Person:

Misra, Madhusmita

Background: Obesity is associated with a relative deficiency of growth hormone, which is predictive of greater visceral fat and markers of cardiovascular risk. The study’s purpose was to use recombinant human growth hormone (rhGH) as a physiologic probe to assess the effects of reversing obesity-related GH deficiency on body composition, cardiovascular risk markers, and insulin resistance. Methods: 22 obese girls 13–21 years old were followed for a randomized 6-month trial of rhGH vs. placebo/no treatment. At baseline and 6-months, DXA was performed for body composition, MRI to measure visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT), and fasting blood drawn for IGF-1, inflammatory cardiovascular risk markers [soluble intercellular adhesion molecule (sICAM), high sensitivity CRP], lipids and HbA1C. An oral glucose tolerance test (OGTT) was performed. Twelve girls completed the 6-month visit. Baseline and mean 6-month change were compared between the groups using the Student t-test and the relationship between variables was determined through multiple regression analysis. Results: After 6-months, the rhGH group maintained IGF-1 levels, and had decreases in total cholesterol (p = 0.03), sICAM-1 (p = 0.04) and HbA1C (p = 0.03) compared to placebo/no treatment. The rhGH group trended towards greater decreases in LDL and 2-hour OGTT glucose. Glucose tolerance did not worsen with rhGH administration. Conclusions: Administering rhGH in small doses is able to stabilize IGF-1 levels in obesity. We have also shown that rhGH administration leads to an improvement in some markers of cardiovacular risk with without adversely affecting glucose tolerance. Trial registration Clinical Trial Registration Number: NCT01169103.

Irisin and FGF21 are novel hormones implicated in the “browning” of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14–21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.

Children with autism spectrum disorders (ASD) have several risk factors for low bone mineral density. The gluten-free, casein-free (GFCF) diet is a complementary therapy sometimes used in ASD that raises concerns for the adequacy of calcium and vitamin D intake. This study evaluated the prescribing practices of calcium and vitamin D supplements and the practice of checking 25-hydroxy vitamin D (25(OH)D) levels by providers in 100 children with ASD, 50 of whom were on the GFCF diet. Fifty-two percent and 46% of children on the GFCF diet were on some form of vitamin D and calcium supplements, respectively, compared to 18% and 14% of those not on this diet. Twenty-four percent of children in the GFCF group had a documented 25(OH)D level compared to none in the non-GFCF group. The data highlight a gap in calcium and vitamin D supplement prescribing practices among providers caring for children with ASD as well as a gap in the practice of checking 25(OH)D levels.

Background: The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT. Purpose We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status. Methods: The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18–25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition. Results: Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones. Conclusions: Our study shows a trend for lower BAT in young female athletes compared with non-athletes, and shows associations of brown fat with menstrual status and body composition. Brown fat may undergo adaptive reductions with increasing energy deficit.

Background: Obesity is prevalent among adolescents and is associated with serious health consequences. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) are bariatric procedures that cause significant weight loss in adults and are increasingly being performed in adolescents with morbid obesity. Data comparing outcomes of RYGB vs. SG in this age-group are scarce. This study aims to compare short-term (1–6 months) and longer-term (7–18 months) body mass index (BMI) and biochemical outcomes following RYGB and SG in adolescents/young adults. Methods: A retrospective study using data extracted from medical records of patients 16–21 years who underwent RYGB or SG between 2012 and 2014 at a tertiary care academic medical center. Results: Forty-six patients were included in this study: 24 underwent RYGB and 22 underwent SG. Groups did not differ for baseline age, sex, race, or BMI. BMI reductions were significant at 1–6 months and 7–18 months within groups (p < 0.0001), but did not differ by surgery type (p = 0.65 and 0.09, for 1–6 months and 7–18 months, respectively). Over 7–18 months, within-group improvement in low-density lipoprotein (LDL) (−24 ± 6 in RYGB, p = 0.003, vs. −7 ± 9 mg/dl in SG, p = 0.50) and non-high-density lipoprotein (non-HDL) cholesterol (−23 ± 8 in RYGB, p = 0.02, vs. −12 ± 7 in SG, p = 0.18) appeared to be of greater magnitude following RYGB. However, differences between groups did not reach statistical significance. When divided by non-alcoholic steatohepatitis stages (NASH), patients with Stage II–III NASH had greater reductions in alanine aminotransferase levels vs. those with Stage 0–I NASH (−45 ± 18 vs. −9 ± 3, p = 0.01) after 7–18 months. RYGB and SG groups did not differ for the magnitude of post-surgical changes in liver enzymes. Conclusion: RYGB and SG did not differ for the magnitude of BMI reduction across groups, though changes trended higher following RYGB. Further prospective studies are needed to confirm these findings.

Objective: Avoidant/restrictive food intake disorder (ARFID) is characterized by food avoidance or dietary restriction not primarily motivated by body weight/shape concerns. Individuals with ARFID can report early satiation, post-prandial fullness, and high inter-meal satiety, but whether these symptoms are related to differences in the biology underlying appetite regulation is unknown. In male and female children and adolescents, we hypothesized that fasting levels of cholecystokinin (CCK), a satiety hormone, would be elevated in participants with ARFID (full or subthreshold) versus healthy controls (HC). Within the ARFID group, we also explored the relations of CCK with weight status, subjective appetite ratings, and ARFID severity and phenotypes. Methods: 125 participants (83 full/subthreshold ARFID and 42 HC, ages 10-23 years; 59% female) underwent fasting blood draws for CCK, completed self-report measures assessing subjective state and trait appetite ratings, and completed a semi-structured interview assessing ARFID severity. Results: Fasting CCK was higher in full/subthreshold ARFID versus HC with a large effect (F(1)=25.0, p<.001, ηp2=.17), controlling for age, sex, and BMI percentile. Within the ARFID group, CCK was not significantly related to BMI percentile, subjective appetite ratings, or ARFID characteristic measures. Conclusion: CCK may contribute to etiology and/or maintenance of ARFID, as children/adolescents with heterogeneous presentations of avoidant/restrictive eating appear to show elevated fasting levels compared to healthy youth. Further research is needed to understand relations between CCK and appetite, weight, and eating behavior in ARFID.

Objective The DSM-5 criteria for avoidant/restrictive food intake disorder (ARFID) include ambiguities. Diagnostic criteria that allow for clinical judgment are essential for clinical practice. However, ambiguities can have major implications for treatment access and comparability and generalizability of research studies. The purpose of this study was to determine the degree to which distinct operationalizations of the diagnostic criteria for ARFID contribute to differences in the frequency of individuals who are eligible for the ARFID diagnosis. Methods Because criteria B, C, and D are rule-outs, we focused on criterion A, identified 19 potential operational definitions, and determined the extent to which these different methods impacted the proportion of individuals who met criteria for ARFID in a sample of children, adolescents, and young adults (n = 80) enrolled in an avoidant/restrictive eating study. Results Within each criterion, the proportion of individuals meeting diagnostic criteria differed significantly across the methodologies (all p values < 0.008). Using the strictest definition of each criterion, 49.4% (n = 40) of participants met criteria for ARFID. In contrast, under the most lenient definition of each criterion, the number nearly doubled, resulting in 96.3% (n = 78) meeting ARFID criteria. Conclusions Comparison of diagnostic definitions for ARFID among children, adolescents, and young adults confirmed a broad range of statistically distinct proportions within a single sample. Our findings support the need for additional contextual support and consensus among disciplines on operationalization in both research and clinical settings.

Syngelaki et al. (Feb. 4 issue)1 describe the efficacy of metformin in reducing gestational weight gain in women with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35. Although their study does not show a reduction in the neonatal birth weight, their results underscore the ability of metformin to reduce gestational weight gain in women with moderate-to-severe obesity without diabetes. One question is whether the exclusion of patients who were started on insulin after the oral glucose-tolerance test would alter the results of the study. Another question is whether a larger sample size would result in significant results for the proportion of women with miscarriages, premature births, or live births across groups. Studies have shown that metformin is safe during pregnancy, with efficacy in treating gestational diabetes mellitus and the polycystic ovary syndrome, and that the drug has no effect on the growth of several cancers.2,3 It would be interesting if the authors of this and concurrent studies were to consider whether the use of metformin during pregnancy in women who are obese (BMI, >30) and those who are not obese (BMI, ≤30) would decrease weight retention after birth.1,4 Postpartum weight retention contributes to obesity in all weight classes, and the use of metformin would be an attractive option to reduce this risk.5

This was a retrospective, observational chart review conducted on a convenience sample of 537 outpatients, aged 16–60 years, referred to an Italian Dietetic and Nutrition University Center. The study aimed to look at the association between a history of child- hood obesity and dieting behaviors with development of eating disorders (EDs) at a later age. Subjects with a history of EDs (n = 118), assessed using both self-report and health records, were compared with those with no EDs (n = 419), who were attending the clinic mainly for primary prevention of metabolic and cardiovascular risk. Logistic regression analysis was performed to assess the association of childhood-onset obesity with develop- ment of an ED at a later age. Childhood-onset obesity, gender, maternal history of eating disorders, and dieting were associated with a positive history of EDs at a later age (p < .05). It is important to raise professional awareness of early symptoms of EDs in children with a history of obesity and treat them accordingly.