Insulin Pump Therapy Is Associated with Less Post-Exercise Hyperglycemia than Multiple Daily Injections: An Observational Study of Physically Active Type 1 Diabetes Patients

Background

S everal studies have determined that the use of continuous subcutaneous insulin infusion (CSII) in adults with type 1 diabetes leads to improvements in blood glucose control, as evidenced by reductions in hemoglobin A_1c (HbA_1c), compared with adults using multiple daily insulin injections (MDI). ^{1 –4} Whether blood glucose responses to exercise, which presents major perturbation in blood glucose levels in patients with type 1 diabetes, generally differ between physically active patients using MDI and CSII in their diabetes self-management is currently unclear. The purpose of this observational study was to examine whether interstitial glucose responses, as measured by continuous glucose monitoring (CGM), to moderate aerobic exercise differ between individuals with type 1 diabetes on an MDI regimen and those receiving insulin by CSII.

Subjects and Methods

The study was approved by the University of Ottawa, the Ottawa Hospitals, and York University Research Ethics Boards. Nineteen (16 male, three female) active individuals with complication-free diabetes receiving insulin by MDI either (n=9) or CSII (n=10) were recruited to take part in the study. Participants were asked to maintain their normal insulin routines while not in the laboratory. Of the nine participants on MDI therapy, five were using intermediate-acting basal insulin (NPH), and four were using insulin analog basal insulin (glargine). All subjects were on rapid-acting analog insulin (aspart or lispro) except for one participant using the combination of NPH basal with regular insulin for meals. Participants came to the laboratory for a preliminary session, where their peak aerobic capacity ( \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$\dot{\rm V} {\rm O}_{2{\rm peak}}$$ \end{document} ) was determined and they were instructed on the use of the CGM system. In a separate visit, participants performed aerobic exercise (either cycling [MDI, n=4; CSII, n=5] or running [MDI, n=5; CSII, n=5]) for 45 min at 60% of their predetermined \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$\dot{\rm V} {\rm O}_{2{\rm peak}}$$ \end{document} . Prior to the session, participants using MDI were asked to decrease their basal (i.e., long- or intermediate-acting insulin) dose by 10%. One hour before exercise, participants using CSII were asked to lower their basal insulin infusion rate by 20–50%, as per recent recommendations ^5,6 and their own personal experiences. This temporary basal rate reduction was advised to last until the end of exercise. Despite this advice, three of the subjects insisted on exercising with their pump disconnected, as per their usual routine. Because the timing of exercise was approximately 4 h after lunch, no change in mealtime insulin was performed. Capillary glucose was tested using a handheld meter every 15 min during exercise to ensure participant safety. Glucose was provided in tablet form (16 g of Dex4; AMG Medical, Montreal, QC, Canada) if capillary glucose concentration dropped below 4.5 mmol/L during exercise. This treatment was repeated as necessary based on capillary blood testing. Post-exercise, participants were asked to manage their glucose levels by adjusting carbohydrate and insulin intake as they normally would for aerobic exercise. All exercise sessions took place at 5:00 p.m. following a day in which no vigorous activity had occurred. All subjects consumed their usual evening meal at approximately 7:30 p.m.

The CGMS^® System Gold^™ (Medtronic, Northridge, CA), which records interstitial glucose levels but does not display the values in real-time, was used for measuring glucose changes during and for 6 h after exercise. At least 24 h prior to the exercise session, CGM sensors were inserted subcutaneously in the gluteal area or the abdomen. Participants performed capillary glucose tests and calibrated the CGM four times daily (before meals and before going to bed). On the day following exercise, participants removed the sensors and returned the CGM units to the researchers. Data were uploaded using a Medtronic Com-Station and Minimed Solutions Software version 3.0 (Medtronic) and were divided into the following time segments for analysis: pre-exercise (2 h), exercise (45 min), early post-exercise recovery (3 h post-exercise), and late post-exercise recovery (3–6 h post-exercise).

A two-way analysis of variance (time vs. insulin delivery) was conducted separately for each of the four time periods. Wilcoxon signed rank tests were used to compare carbohydrate intake during exercise and frequency of nocturnal hypoglycemia between groups. Analyses were performed using SPSS version 18.0 for Windows (SPSS Inc., Chicago, IL). Data are presented as mean±SD values.

Results

Baseline HbA_1c (MDI, 7.2±1.2%; CSII, 7.3±1.1%) and \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$\dot{\rm V} {\rm O}_{2{\rm peak}}$$ \end{document} (MDI, 46.4±10.1 mL/kg/min; CSII, 48.6±7.8 mL/kg/min) did not differ between groups. There were also no differences between groups with respect to body mass index (MDI, 24.9±2.6 kg/m²; CSII, 24.1±3.1 kg/m²) or diabetes duration (MDI, 13.5±10.2 years; CSII, 16.7±11.2 years).

Pre-exercise

Interstitial glucose levels were not significantly different between groups in the 2 h preceding exercise or at the beginning of exercise (Fig. 1).

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FIG. 1.

Changes in glucose levels (A) before exercise, (B) during aerobic exercise, (C) in early (0–3 h) post-exercise recovery, and (D) in late (3–6 h) post-exercise recovery in individuals with type 1 diabetes receiving insulin via continuous subcutaneous insulin infusion (CSII) (open circles) or multiple daily insulin injections (MDI) (solid squares). Significant group×time interactions were found in (C) early and (D) late recovery (both *P<0.05) with MDI patients experiencing more post-exercise hyperglycemia.

Discussion

In this observational study, we found that physically active individuals using CSII therapy experienced less post-exercise hyperglycemia and more stable interstitial glucose concentrations in recovery than those on MDI therapy. It is surprising that changes in blood glucose levels during exercise and in early recovery were comparable between groups despite the fact that patients on CSII have the ability to lower basal insulin infusion rates prior to the activity while MDI patients do not have this opportunity, although we did note that the MDI patients tended to have greater risk for hypoglycemia during the exercise compared with those on CSII. Indeed, the amount of carbohydrate supplementation required during exercise may be considered clinically relevant, if not statistically significant (five of nine participants for a total of 244 g in MDI vs. three of 10 participants for a total of 105 g in CSII). Thus, it would appear that, based on the small number of subjects tested in this study, CSII may provide some protection against exercise-induced dysglycemia.

CSII therapy is often considered to be more flexible than MDI therapy for physically active patients living with type 1 diabetes because basal and bolus insulin delivery can be modified before, during, and after exercise. On the other hand, too aggressive a reduction in basal and/or bolus insulin, as may occur with pump suspension, may contribute to exercise-associated hyperglycemia, particularly in the post-exercise period. ^{7 –9} A limited number of studies have examined the glycemic response to exercise in patients with type 1 diabetes receiving insulin by constant infusion, ^{8,10 –12} although few have actually compared CSII versus MDI. Sonnenberg et al. ¹⁰ found that, when performing 60 min of moderate aerobic exercise in the morning 90 min after breakfast, hypoglycemia occurred in more than half of their CSII participants unless the pre-meal bolus was decreased by 50% and the basal insulin infusion was suspended during exercise. Conversely, Admon et al. ¹² found similar rates of hypoglycemia during 45 min of moderate aerobic activity performed 2 h after breakfast whether basal insulin was suspended or not. Where afternoon exercise was performed (as was the case in our study), Edelmann et al. ¹¹ found that if basal insulin was suspended for 3 h (starting 30 min prior to exercise), it was insufficient to prevent hypoglycemia during exercise. In contrast, Tsalikian et al. ⁸ found that suspending basal insulin at the start of exercise limited the frequency of hypoglycemia during the activity (16% vs. 43% in pump off vs. pump on trials) but resulted in more post-exercise hyperglycemia (27% vs. 4%).

In the present study, we controlled the exercise intensity, duration, and timing as well as provided general guidelines for exercise-related insulin reductions. ^5,6 At the same time, however, because this was primarily an observational study, we allowed participants to ultimately determine their own insulin and mealtime intake regimens, as per their usual self-management strategies. Despite our recommendations for 20–50% basal insulin reductions, three of the participants in the CSII group chose to remove their pump altogether before exercise because of past experiences with hypoglycemia. Had these patients maintained some basal insulin infusion during the activity, we may have observed more hypoglycemia in the CSII group during the activity and lower levels of glycemia in recovery. Indeed, if these subjects had maintained basal insulin infusion during the activity, then the differences in glycemia between MDI and CSII groups in the post-exercise period may have been even more dramatic.

In a previous study comparing MDI to CSII patients, Schiffrin and Parikh ⁹ examined changes in blood glucose during 45 min of moderate (55% \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$\dot{\rm V} {\rm O}_{2{\rm peak}}$$ \end{document} ) cycling performed 2 h after breakfast. As with our study, these investigators reported similar exercise-related changes in glucose between groups, regardless of the adjustments made to pre-exercise insulin dosage. However, unlike our study, Schiffrin and Parikh ⁹ only observed their participants for 60 min post-exercise and therefore provide us with no late post-exercise data with which to compare. In another study, Delvecchio et al. ⁷ examined the effects of late afternoon exercise on blood glucose control in adolescents with type 1 diabetes treated with insulin glargine (a common basal insulin used in MDI therapy) compared with those using CSII where the pump was either turned off or left on. As expected, patients on CSII had a higher risk of hypoglycemia with pump on, compared with when it was off, but this protection against hypoglycemia was also associated with greater post-exercise hyperglycemia. In addition, hypoglycemia was more frequent among CSII users at bedtime if the pump was left on during exercise. ⁷ In contrast to our study, the exercise intensity in the study by Delvecchio et al. ⁷ was not controlled and was likely to be somewhat inconsistent both between and within patients as it involved participation in different sports by adolescents attending a sports camp. CGM was not used during that study, and the authors provide no information as to whether or not post-exercise hyperglycemia rates differed between pump on and pump off.

The lack of rebound hyperglycemia following exercise in the CSII group in our study is not easily explained, especially in light of the fact that all subjects reduced basal insulin infusion rates and three of the participants in this group disconnected their pumps altogether, which has been shown to induce post-exercise hyperglycemia. ^8,9 It is also unclear if the differences observed when the subjects left the laboratory are related to behavioral factors (i.e., food intake, insulin adjustments) or to differences in some other physiological response between the two groups. It is important to recognize that, although changes in interstitial glucose levels during exercise were comparable between groups, more supplementary carbohydrate was needed to prevent hypoglycemia in the MDI group, which may have contributed to their higher glycemia post-exercise. It is also possible that the ability to make more adjustments prior to exercise in order to prevent hypoglycemia reduces the need for extra carbohydrate during exercise for patients on CSII. In addition, CSII users have the ability to adjust immediately to rising glucose levels with small bolus infusion corrections, whereas MDI users may be uncertain about taking an additional insulin injection correction bolus for fear of nocturnal hypoglycemia. As such, treating the fear of hypoglycemia may lead participants on MDI, who are unable to make basal rate insulin adjustments, to err on the side of caution and expose themselves to more post-exercise hyperglycemia.

Our study is the first to show that physically active individuals with type 1 diabetes may have distinctly different post-exercise interstitial glucose profiles when receiving insulin by CSII versus MDI. Based on our findings, it would appear that patients on MDI may have more post-exercise hyperglycemia, which could temper the beneficial effects that aerobic exercise has on overall glycemic control. Whether higher post-exercise interstitial glucose levels in the MDI group occur for physiological reasons or behavioral ones (insulin adjustments and carbohydrate intake) requires further examination. It is also important to acknowledge that, like with most prior studies in this area, ^7,10,12,13 the sample size in this study is small and that generalized conclusions should be tempered. Nonetheless, based on our findings, different strategies to limit post-exercise blood glucose excursions should take into account the method of insulin delivery.