Chrono-restricted Diet and Physical Activity as a New Preventive Strategy for Sarcopenia in Postmenopausal Women With Obesity and Type 2 Diabetes

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.

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