Hypoglycemia is a frequent occurrence in individuals with type 1 diabetes mellitus (T1DM). Endurance exercise presents a challenge to good glycemic control (4,20,37) especially when compared with exercises that contain sprinting or mimic games activities (3,11,14). To avoid the occurrence of exercise-induced hypoglycemia, T1DM individuals are recommended to reduce preexercise rapid-acting insulin and/or consume CHO before and/or during exercise (1).
Research has demonstrated improved blood glucose (BG) concentrations after preexercise insulin reductions of 10%–40% (6), 10%–50% (10), 50%–90% (22), 50%–75% (28), and 25%–75% (38–40). Much of the variation in the findings can be attributed to differences in the insulin regimen used by participants, e.g., neutral protamine Hagedorn insulin (22), Ultralente with prandial insulin lispro (28), or insulin glargine with insulins aspart or lispro (38–40). Although it has been recommended to avoid administration of full rapid-acting insulin dose within 2 h of physical activity owing to the risk of overinsulination of the active musculature during exercise (6,26), administration of reduced doses of rapid-acting insulin with ingestion of CHO within this time has been shown to improve postexercise glycemia (41).
Recommendations for CHO consumption before or during exercise in T1DM individuals range from amounts based on preexercise BG concentration, i.e., <5.6 or <6.7 mmol·L−1 (6,34), from amounts based on exercise duration, e.g., 20–60 g every 30 min (1) or 60 g·h−1 (8), or body mass (1–2 g·kg−1 BM [29,31]). Less thoroughly examined is the potential for CHO consumption to alter endurance exercise performance in T1DM individuals. However, in a study by Ramires et al. (29), withholding neutral protamine Hagedorn porcine insulin for 12 h before exercise followed by administration of 1 g·kg−1 BM of dextrose compared with a CHO-free solution 30 min before cycling at 55%–60% V˙O2max to exhaustion resulted in a 12% improvement in cycling performance in participants with well-controlled T1DM.
Recent interest has focused on a CHO glycemic index (GI) in improving glycemia and altering fuel metabolism in the exercising T1DM (39,40). CHO with a low GI digest at slower rates than CHO with a high GI and are unable to cross the small intestine mucosal cell membrane and enter the bloodstream unless hydrolyzed into monosaccharides (33). Inclusion of low-GI CHO into the daily diets of T1DM individuals resulted in lower mean daily BG (24) and reductions in incidence of hypoglycemia and HbA1c (9,36). Ingestion of the low-GI disaccharide CHO isomaltulose by T1DM individuals has been shown to improve postexercise BG area under the curve by 21% and influence fuel metabolism during running by a lesser suppression of lipid oxidation when compared with dextrose (39). Therefore, somewhat paradoxically, consumption of a low-GI CHO before exercise may reduce CHO combustion during running and aid in maintenance of glycemia during and after exercise when compared with ingestion of a high-GI CHO.
Preservation of CHO stores through combustion of endogenous lipid use is conducive to an improvement in endurance capacity. However, although studies have demonstrated the importance of a CHO’s GI in influencing exercise capacity in nondiabetic individuals by such mechanisms (23), results have been equivocal (41). Furthermore, no research has addressed the relationship between CHO type and endurance performance in T1DM individuals. The functional capacity of T1DM individuals is often lower than in matched individuals without diabetes, and as an example, in the study by Ramires et al. (29), cycling performance to exhaustion was 62% lower (77 ± 6 vs 125 ± 7 min, P < 0.05). Thus, the potential to reduce the magnitude of this “fitness gap” through more refined nutritional supplementation deserves some attention.
Yet, an “exercise-to-exhaustion” endurance model may be an inappropriate tool to use in T1DM individuals given the risk of lowering BG concentrations to potentially hypoglycemic levels before depleting muscle CHO stores from exercise. Alternative models in cycling ergometry advocating completion of a set amount of work has been shown to reduce intrasubject variation compared with endurance capacity models (16). Thus, the use of time or distance trials using a nonmotorized treadmill to retain ecological validity of real-life movement patterns under controlled laboratory conditions might facilitate a deeper insight into the metabolic and performance effects of insulin reduction/CHO administration strategies that avoid placing the T1DM individual at risk of hypoglycemia.
Therefore, the aims of this study were to examine the influence of administration of reduced rapid-acting insulin with ingestion of either a low- or high-GI CHO on glycemia and fuel use during aerobic running and to examine the consequent effects on run performance.
METHODS
Research Design and Methods
Participants.
With UK Research Ethics Committee approval (ref. no. 10/WMW02/35), seven participants with T1DM (two men and five women; age = 34 ± 5 yr, body fat = 23.8% ± 1.9%, body mass index = 25 ± 1.4 kg·m−2), with a duration of diabetes of 16 ± 5 yr and HbA1c of 76.6 ± 6.5 mmol·mol−1, volunteered to participate in this study. Patients were recruited from local clinics and through local advertisements. After receiving a full explanation of the testing protocol, all participants provided informed consent and medical history forms before partaking in the study. All participants were currently regularly exercising for at least 6 months before the study, in moderate glycemic control, with no significant complications, except for mild background retinopathy, and were receiving no additional medication for their diabetes other than insulin. All female participants were taking a progestin-only oral contraceptive pill.
Insulin regimen.
The insulin regimen of each participant was set according to specific algorithms formed as part of their treatment with their diabetes clinician. Participants were familiar with the CHO counting method and were administering 1.3 ± 0.2 U of insulin per 10 g of CHO. Basal insulin dose did not change over the study period and was administered at the same time of day (evening) and at the same anatomical region. All participants were using a basal bolus regimen of insulin glargine (n = 6) or insulin detemir (n = 1) and either insulin lispro (n = 2) or insulin aspart (n = 5) at meal time. The pharmacokinetics and dynamics of insulin aspart and insulin lispro are comparable (27), and their metabolic effects are shown to be equivalent (13). Basal insulins glargine and detemir demonstrate a peakless 24-h profile (12).
Experimental protocol.
Participants initially attended the laboratory for a preliminary test to quantify peak rate of oxygen consumption (V˙O2peak) and peak HR (HRpeak). To obtain these variables, participants completed a continuous incremental treadmill assessment to volitional exhaustion. Beginning at a velocity of 6–8 km·h−1, on a level gradient, treadmill velocity was increased by 1 km·h−1 every 3 min until participants were unable to continue. V˙O2peak, HRpeak, and RER were determined from the final minute of exercise. Participants’ peak cardiorespiratory characteristics in response to the continuous incremental treadmill run test were V˙O2peak = 38.9 ± 4.4 mL·kg−1·min−1, HRpeak = 192 ± 9 beats·min−1, and RERpeak = 1.14 ± 0.05. In addition, to assess the control of deceleration and acceleration of the nonmotorized treadmill belt (Woodway Curve, Weil am Rhein, Germany), participants spent approximately 10 min jogging intermittently followed by three 5-min runs at a self-selected pace. The coefficient of variation of the distance achieved in the second and third runs at a self-selected submaximal pace was 2.23% ± 0.55%.
One week after the preliminary visit, participants attended the exercise physiology laboratory on two occasions, at the same time (between 6:00 and 9:00 a.m.) at least 2 d apart. Participants avoided strenuous activity for 24 h before arriving to the laboratory after an overnight fast, having consumed similar evening meals before each trial (assessed via dietary recording sheets). On arrival to the laboratory, body mass and height were recorded (Seca 770 Digital Scales [Seca, UK] and Stadiometer [Holtain Ltd., UK]). Body composition was estimated using bioelectrical impedance analysis (Bodystat Quadscan 4000; Bodystat Ltd., UK).
Participants were seated and asked about to comment about their perceived feelings of gut fullness and hunger on visual analog scales between 0 and 10 cm based on a modified Borg scale (2). Thereafter, a resting 4-mL venous blood sample was obtained for later determination of HbA1c alongside a 170-μL capillary blood sample for determination of glucose, lactate, pH, and Hct (GEM Premier 3000; Instrumentation Laboratories, UK).
Participants were then informed of the CHO amount to be provided and reduced their normal rapid-acting insulin dose (aspart NovoRapid® or lispro Humalog®) dose by 50% (2.7 ± 0.3 U), which was administered using Novopen3® (NovoNordisk, UK) and Humapen luxura™ (Eli Lilly, UK), respectively, in the leg, arm, or abdomen by individual preference. Participants were then supplied in a randomized fashion with either 41.8 ± 1.3 g of isomaltulose (ISO; Palatinose®; Beneo Group, Mannheim, Germany) or 41.9 ± 1.2 g of dextrose (DEX; MyProtein.com, UK) mixed to a 10% product solution (25) with distilled water and delivered in an opaque sports bottle. This was an equivalent dose of 0.6 g·kg−1 body mass. Participants consumed the test solution within 5 min and remained in a rested, seated position for 2 h with capillary blood samples taken every 30 min during this rest period. Fifteen minutes before exercise, resting measures of respiration (Metamax 3b; Cortex Biophysik, Leipzig, Germany) and HR were determined (RS-400; Polar, Kempele, Finland) with the participants in a supine position.
Exercise Protocols
Incremental run test.
Once resting cardiorespiratory measures were recorded, participants still wearing the portable gas analyzer (Metamax 3b) and HR monitor (Polar RS-400) mounted a motorized treadmill (ERGO ELG55; Woodway GmbH, Germany) to perform a discontinuous incremental protocol consisting of five stages of 4-min exercise with 1.5-min rest between each exercise bout. The exercise intensities were performed at 31% ± 1% V˙O2peak (4.3 ± 0.2 km·h−1), 41% ± 2% V˙O2peak (5.4 ± 0.3 km·h−1), 53% ± 2% V˙O2peak (6.4 ± 0.3 km·h−1), 69% ± 3% V˙O2peak (7.5 ± 0.4 km·h−1), and 80% ± 2% V˙O2peak (8.6 ± 0.5 km·h−1). A 170-μL capillary blood sample was taken within each rest period. On completion of the final run stage, the treadmill belt was stopped and a 5-min rest period began. Participants were allowed to drink water if they desired during this time.
Ten-minute performance run.
Participants then mounted a nonmotorized treadmill (Curve; Woodway GmbH) and completed a 3-min familiarization period before another capillary blood sample was obtained. A 10-min countdown was preprogrammed on the nonmotorized treadmill and the speed display was covered. Stride frequency was determined by video recording (Nikon D5000; Nikon, UK), synchronized with the start of the run test. Stride length was determined from the equation: stride frequency (number of strides) × stride length (m) = distance (m). Distance was noted every 2.5 min, and participants received strong vocal encouragement throughout. In the final 20 s of exercise, participants were asked to rate their perceived level of physical exertion (2). On immediate cessation of running, another capillary blood sample was obtained. After exercise, participants were reseated and remained at rest for the next 15 min drinking water ad libitum. One final capillary blood sample was obtained and analyzed, after which perceived feelings of gut fullness and hunger scales were completed.
Blood samples.
An aliquot of venous blood was collected in a 4-mL Na+EDTA vacutainer and analyzed for HbA1c by HPLC with cation exchange (G7; Tosoh, UK). A 170-μL sample of capillary blood was obtained and immediately measured for BG, pH, lactate, and hematocrit concentrations (GEM3000; Instrumentation Laboratories, Ltd.). If hypoglycemia (defined as BG concentration ≤3.5 mmol·L−1) (28) occurred, participants consumed 20 g (administered as a 10% solution) of the same CHO used in that trial and data from that point onward were removed from the analysis.
Data analysis.
Statistical analysis was performed using SPSS software (version 16; SPSS, Inc., Chicago, IL), with significance set at P ≤ 0.05. Data were tested for normal distribution (Shapiro–Wilk test) and subsequently analyzed using repeated-measures ANOVA on two factors (treatment × time) with Bonferroni adjustment and dependent t-tests carried out where relevant. BG responses were calculated as a change from rest through the subtraction of fasting concentrations from further glucose values within each condition. Substrate oxidation rates were calculated using principles of indirect calorimetry. The calculation of CHO and fat from gas exchange measurements was determined using equations from Jeukendrup and Wallis (18). Data are presented as mean ± SEM.
RESULTS
Resting and Submaximal Exercise
Cardiorespiratory responses.
The cardiorespiratory responses to ingestion of ISO and DEX are presented in Table 1. Resting ventilation and volume of carbon dioxide were significantly elevated in ISO compared with those in DEX (P < 0.05). Concomitant with the greater V˙CO2 under ISO was a higher RER (P < 0.05). Although exercise promoted significant increases in cardiorespiratory variables, there were no significant differences between ISO and DEX at any exercise intensity (Table 1).
;)
TABLE 1: Cardiorespiratory responses at rest and during each submaximal exercise intensity.
BG.
The relative BG responses to ingestion of ISO and DEX are presented in Figure 1A. There was a significant time effect (P = 0.006, ∂η2 = 0.634) and a significant time × condition interaction (P = 0.022, ∂η2 = 0.441) within the BG responses to ISO and DEX. Fasted BG concentrations were not different between conditions (ISO = 9.8 ± 1.3 mmol·L−1 vs DEX = 9.1 ± 0.9 mmol·L−1, P = 0.64). After ingestion of ISO and DEX, BG concentrations remained greater than rest for the duration of the protocol under both conditions (Fig. 1A). Peak BG under ISO was less than that under DEX (ISO = +5.6 ± 0.6 mmol·L−1 vs DEX = +10.0 ± 0.5 mmol·L−1, P < 0.001); moreover, peak BG concentrations occurred at 60 min after ingestion under DEX but at 90 min under ISO (Fig. 1A). Preexercise BG area under the curve was lower under ISO in comparison with DEX (ISO = + 4.0 ± 0.3 mmol·L−1·h−1 vs DEX = +7.0 ± 0.6 mmol·L−1·h−1, P < 0.01). Immediately before beginning the incremental exercise protocol, BG concentrations were not different between the conditions (ISO = +4.8 ± 0.6 mmo·L−1 vs DEX = +6.0 ± 1.6 mmo·L−1, P = 0.35; Fig. 1A). During the submaximal exercise protocol, BG declined with each increase in exercise intensity under ISO (P < 0.01); however, concentrations under DEX did not significantly decline from the 31% to the 80% stage (Fig. 1A; P = 0.33). Although the rate of decline in BG during the submaximal protocol under DEX was not significantly different from ISO (DEX = −0.5 ± 0.5 mmol·L−1 vs ISO −1.4 ± 0.4 mmol·L−1, P = 0.25), BG concentrations elicited at 53% and 69% demonstrated a tendency to be lower under ISO in comparison with DEX (P < 0.1) and were lower under ISO in comparison with DEX (ISO = +2.9 ± 1.1 mmol·L−1 vs DEX +5.0 ± 1.4 mmol·L−1, P = 0.04; Fig. 1A) during the final stage of the submaximal protocol.
FIGURE 1: BG (A), lactate (B), and pH (C) responses to ingestion of ISO and DEX. Data are presented as mean ± SEM. *Between-condition difference (P < 0.05). Hollow sample points indicate a difference from rest (P < 0.05). CHO and insulin were administered immediately after the resting sample. Exercise began immediately after the 120-min sample.
Blood lactate and pH.
The blood lactate responses to ingestion of ISO and DEX are presented in Figure 1B. There was a significant time effect (P = 0.001, ∂η2 = 0.927) and a significant time × condition interaction (P = 0.04, ∂η2 = 0.409). After consumption of ISO, blood lactate concentrations increased and were greater than those elicited under DEX from 30 to 120 min after ingestion (Fig. 1B). Once exercise began, blood lactate concentrations were similar between conditions and increased similarly with each increase in exercise intensity (Fig. 1B). Peak blood lactate concentrations at the end of the submaximal protocol were similar (ISO = 4.9 ± 0.7 mmol·L−1 vs DEX = 4.9 ± 0.7 mmol·L−1, P = 0.98; Fig. 1B). The blood pH responses to ingestion of ISO and DEX are presented in Figure 1C. There was a significant time effect (P = 0.02, ∂η2 = 0.541) but no condition × time interaction (P = 0.66). After consumption of ISO and DEX, blood pH did not significantly change within the preexercise period; however, at the onset of exercise, blood pH decreased with each increase in exercise intensity, with both conditions demonstrating similar time course changes (Fig. 1C).
Resting and Submaximal Fuel Oxidation Rates
Substrate oxidation rates and energy contributions from lipids and CHO at rest and during the submaximal exercise protocol are presented in Figure 2. Resting lipid and CHO oxidation rates were higher and lower, respectively, under DEX when compared with ISO (Figs. 2A and B). Peak lipid oxidation rates occurred, under both conditions, at 31% V˙O2peak (Fig. 2B) with every increase in exercise intensity bringing a concomitant reduction in lipid oxidation rate, such that at 53% V˙O2peak, lipid oxidation rates were similar to rest (Fig. 2B). Peak CHO oxidation rates occurred in the final stage of the protocol with lipid oxidation rates lower than that of rest, under both conditions (Fig. 2B). Total energy used during the submaximal exercise protocol increased, from rest, with each increment in exercise intensity; however, there were no conditional differences in total energy expenditure (Fig. 2C).
FIGURE 2: CHO (A) and lipid oxidation (B) rates and energy contributions (C) at rest and during the submaximal exercise protocol. *Conditional difference (P < 0.05). †Difference in total energy when compared with rest, under both conditions (P < 0.05).
Performance test.
During the performance test, participants exercised at similar aerobic rates of oxygen consumption, under both conditions, during the first (ISO = 69% ± 6% vs DEX = 73% ± 5% V˙O2peak, P = 0.41), second (ISO = 87% ± 6% vs DEX = 90% ± 5% V˙O2peak, P = 0.31), third (ISO = 91% ± 6% vs DEX = 90% ± 6% V˙O2peak, P = 0.65), and fourth quartiles (ISO = 92% ± 5% vs DEX = 92% ± 5% V˙O2peak, P = 0.92). Moreover, the mean exercise intensity elicited during the 10-min protocol was similar between conditions (ISO = 86% ± 6% vs DEX = 85% ± 6% V˙O2peak, P = 0.50). HR responses were similar between ISO and DEX, with exercise eliciting similar percentages of maximum HR (ISO = 98% ± 1% vs DEX = 99% ± 1% HRpeak, P = 0.61). The rise in BG with exercise was similar immediately (ISO = +0.7 ± 0.4 mmol·L−1 vs DEX = +0.7 ± 0.3 mmol·L−1, P = 0.97) and 15 min after exercise (ISO = +1.1 ± 0.5 mmol·L−1 vs DEX = +0.9 ± 0.6 mmol·L−1, P = 0.97). However, BG concentrations immediately and at 15 min after exercise were lower under ISO in comparison with DEX (P < 0.05; Fig. 3A). Overall, there was one occurrence of hypoglycemia in each condition by the same individual.
FIGURE 3: BG (A), lactate (B), and pH (C) responses to the performance test. Data are presented as mean ± SEM. *Between-condition difference (P < 0.05). Hollow sample points indicate change from PRE (P < 0.05).
Preexercise blood lactate responses were similar between conditions (ISO = 3.7 ± 0.6 mmol·L−1 vs DEX = 4.2 ± 0.7 mmol·L−1, P = 0.46; Fig. 3B). Moreover, the immediate postexercise values were also similar between conditions (ISO = 12.2 ± 0.6 mmol·L−1 vs DEX = 12.5 ± 0.8 mmol·L−1, P = 0.57). In addition, there were no conditional differences in the blood pH responses to the performance protocol, with a similar drop in pH values from before to immediately after completion of exercise (ISO = 0.18 ± 0.03 U vs DEX = 0.17 ± 0.01 U, P = 0.63) and 15 min after exercise under both conditions (Fig. 3C).
The performance measures are presented in Table 2. There were no differences in the total or quartile mean number of steps, stride length, speed, or distance covered (P > 0.05).
TABLE 2: Performance measures recorded within each quartile and the total of the 10-min run test.
Gut fullness and hunger.
Perceived feelings of gut fullness increased in both trials after consumption of both CHO, fullness was reported to be greatest after completion of exercise, although there were no conditional differences between trials (Table 3; P = 0.11). Perceived hunger ratings were also highest at rest before CHO ingestion, and ratings were lower in both conditions at the preexercise and postexercise stages. Under DEX, there was a suggestion of appetite suppression after completion of exercise where a drop in hunger feeling was observed as opposed to an increase in ISO (Table 3). There were no conditional differences between CHO (P = 0.54).
TABLE 3: Perceived feelings of hunger and fullness in both trials.
DISCUSSION
This study examined the influence of preexercise administration of reduced rapid-acting insulin with ingestion of a low- or high-GI CHO on glycemia and fuel use during running in T1DM individuals. The results demonstrate improved BG concentrations before, during, and after running and similar high-intensity run performance in T1DM individuals after consumption of isomaltulose compared with dextrose.
Rest
Participants arrived to the laboratory after an overnight fast of 8–10 h. After administration of a 50% reduced rapid-acting insulin dose of ∼3 U and consumption of ∼40 g of CHO, BG concentrations increased half as much in ISO compared with DEX. In addition, peak BG under ISO occurred later and was lower than DEX. Hydrolysis of ISO by a sucrose–isomaltase complex into glucose and fructose in the jejunum of the small intestine results in a slower CHO transport rate into the portal vein circulation (19) and helps explain the differences in resting circulating glucose. There was an increase in blood lactate concentrations in both CHO conditions, but the magnitude of increase in lactate was twofold greater under ISO compared with DEX. In combination with increases in circulating insulin, increased hepatic portal vein glucose concentrations under both CHO conditions promote GLUT2-mediated hepatic glucose uptake, increase glycolysis and, consequently, circulating lactic acid (7). In addition, some glucose may be taken up by red blood cells, muscle, and adipose tissue and contribute to this circulating lactate (7). The increase in hepatic portal vein fructose derived from ISO enters the hepatocyte and phosphorylates to fructose 1-phosphate with conversion to dihydroacetone phosphate and glyceraldehyde, bypassing the rate-limiting enzyme phosphofructokinase (35) and increasing glycolytic rate more than DEX, thus explaining the greater appearance of circulating lactate. Therefore, in agreement with other research findings (39,40), the twofold greater formation of circulating lactate under ISO compared with DEX can be mostly explained by metabolism of the fructose fraction of ISO. During the 2-h preexercise period, there was a reduction in blood lactate concentrations in both CHO conditions with time, which may be due to hepatic lactate uptake, promoting conversion to glucose 6-phosphate and storage as glycogen (35). There were no differences in blood pH across time or condition suggesting that the intracellular and extracellular buffering mechanisms were capable of sequestering the amount of H+ formed by the production of intracellular lactic acid. Concomitant with the greater resting lactate under ISO was a greater CO2 production rate. The increased CO2 may be derived from the conversion of pyruvate to acetyl CoA in mitochondria and/or an increased oxidative phosphorylation rate, which stimulates central respiratory pathways and producing a greater resting ventilation rate. The consequence of the greater V˙E and V˙CO2 was to alter the resting whole body fuel oxidation rates (as determined using principles of indirect calorimetry). Thus, under ISO, there was a 25% greater use of CHO and an equally lower lipid oxidation rate in spite of similar absolute preexercise BG concentrations.
Submaximal Incremental Discontinuous Running
Discontinuous incremental exercise is a useful model to examine changes in whole-body fuel use across a range of exercise intensities. From our data, we found CHO oxidation increased with increasing exercise intensity reaching ∼3.8 g·min−1 at 80% V˙O2peak and lipid use was highest at ∼0.2 g·min−1 at 31% V˙O2peak. The low and progressively declining use of lipid with each successive 4-min run stage is suggestive of a growing need for aerobic and anaerobic CHO use with an increase in exercise intensity (32) and/or a mass action effect of the high preexercise BG (∼15 mmol·L−1) in ISO and DEX contributing to an increased glycolytic flux with subsequent inhibition of mitochondria entry of LCFA suppressing lipid oxidation (5,15,30). Contrary to our findings, a lessening of the suppressive effects of high BG on lipid oxidation with run duration was demonstrated in the study of West et al. (39) where greater lipid and lower CHO oxidation rates were evident in the last 10 min of a 45-min submaximal run after preexercise ingestion of isomaltulose. However, in our study, the stage and/or total run duration may have been too short to reduce BG to a level that might facilitate a lessening of the CHO brake on lipid oxidation given the ∼1-mmol·L−1 drop in BG observed across the five exercise stages compared with ∼5 mmol·L−1 in the study of West et al. (39). Finally, the visually determined blood lactate inflection point was unaffected by the greater resting lactate values in ISO, producing similar “anaerobic threshold” run intensity values in each CHO condition (ISO = 70% ± 4% vs DEX = 68% ± 6% V˙O2peak, P = 0.49; data derived from Fig. 1B).
High-Intensity Running
There were no differences in high-intensity run performance of T1DM individuals between CHO conditions. T1DM participants performed the fixed-duration run on the nonmotorized treadmill at the same run intensity of 85%–86% V˙O2peak and 98%–99% HRpeak under ISO and DEX conditions. Moreover, analysis of video recordings of the 10-min trial revealed completion of a similar number of steps and mean stride length. The achievement of running ∼1.2 km also demonstrated a significant role for anaerobic glycolysis with a ∼8-mmol·L−1 increase and a 0.13-unit drop in preexercise blood lactate and pH, respectively. Despite the trend for a lower BG concentration in ISO before the run test, the marked hyperglycemia in both CHO conditions may have provided a metabolic milieu for the exclusive combustion of exogenous CHO during exercise (15,17). Intense exercise (i.e., ≥80% V˙O2max) results in an eightfold increase in hepatic glucose output, whereas BG use may increase by threefold (21). Importantly, exercise, like insulin, stimulates the translocation of GLUT4 in skeletal muscle to facilitate glucose uptake. Increased catecholamine production is thought to be a major regulator of the hepatic glucose output with intense exercise (21). In healthy subjects, insulin secretion increases during the recovery period after intense exercise, which leads to a normalization of BG. This response is impaired in our T1DM individuals and most likely accounted for the worsening hyperglycemia during the 15-min after running. From a clinical viewpoint, the greater high-intensity exercise-induced hyperglycemia after running under DEX might suggest the need for corrective rapid-acting insulin doses after running, and therefore, recommendation for the use of isomaltulose might be clinically more desirable—potentially combined with a less aggressive insulin reduction strategy before commencing high-intensity exercise.
Isomaltulose seemed equally effective in avoiding hypoglycemia, i.e., ≤3.5 mmol·L−1. There was one occurrence of hypoglycemia in each trial, and this was in the same individual who did report occurrences of poor glycemic control in the previous 6 months. However, the low value occurred later under the low-GI CHO (ISO = 155 min vs DEX = 120 min into the protocol). It was hypothesized that differences in digestion and assimilation rates for these CHO might suggest altered self-reported gut fullness values; however, no such conditional differences were evident between the low- and high-GI CHO and the growing perception of hunger with time was similar in both conditions. It is acknowledged that there was a small participant number recruited in this study. The strict inclusion criteria (i.e., basal bolus regimen, moderate glycemic control, physically fit, and ability to run comfortably) meant that recruiting large numbers was difficult and beyond the pool of available T1DM individuals. Resultant statistical power of this study is ∼62%, and although caution should be taken in interpreting the results, significant conditional effects were demonstrated as a result of all participants’ BG responses responding in the same way, thus pointing to the statistical and clinical significance of the study.
CONCLUSIONS
The results of this study demonstrated improved glycemia before, during, and after running with similar high-intensity run performance in T1DM individuals after consumption of isomaltulose compared with dextrose. From a clinical viewpoint, consideration of the type of CHO to be ingested before exercise is important because our results demonstrate attenuation of the absolute glycemic response to exercise with no detriment in exercise performance. If preformed regularly, such alterations may contribute to an improvement in glycemic control and/or reductions in the need for corrective administration of exogenous insulin. Future research may wish to explore longer-term adherence to such a strategy.
This study was funded by the College of Engineering, Swansea University.
The authors thank the participants for their involvement in this study.
The authors wish to declare no conflict of interest resulting from the findings of this study.
The results of the present study do not constitute endorsement by the American College of Sports Medicine.
REFERENCES
1. American College of Sports Medicine and American Diabetes Association Joint Position Statement: diabetes mellitus and exercise. Med Sci Sports Exerc. 1997; 29 (12): i–vi.
2. Borg G. Ratings of perceived exertion and heart rates during short-term cycle exercise test and their use in a new strength cycling test. Int J Sports Med. 1982; 3 (3): 153–8.
3. Bussau VA, Ferreira LD, Jones TW, Fournier PA. The 10-s maximal sprint: a novel approach to counter an exercise-mediated fall in glycemia in individuals with type 1 diabetes. Diabetes Care. 2006; 29: 601–6.
4. Campaigne BN, Wallberg-Henriksson H, Gunnarsson R. Glucose and insulin responses in relation to insulin dose and caloric intake 12 h after acute physical exercise in men with IDDM. Diabetes Care. 1987; 10: 716–21.
5. Coyle EF, Jeukendrup AE, Wagenmakers AJM, Saris WHM. Fatty acid oxidation is directly regulated by carbohydrate metabolism during exercise. Am J Physiol Endoc Metabol. 1997; 273: E268–75.
6. De Feo P, Di Loreto C, Ranchelli A, et al.. Exercise and diabetes. Acta Biomed. 2006; 77: 14–7.
7. Frayn KN. Metabolic Regulation: A Human Perspective. 3rd ed. Hoboken (NJ): Wiley-Blackwell; 2010. p. 104.
8. Gallen I. Exercise in type 1 diabetes. Diabetic Med. 2003; 20: 1–17.
9. Gilbertson HR, Brand-Miller JC, Thorburn AW, Evans S, Chondros P, Wether GA. The effect of flexible low glycemic index dietary advise versus measured carbohydrate diets on glycemic control in children with type 1 diabetes. Diabetes Care. 2001; 34: 1137–43.
10. Grimm JJ. Exercise in type 1 diabetes. In: Nagi D, editor. Exercise and Sport in Diabetes. Hoboken (NJ): Wiley; 2005. p. 25–43.
11. Guelfi KJ, Jones TW, Fournier PA. The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes. Diabetes Care. 2005b; 28: 1289–94.
12. Gulve EA. Exercise and glycemic control in diabetes: benefits, challenges, and adjustments to pharmacotherapy. Phys Ther. 2008; 88: 1297–321.
13. Homko C, Deluzio A, Jimenez C, Kolaczynski JW, Boden G. Comparison of insulin aspart and lispro: pharmacokinetic and metabolic effects. Diabetes Care. 2003; 26: 2027–31.
14. Iscoe K, Riddell MC. Continuous moderate-intensity exercise with or without intermittent high-intensity work: effects on acute and late glycaemia in athletes with type 1 diabetes mellitus. Diabet Med. 2011; 28 (7): 824–32.
15. Jenni S, Oetliker S, Allemann M. Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus—a prospective single-blinded randomised crossover trial. Diabetologia. 2008; 51: 1457–65.
16. Jeukendrup A, Saris WH, Brouns F, Kester AD. A new validated endurance performance test. Med Sci Sports Exerc. 1996; 28 (2): 266–70.
17. Jeukendrup AE, Wagenmakers AJ, Stegen JH, Gijsen AP, Brouns F, Saris WH. Carbohydrate ingestion can completely suppress endogenous glucose production during exercise. Am J Physiol. 1999; 276 (4 Pt 1): E672–83.
18. Jeukendrup A, Wallis GA. Measurement of substrate oxidation during exercise by means of gas exchange measurements. Int J Sports Med. 2005; 26 (1 suppl): S28–37.
19. Lina BA, Jonker D, Kozianowski G. Isomaltulose (Palatinose): a review of biological and toxicological studies. Food Chem Toxicol. 2002; 40 (10): 1375–81.
20. MacDonald MJ. Postexercise late-onset hypoglycaemia in insulin-dependent diabetic patients. Diabetes Care. 1987; 10: 584–8.
21. Marliss EB, Vranic M. Intense exercise has unique effects on both insulin release and its roles in glucoregulation: implications for diabetes. Diabetes. 2002; 51 (1 suppl): S271–83.
22. Mauvais-Jarvais F, Sobngwi E, Porcher R, et al.. Glucose response to intense aerobic exercise in type 1 diabetes. Diabetes Care. 2003; 26: 1316–7.
23. Moore LJ, Midgley AW, Thomas G, Thurlow S, McNaughton LR. The effects of low- and high-glycemic index meals on time trial performance. Int J Sports Physiol Perform. 2009; 4 (3): 331–44.
24. Nansel TR, Gellar L, McGill A. Effect of varying glycemic index meals on blood glucose control assessed with continuous glucose monitoring in youth with type 1 diabetes on basal-bolus insulin regimens. Diabetes Care. 2008; 31: 695–7.
25. Perrone C, Laitano O, Mayer F. Effect of carbohydrate ingestion on the glycemic response to type 1 diabetic adolescents during exercise. Diabetes Care. 2005; 28: 2537–8.
26. Perry E, Gallen IW. Guidelines on the current best practice for the management of type 1 diabetes, sport and exercise. Prac Diab Intl. 2009; 26: 116–23.
27. Plank J, Wutte A, Brunner G, et al.. A direct comparison of insulin aspart and insulin lispro in patients with type 1 diabetes. Diabetes Care. 2002; 25: 2053–7.
28. Rabasa-Lhoret R, Bourque J, Ducros F, Chiasson J. Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus insulin regimen (Ultralente-Lispro). Diabetes Care. 2001; 24: 625–30.
29. Ramires PR, Forjaz CL, Strunz CM, et al.. Oral glucose ingestion increases endurance capacity in normal and diabetic (type I) humans. J Appl Physiol. 1997; 83 (2): 608–14.
30. Rasmussen BB, Holmback UC, Volpi E, Lindore BM, Paddon-Jones D, Wolfe RR. Malonyl coenzyme A and the regulation of functional carnitinepalmitoyltransferase-1 activity and fat oxidation in human skeletal muscle. J Clin Invest. 2002; 110: 1687–93.
31. Riddell MC, Iscoe K. Physical activity, sport and pediatric diabetes. Pediatr Diabetes. 2006; 7 (1): 60–70.
32. Sidossis LS, Gastaldelli A, Klein S, Wolfe RR. Regulation of plasma fatty acid oxidation during low- and high-intensity exercise. Am J Physiol. 1997; 272: 1065–70.
33. Southgate DAT. Digestion and metabolism of sugars. Am J Clin Nut. 1995; 62 (suppl): 203–11s.
34. Steppel JH, Horton ES. Exercise in the management of type 1 diabetes mellitus. Rev Endocr Metab Disord. 2003; 4: 355–60.
35. Stryer L. Biochemistry. 4th ed. Freeman Press; 1995. p. 570–2.
36. Thomas DE, Elliott EJ, Baur L. Low glycemic index or low glycemic load diets for overweight and obesity. Cochrane Database Sys Rev. 2007; 18: 1–38.
37. Tsalikian E, Maurus N, Beck RW, Janz KF, Chase HP. Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus. J Paediatr. 2005; 147: 528–34.
38. West D, Morton R, Stephens JW, Bain SC, Bracken RM. Effects of rapid-acting insulin reductions on post-exercise glycaemia in people with type 1 diabetes. J Sports Sci. 2010; 28 (7): 781–8.
39. West D, Morton R, Stephens JW, Bain SC, Bracken RM. Isomaltulose improves post-exercise glycemia by reducing CHO oxidation in T1DM. Med Sci Sports Exerc. 2011; 43 (2): 204–10.
40. West D, Stephens JW, Luzio S, et al.. A combined insulin reduction and carbohydrate feeding strategy 30 min before running best preserves blood glucose concentration after exercise through improved fuel oxidation in type 1 diabetes mellitus. J Sports Sci. 2011; 29 (3): 279–89.
41. Wong SH, Chen YJ, Fung WM, Morris JG. Effect of glycemic index meals on recovery and subsequent endurance capacity. Int J Sports Med. 2009; 30 (12): 898–905.
