The Impact Of An Intermittent Energy Restricted Diet On Insulin Sensitivity In Men and Women With Central Obesity
Condition: Obesity, Abdominal
MeSH terms: Obesity; Insulin Resistance; Obesity, Abdominal; Hypersensitivity
Study type: Interventional

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.
    

Intervention name(s): Intermittent Energy Restriction; Continuous Energy Restriction
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Dietary advice to follow 5:2 diet supported by physical activity advice and motivational group support sessions; Dietary advice to follow daily energy restricted diet supported by physical activity advice and motivational group support sessions
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Insulin sensitivity; Weight loss; Intermittent fasting; Sympathetic nervous system