Lowering Impaired Fasting Glucose Levels With Exercise
Condition: Type2 Diabetes
Study type: Interventional

Summary: 
      Morning hyperglycemia plays a role in the future development of insulin resistance and type 2
      diabetes (T2D) (8) and is associated with numerous microvascular and cardiovascular
      complications and renal disease. These augmented morning glucose levels are due to an
      elevated endogenous glucose production (EGP), as a result of a loss of coordination between
      glucose levels and insulin secretion, and possibly hyperglucagonemia during the overnight
      period. Exercise stimulates glucose uptake and increases insulin sensitivity acutely, and may
      be the best lifestyle intervention to minimize the nocturnal rise in glucose levels.
      Prescription of the timing of exercise relative to a meal and/or to the overnight period may
      be particularly critical for individuals that have impaired fasting glucose (IFG) levels.
      Surprisingly little is known about the overnight period when elevated EGP and the synchrony
      between glucose and c-peptide/glucagon levels becomes disturbed. This novel study will
      provide insight into the hormonal/metabolic milieu of a dinner meal, the evening and
      overnight period that occurs in non-obese, OB and OB+IFG individuals; it will also establish
      if the timing of exercise can attenuate nocturnal glucose elevations, and if this is
      associated with improved hormonal synchrony. This project will compare EGP, β-cell function
      and hormonal responses between morning and evening exercise on the postprandial and overnight
      period in obese individuals with/without IFG levels. Fifty-four subjects will be studied
      during the evening meal (EGP and β-cell function), postprandially and through the overnight
      period (1600-0700 h), allowing us to examine some of the potential mechanisms for the
      elevation in overnight glucose levels. This is the first study that will examine this issue
      from pre-dinner through the night while previous studies have only examined chronically
      fasted individuals and this study will lay the groundwork for understanding the pathology of
      the predawn phenomena in OB+IFG individuals. These potentially translational findings may
      impact the efficiency of physician communication to patients concerning exercise. These
      investigators are one of the few groups that study subjects through the overnight period and
      have the facilities and capability to do this research.
    

Detailed description: 
      In individuals with type 2 diabetes (T2D), chronically elevated glucose and insulin levels
      result in numerous health complications. Maintaining tight glucose control is difficult for
      individuals with T2D, particularly in the postprandial period and in the morning period just
      prior to waking. In the postprandial period, the combined effect of insulin resistance and
      beta cell dysfunction results in a prolonged elevation in glucose levels, and augmented
      insulin levels in an attempt to reduce the circulating glucose levels. In the overnight
      period, there is evidence of enhanced endogenous glucose production and of a disruption of
      the interaction between glucose levels and insulin secretion. Early work in individuals with
      T2D demonstrated that with continued fasting, glucose levels stopped declining in the evening
      and subsequently rose throughout the night to reach a morning maximum, and this elevation
      persisted till noon. Additionally these authors demonstrated that insulin levels and insulin
      secretion rates did not parallel the nocturnal glucose changes in individuals with T2D, while
      in the controls the nocturnal glucose and insulin secretion rates coincided. Evidence is also
      emerging that hyperglucagonemia may be occurring in the setting of deficient insulin
      secretion, and may be playing a role in the elevated postprandial glucose levels and in the
      overnight period. These studies provide preliminary evidence that there is disruption in the
      fine coordination between glucose levels and glucagon and insulin secretion, and that this is
      exacerbated more in the overnight period than during the waking hours. Previous studies
      examining the overnight period have been conducted following prolonged fasting (~24-34 h),
      however, most people do not fast for extended periods of time prior to going to bed.
      Additionally, individuals with T2D often know that meal composition the evening prior can
      exacerbate the elevated fasting glucose levels the following morning, thus highlighting the
      need to examine the effect of meal composition on overnight glucose control. To date, very
      little is known about the pathology of why fasting glucose levels are elevated in many obese
      individuals. There appears to be asynchrony between glucose and insulin levels in the
      overnight period but very little research has focused on this phenomenon or how meal
      composition affects overnight glucose levels. This study will provide evidence of potential
      mechanisms for the elevation in overnight glucose levels and the findings will be
      translatable for individuals with impaired fasting glucose (IFG) levels to understand the
      importance of meal composition in the evening period.

      The specific aims of this project are:

        1. To examine the hormonal responses (glucagon, c-peptide, insulin, incretins) in response
           to a meal in the postprandial period and the synchronization between glucose and
           insulin/glucagon during the overnight period in non-obese individuals and obese
           individuals with impaired fasting glucose levels (IFG).

        2. To determine if the meal composition (standard meal: 55% carbohydrate, 20% protein, 25%
           fat vs. high fat/fructose: 40% carbohydrate- 25% fructose, 40% fat, 20% protein) will
           alter the hormonal responses (glucagon, insulin, incretin) in the postprandial period,
           and if this change in meal composition will impact glucagon levels and glucose/c-peptide
           synchrony in the overnight period.

      Experimental design: Subjects will participate three times; 1) no exercise, 2) 2 hr post
      dinner exercise, and 3) morning exercise (~7am). The order in which subjects undergo each
      treatment will be randomized prior to study enrollment. Eligible subjects will initially
      undergo baseline testing for assessment of body composition, exercise stress test and blood
      screening. All subjects will have impaired fasting glucose levels. All subjects will undergo
      3 study days that will start at ~1600 h and continue until 0700 h the following morning. They
      will receive a standard meal (55% carbohydrate, 20% protein, 25% fat) at 1800 h and blood
      samples will be taken from ~4:30 pm until 7 am.
    

Intervention name(s): No exercise; Morning exercise; Evening exercise
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): No exercise will be done on the day of the study night to be tested; Early morning exercise will be done on the day of the study night to be tested; Evening exercise will be done on the day of the study night to be tested
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention