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Introduction The Oral Minimal Model (OMM), a differential-equations based mathematical model of glucose-insulin dynamics, utilizes data from a frequently sampled oral glucose tolerance test (OGTT) to quantify insulin sensitivity ( S I ). OMM-based estimates of S I can detect differences in insulin resistance (IR) across population groups and quantify effects of clinical or behavioral interventions. These estimates of S I have been validated in healthy adults using data from OGTTs with durations from 2 to 7 h. However, data demonstrating how protocol duration affects S I estimates in highly IR populations such as adolescents with obesity are limited. Methods A 6-h frequently sampled OGTT was performed in adolescent females with obesity. Two, 3-, and 4- hour implementations of OMM assuming an exponentially-decaying rate of glucose appearance beyond measured glucose concentrations were compared to the 6-h implementation. A 4- hour OMM implementation with truncated data (4h Tr) was also considered. Results Data from 68 participants were included (age 15.8 ± 1.2 years, BMI 35.4 ± 5.6 kg/m2). Although S I values were highly correlated for all implementations, they varied with protocol duration (2h: 2.86 ± 3.31, 3h: 2.55 ± 2.62, 4h: 2.81 ± 2.59, 4h tr: 3.13 ± 3.14, 6h: 3.06 ± 2.85 x 10-4 dl/kg/min per U/ml). S I estimates based on 2 or 3 h of data underestimated S I values, whereas 4-h S I estimates more closely approximated 6-h S I values. Discussion These results suggest that OGTT protocol duration should be considered when implementing OMM to estimate S I in adolescents with obesity and other IR populations.

Objective Few studies have examined the effects of participants’ diet and activity prior to sample collection on metabolomics profiles, and results have been conflicting. We compared the effects of overnight fasting with or without 3 days of standardized diet and restricted physical activity on the human blood metabolome, and examined the effects of these protocols on our ability to detect differences in metabolomics profiles in adolescent girls with obesity and polycystic ovary syndrome (PCOS) vs. sex and BMI-matched controls. Methods This was a cross-sectional study of 16 adolescent girls with obesity and PCOS and 5 sex and BMI-matched controls. Fasting plasma metabolomic profiles were measured twice in each participant: once without preceding restriction of physical activity or control of macronutrient content (“typical fasting visit”), and again after 12 h of monitored inpatient fasting with 3 days of standardized diet and avoidance of vigorous exercise (“controlled fasting visit”). Moderated paired t-tests with FDR correction for multiple testing and multilevel sparse partial least-squares discriminant analysis (sPLS-DA) were used to examine differences between the 2 visits and to compare the PCOS and control groups with the 2 visits combined and again after stratifying by visit. Results Twenty-three known metabolites were significantly different between the controlled fasting and typical fasting visits. Hypoxanthine and glycochenodeoxycholic acid had the largest increases in relative abundance at the controlled fasting visit compared to the typical fasting visit, while oleoyl-glycerol and oleamide had the largest increases in relative abundance at the typical fasting visit compared to the controlled fasting visit. sPLS-DA showed excellent discrimination between the 2 visits; however, when the samples from the 2 visits were combined, differences between the PCOS and control groups could not be detected. After stratifying by visit, discrimination of PCOS status was improved. Conclusions There were differences in fasting metabolomic profiles following typical fasting vs monitored fasting with preceding restriction of physical activity and control of macronutrient content, and combining samples from the two visits obscured differences by PCOS status. In studies performing metabolomics analysis, careful attention should be paid to acute diet and activity history. Depending on the sample size of the study and the expected effect size of the outcomes of interest, control of diet and physical activity beyond typical outpatient fasting may not be required.

Objective Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and visceral adiposity in adults and boys, but girls with NAFLD are understudied. We sought to evaluate adipose, liver, and skeletal muscle insulin sensitivity in obese adolescent females with or without hepatic steatosis (HS) (intrahepatic triglyceride (IHTG) content >5.5%) along with cardiometabolic components typically associated with IR. Study design 73 obese adolescent girls at high risk for NAFLD were enrolled. Participants underwent fasting labs, an MRI to measure IHTG and visceral fat, 31phosphorous MR spectroscopy for muscle mitochondrial function, 1H MR spectroscopy for intramyocellular lipid (IMCL), bicycle ergometry to assess VO2peak and a 4-phase hyperinsulinemic euglycemic clamp with isotope tracers to measure hepatic and peripheral IR. 29 participants had HS [age 15 yrs(13,16), BMI%ile 98.7(97.4,99.0), IHTG 10.4%(8.0,13.5)] and 44 did not [age 15 yrs(13,17), BMI%ile 98.5(96.2,99.0), IHTG 2.0%(1.1,3.0)]. Results During hyperinsulinemia, participants with HS vs. non-HS had failure to suppress free fatty acids (p = 0.008), endogenous glucose release (p = 0.002), and a lower glucose metabolic rate of disappearance (Rd) (p = 0.012). Girls with NALFD also had higher visceral fat (p, Highlights • We described tissue specific insulin sensitivity in adolescent girls ± NAFLD. • Girls with NAFLD have higher hepatic and muscular insulin resistance. • Intramyocellular lipids and muscle mitochondrial function were not different between groups. • Adipose tissue insulin resistance was not different between groups. • Girls with NAFLD have worst metabolic profile than those without.