Dataset Information

Effects of Aerobic Exercise on Systemic Insulin Degludec Concentrations in People with Type 1 Diabetes.

ABSTRACT:

Background

There is conflicting evidence on the effect of exercise on systemic insulin concentrations in adults with type 1 diabetes.

Methods

This prospective single-arm study examined the effect of exercise on systemic insulin degludec (IDeg) concentrations. The study involved 15 male adults with type 1 diabetes (age 30.7 ± 8.0 years, HbA1c 6.9 ± 0.7%) on stable IDeg regimen. Blood samples were collected every 15 minutes at rest, during 60 minutes of cycling (66% VO₂max) and until 90 minutes after exercise termination. IDeg concentrations were quantified using high-resolution mass-spectrometry and analyzed applying generalized estimation equations.

Results

Compared to baseline, systemic IDeg increased during exercise over time (P < .001), with the highest concentrations observed toward the end of the 60-minute exercise (17.9% and 17.6% above baseline after 45 minutes and 60 minutes, respectively). IDeg levels remained elevated until the end of the experiment (14% above baseline at 90 minutes after exercise termination, P < .001).

Conclusions

A single bout of aerobic exercise increases systemic IDeg exposure in adults on a stable basal IDeg regimen. This finding may have important implications for future hypoglycemia mitigation strategies around physical exercise in IDeg-treated patients.

SUBMITTER: Herzig D

PROVIDER: S-EPMC9846403 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Effects of Aerobic Exercise on Systemic Insulin Degludec Concentrations in People with Type 1 Diabetes.

Herzig David D Groessl Michael M Álvarez-Martínez Mario M Reverter-Branchat Gemma G Nakas Christos T CT Kosinski Christophe C Stettler Christoph C Bally Lia L

Journal of diabetes science and technology 20210930 1

<h4>Background</h4>There is conflicting evidence on the effect of exercise on systemic insulin concentrations in adults with type 1 diabetes.<h4>Methods</h4>This prospective single-arm study examined the effect of exercise on systemic insulin degludec (IDeg) concentrations. The study involved 15 male adults with type 1 diabetes (age 30.7 ± 8.0 years, HbA1c 6.9 ± 0.7%) on stable IDeg regimen. Blood samples were collected every 15 minutes at rest, during 60 minutes of cycling (66% VO<sub>2</sub>ma ...[more]

PMID: 34590906

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Project description:Aims/hypothesisIt is generally recommended to reduce basal insulin doses after exercise to reduce the risk of post-exercise nocturnal hypoglycaemia. Based on its long t½, it is unknown whether such adjustments are required or beneficial for insulin degludec.MethodsThe ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise test in the afternoon. All participants wore blinded continuous glucose monitors for 6 days, measuring the incidence of (nocturnal) hypoglycaemia and subsequent glucose profiles.ResultsWe recruited 18 participants (six women, age 38 ± 13 years, HbA1c 56 ± 8 mmol/mol [7.3 ± 0.8%], mean ± SD). Time below range (i.e. glucose <3.9 mmol/l) the night after the exercise test was generally low and occurrence did not differ between the treatment regimens. During the subsequent whole day, time below range was lower for D40 compared with CON (median [IQR], 0 [0-23] vs 18 [0-55] min, p=0.043), without differences in the number of hypoglycaemic events. Time above range (i.e. glucose >10 mmol/l) was greater for D20-P vs CON (mean ± SEM, 584 ± 81 vs 364 ± 66 min, p=0.001) and D40 (385 ± 72 min, p=0.003).Conclusions/interpretationPost-exercise adjustment of degludec does not mitigate the risk of subsequent nocturnal hypoglycaemia in people with type 1 diabetes. Although reducing degludec reduced next-day time below range, this did not translate into fewer hypoglycaemic events, while postponing degludec should be avoided because of increased time above range. Altogether, these data do not support degludec dose adjustment after a single exercise bout.Trial registrationEudraCT number 2019-004222-22 FUNDING: The study was funded by an unrestricted grant from Novo Nordisk, Denmark.

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:IntroductionInsulin degludec (degludec), an ultra-long-acting basal insulin analogue, provides equivalent glycemic control to other basal insulin analogues, with lower risk of hypoglycemia and flexible dosing. Chinese TREsiba AudiT (CN-TREAT) investigated outcomes with degludec in people with type 2 diabetes (T2D) in routine clinical practice in China.MethodsThis was a retrospective chart review study in adults with T2D initiating or switching to degludec at 50 sites in China between January 2020 and July 2021. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study (EOS; week 20). Secondary endpoints included change from baseline to EOS in fasting plasma glucose (FPG), self-measured plasma glucose (SMPG), daily insulin dose, and rate of hypoglycemia.ResultsData from 936 participants were included (499 insulin-naïve; 437 insulin-experienced). Mean (95% confidence interval [CI]) HbA1c change from baseline to EOS was - 1.48%-points (- 1.57; - 1.38; P < 0.0001) overall: - 1.95%-points (- 2.08; - 1.81; P < 0.0001) in insulin-naïve participants and - 0.95%-points (- 1.08; - 0.82; P < 0.0001) in insulin-experienced participants. Mean (95% CI) changes in FPG and SMPG were - 2.27 mmol/L (- 2.69; - 1.85; P < 0.0001) and - 2.89 mmol/L (- 3.52; - 2.25; P < 0.0001), respectively, with similar reductions in insulin-naïve and insulin-experienced subgroups. Rate of hypoglycemia did not change statistically significantly from baseline to EOS overall, or in insulin-experienced participants, except when adjusted for baseline hypoglycemia. Basal insulin dose did not change statistically significantly in insulin-experienced participants.ConclusionIn routine clinical practice in China, initiation or switching to degludec was associated with improvements in glycemic control in people with T2D, with no increased risk of hypoglycemia.Trial registrationClinialTrials.gov, NCT04227431.

Dataset Information

Effects of Aerobic Exercise on Systemic Insulin Degludec Concentrations in People with Type 1 Diabetes.

Background

Methods

Results

Conclusions

Publications

Effects of Aerobic Exercise on Systemic Insulin Degludec Concentrations in People with Type 1 Diabetes.

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