The Impact Of An Intermittent Energy Restricted Diet On Insulin Sensitivity In Men and Women With Central Obesity
- Conditions
- Obesity, Abdominal
- Interventions
- Behavioral: Intermittent Energy RestrictionBehavioral: Continuous Energy Restriction
- Registration Number
- NCT02679989
- Lead Sponsor
- King's College London
- Brief Summary
An intermittent energy restricted (IER) diet may modify cardio-metabolic disease risk factors compared to an energy-matched continuous energy restricted (CER) diet. A randomised controlled parallel design trial will determine the impact of a short-term IER diet (2 consecutive days of very low calorie diet (VLCD), 5 days moderate energy restriction each week for a 4 week period), compared to a CER diet, on insulin sensitivity in healthy (disease-free) subjects with central obesity.
- Detailed Description
Prediabetes rates in England have showed a marked increase, more than tripling between 2003 and 2011. It is characterised by an impaired fasting glucose or impaired glucose tolerance that increases the risk of progression to type 2 diabetes (T2D). It has been estimated that approximately 90% of T2D is attributed to excess weight. Central obesity is a primary driver of increased cardiometabolic risk due to its lipotoxicity effects, promoting a proinflammatory state that facilitates insulin resistance and beta cell dysfunction. A high waist circumference measurement, indicative of central obesity, is associated with increased risk of cardiovascular diseases and T2D, and is a stronger predictor of T2D than BMI. BMI has limitations as an indicator of adiposity since it doesn't distinguish lean from fat mass, and does not indicate body fat distribution. Conventionally, continuous energy restriction (CER) diets have been used for weight loss, which consist of a constant daily energy deficit relative to total energy expenditure. The impact on weight loss and health of an intermittent energy restriction (IER) approach has only rarely been investigated (although the "5:2 diet" has been popularised in lifestyle books aimed at the general public). An IER diet consists of a predefined period of time severely restricting energy intake, alternated with a period of greater energy intake. This approach was shown to confer metabolic benefits in overweight and obese women at risk of breast cancer with baseline BMI of 2445 (Harvie et al., 2013; Harvie et al., 2011).
Rationale: An IER diet using meal replacements (VLCD foodpacks used as total dietary replacements for 2 consecutive days each week, and a food-based energy-restricted diet for the other 5 days of the week) may modify cardio-metabolic disease risk factors compared to an energy-matched CER diet.
Research question: In centrally obese subjects, assessed by a high waist circumference measurement, does adherence to an IER diet have enhanced cardio-metabolic benefits compared to a CER diet? Hypothesis: Increases in insulin sensitivity following a 4 week dietary intervention with an IER weight loss programme will be greater compared to a standard CER programme.
Objectives:
1. A randomised controlled parallel design trial will determine the impact of a short-term IER diet compared to a CER diet on primary outcome variables (insulin sensitivity) in healthy subjects with a high waist circumference.
2. To assess the impact of an IER diet on secondary outcome variables, including body composition, heart rate variability (HRV, a measure of cardiac autonomic function, including parasympathetic and sympathetic activity), blood pressure, vascular function, other markers of insulin resistance, inflammation/adipokines, plasma lipid profile, plasma norepinephrine, ketosis, the gut microbiome and cognitive function in healthy subjects with a high waist circumference.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- Aged >35-75 years
- Waist circumference above cut-off for high risk of cardio-metabolic disease of >102 cm in men with a Europid, Black African and Caribbean, and other ethnic background and >88 cm in women with a Europid, Black African and Caribbean, and other ethnic background (WHO, 2008), and ≥90 cm in men and ≥80 cm in women with an Asian background (South Asian and East Asian) (Misra et al., 2009).
REFERENCES Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al. (2009). Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. The Journal of the Association of Physicians of India 57: 163170.
WHO (2008). Waist circumference and waist-hip ratio: report of a WHO expert consultation. Geneva, 8-11 December 2008.
- Kidney or cardiovascular disease, cancer, diabetes, gastrointestinal or chronic liver disease;
- previous bariatric surgery or other major surgery (e.g. organ transplantation);
- unable to provide written informed consent;
- have significant psychiatric disorder (e.g. schizophrenia, anxiety, panic disorder, attention deficit disorder, post-traumatic stress disorder, obsessive compulsive disorder) or uncontrolled depression;
- participated in a weight management drug trial in the previous 3 months;
- have binge eating behaviour;
- have uncontrolled epilepsy;
- alcohol or substance abuse;
- currently pregnant, lactating, or planning pregnancy within the study period;
- are using medication clinically deemed to affect metabolic rate and weight (e.g. beta blockers, corticosteroids, diuretics, etc);
- lactose intolerant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intermittent Energy Restriction Intermittent Energy Restriction Weight loss intervention: Intermittent Energy Restriction Continuous Energy Restriction Continuous Energy Restriction Weight loss intervention: Continuous Energy Restriction
- Primary Outcome Measures
Name Time Method RQUICKI day 31 Marker of insulin sensitivity
Revised QUICKI (RQUICKI) Baseline Marker of insulin sensitivity
- Secondary Outcome Measures
Name Time Method Plasma leptin concentration day 31 Fasting
Hip circumference day 31 Waist circumference day 31 Percentage lean body mass day 31 Heart rate variability (resting) day 31 supine
Plasma non-esterified fatty acid concentration day 31 Fasting
Plasma insulin concentration day 31 Fasting
Plasma total cholesterol concentration day 31 Fasting
Homeostasis model assessment estimated insulin resistance (HOMA-IR) day 31 Fasting (calculated from insulin and glucose)
Plasma low density lipoprotein (LDL) cholesterol concentration Baseline Fasting
Plasma triglyceride concentration day 31 Fasting
Body mass index (BMI) Baseline Ambulatory blood pressure daytime Daytime analysis on day 31 day time
Ambulatory blood pressure night-time Night-time analysis on day 31 night-time
Mnemonic Similarity Test day 31 Plasma glucose concentration day 31 Fasting
Plasma LDL cholesterol concentration day 31 Fasting
Plasma HDL cholesterol concentration day 31 Fasting
Plasma soluble alpha-klotho concentration day 31 Fasting
Body weight day 31 Heart rate variability (ambulatory) 24 h recording on day 31 Heart rate variability (sleep-time) day 31 Digital volume pulse - stiffness index (SI) Baseline Stiffness index
Digital volume pulse - SI day 31 Stiffness index
Plasma high density lipoprotein (HDL) cholesterol concentration Baseline Fasting
BMI day 31 Ambulatory blood pressure 24 h 24 h analysis on day 31 24 h
Digital volume pulse - RI day 31 reflection index
Power of food scale day 31 questionnaire
Plasma total cholesterol:HDL cholesterol ratio day 31 Fasting
Plasma adiponectin concentration day 31 Fasting
Plasma interleukin-6 concentration day 31 Fasting
Plasma beta-hydroxybutyrate concentration day 31 Fasting
Plasma norepinephrine concentration day 31 Fasting
Percentage body fat day 31 COPE (not an acronym) Baseline questionnaire
COPE day 31 questionnaire
Heart rate variability (during mental stress) day 31 Digital volume pulse - reflection index (RI) Baseline reflection index
Trial Locations
- Locations (1)
Diabetes & Nutritional Sciences Division, King's College London, Franklin-Wilkins Buiding, 150 Stamford St.
🇬🇧London, England, United Kingdom