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Modeling the acute effects of exercise on insulin kinetics in type 1 diabetes.

ABSTRACT: Our objective is to develop a physiology-based model of insulin kinetics to understand how exercise alters insulin concentrations in those with type 1 diabetes (T1D). We reveal the relationship between the insulin absorption rate ([Formula: see text]) from subcutaneous tissue, the insulin delivery rate ([Formula: see text]) to skeletal muscle, and two physiological parameters that characterize the tissue: the perfusion rate (Q) and the capillary permeability surface area (PS), both of which increase during exercise because of capillary recruitment. We compare model predictions to experimental observations from two pump-wearing T1D cohorts [resting subjects ([Formula: see text]) and exercising subjects ([Formula: see text])] who were each given a mixed-meal tolerance test and a bolus of insulin. Using independently measured values of Q and PS from literature, the model predicts that during exercise insulin concentration increases by 30% in plasma and by 60% in skeletal muscle. Predictions reasonably agree with experimental observations from the two cohorts, without the need for parameter estimation by curve fitting. The insulin kinetics model suggests that the increase in surface area associated with exercise-induced capillary recruitment significantly increases [Formula: see text] and [Formula: see text], which explains why insulin concentrations in plasma and skeletal muscle increase during exercise, ultimately enhancing insulin-dependent glucose uptake. Preventing hypoglycemia is of paramount importance in determining the proper insulin dose during exercise. The presented model provides mechanistic insight into how exercise affects insulin kinetics, which could be useful in guiding the design of decision support systems and artificial pancreas control algorithms.

SUBMITTER: Frank S

PROVIDER: S-EPMC8237803 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUCEGP) and rate of glucose disappearance (AUCRd) over 45 min from exercise start. A novel application of linear regression of Rd across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUCRd increased 12.45 mmol/L (CI = 10.33-14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01-15.26, P < 0.001) whereas AUCEGP increased 1.66 mmol/L (CI = 1.01-2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81-4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUCEGP increased during intense exercise by 2.14 mmol/L (CI = 0.91-3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUCRd equal to 0.06 mmol/L per % above basal rate (CI = 0.05-0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451.NEW & NOTEWORTHY Separating insulin and non-insulin glucose uptake dynamically during exercise in type 1 diabetes has not been done before. We use a multistep process, including a previously described linear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time.

Project description:BackgroundLipoprotein Insulin Resistance Index (LP-IR) and Diabetes Risk Index are novel spectroscopic multimarkers of insulin resistance and type 2 diabetes risk. As the Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) randomized trials have previously demonstrated the ability of exercise training to improve traditional markers of insulin action, the aim of this study was to examine the effects of exercise amount, intensity, and mode on LP-IR and the Diabetes Risk Index.MethodsA total of 503 adults with dyslipidemia [STRRIDE I (n = 194), STRRIDE AT/RT (n = 139)] or prediabetes [STRRIDE-PD (n = 170)] were randomized to control or one of 10 exercise interventions, ranging from doses of 8-23 kcal/kg/week; intensities of 50-75% V̇O2peak; and durations of 6-8 months. Two groups included resistance training and one included dietary intervention (7% weight loss goal). Fasting plasma samples were obtained at baseline and 16-24 h after the final exercise bout. LP-IR, the Diabetes Risk Index, and concentrations of the branched chain amino acids valine and leucine were determined using nuclear magnetic resonance spectroscopy. LP-IR and the Diabetes Risk Index scores range from 0-100 and 1-100, respectively (greater scores indicate greater risk). Paired t-tests determined significance within groups (p < 0.05).ResultsAfter training, six exercise groups significantly improved LP-IR (ranging from -4.4 ± 8.2 to -12.4 ± 14.1), and four exercise groups significantly improved the Diabetes Risk Index (ranging from -2.8 ± 8.2 to -8.3 ± 10.4). The most beneficial interventions for both LP-IR and the Diabetes Risk Index were low amount/moderate intensity aerobic, aerobic plus resistance, and aerobic plus diet.SummaryMultiple exercise interventions improved LP-IR and the Diabetes Risk Index. In those with dyslipidemia, adding resistance to aerobic training elicited a synergistic effect on insulin resistance and type 2 diabetes risk. In individuals with prediabetes, combining a dietary intervention and weight loss with aerobic training resulted in the most robust type 2 diabetes risk improvement.

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Modeling the acute effects of exercise on insulin kinetics in type 1 diabetes.

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