Evaluation of Body Composition,Physical Activity,and Food Intake in Patients with Inborn Errors of Intermediary Metabolism

Children with inborn errors of intermediary metabolism (IEiM) must follow special diets that restrict their intake of essential nutrients and may compromise normal growth and development. We evaluated body composition, bone mineral density, physical activity, and food intake in IEiM patients undergoing dietary treatment. IEiM patients (n = 99) aged 5–19 years and healthy age- and sex-matched controls (n = 98) were recruited and underwent dual-energy X-ray absorptiometry to evaluate anthropometric characteristics and body composition. Data on food intake and physical activity were also collected using validated questionnaires. The height z-score was significantly lower in IEiM patients than controls (−0.28 vs. 0.15; p = 0.008), particularly in those with carbohydrate and amino acid metabolism disorders. Significant differences in adiposity were observed between patients and controls for the waist circumference z-score (−0.08 vs. −0.58; p = 0.005), but not the body mass index z-score (0.56 vs. 0.42; p = 0.279). IEiM patients had a significantly lower total bone mineral density (BMD) than controls (0.89 vs. 1.6; p = 0.001) and a higher risk of osteopenia (z-score < −2, 33.3% vs. 20.4%) and osteoporosis (z-score < −2.5, 7.1% vs. 0%), but none presented fractures. There was a significant positive correlation between natural protein intake and BMD. Our results indicate that patients with IEiM undergoing dietary treatment, especially those with amino acid and carbohydrate metabolism disorders, present alterations in body composition, including a reduced height, a tendency towards overweight and obesity, and a reduced BMD.     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)     

Body Fat Assessment Method Using CT Images with Separation Mask Algorithm

In recent years, the number of obese population in Korea has been growing up along with the economic development, environmental factors, and the change in life style. Considering the growth of obese population and the adverse effect of obesity on health, it is getting more important to prevent and diagnose the obesity with the quantitative measurement of body fat that has become an important indicator for obesity. In this study, we proposed a procedure for the automated fat assessment from computed tomography (CT) data using image processing technique. The proposed method was applied to a single-CT image as well as CT-volume data, and results were correlated to those of dual-energy X-ray absorptiometry (DEXA) that is known as the reliable method for evaluating body fat. Using single-CT images, correlation coefficients between DEXA and the automated assessment and DEXA and the manual assessment were 0.038 and 0.058, respectively (P > 0.05). Hence, there was no significant correlation between three methods using the proposed method with single-CT images. On the other hand, in case of CT-volume data, the above correlation coefficients were increased to 0.826, 0.812, and 0.805, respectively (P < 0.01). Thus, DEXA and the proposed methods with CT-volume data showed highly significant correlation with each other. The results suggest that the proposed automated assessment using CT-volume data is a reliable method for the evaluation of body fat. It is expected that the clinical application of the proposed procedure will be helpful to reduce the time for the quantitative evaluation of patient’s body fat.     

Improving peri-prosthetic bone adaptation around cementless hip stems: A clinical and finite element study

This study assessed whether the Symax™ implant, a modification of the Omnifit^® stem (in terms of shape, proximal coating and distal surface treatment), would yield improved bone remodelling in a clinical DEXA study, and if these results could be predicted in a finite element (FE) simulation study.In a randomized clinical trial, 2 year DEXA measurements between the uncemented Symax™ and Omnifit^® stem (both n = 25) showed bone mineral density (BMD) loss in Gruen zone 7 of 14% and 20%, respectively (p < 0.05). In contrast, the FE models predicted a 28% (Symax™) and 26% (Omnifit^®) bone loss. When the distal treatment to the Symax™ was not modelled in the simulation, bone loss of 35% was predicted, suggesting the benefit of this surface treatment for proximal bone maintenance.The theoretical concept for enhanced proximal bone loading by the Symax™, and the predicted remodelling pattern were confirmed by DEXA-results, but there was no quantitative match between clinical and FE findings. This was due to a simulation based on incomplete assumptions concerning the yet unknown biological and mechanical effects of the new coating and surface treatment.Study listed under ClinicalTrials.gov with number NCT01695213.     

Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys

We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27-33 yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved in very old calorie restricted (CR) monkeys compared to age-matched Controls. Immunohistochemical analysis revealed an age-associated increase in the proportion of Type I fibers in the VL from Control animals that was prevented with CR. The cross sectional area (CSA) of Type II fibers was reduced in old CR animals compared to earlier time points (16-22 years of age); however, the total loss in CSA was only 15% in CR animals compared to 36% in old Controls at ~27 years of age. Atrophy was not detected in Type I fibers from either group. Notably, Type I fiber CSA was ~1.6 fold greater in VL from CR animals compared to Control animals at ~27 years of age. The frequency of VL muscle fibers with defects in mitochondrial electron transport system enzymes (ETS(ab)), the absence of cytochrome c oxidase and hyper-reactive succinate dehydrogenase, were identical between Control and CR. We describe changes in ETS(ab) fiber CSA and determined that CR fibers respond differently to the challenge of mitochondrial deficiency. Fiber counts of intact rectus femoris muscles revealed that muscle fiber density was preserved in old CR animals. We suggest that muscle fibers from CR animals are better poised to endure and adapt to changes in muscle mass than those of Control animals.     

Hounsfield unit for the diagnosis of bone mineral density disease: A proof of concept study

ObjectivesOur aim is to correlate Hounsfield units (HU) from lumbar Computed Tomography scans (CT) with Bone Mineral Density (BMD) values from Dual-energy X-ray Absorptiometry scans (DXA) for the diagnosis of bone mineral density disease.MethodsWe enrolled 114 women, conducted both CT and DXA scans on them to assess the correlations between the mean lowest HU at lumbar vertebrae and the BMD values from DXA scan. Statistical analysis was used to assess the correlations between HU and the patients' BMD and age.ResultsWe noted moderate correlations between the lowest HU at L1–L4 and the BMD from DXA scan which is significant (correlation coefficient, 0.563). DXA scans showed a normal BMD in 33.3% of patients, osteopenia in 43.9%, and osteoporosis in 22.8% respectively. We also determined that a HU of 203 would exclude osteoporosis (90% sensitivity for normal BMD) and a threshold of <91 would exclude normal bone mineral density (86% sensitivity for osteopenia, 60% sensitivity for osteoporosis). Mean HU values consistently decreased with increasing decade of life, from 182.8 ± 42 in the fourth decade to 82.13 ± 32 in the eighth (correlation coefficient, 0.527).ConclusionsHU values are moderately correlated with the patients' age and BMD values from DXA scan, with 203, safely excluding osteoporosis and <91 excluding normal BMD. Prospective studies with a larger number of patients are needed, where multiple thresholds could be applied and more distinguished values for normal bone density, osteopenia, and osteoporosis can be obtained.     

Maternal obesity induced by a ‘cafeteria’ diet in the rat does not increase inflammation in maternal,placental or fetal tissues in late gestation

IntroductionObesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation.MethodsMaternal obesity was established in rats by 8 weeks of pre-pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFα) and expression of inflammatory genes (Tnfα, Il-6, Il-1β, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation.ResultsDespite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL-6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver.ConclusionsMaternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation.     

The phenotype of a flavin-containing monooyxgenase knockout mouse implicates the drug-metabolizing enzyme FMO1 as a novel regulator of energy balance

Flavin-containing monooxygenases (FMOs) of mammals are thought to be involved exclusively in the metabolism of foreign chemicals. Here, we report the unexpected finding that mice lacking Fmos 1, 2 and 4 exhibit a lean phenotype and, despite similar food intake, weigh less and store less triglyceride in white adipose tissue (WAT) than wild-type mice. This is a consequence of enhanced whole-body energy expenditure, due mostly to increased resting energy expenditure (REE). This is fuelled, in part, by increased fatty acid β-oxidation in skeletal muscle, which would contribute to depletion of lipid stores in WAT. The enhanced energy expenditure is attributed, in part, to an increased capacity for exercise. There is no evidence that the enhanced REE is due to increased adaptive thermogenesis; instead, our results are consistent with the operation in WAT of a futile energy cycle. In contrast to FMO2 and FMO4, FMO1 is highly expressed in metabolic tissues, including liver, kidney, WAT and BAT. This and other evidence implicates FMO1 as underlying the phenotype. The identification of a novel, previously unsuspected, role for FMO1 as a regulator of energy homeostasis establishes, for the first time, a role for a mammalian FMO in endogenous metabolism. Thus, FMO1 can no longer be considered to function exclusively as a xenobiotic-metabolizing enzyme. Consequently, chronic administration of drugs that are substrates for FMO1 would be expected to affect energy homeostasis, via competition for endogenous substrates, and, thus, have important implications for the general health of patients and their response to drug therapy.     

Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism

Background and aimsLittle is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism.Methods and resultsFourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed.ConclusionsIn male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT.