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Background: Fasting glucose is higher in pregnancies with obesity (OB); less is known about postprandial (PP) and nocturnal patterns when the diet is eucaloric and fixed or about the continuous-glucose-monitor (CGM) metrics that predict neonatal adiposity (NB%fat). We hypothesized that continuous glucose monitors (CGMs) would reveal higher glycemia in OB vs. normal weight (NW) during Early (14-16 weeks) and Later (26-28 weeks) gestation despite macronutrient-controlled eucaloric diets and elucidate unique predictors of NB%fat., Methods: In a prospective, parallel-group comparative study, a eucaloric diet (NW: 25 kcal/kg; OB: 30 kcal/kg) was provided (50% carbohydrate [20% simple/30% complex; of total calories], 35% fat, 15% protein) to Early and Later gestation groups wearing a blinded CGM for three days. CGM metrics (mean fasting; 1 h and 2 h PP; daytime and nocturnal glucose; percent time-in-range (%TIR: 63-140 mg/dL); PP excursions; and area-under-the-curve [AUC]) were interrogated between groups and as predictors of NB%fat by dual X-ray absorptiometry(DXA)., Results: Fifty-four women with NW (BMI: 23 kg/m 2 ; n = 27) and OB (BMI: 32; n = 27) provided their informed consent to participate. Early, the daytime glucose was higher in OB vs. NW (mean ± SEM) (91 ± 2 vs. 85 ± 2 mg/dL, p = 0.017), driven by 2 h PP glucose (95 ± 2 vs. 88 ± 2, p = 0.004). Later, those with OB exhibited higher nocturnal (89 ± 2 vs. 81 ± 2), daytime (95 ± 2 vs. 87 ± 2), 1 h (109 ± 3 vs. 98 ± 2), and 2 h PP (101 ± 3 vs. 92 ± 2) glucose (all p < 0.05) but no difference in %TIR (95-99%). Postprandial peak excursions for all meals were markedly blunted in both the Early (9-19 mg/dL) and Later (15-26 mg/dL). In OB, the Later group's 24 h AUC was correlated with NB%fat (r = 0.534, p = 0.02). Despite similar weight gain, infants of OB had higher birthweight (3528 ± 107 vs. 3258 ± 74 g, p = 0.037); differences in NB%fat did not reach statistical significance (11.0 vs. 8.9%; p > 0.05)., Conclusions: Despite macronutrient-controlled eucaloric diets, pregnancies with OB had higher glycemia Early and Later in gestation; the Later 24 h glucose AUC correlated with NB%fat. However, glycemic patterns were strikingly lower than current management targets.

Nutrition therapy provides the foundation for treatment of gestational diabetes (GDM), and has historically been based on restricting carbohydrate (CHO) intake. In this paper, randomized controlled trials (RCTs) are reviewed to assess the effects of both low- and higher CHO nutrition approaches in GDM. The prevailing pattern across the evidence underscores that although CHO restriction improves glycemia at least in the short-term, similar outcomes could be achievable using less restrictive approaches that may not exacerbate IR. The quality of existing studies is limited, in part due to dietary non-adherence and confounding effects of treatment with insulin or oral medication. Recent evidence suggests that modified nutritional manipulation in GDM from usual intake, including but not limited to CHO restriction, improves maternal glucose and lowers infant birthweight. This creates a platform for future studies to further clarify the impact of multiple nutritional patterns in GDM on both maternal and infant outcomes.

Objective: Often unrecognized, obstructive sleep apnea (OSA) worsens over pregnancy and is associated with poorer perinatal outcomes. The association between OSA in late pregnancy and metabolic biomarkers remains poorly understood. We tested the hypothesis that OSA in pregnant women with obesity is positively correlated with 24-hour patterns of glycemia and IR despite controlling for diet., Design: Pregnant women (32 to 34 weeks' gestation; body mass index, 30 to 40 kg/m2) wore a continuous glucose monitor for 3 days. OSA was measured in-home by WatchPAT 200™ [apnea hypopnea index (AHI), oxygen desaturation index (ODI; number per hour)]. Fasting blood was collected followed by a 2-hour, 75-g, oral glucose tolerance test to measure IR. Association between AHI and 24-hour glucose area under the curve (AUC) was the powered outcome., Results: Of 18 women (29.4 ± 1.4 years of age [mean ± SEM]), 12 (67%) had an AHI ≥5 (mild OSA). AHI and ODI were correlated with 24-hour glucose AUC (r = 0.50 to 0.54; P ≤ 0.03) and mean 24-hour glucose (r = 0.55 to 0.59; P ≤ 0.02). AHI and ODI were correlated with estimated hepatic IR (r = 0.59 to 0.74; P < 0.01), fasting free fatty acids (fFFAs; r = 0.53 to 0.56; P < 0.05), and waking cortisol (r = 0.49 to 0.64; P < 0.05)., Conclusions: Mild OSA is common in pregnant women with obesity and correlated with increased glycemic profiles, fFFAs, and estimates of hepatic IR. OSA is a potentially treatable target to optimize maternal glycemia and metabolism, fetal fuel supply, and pregnancy outcomes., (Copyright © 2019 Endocrine Society.)

Maternal obesity is associated with increased risk for offspring obesity and non-alcoholic fatty liver disease (NAFLD), but the causal drivers of this association are unclear. Early colonization of the infant gut by microbes plays a critical role in establishing immunity and metabolic function. Here, we compare germ-free mice colonized with stool microbes (MB) from 2-week-old infants born to obese (Inf-ObMB) or normal-weight (Inf-NWMB) mothers. Inf-ObMB-colonized mice demonstrate increased hepatic gene expression for endoplasmic reticulum stress and innate immunity together with histological signs of periportal inflammation, a histological pattern more commonly reported in pediatric cases of NAFLD. Inf-ObMB mice show increased intestinal permeability, reduced macrophage phagocytosis, and dampened cytokine production suggestive of impaired macrophage function. Furthermore, exposure to a Western-style diet in Inf-ObMB mice promotes excess weight gain and accelerates NAFLD. Overall, these results provide functional evidence supporting a causative role of maternal obesity-associated infant dysbiosis in childhood obesity and NAFLD.

There is increasing recognition that maternal glucose concentrations lower than those previously used for diagnosis of gestational diabetes mellitus (GDM) and targeted for treatment can result in excess fetal growth. Yet, mothers with GDM who appear to have optimal glycemic control and mothers with obesity and normal glucose tolerance still have a significantly increased risk for delivering infants who are large for gestational age, or even more importantly, who have increased adiposity at birth. What is less appreciated is that in addition to glucose, maternal lipids are also substrates for fetal fat accretion and that placental lipases can hydrolyze maternal triglycerides (TGs) to free fatty acids for fetal-placental availability. Maternal TG levels are 40% to 50% higher on average in mothers with obesity and GDM compared to those in normal-weight mothers early in pregnancy and are sustained at higher levels throughout gestation. Increasing evidence supports that maternal TG, both fasting and postprandial, are also predictors of newborn adiposity (newborn %fat), a risk factor for childhood obesity, and that early exposure is at least as strong of a risk factor as later exposure in mothers with obesity. In the setting of maternal nutrient excess and maternal insulin resistance, which lead to fetal hyperinsulinemia, excess free fatty acid exposure in the fetus may result in lipid storage and fetal fat development in subcutaneous and possibly other depots. In this commentary, we provide further evidence to make a case for targeting maternal fasting and postprandial TG in mothers with obesity who have elevated TG in early pregnancy to determine whether a TG-lowering interventional approach might limit fetal overgrowth and potentially mitigate the intrauterine contribution to childhood obesity and metabolic disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To model breastfed infant growth and body composition patterns over the first 4 months with multiple bioactive components of human milk (HM) and clinical factors (including maternal BMI status), which are related to growth., Methods: Longitudinal observation of infant growth and body composition from 0 to 4 months among 41 predominantly breastfed infants (25 mothers of Normal-weight and 16 mothers with overweight/obesity). Fasted morning HM samples were collected at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin, cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight-for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and %fat gain were modelled controlling for clinical covariates., Results: HM insulin negatively associated with WLZ trajectory among infants of NW mothers (P = 0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM glucose (P < 0.001) was associated with slower rates of infant FFM gain. Infants of mothers with OW/Ob exhibited slower rates of FFM gain. HM protein, adiponectin and insulin concentrations, and n-6:n-3 ratio were all significant predictors in the model of infant fat mass gain (P < 0.03). Any amount of formula supplementation was associated with faster fat gain (P = 0.002). The model of %fat gain was similar to that of fat mass gain, excepting HM adiponectin was not a significant covariate, and a trend for maternal OW/Ob to correlate with faster %fat gain (P = 0.056)., Conclusions: Bioactive components in HM may contribute to regulation of partitioning of body composition, and these contributions may differ between mothers of normal-weight vs. with OW/Ob., (© 2018 World Obesity Federation.)

Elevated branched chain amino acids (BCAAs: valine, leucine, and isoleucine) are well-established biomarkers of obesity-associated insulin resistance (IR). Mounting evidence suggests that low- and middle-income countries are suffering from a "double burden" of both undernutrition (growth stunting) and overnutrition (obesity) as these countries undergo a "nutrition transition". The purpose of this study was to examine if pre-pregnancy body mass index (BMI, kg/m²) and a daily lipid-based micronutrient supplement (LNS, Nutriset) would lead to cross-sectional differences in circulating levels of branched chain amino acids (BCAAs) in Guatemalan women experiencing short stature during early pregnancy. Using data from an ongoing randomized controlled trial, Women First, we studied women who were normal weight (NW, BMI range for this cohort = 20.1⁻24.1 kg/m²) or overweight/obese (OW/OB, BMI range for this cohort = 25.6⁻31.9 kg/m²), and divided into two groups: those who received daily LNS ≥ 3 months prior to conception through 12 weeks gestation (+LNS), or no LNS (-LNS) ( n = 9⁻10/group). BCAAs levels were obtained from dried blood spot card samples (DBS) assessed at 12 weeks gestation. DBS cards provide a stable, efficient, and reliable means of collecting, transporting, and storing blood samples in low resource or field settings. Circulating maternal leptin, adiponectin, and insulin were determined by immunoassays from serum samples collected at 12 weeks gestation. We found maternal pre-pregnancy body mass index (ppBMI) was associated with higher circulating BCAAs ( r ² = 0.433, p = 0.002) and higher leptin/adiponectin ratio ( r = 0.466, p = 0.044) in -LNS mothers at 12 weeks gestation. +LNS mothers demonstrated no correlations between BCAAs or leptin/adiponectin ratio across ppBMI suggesting LNS may be effective at improving metabolic status in OW/OB mothers during early pregnancy.

Objective: Maternal obesity (OB) accounts for the majority of large-for-gestational-age infants, and newborn percent fat (NB%fat) correlates strongest with childhood OB. In addition to maternal glucose, fasting triglycerides (TGs) may contribute, but postprandial triglycerides (PPTGs) are unstudied. It was hypothesized that fasting TGs and PPTGs are higher in women with OB compared with women with normal weight (NW) throughout pregnancy, correlate more strongly with NB%fat than glucose, and may relate to dietary chylomicron TGs., Methods: Fasting TGs and PPTGs, free fatty acids, glucose, and insulin were prospectively measured 10 times over 4 hours after a controlled liquid breakfast early (14-16 weeks) and later (26-28 weeks) in pregnancy in 27 mothers with NW and 27 with OB. NB%fat was measured by dual x-ray absorptometry., Results: Fasting TGs and PPTGs were already ≥ 30% higher in mothers with OB at 14 to 16 weeks (P < 0.001) versus mothers with NW. In mothers with OB, a simple 1-hour (r = 0.71; P < 0.01) or 2-hour (r = 0.69; P < 0.01) PPTG at 14 to 16 weeks correlated strongest with NB%fat. In mothers with NW, the increase in TGs from early to later pregnancy correlated strongest with NB%fat (r = 0.57; P < 0.01). Maternal glucose did not statistically add to prediction models., Conclusions: These novel data suggest that 1- or 2-hour PPTGs might be a new target for early intervention in pregnancies with OB to prevent excess newborn adiposity and attenuate child OB risk., (© 2018 The Obesity Society.)

Purpose of Review: Excess fetal growth is increasingly recognized as a risk factor for childhood obesity, and mounting evidence supports that maternal glucose is not the only driver. This review focuses on the role of clinically applicable maternal non-glycemic contributors to excess fetal growth, particularly lipids, in addition to amino acids (AA), insulin resistance, inflammation, maternal nutrition, and gestational weight gain (GWG) in obesity and gestational diabetes mellitus (GDM)., Recent Findings: Lipids, specifically triglycerides and free fatty acids, appear to be strong contributors to excess fetal fat accretion and adiposity at birth, particularly in obese pregnancies, which account for the largest number of large-for-gestational-age infants. Maternal pre-pregnancy body mass index (BMI), GWG, insulin resistance, inflammation, and glucose, lipid, and AA concentrations have both independent and interacting effects on fetal growth, operating both early and late in pregnancy. All are sensitive to maternal nutrition. Early vs. later gestational exposure to excess maternal fuels in fasting and postprandial conditions may differentially impact fetoplacental outcomes. Compelling evidence suggests that targeting interventions early in pregnancy beyond glucose may be critical to improve fetal growth patterns.

Introduction: Recent data suggest that in addition to glucose, fetal growth is related to maternal triglycerides (TG). To reach the fetus, TG must be hydrolyzed to free fatty acids (FFA) and transported across the placenta, but regulation is uncertain. Placental lipoprotein lipase (pLPL) hydrolyzes TG, both dietary chylomicron TG (CM-TG) and very-low density lipoprotein TG (VLDL-TG), to FFA. This may promote fetal fat accretion by increasing the available FFA pool for placental uptake. We tested the novel hypothesis that pLPL activity, but not maternal adipose tissue LPL activity, is associated with newborn adiposity and higher maternal TG., Methods: Twenty mothers (n = 13 normal-weight; n = 7 obese) were prospectively recruited. Maternal glucose, insulin, TG (total, CM-TG, VLDL-TG), and FFA were measured at 14-16, 26-28, and 36-37 weeks, and adipose tissue LPL was measured at 26-28 weeks. At term delivery, placental villous biopsies were immediately analyzed for pLPL enzymatic activity. Newborn percent body fat (newborn %fat) was assessed by skinfolds., Results: Placental LPL activity was positively correlated with birthweight (r = 0.48;P = 0.03) and newborn %fat (r = 0.59;P = 0.006), further strengthened by correcting for gestational age at delivery (r = 0.75;P = 0.0001), but adipose tissue LPL was not. Maternal TG and BMI were not correlated with pLPL activity. Additionally, pLPL gene expression, while modestly correlated with enzymatic activity (r = 0.53;P < 0.05), was not correlated with newborn adiposity., Discussion: This is the first study to show a positive correlation between pLPL activity and newborn %fat. Placental lipase regulation and the role of pLPL in pregnancies characterized by nutrient excess and fetal overgrowth warrant further investigation., (Copyright © 2018. Published by Elsevier Ltd.)

Background/objectives: Excessive infant weight gain in the first 6-month of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased threefold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2 weeks and 4 months postpartum., Subjects/methods: Forty-eight infants from normal weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2 weeks) or established (4 months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry., Results: In transitional and established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The amount of changes in infant fat mass and percentage of body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010)., Conclusions: Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.

Over a third of women of childbearing age in the United States are obese, and during pregnancy they are at increased risk for delayed labor onset and slow labor progress that often results in unplanned cesarean delivery. The biology behind this dysfunctional parturition is not well understood. Studies of obesity-induced changes in parturition physiology may facilitate approaches to optimize labor in obese women. In this review, we summarize known and proposed biologic effects of obesity on labor preparation, contraction/synchronization, and endurance, drawing on both clinical observation and experimental data. We present evidence from human and animal studies of interactions between obesity and parturition signaling in all elements of the birth process, including: delayed cervical ripening, prostaglandin insensitivity, amniotic membrane strengthening, decreased myometrial oxytocin receptor expression, decreased myocyte action potential initiation and contractility, decreased myocyte gap junction formation, and impaired myocyte neutralization of reactive oxygen species. We found convincing clinical data on the effect of obesity on labor initiation and successful delivery, but few studies on the underlying pathobiology. We suggest research opportunities and therapeutic interventions based on plausible biologic mechanisms.

The power of continuous glucose monitoring system (CGMS) technology to profile glycemic patterns throughout a 24-h period has benefited the care of individuals with diabetes mellitus for over 10 years. Recently, this technology has been utilized to better understand glucose patterns in pregnancy, especially as they relate to abnormal fetal growth given that adiposity at birth is associated with increased risks for childhood obesity and metabolic syndrome. However, the lack of a standardized approach to defining glucose measures associated with maternal outcomes and fetal growth has greatly limited comparison and pooling of CGMS data among pregnancy trials, hindering our ability to take advantage of the enormous amount of data available to explore these relationships. The purpose of this article is to offer a methodical approach to the identification and extraction of CGMS-derived glucose variables for the characterization of glycemic profiles in pregnant women, particularly focusing on women with gestational diabetes or obesity who are at risk for abnormal fetal growth. A review of the properties of CGMS data and examples of how CGMS data in pregnancy have been reported to date are included. We further define several pregnancy-relevant, CGMS-derived glucose variables and directly apply them to unpublished data to illustrate how these measures might be utilized. This approach offers one possible standardized method to define and analyze these time-sensitive glucose measures to facilitate comparisons among studies and to increase our understanding of how glycemic profiles contribute to excess infant adiposity in pregnant women with and without diabetes.

This study evaluated if the effect of dietary macronutrient composition on adipose tissue lipoprotein lipase (ATLPL) and skeletal muscle lipoprotein lipase (SMLPL) predicted the long-term (over 4 years) changes in body weight and composition in free-living adults. Using a crossover design, 39 healthy subjects (n = 24 normal weight, n = 7 overweight, n = 8 obese) each followed a 2-week isocaloric high-carbohydrate (HC; 55% CHO:25% fat) and high-fat (HF; 30% CHO:50% fat) diet. On day 15 of each diet, biopsies were performed in the fasted state and 6 h after a meal. Body weight and composition were measured annually over 4 years. The outcomes for body weight, fat mass and % body fat were assessed using a linear two-stage mixed model. The mean (±SEM) increase in body weight and fat mass over 4 years was 0.29 ± 0.15 kg/year (P = 0.063) and 0.31 ± 0.15 kg/year (P = 0.051), respectively. The most consistent predictors of future body weight and fat changes were the ΔATLPL and ΔSMLPL responses (0-6 h) to a HC diet/meal. For the HC diet/meal, the subjects who had an increase in ATLPL activity/cell gained more % body fat over 4 years (P = 0.006) whereas subjects who had a decrease in SMLPL activity/g also had an increase in fat mass (P = 0.021). No significant relationships were observed between fasting ATLPL and SMLPL or enzyme responses to meals and any of the outcomes following the HF diet. In free-living adults the variability in tissue-specific lipoprotein lipase (LPL) responsiveness to a HC diet/meal predicts longitudinal changes in body composition.

Objective: We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy., Research Design and Methods: Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured., Results: The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates., Conclusions: This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

Background: Little is known about the comparative effect of weight-loss diets on metabolic profiles during dieting., Objective: The purpose of this study was to compare the effect of a low-carbohydrate diet (< or =20 g/d) with a high-carbohydrate diet (55% of total energy intake) on fasting and hourly metabolic variables during active weight loss., Design: Healthy, obese adults (n = 32; 22 women, 10 men) were randomly assigned to receive either a carbohydrate-restricted diet [High Fat; mean +/- SD body mass index (BMI; in kg/m(2)): 35.8 +/- 2.9] or a calorie-restricted, low-fat diet (High Carb; BMI: 36.7 +/- 4.6) for 6 wk. A 24-h in-patient feeding study was performed at baseline and after 6 wk. Glucose, insulin, free fatty acids (FFAs), and triglycerides were measured hourly during meals, at regimented times. Remnant lipoprotein cholesterol was measured every 4 h., Results: Patients lost a similar amount of weight in both groups (P = 0.57). There was an absence of any diet treatment effect between groups on fasting triglycerides or on remnant lipoprotein cholesterol, which was the main outcome. Fasting insulin decreased (P = 0.03), and both fasting (P = 0.040) and 24-h FFAs (P < 0.0001) increased within the High Fat group. Twenty-four-hour insulin decreased (P < 0.05 for both groups). Fasting LDL cholesterol decreased in the High Carb group only (P = 0.003). In both groups, the differences in fasting and 24-h FFAs at 6 wk were significantly correlated with the change in LDL cholesterol (fasting FFA: r = 0.41, P = 0.02; 24-h FFA: r = 0.52, P = 0.002)., Conclusions: Weight loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs.

Rodent experiments raise the possibility of a regulatory role of peripheral alpha-melanocyte-stimulating hormone (alpha-MSH) in obesity and metabolism, but human data on peripheral alpha-MSH levels remain fragmentary. Because of the possible relationship between alpha-MSH and obesity, we endeavored to test the hypothesis that higher levels of alpha-MSH in obese patients would correlate with leptin levels and with other markers of obesity. Sixty normal-weight to obese healthy men and women participated. Weight, measures of body composition, and diet diaries were obtained; fasting blood was analyzed for alpha-MSH, lipids, glucose, insulin, leptin, and adiponectin. To begin to understand the source of peripherally measured hormones, alpha-MSH was also measured in serum samples from 5 individuals with untreated Addison disease. Levels of alpha-MSH were higher in men vs women (10.1 +/- 4.3 vs 7.6 +/- 3.4 pmol/L, P = .019), and alpha-MSH levels were higher in patients with Addison disease vs controls (17.7 +/- 2.3 vs 8.7 +/- 0.52 pmol/L, P < .001). Measures of adiposity correlated with insulin and leptin in men and women, and with adiponectin in women. alpha-Melanocyte-stimulating hormone levels did not correlate significantly with any parameter of adiposity or diet composition. The elevated alpha-MSH levels in patients with untreated Addison disease suggest possible pituitary secretion of alpha-MSH to the periphery. The lack of correlation between peripheral alpha-MSH and parameters of adiposity suggests that endogenous plasma alpha-MSH levels are not a metric for body composition per se.

Background: The prevention and treatment of obesity is a public health challenge., Objective: We investigated the effects of dietary composition, insulin sensitivity (S(I)), and energy balance on predicted changes in body composition., Design: In a randomized crossover design study, 39 normal-weight (n = 23), overweight (n = 8), and obese (n = 8) men and women (aged 25-36 y) each followed a 15-d isocaloric high-fat (HF; 50% fat) and high-carbohydrate [HC; 55% carbohydrate (CHO)] diet with a 4-6-wk washout period during the first year. During each treatment, energy balance was measured while the subjects were inactive by using indirect calorimetry on day 15, and S(I) was measured by using a euglycemic clamp study (40 mU . m(-2) . min(-1)) on day 16. Weight and body composition were then measured annually for 4 y. The outcomes for fat mass, percentage body fat, and weight were measured by using a linear 2-stage mixed model., Results: CHO balance (day 15) and S(I) (day 16) on the HC diet were highly and significantly correlated (r = 0.55, P < 0.001). On the HC diet, the subjects who had a higher positive CHO balance (day 15) gained less fat mass (P < 0.001), percentage body fat (P = 0.006), and weight (P = 0.024) over time. When adjusted for S(I), CHO balance remained a significant predictor of changes in fat mass (P = 0.021) and percentage body fat (P = 0.025)., Conclusions: On a HC diet, the subjects who had a higher positive CHO balance on day 15 while they were inactive gained less fat mass during 4 y, a predictive effect independent of S(I). As suggested in rodents, the capacity to expand the glycogen pool might reduce energy intake and protect against fat and weight gain.