Sleep Disturbances and Biomarkers of Sarcopenic OBesity

Study Overview
=================
Brief Summary
-----------------
The general objective of this study is to identify biomarkers of sleep quality, sarcopenia, insulin resistance, oxidative stress and inflammation associated with prefrailty in middle-aged and elderly obese subjects through the integrated study of sleep patterns, functional cardiovascular testing, olfactory function and circulating molecules. Results from the SleSOB study will contribute to identify molecular and functional determinants of prefrailty, to allow early targeted interventions and will have important implications for empowerment of elderly citizens to self-management of preventive measures and healthy lifestyle.

Detailed Description
-----------------
Frailty, an age-related state of low physiological reserve and high vulnerability to stressors, impacts on health, functional independence, quality of life and survival; its early detection at the prefrailty stage offers the opportunity for preventive intervention. Sarcopenia, a hallmark of frailty, may occur in association with obesity and worsen functional deterioration. Obesity is strongly associated with insulin resistance and is a risk factor for both cardiometabolic diseases and cognitive impairment. Adipose tissue exerts autocrine and paracrine functions leading to chronic low-grade inflammation and increased oxidative stress that, in turn, decrease muscle density and precipitate muscle strength loss. Sleep disturbances and sarcopenia might be causally related through dysregulation of glucose metabolism and disruption of the secretory pattern of hormones involved in muscle metabolism. Main objective: To establish among young-elderly obese subjects the prevalence of prefrailty as defined by presence of ≥1 of reduced muscle mass, fatigue, weakness, slowness, and low physical activity (Fried's criteria) Secondary objectives: To assess prevalence and severity of sarcopenia as defined by reduced muscle mass coupled with decreased muscle strength and /or reduced functional capacity To establish the cardiometabolic risk profile and its correlation with vitamin D To determine type and extent of sleep abnormalities by validated questionnaires and their association with prefrailty To assess the extent of sympathetic imbalance, arrhythmia burden and olfactory impairment To determine patterns of biomarkers of oxidative stress, inflammatory cytokines, adipokines, myokines, tissue damage and remodeling and correlation with prefrailty and insulin resistance. Study design: Eligible subjects will attend the clinic in the morning in the fasting state to undergo blood samples collection for routine and specific biochemistry; anthropometric measurements: height, weight, body mass index, waist and hip circumference; assement of sarcopenia: muscle strength, gait speed, muscle mass by biomimpedentiometric assessment (BIA) and air displacement pletismography (BODPOD); glucose metabolism biomarker as tissue accumulation of advanced glycation endproducts (AGE); sympathetic activation; interview for medical history and comorbidity registration; screening for cognitive impairment; sleep pattern analysis through questionnaires; olfactory assessment. A wearable system (Win@home, CE0434) for 24 h recording of rhythm, circadian heart rate, respiratory rate and oxygen saturation, posture and physical activity will be applied to each subject for the subsequent 24 hours

Official Title
-----------------
Sleep Disturbances and Biomarkers of Sarcopenic OBesity: Insight Into Mechanisms of Prefrailty

Conditions
-----------------
Sarcopenic Obesity

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obesity : body mass index ≥ 30 and <40 kg/m2 Written informed consent Exclusion Criteria: Diabetes requiring insulin treatment Stage IV chronic kidney dysfunction (estimated glomerular filtration rate <15 ml/min) Liver dysfunction (AST- ALT x 2 times upper normalcy range) Active neoplasms Claustrophobia Psychiatric morbidity or any other condition that impairs the ability to give informed consent

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of prefrailty | Proportion of subjects presenting with one or more of reduced muscle mass, fatigue, weakness, slowness, and low physical activity | Day one | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of sarcopenia | Proportion of subjects presenting with reduced muscle mass (by gender-specific cut offs ) coupled with decreased muscle strength (men ≤ 32 kg, women ≤ 21 kg and/or reduced gait speed (<0.8 mt/sec on a 4 mt course) | Day one | 
| Cardiometabolic risk profile: insulin resistance | Homeostatic Model Assessmenti (HOMA)-insulin resistance index | Day one | 
| Cardiometabolic risk profile: fatty liver | Fatty liver index (FLI) | Day one | 
| Cardiometabolic risk profile: 10-year cardiovascular risk | HeartSCORE | Day one | 
| Sleep abnormalities: idiopathic REM Behaviour Disorder (iRBD) | Answer to screening question for iRBD | Day one | 
| Sleep abnormalities: insomnia severity | Insomnia Severity Index (ISI) score | Day one | 
| Sleep abnormalities: daytime sleepiness | Epworth Sleepiness Scale (ESS) score | Day one | 
| Cardiac rhythm abnormalities | Atrial fibrillation burden during 24 hour home monitoring | Day one | 
| Cardiac dysautonomia: deep breathing test | Expiratory/inspiratory ratio | Day one | 
| Cardiac dysautonomia: lying to standing test | Lying-to standing ratio | Day one | 
| Orthostatic hypotension | Drop ≥20 mmHg in systolic and/or ≥10 mmHg in diastolic blood pressure after 1 and 5 minutes of active standing | Day one | 
| Olfactory function: Total Olfactory Score (TOS) | Sum of Olfactory Threshold, Identification, Discrimination scores | Day one | 
| Screening for cognitive impairment | Mini Mental State Examination (MMSE) score | Day one | 
| Tissue accumulation of Advanced Glycation End-products (AGE) | AGE Reader Score | Day one | 
| Biomarkers of oxidative stress | Malondyaldehyde, aminothiols | Day one | 
| Inflammatory biomarkers | Cytokinesinterleukin-6, interleukin-1beta, tumour ecrosis Factor-alpha, neopterin | Day one | 
| Adipokines | Adiponectin, leptin | Day one | 
| Myokines | Myostatin, irisin | Day one | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insulin resistance, Olfactory impairment, Sleep disturbances, Biomarkers, Prefrailty, Multiplex array, Gait speed