The Impact Of An Intermittent Energy Restricted Diet On Insulin Sensitivity In Men and Women With Central Obesity

Obesity, Abdominal Clinical Trial

— Met-IER  

Official title:

A Randomised Controlled Trial Assessing The Impact Of An Intermittent Energy Restricted Diet On Weight Loss, Insulin Sensitivity and Heart Rate Variability In Men and Women With Central Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02679989
• Other study ID #: Met-IER2016
• Status: Completed
• Phase: N/A
• Start date: February 2016
• Est. completion date: July 2016

Study information

• Verified date: July 2016
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Hypersensitivity
• Insulin Resistance
• Obesity
• Obesity, Abdominal

Intervention

Behavioral:
• Intermittent Energy Restriction
Dietary advice to follow 5:2 diet supported by physical activity advice and motivational group support sessions
• Continuous Energy Restriction
Dietary advice to follow daily energy restricted diet supported by physical activity advice and motivational group support sessions

Locations

Country	Name	City	State
United Kingdom	Diabetes & Nutritional Sciences Division, King's College London, Franklin-Wilkins Buiding, 150 Stamford St.	London	England

Sponsors (2)

Lead Sponsor	Collaborator
King's College London	LighterLife (UK) Ltd

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Harvie M, Wright C, Pegington M, McMullan D, Mitchell E, Martin B, Cutler RG, Evans G, Whiteside S, Maudsley S, Camandola S, Wang R, Carlson OD, Egan JM, Mattson MP, Howell A. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013 Oct;110(8):1534-47. doi: 10.1017/S0007114513000792. Epub 2013 Apr 16. — View Citation

Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG, Son TG, Maudsley S, Carlson OD, Egan JM, Flyvbjerg A, Howell A. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011 May;35(5):714-27. doi: 10.1038/ijo.2010.171. Epub 2010 Oct 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events		Baseline until endpoint: day 31 (+/-1 day)
Primary	Revised QUICKI (RQUICKI)	Marker of insulin sensitivity	Baseline
Primary	RQUICKI	Marker of insulin sensitivity	day 29
Primary	RQUICKI	Marker of insulin sensitivity	day 31
Secondary	Plasma glucose concentration	Fasting	Baseline
Secondary	Plasma glucose concentration	Fasting	day 29
Secondary	Plasma glucose concentration	Fasting	day 31
Secondary	Plasma insulin concentration	Fasting	Baseline
Secondary	Plasma insulin concentration	Fasting	day 29
Secondary	Plasma insulin concentration	Fasting	day 31
Secondary	Plasma non-esterified fatty acid concentration	Fasting	Baseline
Secondary	Plasma non-esterified fatty acid concentration	Fasting	day 29
Secondary	Plasma non-esterified fatty acid concentration	Fasting	day 31
Secondary	Plasma total cholesterol concentration	Fasting	Baseline
Secondary	Plasma total cholesterol concentration	Fasting	day 29
Secondary	Plasma total cholesterol concentration	Fasting	day 31
Secondary	Plasma low density lipoprotein (LDL) cholesterol concentration	Fasting	Baseline
Secondary	Plasma LDL cholesterol concentration	Fasting	day 29
Secondary	Plasma LDL cholesterol concentration	Fasting	day 31
Secondary	Plasma high density lipoprotein (HDL) cholesterol concentration	Fasting	Baseline
Secondary	Plasma HDL cholesterol concentration	Fasting	day 29
Secondary	Plasma HDL cholesterol concentration	Fasting	day 31
Secondary	Plasma triglyceride concentration	Fasting	Baseline
Secondary	Plasma triglyceride concentration	Fasting	day 29
Secondary	Plasma triglyceride concentration	Fasting	day 31
Secondary	Plasma total cholesterol:HDL cholesterol ratio	Fasting	Baseline
Secondary	Plasma total cholesterol:HDL cholesterol ratio	Fasting	day 29
Secondary	Plasma total cholesterol:HDL cholesterol ratio	Fasting	day 31
Secondary	Homeostasis model assessment estimated insulin resistance (HOMA-IR)	Fasting (calculated from insulin and glucose)	Baseline
Secondary	Homeostasis model assessment estimated insulin resistance (HOMA-IR)	Fasting (calculated from insulin and glucose)	day 29
Secondary	Homeostasis model assessment estimated insulin resistance (HOMA-IR)	Fasting (calculated from insulin and glucose)	day 31
Secondary	Plasma adiponectin concentration	Fasting	Baseline
Secondary	Plasma adiponectin concentration	Fasting	day 29
Secondary	Plasma adiponectin concentration	Fasting	day 31
Secondary	Plasma leptin concentration	Fasting	Baseline
Secondary	Plasma leptin concentration	Fasting	day 29
Secondary	Plasma leptin concentration	Fasting	day 31
Secondary	Plasma interleukin-6 concentration	Fasting	Baseline
Secondary	Plasma interleukin-6 concentration	Fasting	day 29
Secondary	Plasma interleukin-6 concentration	Fasting	day 31
Secondary	Plasma beta-hydroxybutyrate concentration	Fasting	Baseline
Secondary	Plasma beta-hydroxybutyrate concentration	Fasting	day 29
Secondary	Plasma beta-hydroxybutyrate concentration	Fasting	day 31
Secondary	Plasma norepinephrine concentration	Fasting	Baseline
Secondary	Plasma norepinephrine concentration	Fasting	day 29
Secondary	Plasma norepinephrine concentration	Fasting	day 31
Secondary	Plasma soluble alpha-klotho concentration	Fasting	Baseline
Secondary	Plasma soluble alpha-klotho concentration	Fasting	day 29
Secondary	Plasma soluble alpha-klotho concentration	Fasting	day 31
Secondary	Body weight		Baseline
Secondary	Body weight		day 29
Secondary	Body weight		day 31
Secondary	Body mass index (BMI)		Baseline
Secondary	BMI		day 29
Secondary	BMI		day 31
Secondary	Waist circumference		Baseline
Secondary	Waist circumference		day 29
Secondary	Waist circumference		day 31
Secondary	Hip circumference		Baseline
Secondary	Hip circumference		day 29
Secondary	Hip circumference		day 31
Secondary	Percentage body fat		Baseline
Secondary	Percentage body fat		day 29
Secondary	Percentage body fat		day 31
Secondary	Percentage lean body mass		Baseline
Secondary	Percentage lean body mass		day 29
Secondary	Percentage lean body mass		day 31
Secondary	Heart rate variability (resting)	supine	Baseline
Secondary	Heart rate variability (resting)	supine	day 29
Secondary	Heart rate variability (resting)	supine	day 31
Secondary	Heart rate variability (ambulatory)		24 h recording at baseline
Secondary	Heart rate variability (ambulatory)		24 h recording on day 29
Secondary	Heart rate variability (ambulatory)		24 h recording on day 31
Secondary	Heart rate variability (sleep-time)		Baseline
Secondary	Heart rate variability (sleep-time)		day 29
Secondary	Heart rate variability (sleep-time)		day 31
Secondary	Heart rate variability (during mental stress)		Baseline
Secondary	Heart rate variability (during mental stress)		day 29
Secondary	Heart rate variability (during mental stress)		day 31
Secondary	Ambulatory blood pressure 24 h		24 h analysis at baseline
Secondary	Ambulatory blood pressure daytime		Daytime analysis at baseline
Secondary	Ambulatory blood pressure night-time		Night-time analysis at baseline
Secondary	Ambulatory blood pressure 24 h		24 h analysis on day 29
Secondary	Ambulatory blood pressure daytime		daytime analysis on day 29
Secondary	Ambulatory blood pressure night-time		night-time analysis on day 29
Secondary	Ambulatory blood pressure 24 h	24 h	24 h analysis on day 31
Secondary	Ambulatory blood pressure daytime	day time	Daytime analysis on day 31
Secondary	Ambulatory blood pressure night-time	night-time	Night-time analysis on day 31
Secondary	Digital volume pulse - stiffness index (SI)	Stiffness index	Baseline
Secondary	Digital volume pulse - SI	Stiffness index	day 29
Secondary	Digital volume pulse - SI	Stiffness index	day 31
Secondary	Digital volume pulse - reflection index (RI)	reflection index	Baseline
Secondary	Digital volume pulse - RI	reflection index	day 29
Secondary	Digital volume pulse - RI	reflection index	day 31
Secondary	Mnemonic Similarity Test		Baseline
Secondary	Mnemonic Similarity Test		day 29
Secondary	Mnemonic Similarity Test		day 31
Secondary	Power of food scale	questionnaire	Baseline
Secondary	Power of food scale	questionnaire	day 29
Secondary	Power of food scale	questionnaire	day 31
Secondary	COPE (not an acronym)	questionnaire	Baseline
Secondary	COPE	questionnaire	day 29
Secondary	COPE	questionnaire	day 31

External Links

•   Primary publication