duration ≥6 yr being treated with insulin and with a HbA1c level ≥9.0% (75 mmol/L), 75% of the fasted and 80% of the non-fasted C-peptide values were above 0.2 nmol/L. CONCLUSIONS: In youth with T2D, a decline in C-peptide is associated with deterioration of metabolic control and the need for insulin treatment. C-peptide levels decrease over time. However, even insulin-treated patients with 6 or more years of T2D and elevated HbA1c levels retain substantial endogenous insulin secretion.

Body mass index changes in youth in the first year after type 1 diabetes diagnosis.

OBJECTIVES: To describe changes in weight and body mass index (BMI) during the first year following diagnosis of type 1 diabetes (T1D) and associations with demographic and clinical characteristics. STUDY DESIGN: The Pediatric Diabetes Consortium includes 7 US centers with prospective longitudinal data from initial T1D diagnosis. This analysis includes 530 youth with diabetes duration of ≥1 year and measures of BMI at 3 and 12 months after diagnosis. BMI trajectory of participants and relationships between the change in BMI z-score from baseline (3 months) to 12 months with demographic characteristics, hemoglobin A1c at baseline, and insulin delivery mode at baseline were evaluated. RESULTS: As a group, BMI z-scores increased sharply from diagnosis for 1-3 months but remained relatively stable from +0.51 at 3 months to +0.48 at 12 months. Children aged 2-<5 years experienced a significant positive change in BMI z-score between 3 and 12 months, and there was a similar trend among girls that did not reach statistical significance. No significant differences were found for race, socioeconomic status, or insulin delivery mode. CONCLUSIONS: These data suggest that increased BMI during the first year of treatment of most youth with T1D reflects regain of weight lost before diagnosis. There is, however, a propensity toward additional weight gain in younger children and girls.

Exposure of mouse embryonic pancreas to metformin enhances the number of pancreatic progenitors.

AIMS/HYPOTHESIS: Developing beta cells are vulnerable to nutrient environmental signals. Early developmental processes that alter the number of pancreatic progenitors can determine the number of beta cells present at birth. Metformin, the most widely used oral agent for treating diabetes, alters intracellular energy status in part by increasing AMP-activated protein kinase (AMPK) signalling. This study examined the effect of metformin on developing pancreas and beta cells. METHODS: Pancreatic rudiments from CD-1 mice at embryonic day 13.0 (E13.0) were cultured with metformin, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR, an AMPK activator) or vehicle control in vitro. In another set of studies, pregnant C57BL/6 mice were treated with metformin throughout gestation. Embryonic (E14.0) and neonatal pancreases were then analysed for their morphometry. RESULTS: In vitro metformin treatment led to an increase in the proliferation and number of pancreatic duodenal homeobox 1-positive (PDX1(+)) progenitors. These results were reproduced by in vitro culture of embryonic pancreas rudiments with AICAR, suggesting that AMPK activation was involved. Similarly, metformin administration to pregnant dams induced an increase in both PDX1(+) and neurogenin 3-positive progenitors in the embryonic pancreas at E14.0 and these changes resulted in an increased beta cell fraction in neonates. CONCLUSIONS/INTERPRETATION: These results indicate that exposure to metformin during gestation modulates the early steps of beta cell development (prior to E14.0) towards an increase in the number of pancreatic and endocrine progenitors. These changes ultimately result in a higher beta cell fraction at birth. These findings are of clinical importance given that metformin is currently used for the treatment of gestational diabetes.

GDF15 knockout does not substantially impact perinatal body weight or neonatal outcomes in mice.

Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used a Gdf15 knockout mouse model (Gdf15-/- ) to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found that Gdf15-/- dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared to Gdf15+/+ dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size, and survival rates were similar between genotypes. There was a modest reduction in birth weight of Gdf15-/- pups, but this difference was no longer evident postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.

Comparative lipidome study of maternal plasma, milk, and lamb plasma in sheep.

Lipids play a critical role in neonate development and breastmilk is the newborn's major source of lipids. Milk lipids directly influence the neonate plasma lipid profile. The milk lipidome is dynamic, influenced by maternal factors and related to the maternal plasma lipidome. The close inter-relationship between the maternal plasma, milk and neonate plasma lipidomes is critical to understanding maternal-child health and nutrition. In this exploratory study, lipidomes of blood and breast milk from Suffolk sheep and matched lamb blood (n = 13), were profiled on day 34 post birth by untargeted mass spectrometry. Comparative multivariate analysis of the three matrices identified distinct differences in lipids and class of lipids amongst them. Paired analysis identified 346 differential lipids (DL) and 31 correlated lipids (CL) in maternal plasma and milk, 340 DL and 32 CL in lamb plasma and milk and 295 DL and 16 CL in maternal plasma and lamb plasma. Conversion of phosphatidic acid to phosphatidyl inositol was the most active pathway in lamb plasma compared to maternal plasma. This exploratory study illustrates the partitioning of lipids across maternal plasma, milk and lamb plasma and the dynamic relationship between them, reiterating the need to study these three matrices as one biological system.

Developmental programming: An exploratory analysis of pancreatic islet compromise in female sheep resulting from gestational BPA exposure.

Developmental exposure to endocrine disruptors like bisphenol A (BPA) are implicated in later-life metabolic dysfunction. Leveraging a unique sheep model of developmental programming, we conducted an exploratory analysis of the programming effects of BPA on the endocrine pancreas. Pregnant ewes were administered environmentally relevant doses of BPA during gestational days (GD) 30-90, and pancreata from female fetuses and adult offspring were analyzed. Prenatal BPA exposure induced a trend toward decreased islet insulin staining and ß-cell count, increased glucagon staining and α-cell count, and increased α-cell/ß-cell ratio. Findings were most consistent in fetal pancreata assessed at GD90 and in adult offspring exposed to the lowest BPA dose. While not assessed in fetuses, adult islet fibrosis was increased. Collectively, these data provide further evidence that early-life BPA exposure is a likely threat to human metabolic health. Future studies should corroborate these findings and decipher the molecular mechanisms of BPA's developmental endocrine toxicity.

Gestational Early-Time Restricted Feeding Results in Sex-Specific Glucose Intolerance in Adult Male Mice.

The timing of food intake is a novel dietary component that impacts health. Time-restricted feeding (TRF), a form of intermittent fasting, manipulates food timing. The timing of eating may be an important factor to consider during critical periods, such as pregnancy. Nutrition during pregnancy, too, can have a lasting impact on offspring health. The timing of food intake has not been thoroughly investigated in models of pregnancy, despite evidence that interest in the practice exists. Therefore, using a mouse model, we tested body composition and glycemic health of gestational early TRF (eTRF) in male and female offspring from weaning to adulthood on a chow diet and after a high-fat, high-sucrose (HFHS) diet challenge. Body composition was similar between groups in both sexes from weaning to adulthood, with minor increases in food intake in eTRF females and slightly improved glucose tolerance in males while on a chow diet. However, after 10 weeks of HFHS, male eTRF offspring developed glucose intolerance. Further studies should assess the susceptibility of males, and apparent resilience of females, to gestational eTRF and assess mechanisms underlying these changes in adult males.