Diet Composition and Physical Inactivity on Insulin Sensitivity and β-cell Function
Condition: Physical Inactivity; Dietary Protein
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      Physical inactivity results in reductions in glucose tolerance and less sensitivity to
      insulin. If this inactivity lasts long enough it can result in insulin resistance and type 2
      diabetes. A high protein diet can reduce elevated glucose levels in individuals with type 2
      diabetes. Thus the investigators are interested in establishing if during a period of
      inactivity if a diet modification can minimize the glucose changes normally observed with
      inactivity. The objective of this project is to determine if short-term high protein (HP)
      feeding protects against the changes in glucose levels normally observed with physical
      inactivity. The investigators will also examine measures of blood vessel function, blood
      lipid and blood pressure.

      Twelve subjects will complete two 10 day study periods of reduced physical activity and will
      be studied before and after each of these study periods. For their testing subjects will have
      the following measurements: postprandial glucose responses to a mixed meal, 24 h free living
      blood pressure control during acute physical inactivity, blood lipids, changes in body
      composition, changes in circadian rhythm using skin temperature (ibutton), measurement of
      aerobic capacity (VO2 max), blood vessel responsiveness (flow mediated dilation -FMD) and
      changes in free living glucose levels (continuous glucose monitoring system (CGMS). Subjects
      will complete two conditions (high protein -HP vs normal protein - NP diets) in a randomized
      cross-over design. In the inactive phase subjects will reduce there steps to &lt;5,000
      steps/d while consuming either a HP or NP diet. Completion of the study will take 8-10 weeks.
    

Detailed description: 
      It is well known that insulin resistance increases the risk of cardiovascular disease and
      type 2 diabetes, which substantially impact mortality and morbidity and presents a
      significant economic burden. Energy restriction with or without exercise has been
      demonstrated to attenuate/reverse the development of insulin resistance and reduce the risk
      of cardiovascular disease and type 2 diabetes. Indeed, accumulating evidence suggests that
      diets high in protein may possess additional protection against the development of insulin
      resistance during energy restriction. Layman et al. found that a high protein diet (HP) (PRO
      125 g/d) compared with an isocaloric high carbohydrate diet (HCHO) (PRO 68 g/d) resulted in
      greater reductions in fasting glucose and 2 h postprandial insulin levels during 16 weeks of
      energy restriction in overweight women. Similarly, a hypocaloric high protein diet (PRO 45%
      vs 20%; 21 d diet treatment) increased glucose oxidation and improved insulin sensitivity
      compared to an isocaloric high carbohydrate diet during a euglycemic hyperinsulinemic clamp
      procedure. In addition, markers of inflammation, β-cell function, and postprandial glucose
      and insulin levels were improved in addition to increased resting energy expenditure after 6
      months of hypocaloric HP compared with HCHO diet in premenopausal women independent of weight
      loss. The increase in REE and improvement in adipose tissue function may be a potential
      mechanism by which HP diet improves β-cell function since NEFAs are lower, which may reduce
      lipotoxicity on the pancreas.

      It is evident that physical inactivity (highlighted from bed rest studies) impairs glucose
      tolerance, insulin sensitivity, vascular function, and muscle protein synthesis in both
      healthy and obese individuals. This model of inactivity, however, is extreme and does not
      recapitulate the physical inactivity paradigm seen in the natural human environment.
      Consequently, a less extreme reduction in daily physical activity (>10,000 steps/d to ~1,500
      steps/d) results in significant reductions in insulin sensitivity, glucose tolerance, and
      insulin-stimulated muscle Akt phosphorylation, suggesting that the impairments in insulin
      sensitivity and glucose tolerance precede changes in body composition. A reduction in
      ambulatory activity is a highly valid and translatable model to study the role of inactivity
      on the development of metabolic disease, as most individuals go through periods of
      inactivity, and it has been shown that a reduction in daily steps decreases insulin
      sensitivity and increases visceral adiposity. To date, no study has tested the effects of
      diet composition on the perturbations of physical inactivity. It is important to know if
      increasing protein intake mitigates the negative perturbations of reduced ambulatory
      activity.

      Thus, the overall objective of this project is to determine the extent to which short-term
      high protein (HP) feeding may protect against the metabolic perturbations of physical
      inactivity (i.e. PPG, hyperinsulinemia, and insulin sensitivity). The investigators will also
      examine measures of vascular function and free living blood pressure in addition to lipemic
      responses (i.e. FFAs, triglycerides, cholesterol, and lipoproteins) to determine if HP diet
      impacts vascular function and lipemic responses during short term physical inactivity.

      Trial Objectives and Purpose

      The specific aims of this project include the following:

      Specific Aim 1: To determine if HP diet during a period of low physical activity will lower
      the insulin response to a meal, and help to maintain insulin sensitivity and β-cell function
      during a laboratory based mixed meal test (MMT) with stable isotope tracers.

      Specific Aim 2: To determine if a HP diet during a period of low physical activity will
      maintain glycemic control measured by continuous glucose monitoring (CGM) in healthy,
      recreationally active, young individuals.
    

Intervention name(s): normal protein diet; high protein intake
Intervention type(s): Behavioral; Behavioral
Intervention description(s): subjects will undergo 10 days of low physical activity while consuming a normal protein diet; subjects will undergo 10 days of low physical activity while consuming a high protein diet
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science