Obesity and Bone: A Complex Relationship

There is a large literature on the relationship between obesity and bone. What we can conclude from this review is that the increase in body weight causes an increase in BMD, both for a mechanical effect and for the greater amount of estrogens present in the adipose tissue. Nevertheless, despite an apparent strengthening of the bone witnessed by the increased BMD, the risk of fracture is higher. The greater risk of fracture in the obese subject is due to various factors, which are carefully analyzed by the Authors. These factors can be divided into metabolic factors and increased risk of falls. Fractures have an atypical distribution in the obese, with a lower incidence of typical osteoporotic fractures, such as those of hip, spine and wrist, and an increase in fractures of the ankle, upper leg, and humerus. In children, the distribution is different, but it is not the same in obese and normal-weight children. Specifically, the fractures of the lower limb are much more frequent in obese children. Sarcopenic obesity plays an important role. The authors also review the available literature regarding the effects of high-fat diet, weight loss and bariatric surgery.

A CLINICAL STUDY OF THYROID DYSFUNCTION IN OVERWEIGHT AND OBESE PATIENT-A HOSPITAL BASED STUDY

To find out thyroid hormone profile (Serum T3, T4, TSH level) in overweight and obese subjects of either sex and age. (18-60 yrs.) This study was undertaken to find out relationship between thyroid function tests with overweight and obesity. Methods: A cross sectional study was conducted in the Medicine Department of Jhalawar Medical College. Approximately overweight and obese patient of BMI >25 come in to OPD or emergency department & admitted in Jhalawar hospital. Total 100 subjects taken for study which fulfil the inclusion and exclusion criteria of study. Results: In our study, Maximum 3 (50%) hypothyroid patient had extremely risk of obesity having BMI >40 and 4 (28.6%) patient having very high risk obesity BMI 35-40 and 6 (18.75%) patient having high risk BMI 30-35 and only 6 (12.5%) patient having BMI 25-30 overweight (low risk) patient. Conclusion: This study concludes that obesity increases the risk of hypothyroidism, which is more common among, younger female than males. in this study some overweight and obese subject were found both clinically and biochemically hypothyroid and some subject are found only biochemically hypothyroid.

A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model: Relevance for COVID-19 Patients

Ivermectin (IVM) and moxidectin (MOX) are used extensively as parasiticides in veterinary medicine. Based on in vitro data, IVM has recently been proposed for the prevention and treatment of COVID-19 infection, a condition for which obesity is a major risk factor. In patients, IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM, MOX, and a third analog, eprinomectin (EPR). An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX, and EPR were administered intravenously, in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX but was reduced for IVM and EPR, compared to the initial control state. However, when scaled by body weight (L/day/kg), plasma clearance was reduced by 55, 42, and 63%, for IVM, MOX and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased, in absolute values (L), by obesity. For IVM and MOX, this obese dog model suggests that the maintenance doses in the obese subject should be based on lean body weight rather than total weight. On the other hand, the loading dose, when required, should be based on the total body weight of the obese subject.

Evaluation of serum irisin, retinol-binding protein-4 in human obesity

Retinol-binding protein 4(RBP4), and irisin originally described as an adipocyte-specific hormone, has been suggested to be an important link between obesity, insulin resistance and diabetes. To test the hypothesis that irisin and RBP4, and insulin concentrations will be higher in obese subject than in normal weight. A total of 176 individuals were evaluated, which divided into three groups according to BMI. Group I (Normal Weight group n=75), Group II (Over Weight group, n=50), Group III (Obese group, n=51). Serum irisin RBP4and insulin levels were evaluated by enzyme-linked immunosorbent assay. The statistical analysis (students t-test) exhibited significant (P> 0.0001)elevation for Serum RBP4 , Irisin, and insulin in over weight and obese groups compared with normal weight groups{(57.6 ± 16.0), and (70.1 ± 19.9)vs (41.8 ± 13.3) µg/ml ; p< 0.001},{(168.19 ± 11.71) and (171.35 ± 11.81) vs(146.19 ± 9.13) ng/mL: p< 0.05},{(7.25 ± 2.04), and (9.02 ± 4.75) vs (4.91±1.87) mU/mL; p< 0.001} respectively. Linear regression analysis showed significant positive correlations between serum insulin with RBP4 and, Irisin.

Daptomycin Pharmacokinetics in Adolescents Undergoing Hemodialysis and Peritoneal Dialysis: A Case Series With Pharmacokinetic Modeling

BACKGROUND Children who undergo hemodialysis (HD) and peritoneal dialysis are at increased risk of infection. Daptomcyin is used to treat resistant infections; however, the pharmacokinetics of daptomycin in pediatric and adolescent dialysis patients remain unknown. METHODS We report the safety and pharmacokinetics of a single intravenous 5 mg/kg dose of daptomycin for 6 individuals age 12 to 17 years old who underwent HD or continuous cycling peritoneal dialysis (CCPD). Daptomycin concentrations from all samples were determined by high-performance liquid chromatography. A non-compartmental analysis was performed to compare the pharmacokinetic parameters among HD and CCPD patients. A population pharmacokinetic model was developed to describe the concentration-time profiles of daptomycin in plasma, urine, and dialysis effluent. Monte Carlo simulations were performed to assess the pharmacodynamic outcomes. RESULTS All subjects tolerated the single dose of daptomycin. During HD, significant drug removal was observed, compared with CCPD (26% vs 5% of total dose). A low daptomycin renal clearance (&lt;12% of total clearance) with moderate variability (40.5%) was observed among subjects with residual renal function. An anuric and obese subject who received CCPD treatment appeared to have &gt;80% higher daptomycin area under the plasma concentration-time curve than the other CCPD subjects. Dosing regimens that achieved predefined pharmacodynamic targets were reported. CONCLUSIONS Daptomycin clearance was faster in 12- to 17-year-old patients receiving HD than CCPD. Administration of daptomycin immediately after HD reduces drug loss. The CCPD treatment, anuria, and obesity may increase the risk for drug accumulation. Our pharmacokinetic model can be further used to optimize dosing regimens of daptomycin in this population.

Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients.

Background and Purpose: Based on in vitro data, ivermectin (IVM) has been proposed for the prevention and treatment of COVID-19, a condition for which obesity is a major risk factor. IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM and two analog compounds, moxidectin (MOX) and eprinomectin (EPR). Experimental Approach: An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX and EPR were administered intravenously, simultaneously in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. Key Results: In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX and reduced for IVM and EPR, compared to the initial control state. When scaled by body weight (L/day/kg), plasma clearance was reduced by 42, 55 and 63%, for MOX, IVM and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased in absolute values (L) by obesity. Conclusion and Implications: For IVM and MOX, the obese dog model suggests that the maintenance dose should not be adjusted by total body weight in the obese subject but should be based on lean body weight. On the other hand, the loading dose should be computed based on the total body weight of the obese subject.

New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease

Non-alcoholic or recently re-defined metabolic associated fatty liver disease (MAFLD), a spectrum of progressive hepatic disease, has become a public health issue in obese children and adolescents. MAFLD is a complex metabolic disease strongly associated with obesity and insulin resistance. It is not known why not every obese subject will develop MAFLD. Different ethnic/racial groups display differences in MAFLD prevalence, indicating genetic factor plays a role. In the past two decades, sequence variations in genetic loci, including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, etc. have been shown to confer susceptibility to MAFLD in children and adults. This review article provides an updated viewpoint of genetic predictors related to pediatric MAFLD. We discuss whether these susceptible genes can be clinically used for risk stratification and personalized care. Understanding human genetics and molecular mechanisms can give important information not only for prediction of risk but also on how to design drugs. In view of current epidemic of MAFLD worldwide, it is necessary to identify which children with MAFLD progress rapidly and need earlier intervention. In the future, a comprehensive analysis of individualized genetic and environmental factors may help assess the risk of children with MAFLD and personalize their treatment.

CARDIOVASCULAR PARAMETERS IN OBESE AND NORMAL WEIGHT PEOPLE: A COMPARATIVE STUDY

Introduction: Obesity can be classified as generalized obesity (GO) and abdominal obesity (AO) and obese population have higher rates of mortality and morbidity compared to non-obese individuals. World Health Organization (WHO) has defined overweight and obesity as abnormal or excessive fat accumulation that presents a risk to health. A commonly used simple measure to classify overweight and obesity in adults is body mass index (BMI). BMI is defined as a person's weight in kilograms divided by the square of his height in meters (kg/m2). WHO defines overweight when BMI is greater than or equal to 25; and obesity when BMI is greater or equal to 30 but in Asians, the cut-offs for overweight (≥23.0kg/m2) and obesity (≥25.0kg/m2) are lower than WHO criteria due to risk factors and morbidities MATERIAL AND methods: A sample of 50 male and 50 female obese patients with body Mass Index > 30 kg/m2 and also 50 male and 50 female non obese patients with body Mass Index of 18.50 – 24.99 kg/m2 were selected. Sample was randomly selected. A pilot study was carried out on 20 patients to ensure feasibility, and time needed for completing the study. Results: A total of 200 participants were included in the study of which 100 were obese and 100 were non obese subject. Comparison of cardiac paramenters between obese and non obese individual was done like hrart rate, systolic and diastolic blood pressure, mean arterial pressure and pulse pressure. Demographic variables were also compared. Conclusion: The strong association of obesity with cardiovascular disease necessitates the importance of prevention and control of obesity and it should begin in early child hood also proper diet and regular medical check-up should be carried out to cope up with the problem of obesity.

Three-Dimensional Ankle Exercise with Combined Isotonic Technique for an Obese Subject with Plantar Fasciitis: A Case Study

Background and objectives: Obese people have many foot-related disorders and plantar fasciitis (PF) is the most common disorder among them. However, research on the role of therapeutic exercises in PF is lacking and there is no evidence to suggest its benefits. As such, a further insight into therapeutic exercises is needed within this group. This case study investigated the effect of three-dimensional (3D) ankle exercises using a combined isotonic (CI) technique on function and balance in an obese subject with PF. Material and methods: The subject in this study was a 28-year-old obese woman who was diagnosed with PF by an orthopedic surgeon. A 3D ankle exercise program was commenced three times a week for 15 min over 4 weeks. The evaluations were conducted at five intervals: pre-test, and at 1, 2, 3 and 4 weeks from the initiation of the intervention. The tests were conducted in the following order: the patient-specific functional scale test (PSFS), an ultrasound of the plantar fascia, the heel pressure and balance test, the pressure pain threshold (PPT), and the 4-way ankle strength test. Results: The mean score of the PSFS test reduced by 70.55% after 4 weeks of the intervention. The thickness of the plantar fascia and heel pressure measured during single-leg standing decreased by 6.67% and 10.37%, respectively, after 4 weeks of the intervention. The anteroposterior and medial-lateral balance ability showed improvements of 8.29% and 8.61%, respectively, after 4 weeks of the intervention. The PPT improved by 38.01% after 4 weeks of the intervention. In the 4-way ankle strength test, dorsiflexion, plantar flexion, inversion, and eversion increased by 14.46%, 9.63%, 4.3% and 13.25%, respectively, after 4 weeks of the intervention. Conclusion: 3D ankle exercises utilizing the CI technique were shown to be effective in improving foot function, pressure pain, and muscle strength in dorsiflexion and inversion in an obese patient with PF.