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

NCT ID: NCT02679989

Last Updated: 2019-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2016-07-31

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.

Conditions

Obesity, Abdominal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Intermittent Energy Restriction

Weight loss intervention: Intermittent Energy Restriction

Group Type: EXPERIMENTAL

Intermittent Energy Restriction

Intervention Type: BEHAVIORAL

Dietary advice to follow 5:2 diet supported by physical activity advice and motivational group support sessions

Continuous Energy Restriction

Weight loss intervention: Continuous Energy Restriction

Group Type: ACTIVE_COMPARATOR

Continuous Energy Restriction

Intervention Type: BEHAVIORAL

Dietary advice to follow daily energy restricted diet supported by physical activity advice and motivational group support sessions

Interventions

Intermittent Energy Restriction

Dietary advice to follow 5:2 diet supported by physical activity advice and motivational group support sessions

Intervention Type: BEHAVIORAL

Continuous Energy Restriction

Dietary advice to follow daily energy restricted diet supported by physical activity advice and motivational group support sessions

Intervention Type: BEHAVIORAL

Eligibility Criteria

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

LighterLife (UK) Ltd

UNKNOWN

Sponsor Role: collaborator

King's College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wendy Hall, PhD

Role: PRINCIPAL_INVESTIGATOR

King's College London

Locations

Diabetes & Nutritional Sciences Division, King's College London, Franklin-Wilkins Buiding, 150 Stamford St.

London, England, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 23591120 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20921964 (View on PubMed)

Allaf M, Elghazaly H, Mohamed OG, Fareen MFK, Zaman S, Salmasi AM, Tsilidis K, Dehghan A. Intermittent fasting for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2021 Jan 29;1(1):CD013496. doi: 10.1002/14651858.CD013496.pub2.

Reference Type: DERIVED

PMID: 33512717 (View on PubMed)

Kim C, Pinto AM, Bordoli C, Buckner LP, Kaplan PC, Del Arenal IM, Jeffcock EJ, Hall WL, Thuret S. Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial. Nutrients. 2020 Feb 28;12(3):638. doi: 10.3390/nu12030638.

Reference Type: DERIVED

PMID: 32121111 (View on PubMed)

Pinto AM, Bordoli C, Buckner LP, Kim C, Kaplan PC, Del Arenal IM, Jeffcock EJ, Hall WL. Intermittent energy restriction is comparable to continuous energy restriction for cardiometabolic health in adults with central obesity: A randomized controlled trial; the Met-IER study. Clin Nutr. 2020 Jun;39(6):1753-1763. doi: 10.1016/j.clnu.2019.07.014. Epub 2019 Jul 30.

Reference Type: DERIVED

PMID: 31409509 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/31409509

Primary publication

Other Identifiers

Met-IER2016

Identifier Type: -

Identifier Source: org_study_id