The effects of anorexia nervosa on bone metabolism in female adolescents

Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bone turnover, calcium, and hormonal status in 19 adolescent girls with AN (mean +/- SEM, 16.0+/-0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19+/-5 months. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 SD below the mean in 42% of patients, and lateral spine BMD was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P \u3c 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2+/-1.9 vs. 23.3+/-1.6 pg/mL (P = 0.01); free testosterone, 0.70+/-0.17 vs. 1.36+/-0.14 pg/mL (P = 0.01)] although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9+/-2.1 vs. 16.5+/-1.8 ng/mL; P \u3c 0.0001). Insulin-like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219+/-41 vs. 511+/-35 ng/mL; P \u3c 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P \u3c 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1+/-6.4 vs. 59.2+/-5.2 ng/mL; BSAP, 27.9+/-4.0 vs. 40.6+/-3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r2 = 0.72; P = 0.002; BSAP: r2 = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia in adolescents with AN

Myocardial Tissue Remodeling in Adolescent Obesity

Background: Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue‐level markers within the myocardium that precede organ‐level alterations have not been described. Methods and Results: We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m2, including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years; BMI, 20.1±3.5 kg/m2) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size‐adjusted limits), interstitial matrix expansion by CMR extracellular volume fraction (ECV) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire population (r=0.58, P<0.001) and with high‐sensitivity C‐reactive protein (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c (r=0.76, P<0.0001) in the obese stratum. Conclusions: Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function

Regional body composition in adolescents with anorexia nervosa and changes with weight recovery

BACKGROUND: Studies of regional fat distribution in adults with anorexia nervosa (AN) have shown decreased extremity fat at baseline and increased trunk fat with weight recovery, resulting in truncal adiposity. Little is known about fat distribution in adolescents with AN, especially with weight recovery. OBJECTIVE: We sought to determine whether regional fat distribution in adolescents with AN is comparable with that in healthy adolescents and whether weight recovery results in increased trunk fat and truncal adiposity. DESIGN: In 21 adolescent girls with AN and 21 control subjects matched for age and pubertal stage, we measured body-composition variables with dual-energy X-ray absorptiometry at baseline, 6 mo, and 12 mo. Weight recovery was defined as a \u3e or = 10% increase in body mass index. RESULTS: At baseline, the girls with AN had a lower percentage of trunk fat than did the control subjects, whereas the percentage of extremity fat was not significantly different between the groups. Weight recovery in 13 subjects with AN resulted in an increased percentage of trunk fat and an increased ratio of trunk fat to extremity fat; however, this ratio did not exceed that of control subjects. CONCLUSIONS: In adolescents with AN, trunk fat rather than extremity fat is reduced. Weight recovery is associated with increased trunk fat and an increased ratio of trunk fat to extremity fat. In contrast with previous findings in adults, this most likely represents normalization of fat distribution rather than development of truncal adiposity

HbA1c After a Short Period of Monotherapy With Metformin Identifies Durable Glycemic Control Among Adolescents With Type 2 Diabetes.

OBJECTIVE: To determine whether clinically accessible parameters early in the course of youth-onset type 2 diabetes predict likelihood of durable control on oral therapy. RESEARCH DESIGN AND METHODS: TODAY was a randomized clinical trial of adolescents with type 2 diabetes. Two groups, including participants from all three treatments, were defined for analysis: 1) those who remained in glycemic control for at least 48 months of follow-up and 2) those who lost glycemic control before 48 months. Outcome group was analyzed in univariate and multivariate models as a function of baseline characteristics (age, sex, race/ethnicity, socioeconomic status, BMI, waist circumference, Tanner stage, disease duration, depressive symptoms) and biochemical measures (HbA(1c), C-peptide, lean and fat body mass, insulin inverse, insulinogenic index). Receiver operating characteristic curves were used to analyze HbA(1c) cut points. RESULTS: In multivariate models including factors significant in univariate analysis, only HbA(1c) and insulinogenic index at randomization remained significant (P < 0.0001 and P = 0.0002, respectively). An HbA(1c) cutoff of 6.3% (45 mmol/mol) (positive likelihood ratio [PLR] 3.7) was identified that optimally distinguished the groups; sex-specific cutoffs were 6.3% (45 mmol/mol) for females (PLR 4.4) and 5.6% (38 mmol/mol) for males (PLR 2.1). CONCLUSIONS: Identifying youth with type 2 diabetes at risk for rapid loss of glycemic control would allow more targeted therapy. HbA(1c) is a clinically accessible measure to identify high risk for loss of glycemic control on oral therapy. Adolescents with type 2 diabetes unable to attain a non–diabetes range HbA(1c) on metformin are at increased risk for rapid loss of glycemic control