Meal Pattern and Metabolic Parameters
Condition: Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      In this study investigators will compare the health effect of two different meal patterns. In
      one, participants will consume food according to an 'irregular meal pattern' (minimum 3
      meals, maximum 9 meals per day) and in the other 'regular meal pattern' (6 meals per day) for
      two weeks. The energy requirement of the participants will be calculated to maintain body
      weight during the study. Participants will be provided with all the food to be consumed
      during the study.

      Initially, interested individuals will attend a screening visit in which they will complete
      questionnaires on medical health, eating habits and physical activity. Height, weight and
      waist circumference will be measured at this visit. Thereafter, participants will be assigned
      to a 2-week period following one of the two meal-patterns. There will be a 2-week period
      between the two interventions when they will consume their normal diet and at the end of
      this, participants will undertake the next meal pattern. During the two phases participants
      will be asked to wear an armband (which detects movement and measures heat loss), to assess
      their energy expenditure and an interstitial glucose monitoring device will be worn for seven
      days. Before and after each 2-week intervention, participants will come to the laboratory for
      a mixed-meal tolerance test. Blood samples will be obtained before and for 3hrs after eating
      to evaluate the health effects of the meal patterns. Energy expenditure will be measured by
      ventilated-hood indirect calorimetry and the armband device. At the end of the 3hr post
      prandial period, participants will be offered an ad libitum pasta lunch and be asked to eat
      until they feel comfortably full.

      During each of the 2-week periods, participants will be asked to record their food intake and
      record their appetite sensations on specific days.
    

Detailed description: 
      Background. Greater variation in meal pattern from day to day might affect energy balance
      and, in consequence, the control of body weight. However, studies which have evaluated the
      impact of an irregular meal pattern on energy metabolism, in adults, are few. Several
      experimental studies by Farshchi et al. have shown that there are potentially important
      negative health consequences associated with erratic/irregular eating patterns. Higher
      fasting levels of total-cholesterol and low density lipoprotein (LDL)-cholesterol, a decrease
      in thermic effect of food (TEF), and reduced insulin sensitivity, were observed in healthy
      women after 14 days of irregular eating. Subsequent studies have confirmed this in overweight
      subjects and also provided evidence of alterations in subjective appetite which may influence
      ad-libitum food intake (Lara et al, unpublished).

      Recently, experimenters have shown a decrease in thermogenesis in response to a test meal,
      and greater postprandial blood glucose concentration in 11 normal weight women following
      two-weeks of irregular eating in contrast to a regular pattern.

      The present study will study the effect of an irregular meal pattern in obese women who
      demonstrate fasting insulin resistance (IR).

      Aims:

      to investigate the effects of meal pattern on energy expenditure, postprandial thermogenesis,
      postprandial blood glucose, fasting lipid profile and fasting insulin sensitivity in obese
      women with insulin resistance.

      Experimental protocol. 10 women with a homeostatic model assessment - insulin resistance
      (HOMA-IR) ≥1.8, body mass index between 28 and 40 kg/m2, aged 18-45 years, and who are
      otherwise healthy, will be recruited. Interested individuals will have an initial medical
      screening to confirm suitability. Those who are recruited will be asked to then complete a 7
      days food diary before participating in the study. The whole study will last for a total of 6
      weeks. During the first 2 weeks participants will adopt one of two meal patterns, followed by
      a two-week washout period during which they resume their habitual diet and meal pattern. A
      second 2-week intervention will then follow, in which the alternative meal pattern is
      adopted. The meal patterns will be 1) regular - 6 daily meals or snacks for 2 weeks, or 2)
      irregular - a different number (between 3 and 9) of meals/snacks every day. Allocation of the
      order in which the diets are tested will be randomized at the point of recruitment with
      participant number assigned sequentially. All foods to be consumed during weeks1, 2, 5 and 6
      will be provided free of charge, and will comprise foods commonly consumed in the British
      diet, in quantities designed to keep body weight constant during the study. Participants will
      complete food diaries over the whole study period. They will be asked to wear a 'SenseWear'
      armband (SWA) device (attached to an upper arm) to allow physical activity and energy
      expenditure to be estimated during weeks1, 2, 5 and 6. Participants will attend the
      laboratory on the 6th day of each intervention phase to have a continuous interstitial
      glucose monitoring probe inserted in the subcutaneous abdominal fat pad at the level of the
      umbilicus. Participants will measure their blood glucose four times a day, using a
      fingerprick sample and pocket glucose analyser, to calibrate the continuous glucose monitor.
      After three days participants will be asked to come back to have this device removed.

      Subjective appetite (hunger, fullness, etc.) will be assessed using visual analogue scales
      (VAS) during the intervention (at the end of each week, and whilst the glucose monitor is
      being worn).

      Before and after each intervention period, participants will visit the laboratory after
      fasting overnight. At 8:30 am a cannula will be inserted into a hand vein, with the hand
      placed in a hot-air box, for subsequent blood sampling. Indirect calorimetry will be
      performed to determine energy expenditure, carbohydrate and lipid oxidation rates and changes
      in the thermic response to a milkshake test drink providing 10 kcals/kg body weight, and
      comprising 35% of energy as fat, 15% as protein, and 50% as carbohydrate. The SWA device will
      also be placed on the upper left arm to estimate energy expenditure during the laboratory
      visit. Blood samples will be obtained before and every 15 minutes for 3 hours after eating.
      Indirect calorimetry and SWA will be measured concurrently for the duration of the laboratory
      visit. Fasting blood samples will be used to measure total-, high density lipoprotein (HDL)-,
      LDL-, and very low density lipoprotein (VLDL)-cholesterol, triglycerides, glucose and
      insulin. Blood samples obtained after the test drink will also be used to measure glucose,
      insulin and hormones related to appetite. After the 3hr postprandial period, a test meal
      (pasta) will be provided as ad-libitum meal and participants will be asked to fill VAS to
      assess subjective appetite sensations.

      Measurable end points of the study

        -  24hr Energy expenditure during the two phases (irregular versus regular meal pattern)

        -  Fasting lipids, insulin, glucose and glucose profiles during the continuous monitoring

        -  Insulin, glucose and gut hormone (Glucagon-Like Peptide 1, Ghrelin and Peptide YY)
           responses to the test drink

        -  Postprandial thermogenic response to a test drink

        -  Ratings of subjective appetite during the study Sample size and statistical power Using
           1 sample t-test model, power calculated at the level of 0.8. Primary end point =
           difference in thermic effect of food 'TEF' (kcal/min) over 180min. Results obtained from
           study previous studies indicated the incremental area under the TEF curve after regular
           eating was 25.8 (SD 6.8) kcal and after irregular eating was 14.8 (SD 11.7) kcal. With a
           cross-over design, 10 subjects in each group would be able to detect a change in TEF
           with the power of 80% at the level of 0.05 significance.
    

Intervention name(s): Regular meal pattern; Irregular meal pattern
Intervention type(s): Other; Other
Intervention description(s): a 14-day period of eating 6 meal per day; a 14-day period of eating between 3 and 9 meal per day
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Insulin Resistance; Meal pattern; Obese