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Sleep Disturbances and Biomarkers of Sarcopenic OBesity

Conditions
Sarcopenic Obesity
Registration Number
NCT03175601
Lead Sponsor
Istituto di Fisiologia Clinica CNR
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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
100
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Prevalence of prefrailtyDay one

Proportion of subjects presenting with one or more of reduced muscle mass, fatigue, weakness, slowness, and low physical activity

Secondary Outcome Measures
NameTimeMethod
Cardiac dysautonomia: deep breathing testDay one

Expiratory/inspiratory ratio

Screening for cognitive impairmentDay one

Mini Mental State Examination (MMSE) score

Cardiometabolic risk profile: fatty liverDay one

Fatty liver index (FLI)

Tissue accumulation of Advanced Glycation End-products (AGE)Day one

AGE Reader Score

MyokinesDay one

Myostatin, irisin

Cardiometabolic risk profile: 10-year cardiovascular riskDay one

HeartSCORE

Sleep abnormalities: idiopathic REM Behaviour Disorder (iRBD)Day one

Answer to screening question for iRBD

Sleep abnormalities: daytime sleepinessDay one

Epworth Sleepiness Scale (ESS) score

Cardiometabolic risk profile: insulin resistanceDay one

Homeostatic Model Assessmenti (HOMA)-insulin resistance index

Prevalence of sarcopeniaDay one

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)

Sleep abnormalities: insomnia severityDay one

Insomnia Severity Index (ISI) score

Cardiac rhythm abnormalitiesDay one

Atrial fibrillation burden during 24 hour home monitoring

Orthostatic hypotensionDay one

Drop ≥20 mmHg in systolic and/or ≥10 mmHg in diastolic blood pressure after 1 and 5 minutes of active standing

AdipokinesDay one

Adiponectin, leptin

Cardiac dysautonomia: lying to standing testDay one

Lying-to standing ratio

Olfactory function: Total Olfactory Score (TOS)Day one

Sum of Olfactory Threshold, Identification, Discrimination scores

Biomarkers of oxidative stressDay one

Malondyaldehyde, aminothiols

Inflammatory biomarkersDay one

Cytokinesinterleukin-6, interleukin-1beta, tumour ecrosis Factor-alpha, neopterin

Trial Locations

Locations (1)

Istituto di Fisiologia Clinica del CNR UOS Milano

🇮🇹

Milano, Italy

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