Circadian Clock, Obesity, Post Menopause, Sarcopenia, Type 2 Diabetes
Conditions
Keywords
Timing of eating, Timing of exercise, Muscle Function, Metabolic Health, Obesity, Menopause, women
Brief summary
The aim of TIMEDIAB is to demonstrate that early TRE (eTRE) combined to late (afternoon) exercise will outperform eTRE combined to morning exercise on muscle function as primary endpoint, and glucose homeostasis as secondary endpoint
Detailed description
Overweight, obesity, aging and menopause are all independent risk factors in the development of type 2 diabetes mellitus (T2DM). Older women with T2DM are at especially high risk for sarcopenia, i.e. loss of skeletal muscle mass and force, and cardiovascular diseases. The first line of T2DM treatment is based on lifestyle changes including weight loss and physical activity. One major current medical challenge is to find novel lifestyle therapies able to reduce cardiometabolic risk while perserving muscle mass in obese older individuals. As a result, intermittent fasting approaches, including time-restricted feeding/eating (TRF/TRE), have been offered as alternative dietary strategies that may have beneficial effects on weight control and T2DM. It has been recently observed that long-term TRF improve glucose homeostasis while perserving muscle mass and force in female obese mice. The purpose of TIMEDIAB is to demonstrate that early TRE (eTRE) combined to late (afternoon) exercise will outperform eTRE combined to morning exercise on various components of muscle health as primary endpoint, and blood glucose control, body composition, energy balance, cardiovascular risk, and metabolic health as secondary endpoints. This study will pave the way to larger scale randomized clinical trials investigating the long-term effects/benefits of such intervention and in other target populations.
Interventions
OTHERAntidiabetic diet (control)
Standard antidiabetic diet
OTHEReTRE diet
eTRE for a total duration of 12 weeks. During the eTRE, volunteers will have to eat and drink (meals + snacks, medication) exclusively during an 8-hour period which will extend between 6 a.m. (flexible: or 7 a.m. or 8 a.m.) in the morning and 2 p.m. (depending on the chosen start time: or 3 p.m. or 4 p.m.), which corresponds to a fasting period of 16 hours per day
OTHERPhysical activity in the morning
Physical exercise will consist of 3 weekly morning sessions that will combine aerobic and resistance exercises
OTHERPhysical activity in the afternoon
The physical exercise will consist of 3 weekly afternoon sessions that will combine aerobic and resistance exercises.
Sponsors
University Hospital, Toulouse
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Post-menopausal women (amenorrhea for at least 12 months, confirmed by gonadotrophins measures) * Age range 45-70 years * T2DM diagnosed for more than 1 year * Subjects with T2DM treated with lifestyle control alone or associated with metformine ± DPP4 inhibitors * Ability to sign written informed consent before any study-specific procedure * Subject considered as reliable and capable of adhering to protocol * Subjects with Body Mass Index (BMI)≥ 30 kg/m² * Baseline eating period ≥ 14 h per day (as estimated by 95% eating interval)
Exclusion criteria
* Subjects on T2DM injectable medication or drugs able to induce hypoglycemia (glinides, sulfonylurea) * Subjects with HbA1c \> 8% * Subjects with any of the following medical conditions: * Congestive cardiac failure * Stage 4 chronic kidney disease (i.e. eGFR \< 30 ml/min/1.73 m2) * Liver cirrhosis or chronic liver disease * Any medical condition that in the opinion of the investigator could jeopardize or compromise the subject's ability to participate in the study * Subjects with previous or present history of serious eating disorder * Subjects not able to understand the informed consent form or fasting diary instructions * Subjects currently participating or has participated in another study of an investigational medication or an investigational medical device within the last 30 days * Women with menopause hormone replacement therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in skeletal muscle function | 4 years | Change in skeletal muscle function, assessed by 30-CTS score at inclusion (baseline) and 12 weeks after diet/exercise program; This test is used to assess lower limb strength. The score corresponds to the total number of standing positions correctly performed within the allotted 30 seconds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in muscle function | 4 years | Change in muscle function assessed by various tests, such as: \- TUG Score ( calculates the time it takes to get up from a chair without using your arms. A time \<10 seconds is normal; 10\>time\<20 is a marker of frailty; time \<20 seconds:the elderly person is at high risk of falling). |
| • Change in M value measured by hyperinsulinemic euglycemic clamp | 4 years | Systemic insulin sensitivity will be assessed using a euglycemic hyperinsulinemic clamp, oral hyperglycemia, and insulin signaling pathway studies. The M value (unitless measurement) determined during the clamp will be the marker of systemic insulin sensitivity. |
| Change in HbA1c, during an oral glucose tolerance test | 4years | Change in HbA1c (in percentage), during an oral glucose tolerance test |
| Change in fasting glucose, during an oral glucose tolerance test | 4years | Change in fasting glucose (g/l), during an oral glucose tolerance test |
| Change in 2h blood glucose, during an oral glucose tolerance test | 4 years | Change in 2h blood glucose (g/l), during an oral glucose tolerance test |
| Change of the insulin resistance index (HOMA-IR) | 4years | Change of the insulin resistance index (HOMA-IR) from fasting parameters: from fasting insulin levels (mU/mL) and fasting blood glucose levels (mmol/L) |
| Change of the insulin sensitivity index (HOMAβ) | 4years | Change of the insulin sensitivity index (HOMAβ) from fasting parameters: from fasting insulinemia (mU/mL) and fasting blood glucose (mmol/L) |
| Change in body weight (kg) | 4years | — |
| Change in body mass index (kg/m2) | 4years | — |
| Change in waist circumference (cm) | 4years | — |
| Change in waist-to-hip ratio (without unit) | 4years | — |
| Change in body composition | 4years | Change in body composition (fat mass, lean mass, bone mass, muscle mass) |
| Change in blood pressure | 4years | Change in systolic and diastolic pressure (mmHg) |
| Change in plasma lipid profile | 4years | Liver and muscle lipid content will be measured by MRI. |
| Change in visceral fat (kg) | 4 years | — |
| Change in liver fat (kg) | 4 years | — |
| Change in muscle fat (kg) | 4 years | — |
Countries
France
Contacts
CONTACTMONTASTIER Emilie, MD
CONTACTTOMASIK Audrey
PRINCIPAL_INVESTIGATORMONTASTIER Emilie, MD
University Hospital, Toulouse
Outcome results
None listed