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.

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.

Correction: Using financial incentives to promote physical activity in American Indian adolescents: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0198390.].

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.

Weight Loss Results in Increased Expression of Anti-Inflammatory Protein CRISPLD2 in Mouse Adipose Tissue.

OBJECTIVE: Obesity is a major risk factor for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus, whereas weight loss is associated with improved health outcomes. It is therefore important to learn how adipose contraction during weight loss contributes to improved health. It was hypothesized that adipose tissue undergoing weight loss would have a unique transcriptomic profile, expressing specific genes that might improve health. METHODS: This study conducted an RNA-sequencing analysis of the epididymal adipose tissue of mice fed either a high-fat diet (HFD) or a regular rodent chow diet (RD) ad libitum for 10 weeks versus a cohort of mice fed HFD for the first 5 weeks before being swapped to an RD for the remainder of the study (swapped diet [SWAP]). RESULTS: The swapped diet resulted in weight loss, with a parallel improvement in insulin sensitivity. RNA sequencing revealed several transcriptomic signatures distinct to adipose tissue in SWAP mice, distinguished from both RD and HFD adipose tissue. The analysis found a unique upregulated mRNA that encodes a secreted lipopolysaccharide-binding glycoprotein (CRISPLD2) in adipose tissue. Whereas cellular CRISPLD2 protein levels were unchanged, plasma CRIPSLD2 levels increased in SWAP mice following weight loss and could correlate with insulin sensitivity. CONCLUSIONS: Taken together, these data demonstrate that CRISPLD2 is a circulating adipokine that may regulate adipocyte remodeling during weight loss.

Effect of Obesity and Exercise Training on Plasma Amino Acids and Amino Metabolites in American Indian Adolescents.

CONTEXT: Amino acids (AAs) and their metabolites are altered with obesity and may be predictive of future diabetes in adults, but there are fewer studies on AAs, as well as conflicting findings on how they vary with obesity, in adolescents. OBJECTIVE: To determine whether plasma AAs vary with body composition and insulin sensitivity and are altered in response to exercise training. DESIGN: Cross-sectional, and an exercise intervention. SETTING: Tribal wellness center. PARTICIPANTS: American Indian boys and girls, 11 to 17 years of age with obesity (Ob, n = 58) or normal weight (NW, n = 36). INTERVENTION: The Ob group completed 16 weeks of aerobic exercise training. MAIN OUTCOME MEASURE: A panel of 42 plasma AAs. RESULTS: Compared with the NW group, the Ob group had lower aerobic fitness and insulin sensitivity (interactive homeostasis model assessment 2), 17 AAs that were higher, and 7 AAs that were lower. Branched-chain AAs (+10% to 16%), aromatic AAs (+15% to 32%), and glutamate were among the higher AAs; all were positively correlated with body fat and negatively correlated with insulin sensitivity. The lysine metabolite 2-aminoadipic acid (2-AAA) and the valine metabolite ß-aminoisobutyric acid (BAIBA) were 47% higher and 29% lower, respectively, in the Ob group, and were positively (2-AAA) and negatively (BAIBA) correlated with insulin sensitivity. Exercise training increased aerobic fitness by 10%, but body composition, insulin sensitivity, and AAs were not significantly changed. CONCLUSIONS: Several plasma AAs are altered in American Indian adolescents with obesity and are associated with insulin sensitivity, but they were not altered with this exercise intervention.

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.

Using financial incentives to promote physical activity in American Indian adolescents: A randomized controlled trial.

American Indians (AI) have high prevalence of diabetes in youth and may benefit from increasing physical activity as a strategy to improve metabolic health. We tested whether financial incentives would elicit greater frequency and/or duration of exercise in AI youth at high risk for developing diabetes. Overweight/obese AI boys and girls, 11-20 years old, were instructed to exercise on 3 days/week for 48 weeks at a tribal wellness center. The program was divided into three, 16-week-long phases to test different financial incentive strategies. Within each phase participants were randomly assigned to one of two groups that received different payments for exercise. Phase 1 was designed to test whether the size of the incentive would affect exercise frequency. In Phase 1, the number of exercise sessions did not differ between the group receiving a modest fixed-value payment per exercise session and the group receiving enhanced incentives to exercise more frequently (26 ± 3 versus 28 ± 2 sessions, respectively, p = 0.568). In Phase 2, the provision of an enhanced financial incentive to increase exercise duration resulted longer sessions, as the incentivized and standard payment groups exercised 38 ± 2 versus 29 ± 1 minutes per session (p = 0.002), respectively. In Phase 3, the effect of reducing the incentives on maintenance of exercise behaviors was inconclusive due to high participant withdrawal. Aerobic fitness increased 10% during Phase 1 but was unchanged thereafter. Insulin sensitivity and body composition were unchanged during the study. In conclusion, enhanced financial incentives increased the duration of exercise sessions, but had minimal effects on exercise participation. These results indicate that financial incentives hold promise in motivating previously sedentary, overweight/obese adolescents to exercise longer, but motivating them to sustain an exercise program remains the major challenge. TRIAL REGISTRATION: ClinicalTrials.gov NCT01848353.

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.

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.

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.

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.

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.

Oxidized HDL and LDL in adolescents with type 2 diabetes compared to normal weight and obese peers.

OBJECTIVE: Obesity and type 2 diabetes mellitus (T2DM) are associated with oxidative stress. Oxidative damage of high-density lipoprotein (oxHDL) leads to a dysfunctional molecule, potentially a mediator and/or marker of cardiometabolic disease. We tested the hypothesis that circulating concentration of oxHDL is higher in obese (Ob) or T2DM adolescents compared to normal-weight (NW) peers. METHODS: In 37 NW, 38 Ob, and 42 T2DM adolescents, ages 11-18 y, fasting concentrations of HDL and LDL cholesterol, oxHDL, oxidized low-density lipoprotein (oxLDL), and myeloperoxidase (MPO) were measured. RESULTS: Compared to the NW group, oxHDL in the Ob group was not different, but was 65% higher (p < 0.01) in the T2DM group. Within the T2DM group oxHDL was higher in boys than in girls, but this sex difference was not evident in NW or Ob groups. OxLDL was 23% higher in Ob (p = 0.02), and 56% higher in T2DM (p < 0.01) versus NW and did not differ between boys and girls. MPO was not different between NW and Ob but was 88% (p < 0.02) higher in T2DM compared to NW. Contrary to our hypothesis MPO and insulin resistance (HOMA-IR) were not correlated with oxHDL. OxHDL was positively associated with oxLDL and lean body mass while oxLDL was positively associated with apolipoprotein B, triglycerides, HOMA-IR and trunk fat. CONCLUSIONS: The higher concentrations of oxHDL and oxLDL, along with higher MPO in children with T2DM reflect higher oxidative stress compared with obesity alone and potentially increased cardiovascular disease risk in youth with T2DM.

Effect of insulin sensitizer therapy on amino acids and their metabolites.

AIMS: Prior studies have reported that elevated concentrations of several plasma amino acids (AA), particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. METHODS: We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI ~30kg/m(2)) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45mg per day) plus metformin (1000mg twice per day, N=12 participants) or placebo (N=13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. RESULTS: Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. CONCLUSIONS: Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites.

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.