Insulin Resistance, Maternal-Fetal Relations, Muscle Weakness
Conditions
Keywords
Obesity, Epigenesis, Genetic, Exercise Therapy
Brief summary
The prevalence of obesity in the developed world has increased markedly over the last 20 years. Considering the prevalence of obese and overweight adult subjects, and the fact that pregnancy itself induces a state of insulin resistance and inflammation, maternal obesity may be the most common health risk for the developing fetus. It is well established that what we eat has a major impact on our health. However, there is growing evidence to suggest that diet during pregnancy and lactation may be particularly important as not only does it influence the health of the mother, it may have a permanent effect on the health of her children and even her grandchildren. The concept that environmental factors, such as nutrition during early development, influence both our health span and lifespan has been termed the developmental origins of health and disease hypothesis. The objective of the study are: * to compare subjects with frailty (condition developed with ageing) with controls and characterize the unhealthy aged condition with the measurements described below * to examine if signs of frailty can be reversed by lifestyle induced modifications (exercise training programme) of its primary components (IR, sarcopenia, psychological profile) in offspring of overweight/obese (OOM) vs lean mothers (OLM). The study consists of 37 frail old subjects, age ≥ 65 sub-grouped in 17 OOM, and 20 OLM and 11 non frail controls. These subjects will be studied with positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI) and spectroscopy (MRS) and ultra sounds (US). In addition functional MRI (fMRI) will be performed. Adipose tissue biopsies will be taken. Subjects will undergo characterization of biohumoral markers, a 75 g oral glucose tolerance test, imaging biomarkers (PET/CT, US, fMRI-MRS), genetic biomarkers (DNA and telomere damage) and inflammatory biomarkers (macrophage infiltration) before and after the 4-month lifestyle intervention period (physical exercise). By PET/CT it will be measured tissue-specific IR in skeletal muscle, adipose tissue, liver, myocardium and targeted brain regions. MRS will be used to measure organ steatosis in the skeletal muscle and liver, MRI will be used to measure fat masses in abdominal areas, and fMRI will be performed to assess activation in brain regions regulating cognition and appetite/energy control. US will be used to assess cardiovascular markers (IMT, strain and function).
Interventions
BEHAVIORALExercise Training
Three times a week, for four months.
Sponsors
University of Turku
University of Helsinki
Fondazione C.N.R./Regione Toscana G. Monasterio, Pisa, Italy
Istituto Superiore di Sanità
Turku University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Subjects must be already participating the Helsinki Birth Cohort Study Frailty Groups Inclusion Criteria: * (Frailty) with lowest half of adult grip strength (measured 2001-2004) * Group OM: (Offspring of Obese mothers) Highest quartile of maternal BMI * Group LM: (Offspring of Normal weight/Lean mothers) Lowest two quartiles of maternal BMI Control group Inclusion Criteria: * (no Frailty) with highest half of adult grip strength (measured 2001-2004) * Offspring of normal weight mothers
Exclusion criteria
* Subjects whose mothers were pre-eclamptic during pregnancy * Oral corticosteroid or Warfarin therapy * Recent myocardial infarction * Severe chronic disorder that can prevent to participate the intervention * Chronic atrial fibrillation and pacemaker * Cancer less than 5 years ago * Current smoking * Diabetes requiring insulin treatment or fasting glucose more than 7 mmol/l * Weight more than 170 kg and Waist circumference \> 150 cm * Inner ear implants * Metal objects in body including metallic prostheses, artificial valve prostheses, surgical clips, braces, foreign fragments or tattoo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline group comparison and Change from Baseline in Insulin-stimulated whole body and organ-specific glucose uptake at 4 months | At day 1 and after 4 months of intervention (for the 15 controls only at baseline) | Assessed via 18F-Fluorodeoxyglucose (FDG)-PET/CT+Clamp technique |
| Baseline group comparison and Change from Baseline in Epigenetic characterization of DNA samples (Telomere length, H2A.X phosphorilation, mtDNA deletion, p66) at 4 months | At day 1 and after 4 months of intervention (for the 15 controls only at baseline) | Telomere length, H2A.X phosphorilation, mtDNA deletion are measurements performed in Pisa, National Research Council p66 presence is measured in Rome, Istituto Superiore di Sanita' |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline group comparison and Change from Baseline in Fat masses and content via MRI and MRS at 4 months | At day 1 and after 4 months of intervention (for the 15 controls only at baseline) | Adipose tissue fat masses in different depots (subcutaneous, visceral, pericardial) Liver, skeletal muscle, vertebral fat content |
| Baseline group comparison and Change from Baseline in MRI brain anatomy and fMRI characterization of activation response to food stimuli of different brain regions at 4 months | At day 1 and after 4 months of intervention | MRI anatomy: White matter volume, Cortex thickness, Nerve tracks found with Diffusor Tension Imaging fMRI will be used to identify different brain regions activated by food stimuli while subjects perform three different task: watch the food, think of eating the food, control the urge to eat the food. |
Countries
Finland
Outcome results
None listed