A pilot study of the effects of a high-intensity aerobic exercise session on heart rate variability and arterial compliance in adolescents with or without type 1 diabetes.

Arterial compliance and autonomic regulation are predictors of cardiovascular disease. In adults, both are altered chronically by type 1 diabetes (T1D) and acutely by exercise; however, the effects of T1D and exercise are less clear in adolescents. We measured short-term effects of a high-intensity aerobic interval exercise session on cardiovascular and metabolic variables in normal weight adolescents with T1D or without T1D (Control). Energy expenditure (EE), heart rate variability (HRV), arterial compliance, and blood pressure (BP) were measured before exercise (baseline) and three times over 105 minutes postexercise. The T1D and control groups had similar cardiorespiratory fitness and accelerometer-measured physical activity. The T1D group had higher EE and fat oxidation throughout the trial, but postexercise changes were similar between groups. HRV transiently declined following exercise in both groups, but the T1D group had lower HRV at baseline. Among the measures of arterial compliance, the augmentation index declined postexercise while carotid-femoral pulse wave velocity and large artery elastic index remained unchanged. Central and brachial BP were unchanged following exercise until the final measurement, when a small increase occurred. However, arterial compliance and BP did not differ between groups. These results demonstrate that normal weight adolescents with T1D have impaired autonomic function and increased EE and fat oxidation compared to peers without diabetes who have similar levels of fitness and physical activity. However, acute cardiometabolic responses to exercise are normal in T1D with adequate glycemic control. Changes in arterial compliance and BP may take longer to emerge in relatively healthy adolescents with T1D.

Collaborative implementation of a community-based exercise intervention with a partnering rural American Indian community.

BACKGROUND: The prevalence and socioeconomic burden of childhood obesity and diabetes has increased rapidly in the United States in the last 30 years. American Indians have the highest prevalence of type 2 diabetes among newly diagnosed youth in the country. Contributing factors include environmental, behavioral, and genetic components. Some American Indian tribal communities have explored innovative ways to combat this epidemic including collaborations with academic centers on community-based research. METHOD: From 2012 to 2017, the University of Oklahoma Health Science Center and the Choctaw Nation of Oklahoma partnered on a National Institutes of Health-funded project to determine if financial incentives would elicit an increase in physical activity in Native youth. This was a community-based behavioral intervention for overweight or obese American Indian youth ages 11-20 living in a rural community at risk for developing diabetes. RESULTS: Tribal leaders and staff identified culturally appropriate strategies to aid implementation of the trial in their community. Their identified implementation strategies helped standardize the study in order to maintain study integrity. The mutually agreed strategies included co-review of the study by tribal and University research review boards (but designation of the Choctaw Nation review board as the "Board of Record"), training of community-based staff on research ethics and literacy, standardization of the informed consent process by videotaping all study information, creation of a viable and culturally appropriate timeline for study implementation, adapting tribal wellness center operations to accommodate youth, and development of effective two-way communication through training sessions, on-site coordination, and bi-monthly conference calls. CONCLUSION: In an effort to partner collectively on a randomized clinical research trial to combat childhood diabetes, tribal leaders and staff implemented strategies that resulted in a culturally appropriate and organized community-based behavioral intervention research project.

A single exercise session increases insulin sensitivity in normal weight and overweight/obese adolescents.

We measured the effect of an aerobic exercise session on postprandial glucose control in adolescents with habitually low-physical activity. The goal was to determine if the acute or residual response of exercise was altered in people who are overweight/obese (OW/Ob). Eleven normal weight, body mass index (NW, BMI = 48 ± 13 percentile) and 12 OW/Ob (BMI = 91 ± 5 percentile) participants completed 3 trials. In the no exercise (No Ex) trial, participants rested quietly before and after consuming a test meal. In the other 2 trials, a 45-minute aerobic exercise session was performed either 17-hour (Prior Day Ex) or 40 minutes (Same Day Ex) before the test meal. On all trials, the OW/Ob group had higher fasting glucose (~6%) and insulin (~66%), and lower insulin sensitivity (~9%) than the NW group. The Same Day Ex and Prior Day Ex trials resulted in reduced area under the curve for glucose (6% on both trials, P < .01) and insulin (15% and 13%, respectively, P < .03), and increased insulin sensitivity (8% and 6%, respectively, P < .01). The magnitudes of those effects did not differ between the NW and OW/Ob groups. Plasma fatty acids declined and carbohydrate oxidation increased after the meal, but did not differ among trials or groups. The results demonstrate that moderate intensity aerobic exercise increases insulin sensitivity in NW and OW/Ob adolescents and that the beneficial effects of exercise last up to 17 hours. The acute impact of exercise on metabolic health in adolescents is not impaired in overweight/obese participants.

Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents.

Spexin is a novel peptide that has been reported to be down regulated in obese adults and children and in normoglycemic adults following glucose ingestion. Spexin may therefore have a role in metabolic regulation. The purpose of the current study was to determine the effect of obesity and type 2 diabetes (T2DM), and the effect of glucose ingestion on circulating spexin concentration in adolescents. Boys and girls (mean age 16 years old) classified as healthy normal weight (NW, n = 22), obese (Ob, n = 10), or obese with T2DM (n = 12) completed measurements of body composition, blood pressure, cardiorespiratory fitness, and blood concentrations of glucose, insulin, and lipids. The median fasting serum spexin concentration did not differ between groups (NW: 0.35; Ob: 0.38, T2DM: 0.34 ng/mL, respectively). In 10 NW participants who completed a standard oral glucose tolerance test, spexin concentration was unchanged at 30 and 120 minutes relative to the fasting baseline. Finally, spexin was not significantly correlated with any of the body composition, fitness, or blood biochemical measurements. These data do not support the proposed role of spexin as a metabolic regulator or biomarker of glucose control in adolescents.

Overview of Pediatric Nonalcoholic Fatty Liver Disease: A Guide for General Practitioners.

IMPORTANCE: Nonalcoholic fatty liver disease (NAFLD) is rapidly evolving into one of the most common pediatric liver diseases and currently is the most common cause for liver transplantation in young adults. Therefore, early recognition of risk factors, disease prevention, and diagnosis during childhood is paramount for effective management. OBJECTIVE: The primary objective of this review is to discuss updated recommendations for screening, diagnosis and management of NAFLD. The secondary objective is to review the extent and impact of pediatric NAFLD in Oklahoma through our center's participation in a multi-center prospective study. EVIDENCE REVIEW: We reviewed updated guidelines from the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), the approach used in our clinic and data from a multi-center collaboration on NAFLD, known as TARGET-NASH. FINDINGS: Our review highlights that obese and Hispanic children are at greatest risk for developing NAFLD. Screening with ALT should be considered between ages 9-11 years for children with BMI more than the 95th percentile. Liver biopsy is the gold standard for diagnosis of NAFLD and currently lifestyle modification is the only effective therapy for management of NAFLD. CONCLUSION AND RELEVANCE: All obese children, especially those who are Hispanics or have a family history of NAFLD should be considered for screening with serum ALT between the ages of 9 and 11 years. Children with ALT values that are elevated more than twice the upper limit of normal for more than 3 months must be referred to pediatric hepatology for timely evaluation.

The Effect of Handcycle Ergometer Exercise on Glucose Tolerance in Ambulatory and Non-Ambulatory Adolescents.

PURPOSE: Whole body or leg exercise before a meal can increase insulin sensitivity, but it is unclear whether the same can occur with upper body exercise since a smaller muscle mass is activated. We measured the impact of a single session of handcycle exercise on glucose tolerance and insulin sensitivity. METHODS: Nonambulatory (Non-Amb) adolescents with spina bifida or cerebral palsy (4F/3M), or ambulatory peers (Control, 4F/7M) completed 2 glucose tolerance tests on separate days, preceded by either rest or a 35-min bout of moderate-to-vigorous intermittent handcycle exercise. RESULTS: The Non-Amb group had higher body fat (mean ± SD: 38 ± 12%, Control: 24 ± 9, p = .041) but similar VO2peak (17.7 ± 6.1 ml/kg/min, Control: 21.1 ± 7.9). Fasting glucose and insulin were normal for all participants. Compared with the rest trial, exercise resulted in a reduction in glucose area under the curve (11%, p = .008) without a significant group x trial interaction and no difference in the magnitude of change between groups. Insulin sensitivity was increased 16% (p = .028) by exercise in the Control group but was not significantly changed in the Non-Amb group. CONCLUSION: A single bout of handcycle exercise improves glucose tolerance in adolescents with and without mobility limitations and could therefore help maintain or improve metabolic health.

Glycemic Variability Is Associated with Markers of Vascular Stress in Adolescents.

OBJECTIVES: We used continuous glucose monitoring to test the hypothesis that mean amplitude of glycemic excursions (MAGE) is associated with circulating markers of oxidative and vascular stress in adolescents with habitually low physical activity classified as healthy weight, healthy obese, or obese with type 2 diabetes mellitus (T2DM). STUDY DESIGN: A group of 13- to 21-year-olds (healthy weight = 12, healthy obese = 10, T2DM = 12) wore a continuous glucose monitor and step activity monitor for 5 days. RESULTS: Physical activity was similar among groups (6551 ± 401 steps/d), but aerobic fitness (peak rate of oxygen consumption) was lower (P < .05) in T2DM (15.6 ± 1.8 mL/kg/min) than either healthy weight (26.2 ± 2.2) or healthy obese (24.4 ± 2.5). MAGE (mg/dL) was higher (P < .01) in T2DM (82 ± 10) vs healthy obese (33 ± 3) and healthy weight (30 ± 3). Average glucose followed a similar pattern as MAGE. Oxidized low density lipoprotein was higher (P < .05) in T2DM (70.3 ± 5.0 U/L) and healthy obese (58.1 ± 3.8) than healthy weight (48.4 ± 2) and positively correlated with MAGE (r = 0.77). Other stress markers that were both elevated in T2DM and correlated with MAGE included E-selectin (r = 0.50), intercellular adhesion molecule 1 (r = 0.35), and C-reactive protein (r = 0.52); soluble receptor for advanced glycosylation end product was lower in T2DM and inversely correlated with MAGE (r = -0.38). CONCLUSIONS: MAGE is highest in obese youth with T2DM. The associations between MAGE and oxidative stress markers support the proposed contribution of glycemic variability to risk for future cardiovascular disease.

Lower resting energy expenditure and fat oxidation in Native American and Hispanic infants born to mothers with diabetes.

OBJECTIVE: To determine whether exposure to diabetes in utero affects resting energy expenditure (REE) and fuel oxidation in infants. STUDY DESIGN: At 35 ± 5 days after birth, body composition and REE were measured in full-term offspring of Native American and Hispanic women with either well-controlled diabetes (13 girls, 11 boys) or normal healthy pregnancies (18 girls, 17 boys). RESULTS: Control of dysglycemia during gestation in the women with diabetes mellitus met current clinical standards, shown by average glycated hemoglobin (5.9 ± 0.2%; 40.6 ± 2.3 mmol/mol). Infant body mass (offspring of women with diabetes: 4.78 ± 0.13, control offspring: 4.56 ± 0.08 kg) and body fatness (offspring of women with diabetes: 25.2 ± 0.6, control offspring: 24.2 ± 0.5 %) did not differ between groups. REE, adjusted for lean body mass, was 14% lower in offspring of women with diabetes (41.7 ± 2.3 kJ/h) than control offspring (48.6 ± 2.0, P = .025). Fat oxidation was 26% lower in offspring of women with diabetes (0.54 ± 0.05 g/h) than control offspring (0.76 ± 0.04, P < .01) but carbohydrate oxidation did not differ. Thus, fat oxidation accounted for a lower fraction of REE in the offspring of women with diabetes (49 ± 4%) than control offspring (60 ± 3%, P = .022). Mothers with diabetes were older and had higher prepregnancy body mass index than control mothers. CONCLUSIONS: Well-controlled maternal diabetes did not significantly affect body mass or composition of offspring at 1-month old. However, infants with mothers with diabetes had reduced REE and fat oxidation, which could contribute to adiposity and future disease risk. Further studies are needed to assess the impact differences in age and higher prepregnancy body mass index.

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus.

BACKGROUND: Offspring of women with diabetes mellitus (DM) during pregnancy have a risk of developing metabolic disease in adulthood greater than that conferred by genetics alone. The mechanisms responsible are unknown, but likely involve fetal exposure to the in utero milieu, including glucose and circulating adipokines. The purpose of this study was to assess the impact of maternal DM on fetal adipokines and anthropometry in infants of Hispanic and Native American women. METHODS: We conducted a prospective study of offspring of mothers with normoglycemia (Con-O; n = 79) or type 2 or gestational DM (DM-O; n = 45) pregnancies. Infant anthropometrics were measured at birth and 1-month of age. Cord leptin, high-molecular-weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF) and C-peptide were measured by ELISA. Differences between groups were assessed using the Generalized Linear Model framework. Correlations were calculated as standardized regression coefficients and adjusted for significant covariates. RESULTS: DM-O were heavier at birth than Con-O (3.7 ± 0.6 vs. 3.4 ± 0.4 kg, p = 0.024), but sum of skinfolds (SSF) were not different. At 1-month, there was no difference in weight, SSF or % body fat or postnatal growth between groups. Leptin was higher in DM-O (20.1 ± 14.9 vs. 9.5 ± 9.9 ng/ml in Con-O, p < 0.0001). Leptin was positively associated with birth weight (p = 0.0007) and SSF (p = 0.002) in Con-O and with maternal hemoglobin A1c in both groups (Con-O, p = 0.023; DM-O, p = 0.006). PEDF was positively associated with birth weight in all infants (p = 0.004). Leptin was positively associated with PEDF in both groups, with a stronger correlation in DM-O (p = 0.009). At 1-month, HMWA was positively associated with body weight (p = 0.004), SSF (p = 0.025) and % body fat (p = 0.004) across the cohort. CONCLUSIONS: Maternal DM results in fetal hyperleptinemia independent of adiposity. HMWA appears to influence postnatal growth. Thus, in utero exposure to DM imparts hormonal differences on infants even without aberrant growth.

Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 µg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.

Elevated plasma pigment epithelium-derived factor in children with type 2 diabetes mellitus is attributable to obesity.

BACKGROUND: Pigment epithelium-derived factor (PEDF) is a member of the serpin family secreted by adipocytes. Plasma PEDF is increased in obese children and adults. Adults with type 2 diabetes mellitus (T2DM) have higher circulating PEDF but there are no reports in children with T2DM. OBJECTIVE: To compare PEDF concentration in children with T2DM to normal weight and obese children without T2DM and determine associations with anthropometric or serum factors. METHODS: Participants were 34 obese children with T2DM diagnosed by American Diabetes Association (ADA) criteria, 61 normal weight [body mass index (BMI) 25-75 percentile] and 63 obese (BMI ≥ 95 percentile) children of age 8-18 yr. Plasma PEDF was measured in fasting plasma samples. Anthropometric, serum, and body composition (dual-energy x-ray absorptiometry, DXA) data were obtained for each subject to identify potential predictor variables. RESULTS: PEDF was 55% higher (p = 0.001) in the T2DM group compared with normal weight children, but did not differ from obese children. In the T2DM group, fat mass and lean mass both individually predicted PEDF (r² = 0.22 and 0.17, p = 0.02 and p < 0.01, respectively). PEDF was positively correlated with homeostatic model assessment - insulin resistance (HOMA-IR) when all groups were combined (r² = 0.15, p<0.001). CONCLUSIONS: Plasma PEDF was similar in the T2DM and obese groups, therefore, obesity, rather than diabetes, may account for the higher PEDF in children with T2DM compared with normal weight children. PEDF was positively associated with both lean mass and fat mass both of which may contribute to the circulating level of the protein, and potentially to PEDF's association with insulin resistance in obese children with and without diabetes.

Arterial compliance in obese children: implications for cardiovascular health.

Recent work showed that arterial compliance may be elevated unexpectedly in obese children, attributable to accelerated growth and maturation. We hypothesize that children with obesity or Type 2 diabetes may reach peak arterial maturation earlier in life and then experience an earlier, and potentially more rapid, decline in arterial compliance, leading toward earlier cardiovascular disease development.

Arterial compliance is increased in children with type 2 diabetes compared with normal weight peers but not obese peers.

BACKGROUND: We reported that obesity was associated with increased arterial compliance in children, possibly due to accelerated vascular maturation. Here, we explored the additional burden of type 2 diabetes (T2DM) on vascular function in children. METHODS: Fifty normal weight [body mass index (BMI) 25-75%], 58 obese (BMI ≥ 95%), and 34 children with T2DM diagnosed by American Diabetes Association (ADA) criteria ages 10-18 yr were studied. Large and small artery elasticity (LAEI and SAEI, respectively) were measured by diastolic pulse-wave contour analysis. RESULTS: SAEI was 27% higher in children with T2DM compared to normal weight children (p = 0.005). Mean LAEI for those with T2DM not different from either group. In the group with T2DM, both SAEI and LAEI increased with age up to 16 yr, but declined thereafter. The strongest multivariable model predicting SAEI in children with T2DM combined lean mass, systolic blood pressure (SBP), and glucose (r2 = 0.59); for predicting LAEI, the strongest model included height, SBP, and low-density lipid-cholesterol (r2 = 0.61). CONCLUSION: The lower arterial compliance in older adolescents with T2DM compared to that of their peers without diabetes may indicate a premature maturation of the vascular system; however, follow-up will clarify whether these vascular changes portend an early increase in diabetes-associated cardiovascular disease risk.

Postprandial improvement in insulin sensitivity after a single exercise session in adolescents with low aerobic fitness and physical activity.

The purpose of this study was to determine the acute and residual impact of a single exercise bout on meal glucose control in adolescents with habitually low physical activity. Twelve adolescents (seven females/five males, 14 ± 2 yr) completed three trials. One trial [No Exercise (No Ex)] was completed after refraining from vigorous activity for ≥ 3 d. On the other two trials, a 45-min aerobic exercise bout at 75% peak heart rate was performed either 17-h Prior Day Exercise (Prior Day Ex) trial or 1-h Same Day Exercise (Same Day Ex) trial before consuming the test meal (2803 kJ, 45/40/15% energy as carbohydrate/fat/protein, respectively). Compared to No Ex, insulin sensitivity (SI) (minimal model analysis) was increased by 45% (p < 0.03) and 78% (p < 0.01) on the Prior Day Ex and Same Day Ex trials, respectively. This improvement in glucose control was supported by corresponding reductions in the net area under the curve for glucose, insulin, and c-peptide, although there was no change in postprandial suppression of fatty acids. These results show that SI is improved with a single bout of moderate intensity exercise in adolescents with habitually low physical activity and that the residual beneficial effect of exercise lasts at least 17 h. This finding highlights the plasticity of exercise responses in youth and the importance of daily exercise for metabolic health.

Light activity following a meal and postprandial cardiometabolic risk in adolescents.

The purpose of this study was to determine if light physical activity (LPA) minimizes the impairment of cardiometabolic risk factors following a typical meal in adolescents. Eighteen adolescents (50% male, 14.8 ± 2.3 yrs) consumed a meal (32% fat, 14% protein, 53% carbohydrate), then completed a walking (1.5 mph for 45 min of each hour) or sitting treatment for 3 hr in randomized order on separate days. Following the meal, HDL cholesterol declined 4.8% but remained higher during walking at 3 hr (42.1 mg/dl ± 9.3) than sitting (8.4% decline; 40.5 mg/dL ± 9.9; treatment x time interaction, p < .03). The 3-hr insulin was lower after walking (24.8 µIU/ml ± 33.4) than sitting (37.8 µIU/ml ± 34.7; treatment x time interaction, p < .0001). Triglycerides increased by ~40% above baseline at 1 and 2 hr, with higher values for walking (treatment x time interaction, p < .02). However by 3 hr, triglycerides were not different from baseline. Area under the curve (AUC) analyses were not significantly different between treatments for any outcomes. Although minor, LPA appears to mitigate the undesirable postprandial changes in HDL cholesterol and insulin but not triglycerides, following a typical meal in adolescents.

Postprandial triglycerides and fibroblast growth factor 19 as potential screening tools for paediatric non-alcoholic fatty liver disease.

BACKGROUND: Better screening tools for paediatric NAFLD are needed. We tested the hypothesis that the postprandial triglyceride (TG) and fibroblast growth factor 19 (FGF19) response to an abbreviated fat tolerance test (AFTT) could differentiate adolescents with NAFLD from peers with obesity and normal weight. METHODS: Fifteen controls with normal weight (NW), 13 controls with obesity (OB) and 9 patients with NAFLD completed an AFTT. Following an overnight fast, participants consumed a high-fat meal. TG and FGF19 were measured at baseline and 4 h post-meal. Liver steatosis and fibrosis were measured via Fibroscan. RESULTS: Fasting TG and FGF19 did not differ among groups; 4 h TG in the NAFLD and OB groups were greater (197 ± 69 mg/dL; 157 ± 72 mg/dL, respectively) than NW (105 ± 45 mg/dL; p < 0.05) and did not differ from one another. Within the entire cohort, 4 h TG were stratified by high and low steatosis. Adolescents with high steatosis had 98% greater 4 h TG than adolescents with low steatosis. 4 h FGF19, but not fasting FGF19, was higher in children with low steatosis compared with high steatosis (p < 0.05). Using area under the receiver operating curve (AUROC), the only biochemical outcome with diagnostic accuracy for NAFLD was 4 h TG (0.77 [95% CI: 0.60-0.94; p = 0.02]). CONCLUSIONS: The postprandial TG response is increased in adolescents with obesity with hepatic steatosis, with or without NAFLD. Our preliminary analysis demonstrates 4 h TG differentiate patients with NAFLD from those without, supporting a role for the AFTT as a screening tool for paediatric NAFLD.

Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement.

Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replacement. Using l-[1,2-¹³C]leucine as a tracer, we measured the fractional synthetic rate of mitochondrial as well as sarcoplasmic and mixed muscle proteins in 18 participants during sustained (7-h) insulin or saline infusion (n = 9 each). We also measured muscle ATP production, mitochondrial enzyme activities, mRNA levels of mitochondrial genes, and phosphorylation of signaling proteins regulating protein synthesis. The concentration of circulating essential AA decreased during insulin infusion. Mitochondrial, sarcoplasmic, and mixed muscle PS rates were also lower during insulin (2-7 h) than during saline infusions despite increased mRNA levels of selected mitochondrial genes. Under these conditions, insulin did not alter mitochondrial enzyme activities and ATP production. These effects were associated with enhanced phosphorylation of Akt but not of protein synthesis activators mTOR, p70(S6K), and 4EBP1. In conclusion, sustained physiological hyperinsulinemia without AA replacement did not stimulate PS of mixed muscle or protein subfractions and did not alter muscle mitochondrial ATP production in healthy humans. These results support that insulin and AA act in conjunction to stimulate muscle mitochondrial function and mitochondrial protein synthesis.

The effect of a high fat meal on heart rate variability and arterial stiffness in adolescents with or without type 1 diabetes.

AIM: Type 1 diabetes (T1D) is associated with increased arterial stiffness and cardiac autonomic neuropathy. We tested whether those variables are acutely affected by a high fat meal (HFM). METHODS: Responses to a HFM were measured in adolescents with T1D (N = 14) or without T1D (Control, N = 21). Heart rate variability (HRV), arterial stiffness, blood pressure (BP), and energy expenditure (EE) were measured before (baseline) and four times over 180 min postprandially. RESULTS: T1D had higher blood glucose and insulin, but the suppression of fatty acids (~40%) and rise in triglycerides (~60%) were similar between groups. T1D had 9% higher EE, but postprandial increase in EE was similar to Controls. T1D had ~7 to 24% lower baseline HRV but a similar postprandial decline of ~8 to 25% as Controls. Both groups had a similar 2 to 5% increase in BP after the meal. Rate pressure product increased postprandially in both groups and was higher in T1D. Pulsewave velocity and augmentation index did not differ between groups or change postprandially. CONCLUSION: Adolescents with T1D have evidence of cardiac autonomic dysfunction and increased EE, but those variables, along with arterial stiffness, are not acutely made worse by a HFM.

Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms.

Non-alcoholic fatty liver disease (NAFLD) is the number one chronic liver disease worldwide and is estimated to affect nearly 40% of obese youth and up to 10% of the general pediatric population without any obvious signs or symptoms. Although the early stages of NAFLD are reversible with diet and lifestyle modifications, detecting such stages is hindered by a lack of non-invasive methods of risk assessment and diagnosis. This absence of non-invasive means of diagnosis is directly related to the scarcity of long-term prospective studies of pediatric NAFLD in children and adolescents. In the majority of pediatric NAFLD cases, the mechanisms driving the origin and rapid progression of NAFLD remain unknown. The progression from NAFLD to non-alcoholic steatohepatitis (NASH) in youth is associated with unique histological features and possible immune processes and metabolic pathways that may reflect different mechanisms compared with adults. Recent data suggest that circulating microRNAs (miRNAs) are important new biomarkers underlying pathways of liver injury. Several factors may contribute to pediatric NAFLD development, including high-sugar diets, in utero exposures via epigenetic alterations, changes in the neonatal microbiome, and altered immune system development and mitochondrial function. This review focuses on the unique aspects of pediatric NAFLD and how nutritional exposures impact the immune system, mitochondria, and liver/gastrointestinal metabolic health. These factors highlight the need for answers to how NAFLD develops in children and for early stage-specific interventions.