The use of algorithmic insulin dose adaptations and carbohydrate intake in children with type 1 diabetes (T1D) has led to a global improvement in glycemic control 15 hours after exercising, according to research results published in Frontiers in Endocrinology.

In a previous study—the TREAD-DIAB trial—researchers evaluated the needs of children and adolescents in terms of insulin modifications during sports, with results indicating the possibility to normalize subcutaneous glucose for patients through continuous subcutaneous insulin infusion therapy. However, this goal was difficult to achieve in young patients taking multiple daily injections. To address this, researchers conducted the CAR2DIAB trial in order to fine-tune insulin injections and carbohydrate intake in patients regardless of treatment regimen.

CAR2DAIB was a nonrandomized, controlled, monocentric, intervention clinical trial in children and adolescents with T1D who attended an outpatient clinic at a tertiary care center. Participants took part in 2 consecutive sessions of monitored exercise: the first in the outpatient clinic and the second in “real-world” settings, such as playing sports.  Patients were evaluated for age, sex, Tanner stage, height, weight and body mass index (BMI), as well as duration of T1D diabetes, associated diseases, general physical health, and glycated hemoglobin (HbA1c).


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All patients used FreeStyle Libre®, a continuous glucose monitoring system (CGM) manufactured by Abbott. They were required to self-monitor capillary blood glucose when hypoglycemia symptoms were present.

The study included 12 adolescents with T1D diabetes aged 11 to 18 years-old and 12 control participants aged 10 to 17 years-old with no history of diabetes or heart disease; both cohorts were similar in terms of age, gender, and biometrics. In the study cohort, patients were taking no medications other than insulin (10 participants as multiple daily injections and 2 participants with pump therapy) and had diabetes control levels that corresponded with pediatric diabetes care conventions. No diabetic ketoacidosis (DKA) or severe hypoglycemia events took place in the last 5 years.

During the first exercise test, patients underwent 26.9±3.2 minutes of moderate-to- vigorous exercise on a treadmill.  Resting and peak heart rates, baseline and peak systolic and diastolic blood pressures, peak oxygen uptake, exercise capacity, and respiratory exchange ratio were all evaluated. EKG variables, left ventricular systolic function, and lung function tests were all obtained before and after 3 minutes of exercise. Cardiovascular parameters were similar across cohorts, excluding resting systolic blood pressure and diastolic interventricular septum thickness, which were both lower in the diabetes group.

During the second exercise test, patients exercised for a mean of 59.1±21.6 minutes over a distance of 3.8±1.8 km. Maximal and minimal heart rates were 164.6±26.9 and 129.4±27.8 bpm, respectively. Estimated caloric consumption was 438.1±142.4 calories.

Insulin administration modifications during the second exercise session were instituted on either prandial rapid or basal insulin scheduled before, during, or up to 15 hours after exercise sessions.

The most frequently applied change was a reduction in basal insulin during the night (89%) corresponding with a decrease of 15±8.9% of the total basal dose. Rapid insulin decreases were instituted in 78% of patients for a 14.2%±4.9% reduction before exercise, and in 22% of patients for a 15.1%±7.1% reduction after exercise.

Five periods were assessed to analyzed subcutaneous glucose data: test exercise plus 0 to 0.5 hours, test exercise plus 0.5 to 4 hours (afternoon-evening), test exercise plus 4 to 8 hours (evening-nighttime), test exercise plus 8-12 hours (nighttime), and test exercise plus 12 to 15 hours (late night).

When 15-hour periods were evaluated as a whole, mean subcutaneous glucose values improved from 123±63 mg/dl during the first exercise session to 104±58 mg/dl during the second exercise session. A global increase of time-in-range and higher proportion of hypoglycemia was noted. Coefficients of variation were also similar between the two sessions (51% and 52%, respectively). 

During the test exercise period and the afternoon-evening periods, mean subcutaneous glucose decreased in exercise session 2 compared with session 1. Subcutaneous glucose variability increased with lower percentages of subcutaneous values within time-in-range, higher levels of hyperglycemia during the first period, and higher levels of both hyper- and hypoglycemia during the afternoon-evening period.

Global subcutaneous glucose curves during exercise session 2 were negatively impacted by individual 3-hour peaks of hyperglycemia at 1 hour after exercise, resulting in an increase in coefficients of variation during the second sessions of tests.

The evening-nighttime periods after exercise session 2 was characterized by a “marked decrease” in mean subcutaneous glucose, primarily due to a net increase of 24% and 18.8% of time spent in hypoglycemia below 70 and 60 mg/dl, respectively.

The nighttime period was marked by lower subcutaneous glucose variability, improved mean subcutaneous glucose levels, and lower percentages of hypo- and hyperglycemia vs the first exercise sessions. Similar trends in the late-night periods were noted.

Baseline HbA1c levels were found to influence subcutaneous glucose values during both exercise sessions, compared with diabetes duration and insulin dose regimen which did not.

A majority of patients experienced hypoglycemia during the day or night: 83% and 92% vs 75% and 75%, respectively.

Frequency and duration of diurnal and nocturnal hypoglycemia were not different between subgroups during both exercise sessions. No differences were noted in terms of frequency of hypoglycemia <70 mg/dl during the afternoon-evening, nighttime, and late-night periods. During the evening-nighttime periods, mean proportion of hypoglycemia <70 mg/dl rose from 8.8% to 32.8%.

Both recommendations and solutions for fast-acting carbohydrate intake were provided to patients during the first exercise session. A total of 55.5% required fast-acting carbohydrate supplements the day before the test; 100% needed extra carbohydrates on the day of the second test, and 77.8% needed extra carbohydrates during the day after the test.

“Application of algorithmic adaptations of insulin doses and carbohydrate intake in pediatric diabetic patients has globally improved glycemic control during 15 hours after real-time exercises performed by children and adolescents with T1Ddiabetes,” the researchers wrote.

“Because intervention protocols for treatment adaptation during sports will remain influenced by an irreducible level of confounding factors, it is important to envision intervention protocols that introduce the lowest levels of variables and which focus on sports practicing in real-life settings with the aim to propose individualized education and care,” they concluded.

Reference

Lysy PA, Absil H, Gasser E, Boughaleb H, Barrea T, Moniotte S. Combined algorithm-based adaptations of insulin dose and carbohydrate intake during exercise in children with type 1 diabetes: results from the CAR2DIAB Study. 2021;12:658311. doi: 10.3389/fendo.2021.658311

This article originally appeared on Endocrinology Advisor