This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: A number of studies have evaluated the incidence of hypoglycemia during or immediately following exercise in children and adolescents with Type-1 Diabetes Mellitus (T1DM). DirecNet recently completed a study that was designed to more carefully define the effect of afternoon exercise on the relative risk of hypoglycemia during exercise and during the following night in a cohort of 50 children with T1DM who were using an intensive diabetes management regimen involving either insulin pumps or multiple daily insulin injections. A carefully-controlled, cross-over design that involved a supervised and standardized exercise protocol was utilized to compare the frequency of hypoglycemia during exercise and overnight following afternoon exercise with that following a sedentary day in a clinical research center setting. We specifically chose to have the subjects exercise in the late afternoon as children and adolescents often are more active at the end of the school day, when different athletic practice and game sessions take place. In addition, the duration and intensity of the exercise regimen was designed to mimic a typical length of time children are involved in such activities. The study procedures specified the use of similar insulin doses on both the exercise and sedentary day. Specifically, the subject's usual routine for a sedentary day was followed on the exercise day even if the subject typically would have lowered his or her basal insulin replacement during exercise or overnight, on days of unusually intense physical activity. This approach allowed us to examine the effect of exercise per se on the risk of nocturnal hypoglycemia and it is clinically relevant, since many youngsters on pumps or who receive pre-breakfast doses of glargine insulin do not or cannot adjust their overnight basal insulin. The findings of this study supported the well-recognized clinical observation that exercise has benefit in lowering plasma glucose levels both during and following exercise in children with T1DM. Our findings also supported the use of flexible diabetes management regimens that attempt to adjust food intake and insulin dosing during or on evenings following exercise to reduce the risk of hypoglycemia during exercise or overnight following hypoglycemia. In the present study, DirecNet attempts to evaluate the most effective methods of adjusting insulin doses during exercise in order to maximize the benefits and safety of exercise in children with T1DM by preventing hypoglycemia during and following exercise. Goals: The primary objective of the study is to determine the effects of discontinuing a subject's basal rate during exercise on the glucose level during and following exercise.
We aim to determine whether discontinuing the basal rate during exercise reduces the incidence of hypoglycemia compared with continuing the basal rate. Additionally, we aim to determine whether the decrease in blood glucose during exercise is less when the basal rate is discontinued compared with when the basal rate is continued, whether discontinuing the basal rate during exercise increases the incidence of hyperglycemia and/or positive ketones compared with continuing the basal rate, and how changes in free fatty acids, free insulin, beta-hydroxybuterate, and adiponectin differ under the two study conditions. The accuracy of a continuous glucose sensor will be examined. In our initial exercise study, the Continuous Glucose Monitoring System (CGMS) showed a slight systematic bias during exercise towards higher blood glucose levels compared with the central lab values. The accuracy of a home glucose meter may be examined. HbA1c monitors are available for home use. The accuracy of one or more of these devices will be examined as an ancillary study. Experimental Design: In this study protocol, each subject has two visits. During each visit, a structured exercise protocol is completed in the late afternoon. During one of the visits (ordered through randomization), the subject's usual basal rate will be continued and during the other visit, the basal rate will be discontinued. The study population includes 55 subjects between 8.0 and 18.0 yrs old with T1DM and HbA1c 10.0% using an insulin pump.
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