Lowering Impaired Fasting Glucose Levels With Exercise

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.