Loretta DiPietro - US grants

The past 3 years have been extremely productive. During this time, three waves of volunteers (approximately 22 volunteers per wave) participated in training. Each of these waves trained 3-4 times/week for 4-6 monthls. Physiological measurements on these volunteers before and after training included measurement of abdominal fat using computed tomograpny, determinations of lipid concentrations, stress hormone responses to cognitive and physical challenges, and glucose responses to an oral glucose challenge. In addition, a number of experiments relating exercise, water immersion and temperature to body fluid regulation have been performed. The study thus far has culminated in 6 published abstracts and 6 papers either in press or in review. Currently we are competing for renewal funds in order to continue our study of exercise, body fluid balance and metabolism in older people.

Older age is associated with a decline in glucose tolerance which itself is an important precursor to the development of non-insulin-dependent mellitus (NIDDM) and subsequent cardiovascular disease (CVD). We propose that the decline in glucose tolerance with aging can be accounted for, to a significant extent, by the concomitant decline in physical activity. Thus, the overall purpose of the proposed study is to determine the impact of aerobic exercise on improvements in glucose regulation in older people. To date we have established the reliability of the clamp procedure on 3 younger subjects and 2 older subjects. In addition we have tested the acute effects of a single bout of exercise (75-80% max) on 12 hour or 24 hour glucose disposal in 8 subjects.

[unreadable] DESCRIPTION (applicant's description): Glucose tolerance declines progressively with aging, and this decline in metabolic resiliency can be attributed primarily to factors secondary to aging, such as changes in body composition and low levels of physical activity. Insufficient insulin secretion is also an important contributor; however, as impaired [unreadable]-cell compensation to aging- and disuse-related insulin resistance may indeed accelerate the risk of developing post-challenge hyperglycemia and consequent type 2 diabetes and cardiovascular disease in older age. The purpose of this proposal is to examine the extent to which different exercise protocols impact post-prandial and 24-h glycemic control (measured using a continuous glucose monitoring system; CGMS) in older people at risk for type 2 diabetes. Specific aims are: 1) To compare the short-term effectiveness of a traditional exercise [unreadable] condition involving 45 min of sustained walking at lower intensity (~3.0 METs) performed in the [unreadable] morning (TEM), with the same condition performed in the afternoon (TEA) on improvements in postprandial and 24-h glycemic control in inactive older people with impaired glucose tolerance (IGT); 2a) To compare the short-term effectiveness of a novel "Eat and Move" exercise condition [EM; 15 min of walking (~3.0 METs) performed 30 min after each of 3 standard meals] with TEM and TEA on improvements in glycemic control in these same older people; and 2b) To determine the influence of sex and of abdominal fat on post-meal exercise-related improvements in post-prandial and 24-h glycemic control in these older men and women. While a post-meal exercise paradigm has been used as an effective strategy for gestational diabetes, its potential among older populations with compromised [unreadable]-cell function has not been studied. The clinical relevance of shorter, but more frequent, bouts of lower-intensity exercise is substantial as older people are far more likely to engage in that type of physical activity on a regular basis. Given the excess disease burden associated with hyperglycemia in older age, and the recognized value of chronic disease prevention, there are enormous public health benefits to designing exercise programs that are enjoyable and effective within the populations needing them the most. PUBLIC HEALTH RELEVANCE: Post-prandial hyperglycemia may represent the rate-limiting factor in slowing the progression from impaired glucose tolerance toward frank type 2 diabetes and cardiovascular disease. Post-meal exercise may be an effective strategy for supplementing endogenous insulin action for improved post-prandial and 24-h glycemic control in older age. The clinical relevance of shorter, but more frequent, bouts of lower-intensity exercise is substantial as older people are far more likely to engage in that type of physical activity on a regular basis. Given the excess disease burden associated with hyperglycemia in older age, and the recognized value of chronic disease prevention, there are enormous public health benefits to designing exercise programs that are enjoyable and effective within the populations needing them the most. [unreadable] [unreadable] [unreadable]

? DESCRIPTION (provided by applicant): The modern-day lifestyle is characterized by a majority of time spent sitting throughout the day. Older people may be especially vulnerable to the harmful effects of prolonged sitting due to a loss of physiologic reserve and the fact that the prevalence of excessive sitting may be especially high in this sector of the population. Metabolic flexibility and glycemic control decline progressively with aging; however, this can be attributed primarily to factors secondary to aging. Indeed, sedentary living is a challenge to metabolic control -especially in older age when insufficient insulin secretion and multi-tissue insulin resistance are also important contributors to impaired glycemic control. Unfortunately, there are few well-controlled human studies testing variations in the degree of metabolic dysregulation resulting from prolonged sitting and whether minimal intensity walking can improve resistance to such dysregulation. The purpose of this proposal is to examine whether low-intensity post-meal walking is an effective counter-measure to prolonged (uninterrupted) sitting for improving glycemic control and metabolic flexibility in older people (=65 y) at risk for type 2 diabetes due o impaired fasting glucose (IFG). Specific aims are: 1) to determine the continuous kinetics of 24h glycemic control under separate conditions of prolonged sitting or intermittent, low-intensity post-meal walking in inactive older people (N=45) with IFG; 2) to determine the enduring effects of a 16-week home-based program of low- intensity post-meal (PM) walking (3x15 min/day performed 1/2 h after each meal on 5 days/week; n=15) vs. intermittent (INT) walking (3x15 min performed 1h before each meal on 5 days/week; n=15) vs. 45 min of sustained (SUS)walking (performed between 9 and 10:30 AM on 5 days/week; n=15) on several biomarkers of insulin sensitivity, glycemic control and lipid metabolism in this same study sample; and 3) to determine whether 16 weeks of lower-intensity training improves resistance to metabolic dysregulation with prolonged sitting. If successful, this strategy would have substantial geriatric relevance - especially since it can be utilized by more frail segments of the older adult population. Given the prominence of the sedentary lifestyle and the excess disease burden associated with disuse and hyperglycemia in older age, there are enormous public health benefits to designing countermeasures that are enjoyable and effective within the populations needing them the most.