Approximately 24 million older adults have prediabetes. Obesity, age related decreases in lean mass and increases in fat mass, and sedentary lifestyle have been associated with functional and cognitive decline in older adults. Innovative lifestyle strategies to treat obesity and pre-diabetes are critically needed. The proposed research will demonstrate that time restricted eating combined with resistance training is an effective non-pharmacological therapy to help obese prediabetic individuals reduce body fat, maintain lean mass, prevent progression of prediabetes to diabetes, and improve cognition.

Obesity, age related decreases in lean mass and increases in fat mass, and sedentary lifestyle have been associated with functional and cognitive decline in older adults. It is expected that the proportion of the population of over 65 will continue to increase as will the number of older adults with pre-diabetes. Treatment of pre-diabetes and improved functionality and cognition in older adults include maintaining a healthy weight and regular exercise. While daily calorie restriction is the most common prescription for weight loss, intermittent fasting is an alternative to daily calorie restriction producing significant weight loss. Currently, the most popular form of intermittent fasting is time restricted eating (TRE). TRE typically involves confining the eating window to 6-10 h and fasting for the remaining hours of the day. During the eating window, individuals are not required to count calories or monitor food intake in any way. Current TRE data shows promising results for diet alone including natural calorie restriction, weight loss, decreased blood pressure and increased insulin sensitivity all while maintaining a high adherence. To our knowledge, TRE combined with resistance training (RT) or endurance training (EN)has only been examined in lean resistance trained young adults, never in older adults or adults with overweight or obesity. Hypothesis: The present proposal will test the following hypothesis: (1) Both combination groups will lose significantly more weight than TRE alone or the control. The TRE + RT group will significantly decrease fat mass and increase lean mass more than the TRE + EN, TRE alone or control group. The TRE + RT will lose the same amount of body weight but maintain more lean mass than the TRE+EN group; (2a) The TRE+RT group will experience greater improvements in insulin sensitivity, insulin resistance, HbA1c and other metabolic disease variables (fasting insulin, triglycerides, LDL cholesterol, and blood pressure) versus the TRE+EN group after the 8-week trial due to reductions in body weight and greater retention of lean mass; (2b) TRE combined with both EN and RT will be safe in older adults with no significant intervention related adverse events; (3) TRE combined with both EN and RT will improve attention and executive function and working memory in the physical activity groups more than diet alone or the control group. Methods: To test these objectives, a 10-week parallel-arm pilot trial will be implemented. Older adults with overweight or obesity and pre-diabetes will be assigned to one of four groups: (1) TRE group, ad-libitum eating between 12:00-20:00 (n=50) (2) TRE + EN ad-libitum eating between 12:00-20:00 with 3-5 days of supervised endurance exercise per week (n=50) (3)TRE + RT group, ad-libitum eating between 12:00-20:00 with 3-5 days of supervised resistance training per week (n=50) or (4) Control group, no change in diet or physical activity (n=50). Significance: If the aims of this application are achieved, this study will be the first to show that TRE with physical activity is safe in older adults and can be implemented as an alternative to traditional dieting (i.e. daily calorie restriction) for weight management and lean mass retention. This study will also show that TRE can be used as an effective non-pharmacological therapy to improve insulin sensitivity, decrease metabolic risk factors, and improve cognition in older individuals with obesity and pre-diabetes.

Inclusion Criteria:

• Age between 50 to 70 years old
• BMI between 25 and 50 kg/m2
• Pre-diabetic or insulin resistant (fasting glucose: 100-125 mg/dl, HBA1c 5.7%-6.4%, or HOMA-IR >2.5)
• Sedentary or lightly active 24
• Are post menopausal (absence of menstrual cycle for 1 year)

Exclusion Criteria:

• Diabetic (fasting glucose: >126 mg/dl or HBA1c >6.5%)
• Have a history of eating disorders (anorexia, bulimia, or binge eating disorder)
• Have uncontrolled hypertension, any other cardiovascular disease, or history of aneurysm
• History of alcohol dependance (score >20 from Alcohol and Health Questionnaire)25
• Are not weight stable for 3 months prior to the beginning of study (weight gain or loss > 4 kg)
• Are not able to keep a food diary or activity log for 7 consecutive days during screening
• Are taking drugs that influence study outcomes (weight loss, glucose-lowering medications)
• Are premenopausal, perimenopausal or have an irregular menstrual cycle (menses that does not appear every 27-32 days)
• Mobility disability (unable to exercise for 40-60 minutes 3-5 days/week)
• Diagnosed comorbidities including systemic diseases (Parkinson's cirrhosis, renal disease or systemic rheumatic conditions), cancer, or cognitive impairment
• Are night shift workers
• Are smokers

10 weeks

Time restricted eating and increases in physical activity only hold minimal risk, however serious adverse events and all cause mortality were monitored per the OSP and the OVCR.