Effects of Metformin-Single Therapy on the Level of Inflammatory Markers in Serum of Non-Obese T2DM Patients with NAFLD.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is associated with inflammation and subsequent increase in cardiovascular risk. Because of its widespread presence and distribution, invasive diagnostic procedures (i.e., liver biopsy) are reserved for a limited number of subjects. With liver ultrasound, Fatty liver index (FLI) and fibrosis-4 (FIB-4) scores non-invasively assess liver steatosis and fibrosis. We aimed to evaluate the changes in inflammatory markers and FLI/FIB-4 scores in non-obese metformin-treated type 2 diabetes patients (T2DM) with NAFLD. METHODS: All subjects underwent abdominal ultrasound aiming for NAFLD stratification (grade 1 to 3 according to its severity). Metabolic parameters (morning glycaemia, HbA1C, lipids, liver function tests), serum inflammatory markers (C-reactive protein, ferritin, and nitric oxide) and FLI/- FIB-4 were calculated. RESULTS: FLI score and ultrasound NAFLD grades were found to correlate (p<0.05). We observed a significant correlation between the levels of ferritin and C-reactive protein (CRP) (p<0.05), and the FLI (p<0.05). Body weight (BW) (p<0.05), waist circumference (WC) (p<0.05), the levels of HbA1c (p<0.05), transferrin (p<0.05), insulin (p<0.05), and FLI score (p<0.05) significantly differed between groups as defined by the severity of NAFLD. CONCLUSION: This pilot study suggests that the serum inflammatory markers at the average normal values point to the sufficiency of metformin-single therapy in inflammation control in non-obese T2DM patients with NAFLD.

Case Report: Low Bone and Normal Lean Mass in Adolescents With Complete Androgen Insensitivity Syndrome.

Introduction: Osteopenia and osteoporosis have been reported in adults with Complete Androgen Insensitivity Syndrome (CAIS). Little is known about changes in bone mineral density (BMD) in adolescents with CAIS and whether it is affected by early gonadectomy. Body composition data have not been reported. Methods: Single-center, retrospective study of CAIS adolescents who underwent dual-energy x-ray absorptiometry (DXA) (Hologic, Horizon A). Body composition is presented as lean and fat mass indices (LMI, FMI). Z-scores for lumbar spine areal BMD (LBMD), total body less head (TBLH), bone mineral content (BMC), LMI, and FMI were calculated using female normative data. Results are expressed as median and min, max. Results: Six females with genetically confirmed CAIS were identified-one with intact gonads and five with history of gonadectomy at 2-11 months. In the subject with intact gonads, LBMD-Z and TBLH BMC-Z were -1.56 and -1.26, respectively, at age 16 years. Among those with gonadectomy, LBMD-Z was -1.8 (-3.59 to 0.49) at age 15.6 years (12-16.8) and decreased in all three subjects who had longitudinal follow-up despite hormone replacement therapy (HRT). Adherence to HRT was intermittent. LMI-Z and FMI-Z were 0.1 (-1.39 to 0.7) and 1.0 (0.22 to 1.49), respectively. Conclusions: These limited data indicate that adolescents with CAIS have bone mass deficit. Further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual. Data on lean mass are reassuring.

Insulin Requirements and Carbohydrate to Insulin Ratio in Normal Weight, Overweight, and Obese Women With Type 1 Diabetes Under Pump Treatment During Pregnancy: A Lesson From Old Technologies.

Aim: The primary aim of this study was to assess insulin requirements and carbohydrate to insulin ratio (CHO/IR) in normal weight, overweight, and obese pregnant women with type 1 diabetes across early, middle, and late pregnancy. Methods: In this multicenter, retrospective, observational study we evaluated 86 of 101 pregnant Caucasian women with type 1 diabetes under pump treatment. The women were trained to calculate CHO/IR daily by dividing CHO grams of every single meal by insulin units injected. Since the purpose of the study was to identify the CHO/IR able to reach the glycemic target, we only selected the CHO/IR obtained when glycemic values were at target. Statistics: SPSS 20. Results: We studied 45 normal weight, 31 overweight, and 10 obese women. Insulin requirements increased throughout pregnancy (p < 0.0001 and <0.001 respectively) in the normal and overweight women, while it remained unchanged in the obese women. Insulin requirements were different between groups when expressed as an absolute value, but not when adjusted for body weight. Breakfast CHO/IR decreased progressively throughout pregnancy in the normal weight women, from 13.3 (9.8-6.7) at the first stage of pregnancy to 6.2 (3.8-8.6) (p = 0.01) at the end stage, and in the overweight women from 8.5 (7.1-12.6) to 5.2 (4.0-8.1) (p = 0.001), while in the obese women it remained stable, moving from 6.0 (5.0-7.9) to 5.1 (4.1-7.4) (p = 0.7). Likewise, lunch and dinner CHO/IR decreased in the normal weight and overweight women (p < 0.03) and not in the obese women. The obese women gained less weight than the others, especially in early pregnancy when they even lost a median of 1.25 (-1 -1.1) kg (p = 0.005). In early pregnancy, we found a correlation between pregestational BMI and insulin requirements (IU/day) or CHO/IR at each meal (p < 0.001 and p = 0.001, respectively). In late pregnancy, a relationship between pre-gestational BMI and CHO/IR change was found (P = 0.004), as well as between weight gain and CHO/IR change (p=0.02). The significance was lost when both variables were included in the multiple regression analysis. There was no difference in pregnancy outcomes except for a higher pre-term delivery rate in the obese women. Conclusion: Pre-gestational BMI and weight gain may play a role in determining CHO/IR during pregnancy in women with type 1 diabetes under pump treatment.

Actual versus ideal body weight dosing of sugammadex in morbidly obese patients offers faster reversal of rocuronium- or vecuronium-induced deep or moderate neuromuscular block: a randomized clinical trial.

BACKGROUND: This randomized, double-blind trial evaluated sugammadex-mediated recovery time from rocuronium- or vecuronium-induced moderate (M-) or deep (D-) neuromuscular block in morbidly obese adults dosed by actual (ABW) or ideal body weight (IBW). METHODS: Adults with BMI ≥40 kg/m2 were randomized to 1 of 5 groups: M-neuromuscular block, sugammadex 2 mg/kg ABW; M-neuromuscular block, sugammadex 2 mg/kg IBW; M-neuromuscular block, neostigmine 5 mg, and glycopyrrolate 1 mg; D-neuromuscular block, sugammadex 4 mg/kg ABW; or D-neuromuscular block, sugammadex 4 mg/kg IBW. Supramaximal train of four (TOF) stimulation of the ulnar nerve (TOF-watch SX®) monitored recovery. Primary endpoint was time to TOF ratio ≥ 0.9 for ABW and IBW groups pooled across neuromuscular blocking agent (NMBA)/blocking depth, analyzed by log-rank test stratified for agent and depth. Prespecified safety outcomes included treatment-emergent bradycardia, tachycardia, and other arrhythmias, and adjudicated hypersensitivity and anaphylaxis. RESULTS: Of 207 patients randomized, 188 received treatment (28% male, BMI 47 ± 5.1 kg/m2, age 48 ± 13 years). Recovery was 1.5 min faster with ABW vs IBW dosing. The sugammadex 2 mg/kg groups recovered 9-fold faster [time 0.11-fold, 95% CI 0.08 to 0.14] than the neostigmine group. ABW (5.3%) and IBW (2.7%) groups had similar incidences of recovery time > 10 min (95% CI of difference: - 4.8 to 11.0%); 84% for neostigmine group. Re-curarization occurred in one patient each in the 2 mg/kg IBW and neostigmine groups. Prespecified safety outcomes occurred with similar incidences. CONCLUSIONS: ABW-based sugammadex dosing yields faster reversal without re-curarization, supporting ABW-based sugammadex dosing in the morbidly obese, irrespective of the depth of neuromuscular block or NMBA used. TRIAL REGISTRATION: Registered on November 17, 2017, at ClinicalTrials.gov under number NCT03346070 .

Allostatic Load Effects on Cortical and Cognitive Deficits in Essentially Normotensive, Normoweight Patients with Schizophrenia.

Reduced cortical gray matter integrity and cognitive abilities are among core deficits in schizophrenia. We hypothesized that higher allostatic load (AL) that accounts for exposure to chronic stress is a contributor to structural and cognitive deficits in schizophrenia. One hundred and sixty-seven schizophrenia patients who were on average with normal weight, normal systolic, and diastolic blood pressure and 72 healthy controls were enrolled in the study. Group differences in subclinical cardiovascular, metabolic, immune, and neuroendocrine biological markers as indexed by AL and contribution of AL components to the structural and cognitive deficits in schizophrenia were explored. Compared with controls, schizophrenia patients who were normotensive, normoweight, and had low total cholesterol levels still had significantly higher AL mainly due to lower high-density lipoprotein cholesterol and higher heart rate, waist-hip ratio, hemoglobinA1c, hypersensitive C-reactive protein, and overnight-urine cortisol levels. Patients also had decreased whole-brain mean cortical thickness, and lower cognition assessed by the MATRICS consensus cognitive battery. AL was inversely correlated with mean cortical thickness and cognition in schizophrenia, while none of these relationships existed in controls. Mediation analyses showed the effect of AL on cognitive deficits in schizophrenia was significantly mediated by cortical thinning, and the most significant mediating cortical area was the left superior frontal gyrus. Cortical thickness may act as a mediator between AL and cognitive deficits in schizophrenia. Early intervention strategies to reduce cortical thinning and cognitive dysfunction in schizophrenia should target specific aspects of their high AL in addition to weight gain, hypertension and high cholesterol levels.

Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men.

CONTEXT: Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians. DESIGN AND SETTING: To investigate the relationships between decreased AN level, impaired ATIS, and metabolic abnormalities, we studied 94 Japanese men whose body mass index was less than 25 kg/m2. We divided the subjects into 4 groups based on their median AN level and ATIS, the latter calculated as the degree of insulin-mediated suppression of free fatty acids during hyperinsulinemic euglycemic clamp, and compared the metabolic parameters in the 4 groups. RESULTS: The High-ATIS/High-AN group (n = 29) showed similar anthropometric data to the High-ATIS/Low-AN group (n = 18). In contrast, both the Low-ATIS/High-AN (n = 18) and Low-ATIS/Low-AN (n = 29) groups showed significantly lower muscle insulin sensitivity than the High-ATIS groups. The intrahepatic lipid level in the Low-ATIS/Low-AN group was significantly higher than that in the High-ATIS groups. In addition, the Low-ATIS/Low-AN group had a significantly higher fasting serum triglyceride level and significantly lower high-density lipoprotein cholesterol level than the other 3 groups. CONCLUSIONS: In nonobese Japanese men with high ATIS, the AN level was not associated with metabolic characteristics. On the other hand, subjects with low ATIS showed reduced muscle insulin sensitivity, and those with a decreased AN level demonstrated multiple metabolic abnormalities, represented by fatty liver and dyslipidemia.

The Role of Underweight in Active Life Expectancy Among Older Adults in Japan.

OBJECTIVES: It is underweight, rather than overweight or obesity, that has been a pressing public health concern in Japan. This study examines the impact of being underweight on the health of older Japanese men and women, measured by active life expectancy at age 65. Following the Japanese government's guideline, underweight in this study is defined using the body mass index (BMI) value of 20. METHOD: Data came from five waves (1999-2009) of the Nihon University Japanese Longitudinal Study of Aging (NUJLSOA). We used the Interpolation of Markov Chain approach to estimate the number of years underweight (BMI < 20), normal weight (20 < BMI < 25), and overweight (25 < BMI) individuals were expected to live without difficulty in activities of daily living (ADLs) or instrumental ADLs. RESULTS: We found differences in life and health expectancies across the three weight categories. Underweight people were expected to live the shortest lives and spend the fewest years in an active state compared with normal and overweight individuals. Results remained unchanged even when accounting for educational attainment, smoking history, and a count of existing chronic conditions. DISCUSSION: Being underweight is associated with poor quality of life lived among Japanese older adults. This finding suggests the importance of maintaining proper weight and avoids nutritional risks at advanced ages.

Effects of an Indoor Cycling Program on Cardiometabolic Factors in Women with Obesity vs. Normal Body Weight.

The study aimed to provide evidence on the impact of indoor cycling (IC) in reducing cardiometabolic risk factors. The study compares the effects of a 3 month IC program involving three 55 min sessions per week on women aged 40-60 years, with obesity (OW, n = 18) vs. women with normal body weight (NW, n = 8). At baseline and at the end of the study, anthropometric parameters, oxygen uptake (VO2 peak), and serum parameters: glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), insulin, human anti-oxidized low-density lipoprotein antibody (OLAb), total blood antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), endothelial nitric oxide synthase (eNOS), C-reactive protein (CRP), lipid accumulation product (LAP), and homeostasis model assessment of insulin resistance index (HOMA IR) were determined. Before the intervention, VO2 peak and HDL-C levels were significantly lower and levels of TG, LAP, insulin, HOMA-IR, and CRP were significantly higher in the OW group compared to those in the NW group. After the intervention, only the OW group saw a decrease in body mass, total cholesterol, OLAb, TBARS, and CRP concentration and an increase in total body skeletal muscle mass and HDL-C concentration. In response to the IC training, measured indicators in the OW group were seen to approach the recommended values, but all between-group differences remained significant. Our results demonstrate that IC shows promise for reducing cardiometabolic risk factors, especially dyslipidemia. After 12 weeks of regular IC, the metabolic function of the OW group adapted in many aspects to be more like that of the NW group.

Gut Microbiota Diversity in Lean Athletes Is Associated with Positive Energy Balance.

INTRODUCTION: In contrast to obesity, little is known about the human lean phenotype associated with gut microbiota composition. OBJECTIVE: We aimed to investigate whether the bacterial composition of lean athletes with a positive energy balance differs from the equal-calorie food group. METHODS: Twenty-four male participants were included in this cross-sectional study: lean athletes with a positive energy balance (LA, n 12) and control group athletes (CTRLs, n 12). Nutritional data, resting and total energy expenditure, and body composition were determined. DNA was extracted from stool samples and subjected to 16S rRNA gene analysis. RESULTS: We found 7 differentially abundant bacterial taxa between the LA and CTRL groups. Of those, 5 were significantly less abundant and 2 were enriched in the LA group. The following categories significantly associated with the community structure were identified: body fat parameters, BMI, energy intake and expenditure, oxygen consumption, and respiratory exchange ratio. CONCLUSIONS: Although we are far from a detailed interpretation of lean human body maintenance, the primary findings of our study suggest that gut microbial composition may be a factor influencing the regulation of weight gain in lean athletes with a positive energy balance.

Prevalence of abdominal obesity in non-obese adolescents: a North Indian adolescent study.

Context Childhood obesity is defined based on body mass index (BMI) criteria. Asian adults have more abdominal adiposity as compared to Western people for an equivalent BMI. Similarly, children who are non-obese/overweight by BMI criteria may have abdominal obesity. It is important to identify and target this population to reduce future cardiovascular risk. Objective To evaluate and inter-relate the prevalence of obesity subtypes (generalized and abdominal) in school going adolescents. Methods A randomized cross-sectional community based study was conducted, which was carried out in 13 schools of Chandigarh, a North Indian city. 10,037 school going adolescents of age 10-18 years were evaluated. Results The prevalence of overweight and generalized obesity in present study was 9.3 and 4.9% respectively. Generalized obesity was observed in 4.2% of males and 5.7% of females (p-Value = 0.001). The abdominal obesity was noted in 5.4% of children and its prevalence increased progressively with age. The prevalence was highest in 16-18 years age-group (7.6%, p<0.001). 39.3% of abdominally obese subjects were not obese by BMI criteria, while prevalence of abdominal obesity in nonobese adolescents was 2.24%. It was more prevalent in females (3.7%) than males (3%, p=0.025). Prevalence of obesity was 7.9 and 1.8% in private and government schools respectively (p<0.001). Conclusions Abdominal obesity is more prevalent than generalized obesity and shows increasing trend with age. Interestingly, over one third of centrally obese adolescents are not obese by BMI criteria. This underlines the importance of waist circumference measurement in addition to BMI while assessing obesity.

Association of sleep characteristics with adiposity markers in children.

Background Accumulating evidence suggests a relationship between sleep alterations and overweight/obesity in children. Our aim was to investigate the association of sleep measures other than obstructive sleep apnea or sleep duration with overweight/obesity and metabolic function in children. Methods We conducted a prospective cohort study in school- aged children (aged 5 to 8 years, prepubertal, and 12 to 15 years, pubertal) with overweight/obesity and normal-weight children. All children underwent a standardized in-laboratory polysomnography followed by a fasting blood assessment for glucose and metabolic testing. Subjective sleep measures were investigated by a 7-day sleep diary and questionnaire. We analyzed prepubertal and pubertal groups separately using logistic regression and partial correlation analyses. Results A total of 151 participants were analyzed. Overweight/obese children had significantly higher odds for arousal index (prepubertal children: 1.28, Confidence interval (CI): 1.06, 1.67; pubertal children: 1.65, CI: 1.19, 2.29) than normal-weight children, independent of age and gender. In prepubertal children, arousal-index was positively associated with C-peptide (r=0.30, p=0.01), whereas Minimum O2 saturation was negatively associated with triglycerides (r=-0.34, p=0.005), adjusting for age and sex. However, associations were attenuated by further adjustment for body mass index standard deviation scores (BMI-SDS). In pubertal children, higher level of apnea-hypopnea-index and pCO2 predicted increased lipoprotein (a) levels (r=0.35, p=0.03 and r=0.40, p=0.01, respectively), independent of age, sex, and BMI-SDS. A negative association was found between pCO2 and high-density lipoprotein (HDL)-cholesterol (r=-0.40, p=0.01). Conclusions Overall, we report that sleep quality as measured by arousal index may be compromised by overweight and obesity in children and warrants attention in future intervention programs.

Longitudinal Changes in Fat Mass and the Hippocampus.

OBJECTIVE: This study aimed to investigate cross-sectional and longitudinal associations between fat mass (i.e., body mass index [BMI], waist circumference [WC], and waist to hip ratio [WTHR]) and hippocampal volumes. METHODS: UK Biobank participants (N = 20,395) aged 40 to 70 years (mean follow-up = 7.66 years), were included and categorized into one of four groups, which represented their baseline fat mass status and trajectory of change by follow-up assessment: normal weight to overweight/obesity, overweight/obesity to normal weight (ON), normal weight stable (NS), or overweight/obesity stable (OS). Regression models used NS (WC < 80 cm in women and < 94 cm in men; WTHR < 0.85 in women and < 0.90 in men; BMI < 25 kg/m2 in women and men) as the reference group. Hippocampal volumes were automatically segmented using the FMRIB Software Library. RESULTS: Compared with NS, OS (BMI: B = -62.23 [SE = 16.76]; WC: B = -145.56 [SE = 16.97]; WTHR: B = -101.26 [SE = 19.54]) and ON (BMI: B = -61.1 [SE = 30.3]; WC: B = -93.77 [SE = 24.96]; WTHR: B = -69.92 [SE = 26.22]) had significantly lower hippocampal volumes. CONCLUSIONS: The detrimental effects of overweight/obesity may extend beyond the duration of overweight/obesity itself.

[Tracking of physical fitness during chilhood: Longitudinal findings from the Diagnoform program]. / Évaluation de la condition physique durant l'enfance dans le nord de la France : le programme Diagnoform.

BACKGROUND: A high level of physical fitness is associated with cardiovascular health in adolescents. We describe change in physical fitness levels assessed at two time points over 3 years. METHODS: The study presents a longitudinal design, with the first phase data collection at 8 years and the second phase carried out at 11 years. A total of 516 children (254 boys) aged to 7.7±0.4 years (in 2010) and 10.9±0.4 years (in 2010) and 10.9 ± 0.4 years (in 2013) participated to the study. Cardiorespiratory fitness, muscular strength, speed, and agility were assessed in this study. For each physical fitness test, determination of the situation (in terms of percentiles) of each child in 2010 and then in 2013 compared to national standards. The 2010 and 2013 percentiles are then compared using the Wilcoxon signed rank test. RESULTS: Muscular strength, agility and cardiorespiratory fitness decrease in both sex (p<0.01). A significant decrease was also found for all physical fitness components in normal weight children (p<0.05). For normal weight children in 2010 who became overweight or obese in 2013, there was a significant decrease in scores of cardiorespiratory fitness and agility tests (p<0.05). For overweight children in 2010 becoming from to normal weight status in 2013, only the agility test decreased significantly (p<0.05). Children being overweight or obese in 2010 and remaining in 2013, had a significant decrease in their physical fitness levels (p<0.05). CONCLUSIONS: Our results indicate that the physical fitness of French youth decrease between childhood and early adolescence. Developing and introducing a health promotion curriculum in the French schools is suggested to improve health and physical fitness.

Respiratory management in severe acute respiratory syndrome coronavirus 2 infection.

The severe acute respiratory syndrome coronavirus 2 pandemic is to date affecting more than a million of patients and is challenging healthcare professionals around the world. Coronavirus disease 2019 may present with a wide range of clinical spectrum and severity, including severe interstitial pneumonia with high prevalence of hypoxic respiratory failure requiring intensive care admission. There has been increasing sharing experience regarding the patient's clinical features over the last weeks which has underlined the need for general guidance on treatment strategies. We summarise the evidence existing in the literature of oxygen and positive pressure treatments in patients at different stages of respiratory failure and over the course of the disease, including environment and ethical issues related to the ongoing coronavirus disease 2019 infection.

Effect of 4 Weeks of Foot Orthosis Intervention on Ambulatory Capacities and Posture in Normal-Weight and Obese Patients.

BACKGROUND: Several works have shown the benefits of foot orthosis intervention on postural stability in healthy individuals and patients with foot malalignment. However, the effects of foot orthoses on the daily ambulatory activities explored by the Six-Minute Walk Test (6MWT) were never examined. We hypothesized that foot orthoses could increase the gait distance and attenuate the post-6MWT posture alterations already reported in healthy individuals. METHODS: In ten normal-weight (NW) and ten obese patients with foot malalignment and/or abnormal foot arch, we examined the benefits of 4 weeks of custom-molded orthosis intervention (D30) on 6MWT gait distance, fatigue sensation scores, ankle plantarflexion force, and post-6MWT sway of the center of pressure (COP) measured by a pedobarographic platform. Data were compared with those measured in two control-matched groups of ten NW and ten obese individuals, explored at study inclusion and at D30. RESULTS: At study inclusion, the post-6MWT changes in COP surface and the medial and lateral COP deviations were significantly higher in obese participants who needed to wear the foot orthoses compared with obese control subjects. The foot orthosis intervention significantly improved the ambulatory performances of NW and obese individuals during the 6MWT, attenuated the bodily fatigue sensation after the 6MWT, and reduced the post-6MWT COP deviations, with the benefits of insoles being significantly accentuated in obese participants. CONCLUSIONS: Four weeks of foot orthosis intervention significantly increases gait distance and is an effective means to reduce postural sway after walking.