the study population consisted of 11 male type 1 diabetic patients ( mean  sem ; age 24  2 years , bmi 22.6  0.6 , duration of diabetes 15  2 years , hba1c 7.7  0.3% , 61  3.4 mmol / mol , vo2peak 53  1 ml  kg  min ) .
patients were eligible for inclusion if they were between 18 and 35 years of age with a duration of diabetes > 2 years on enrollment .
patients were treated with a stable basal - bolus insulin regimen composed of either insulin glargine ( n = 8) or detemir ( n = 3 ) and fast - acting insulin analogs aspart ( n = 10 ) or lispro ( n = 1 ) for a minimum of 6 months .
patients were regularly and consistently active ( participating in aerobic - based exercise for at least 30 min at a time , three times per week ) , free of diabetes - related complications , including hypoglycemia unawareness , and receiving no additional medication other than insulin .
patients attended a preliminary screening visit , in which a comprehensive medical history and physical examination wasconducted .
additionally , patients completed a cardiopulmonary exercise stress test to assess cardiac function in response to exercise .
all screening procedures complied with american college of sports medicine ( acsm ) guidelines for exercise testing and prescription ( 23 ) .
eligible patients underwent randomization by a computer program to determine the sequence of three crossover arms .
peak cardiorespiratory parameters were collected during the completion of an incremental - maximal treadmill run protocol ( 11,12 ) .
the treadmill run started at a velocity of 8 km  h and increased 1 km  h every 3 min to volitional exhaustion , as per west et al .
anthropometric variables were also collected ( body mass , stature , and bmi ) . visits 2 , 3 , and 4 were experimental trials .
patients were fitted with a continuous glucose monitoring system ( cgms ; ipro2 , medtronic diabetes , northridge , ca ) a minimum of 24 h before attending the laboratory and replicated their diet and activity patterns for 24 h prior to main trials .
the ipro2 ( medtronic diabetes , northridge , ca ) system consists of a needle - like sensor that is inserted into subcutaneous tissue .
sensor readings are obtained and stored in the memory of the monitor , which is attached to the indwelling sensor .
patients wore enlite sensors ( medtronic minimed , northridge , ca ) , which were placed in the postural - lateral abdominal region to minimize the physiological time lags between blood and interstitial glucose ( 24 ) .
the sensor was inserted 24 h prior to each main trial , with the site of insertion replicated between trials .
sensors were removed 24 h after leaving the laboratory . during sensor wear , patients self - recorded capillary blood glucose concentrations at least four times per day for calibration purposes using a testing meter ( glucomen lx ; menarini diagnostics , berkshire , u.k . ) .
sensor data were retrospectively processed using carelink ipro software ( medtronic diabetes ) and ipro2 retrospective algorithm ( medtronic diabetes ) calibration routines .
patients arrived at the laboratory after an overnight fast , having replicated their diet in the previous 24 h ( assessed using weighed dietary recording sheets ) .
additionally , patients were instructed to maintain their normal insulin regimen , with basal insulin dose standardized ( dose , injection site , and time of injection ) across trials .
, hoofddorp , the netherlands ) , which they were instructed to wear in the previous 24 h. patients were required to avoid strenuous activity in the previous 48 h and maintain similar activity patterns between trials .
all main trials were conducted on a morning ( 08:00 a.m. ) , with a minimum of 7 days between trials ; patients replicated their trial start time across conditions .
after arrival to the laboratory , patients were seated while a 20-gauge cannula ( vasofix ; b. braun melsungen ag , melsungen , germany ) was inserted into the antecubital vein of their nondominant arm .
a 6-ml resting venous blood sample was taken , of which 20 l was used for the immediate quantification of glucose and lactate ( biosen c - line ; ekf diagnostic gmbh , london , u.k . ) and 10 l was analyzed for hemoglobin and hematocrit ( hemo control ; ekf diagnostic gmbh ) , which was used to correct for changes in plasma volume ( 25 ) .
venous blood ( 5 ml ) was collected in a serum separation tube that was centrifuged for 15 min at 3,000 rev  min and stored at 80c for later analysis of rapid - acting insulin ( invitron insulin assay ; invitron , monmouth u.k . ) and -hydroxybutyrate ( ranbut ; randox laboratories , london , u.k . ) .
rapid - acting insulin was measured in patients using basal insulin glargine only . immediately after this sample , patients administered a 25% ( 1.8  0.1 iu ) dose ( i.e. , a 75% reduction ) of rapid - acting insulin into the abdomen , as recommended by rabasa - lhoret et al .
all patients were familiar with carbohydrate counting and were administering 1.0  0.1 iu of rapid - acting insulin per 10 g of carbohydrate .
the injection site was standardized across trials through administration at half the distance between the anterior - superior iliac crest and the naval .
insulin aspart and lispro were administered using novopen3 ( novonordisk , bagsvaerd , denmark ) and humapen luxura ( eli lilly , london , u.k . ) , respectively .
after administration of the reduced rapid - acting insulin dose , patients consumed a cereal - based breakfast meal ( frosted flakes , semiskimmed milk , and peaches ) equating to 1 g carbohydrate  kg bm ( 380  10 kcal ) within a 5-min period .
after consuming breakfast , patients remained rested , with blood samples collected at 30 and 60 min after the ingestion of the meal .
sixty minutes after breakfast , patients performed 45 min of steady - state treadmill ( woodway , weil am rhein , germany ) running at 72.5  0.9% vo2peak , an intensity that falls within the recommendations of acsm ( 23 ) for exercising individuals with diabetes .
breath - by - breath respiratory parameters ( metalyzer 3b ; cortex , leipzig , germany ) and heart rate ( s810 ; polar , kempele , finland ) were continuously recorded throughout exercise .
after the cessation of exercise , blood samples were collected at 0 , 5 , 15 , 30 , and 60 min postexercise . at 60 min postexercise , in a randomized and counter - balanced fashion , patients administered a full ( 7.5  0.3 iu ) , 75% ( 5.6  0.2 iu ) , or 50% ( 3.7  0.1 iu ) rapid - acting insulin dose , which was injected into the contralateral abdominal site to the pre - exercise , rapid - acting insulin dose .
patients then consumed a pasta - based lunch meal ( pasta , tomato - based sauce , cheddar cheese ) , equating to 1 g carbohydrate  kg bm ( 660  21 kcal ) , and then remained at rest for 180 min postmeal .
blood samples were collected every 30 min throughout the postmeal period ; patients could drink water ad libitum .
hypoglycemia was defined as a blood or interstitial glucose concentrations of 3.9 mmol  l ( 15 ) .
if patients experienced hypoglycemia during the laboratory period , a 20-g carbohydrate bolus was administered ( lucozade ; glaxosmithkline , middlesex , u.k . ) . during cgms
wear , patients were required to replicate their diet across trials through the use of a weighed food diary . dietary intake and insulin administration was self - recorded , with patients required to indicate if additional carbohydrate intake had been ingested to correct falling blood glucose .
patients were required to keep meal times and rapid - acting insulin dose consistent across trials .
patients continued to record a minimum of four capillary blood glucose concentrations daily for cgms calibration .
statistical analysis was performed using pasw statistics software ( ibm pasw version 18 ; ibm , armonk , ny ) .
a repeated - measures anova on three levels ( condition  time ) was conducted , with bonferroni - corrected pairwise comparisons and paired samples student t test used to examine time and treatment effects , respectively .
area under the curve was calculated using the methods described by wolever and jenkins ( 26 ) .
the study population consisted of 11 male type 1 diabetic patients ( mean  sem ; age 24  2 years , bmi 22.6  0.6 , duration of diabetes 15  2 years , hba1c 7.7  0.3% , 61  3.4 mmol / mol , vo2peak 53  1 ml  kg  min ) .
patients were eligible for inclusion if they were between 18 and 35 years of age with a duration of diabetes > 2 years on enrollment .
patients were treated with a stable basal - bolus insulin regimen composed of either insulin glargine ( n = 8) or detemir ( n = 3 ) and fast - acting insulin analogs aspart ( n = 10 ) or lispro ( n = 1 ) for a minimum of 6 months .
patients were regularly and consistently active ( participating in aerobic - based exercise for at least 30 min at a time , three times per week ) , free of diabetes - related complications , including hypoglycemia unawareness , and receiving no additional medication other than insulin .
patients attended a preliminary screening visit , in which a comprehensive medical history and physical examination wasconducted .
additionally , patients completed a cardiopulmonary exercise stress test to assess cardiac function in response to exercise .
all screening procedures complied with american college of sports medicine ( acsm ) guidelines for exercise testing and prescription ( 23 ) .
eligible patients underwent randomization by a computer program to determine the sequence of three crossover arms .
peak cardiorespiratory parameters were collected during the completion of an incremental - maximal treadmill run protocol ( 11,12 ) .
the treadmill run started at a velocity of 8 km  h and increased 1 km  h every 3 min to volitional exhaustion , as per west et al .
anthropometric variables were also collected ( body mass , stature , and bmi ) . visits 2 , 3 , and 4 were experimental trials .
patients were fitted with a continuous glucose monitoring system ( cgms ; ipro2 , medtronic diabetes , northridge , ca ) a minimum of 24 h before attending the laboratory and replicated their diet and activity patterns for 24 h prior to main trials .
the ipro2 ( medtronic diabetes , northridge , ca ) system consists of a needle - like sensor that is inserted into subcutaneous tissue .
sensor readings are obtained and stored in the memory of the monitor , which is attached to the indwelling sensor .
patients wore enlite sensors ( medtronic minimed , northridge , ca ) , which were placed in the postural - lateral abdominal region to minimize the physiological time lags between blood and interstitial glucose ( 24 ) . the sensor was inserted 24 h prior to each main trial , with the site of insertion replicated between trials .
wear , patients self - recorded capillary blood glucose concentrations at least four times per day for calibration purposes using a testing meter ( glucomen lx ; menarini diagnostics , berkshire , u.k . ) .
sensor data were retrospectively processed using carelink ipro software ( medtronic diabetes ) and ipro2 retrospective algorithm ( medtronic diabetes ) calibration routines .
patients arrived at the laboratory after an overnight fast , having replicated their diet in the previous 24 h ( assessed using weighed dietary recording sheets ) .
additionally , patients were instructed to maintain their normal insulin regimen , with basal insulin dose standardized ( dose , injection site , and time of injection ) across trials .
, hoofddorp , the netherlands ) , which they were instructed to wear in the previous 24 h. patients were required to avoid strenuous activity in the previous 48 h and maintain similar activity patterns between trials .
all main trials were conducted on a morning ( 08:00 a.m. ) , with a minimum of 7 days between trials ; patients replicated their trial start time across conditions .
after arrival to the laboratory , patients were seated while a 20-gauge cannula ( vasofix ; b. braun melsungen ag , melsungen , germany ) was inserted into the antecubital vein of their nondominant arm .
a 6-ml resting venous blood sample was taken , of which 20 l was used for the immediate quantification of glucose and lactate ( biosen c - line ; ekf diagnostic gmbh , london , u.k . ) and 10 l was analyzed for hemoglobin and hematocrit ( hemo control ; ekf diagnostic gmbh ) , which was used to correct for changes in plasma volume ( 25 ) .
venous blood ( 5 ml ) was collected in a serum separation tube that was centrifuged for 15 min at 3,000 rev  min and stored at 80c for later analysis of rapid - acting insulin ( invitron insulin assay ; invitron , monmouth u.k . ) and -hydroxybutyrate ( ranbut ; randox laboratories , london , u.k . ) .
rapid - acting insulin was measured in patients using basal insulin glargine only . immediately after this sample
, patients administered a 25% ( 1.8  0.1 iu ) dose ( i.e. , a 75% reduction ) of rapid - acting insulin into the abdomen , as recommended by rabasa - lhoret et al .
all patients were familiar with carbohydrate counting and were administering 1.0  0.1 iu of rapid - acting insulin per 10 g of carbohydrate .
the injection site was standardized across trials through administration at half the distance between the anterior - superior iliac crest and the naval .
insulin aspart and lispro were administered using novopen3 ( novonordisk , bagsvaerd , denmark ) and humapen luxura ( eli lilly , london , u.k . ) , respectively .
after administration of the reduced rapid - acting insulin dose , patients consumed a cereal - based breakfast meal ( frosted flakes , semiskimmed milk , and peaches ) equating to 1 g carbohydrate  kg bm ( 380  10 kcal ) within a 5-min period . after consuming breakfast , patients remained rested , with blood samples collected at 30 and 60 min after the ingestion of the meal .
sixty minutes after breakfast , patients performed 45 min of steady - state treadmill ( woodway , weil am rhein , germany ) running at 72.5  0.9% vo2peak , an intensity that falls within the recommendations of acsm ( 23 ) for exercising individuals with diabetes .
breath - by - breath respiratory parameters ( metalyzer 3b ; cortex , leipzig , germany ) and heart rate ( s810 ; polar , kempele , finland ) were continuously recorded throughout exercise .
after the cessation of exercise , blood samples were collected at 0 , 5 , 15 , 30 , and 60 min postexercise . at 60 min postexercise , in a randomized and counter - balanced fashion , patients administered a full ( 7.5  0.3 iu ) , 75% ( 5.6  0.2 iu ) , or 50% ( 3.7  0.1 iu ) rapid - acting insulin dose , which was injected into the contralateral abdominal site to the pre - exercise , rapid - acting insulin dose .
patients then consumed a pasta - based lunch meal ( pasta , tomato - based sauce , cheddar cheese ) , equating to 1 g carbohydrate  kg bm ( 660  21 kcal ) , and then remained at rest for 180 min postmeal .
blood samples were collected every 30 min throughout the postmeal period ; patients could drink water ad libitum .
hypoglycemia was defined as a blood or interstitial glucose concentrations of 3.9 mmol  l ( 15 ) .
if patients experienced hypoglycemia during the laboratory period , a 20-g carbohydrate bolus was administered ( lucozade ; glaxosmithkline , middlesex , u.k . ) .
during cgms wear , patients were required to replicate their diet across trials through the use of a weighed food diary . dietary intake and insulin administration was self - recorded , with patients required to indicate if additional carbohydrate intake had been ingested to correct falling blood glucose .
patients were required to keep meal times and rapid - acting insulin dose consistent across trials .
patients continued to record a minimum of four capillary blood glucose concentrations daily for cgms calibration .
statistical analysis was performed using pasw statistics software ( ibm pasw version 18 ; ibm , armonk , ny ) .
a repeated - measures anova on three levels ( condition  time ) was conducted , with bonferroni - corrected pairwise comparisons and paired samples student t test used to examine time and treatment effects , respectively .
area under the curve was calculated using the methods described by wolever and jenkins ( 26 ) .
patients displayed similar glycemic control during the 24 h before arriving to the laboratory , with similar mean ( full , 8.6  0.4 ; 75% , 7.7  0.5 ; 50% , 8.1  0.6 mmol  l ; p = 0.451 ) and total interstitial glucose area under the curve ( full , 12,389  705 ; 75% , 10,986  765 ; 50% ,
11,385  791 mmol  l  min ; p = 0.400 ) across trials . during this time , dietary patterns were similar , with no differences in total energy intake ( full , 2,249  110 ; 5% , 2,290  178 ; 50% , 2,130  128 kcal ; p = 0.750 ) , with percentage contribution from carbohydrate ( full , 52  3 ; 75% , 49  4 ; 50% , 49  4% ; p = 0.844 ) , fat ( full , 29  3 ; 75% , 30  3 ; 50% , 33  3% ; p = 0.958 ) , and protein ( full , 18  2 ; 75% , 21  3 ; 50% , 18  2% ; p = 0.843 ) similar between conditions .
no differences were observed in activity patterns with similar total steps recorded across conditions ( full , 7,507  124 ; 75% , 8,028  119 ; 50% , 8,056  138 steps ; p = 0.627 ) .
1 . there was a significant time effect ( p < 0.001 , partial- = 0.643 ) and a significant condition  time interaction for absolute blood glucose concentrations ( p < 0.001 , partial- = 0.290 ) .
fasting blood glucose concentrations were similar between conditions ( full , 7.2  0.9 ; 75% , 7.1  0.7 ; 50% , 7.1  0.6 mmol  l ; p = 0.594 ) .
after the ingestion of the breakfast meal and reduced rapid - acting insulin dose , blood glucose peaked at 60 min and was similar across conditions ( fig .
there were no differences in fasting serum insulin ( p = 0.989 ) or -hydroxybutyrate ( p = 0.962 ) concentrations across conditions ( table 1 ) .
pre - exercise serum insulin and -hydroxybutyrate responses were similar across conditions ( p > 0.05 ) ( table 1 ) .
transparent sample point within a condition indicates significant difference from premeal concentrations ( p  0.05 ) . *
significantly different from full ( p  0.05 ) ; * * significantly different from full and 75% ( p  0.05 ) .
note that test meal and insulin were administered immediately after rest and 60-min postexercise sample points .
serum insulin and -hydroxybutyrate responses during the trials there were no differences in exercising rates of % vo2peak ( full , 73.8  0.01 ; 75% , 72.8  0.01 ; 50% , 70.8  0.01% ; p = 0.575 ) or peak heart rate ( full , 80  2 ; 75% , 79  3 ; 50% , 79  1% ; p = 0.631 ) .
the decline in blood glucose with exercise was similar across conditions ( full ,  = 6.8  0.03 ; 75% ,  = 6.9  0.03 ; 50% ,  = 6.2  0.03 mmol  l ; p = 0.891 ) ; moreover , patients elicited similar peak lactates immediately postexercise ( full , 3.7  0.6 ; 75% , 3.8  0.5 ; 50% , 3.7  0.5 mmol  l ; p = 0.965 ) .
there were no incidences of hypoglycemia during exercise , with all patients completing the exercise protocol on each occasion .
after the postexercise meal and rapid - acting insulin dose , total serum insulin area under the curve was significantly lower under 50% ( 21,748  4,799
pmol  l  min , p = 0.004 ) and 75% ( 33,351  5,634
individual peak serum insulin concentrations were lowest under 50% ( 83  29 pmol  l  min ) compared with 75% ( 196  42 pmol  l  min , p = 0.017 ) and full ( 229  44 pmol  l  min , p = 0.020 ) .
blood glucose concentrations decreased under full and 75% ; however , under 50% , blood glucose was preserved , eliciting similar concentrations to premeal ( fig .
1 ) . during this time , five patients experienced hypoglycemia under full and two under 75% , whereas under 50% , all patients were protected .
furthermore , some participants experienced multiple bouts of hypoglycemia , with total episodes across each trial greatest under full ( full , n = 9 ; 75% , n = 6 ; 50% , n = 0 ) . on average , blood glucose concentrations were 2.8  0.2 mmol  l before receiving carbohydrate supplementation . upon leaving the laboratory on 180 min postmeal ,
blood glucose concentrations were greater under 50% when compared with full and 75% ( fig .
1 ) . there were no conditional differences in blood lactate responses ( p = 0.996 ) or serum -hydroxybutyrate ( p = 0.076 ) ( table 1 ) .
50% prevented hypoglycemia for a further 4 h , meaning the first hypoglycemic episode under 50% occurred at 8 h postexercise . during the evening ( fig .
2 ) , total interstitial glucose area under the curve was significantly greater under 50% ( 2,709  245 mmol  l  min ) when compared with full ( 1,706  247 mmol  l  min , p <
0.001 ) and 75% ( 1,860  244 mmol  l  min , p < 0.001 ) .
data presented as mean ( sem error bars have been removed for reader clarity ) .
black line , full ; blue line , 75% ; red line , 50% . *
* interstitial glucose area under the curve is significantly different from full and 75% ( p  0.05 ) .
vertical dashed line breaks indicate evening , nocturnal , or morning periods . by 9 h postexercise ,
glycemia under 50% had decreased over time , with concentrations lower than those elicited upon leaving the laboratory ( fig .
interstitial glucose concentrations became comparable across conditions and were lowest during the night ( fig .
all patients experiencing hypoglycemia during the laboratory period also experienced further hypoglycemic episodes during sleep .
the total number of hypoglycemic episodes during the postlaboratory phase was lowest under 50% ( table 2 ) .
of the total hypoglycemic episodes across all trials , 82% occurred nocturnally ( table 2 ) .
additionally , the number of patients who self - corrected blood glucose to prevent further declines in glycemia was less under 50%
( n = 2 ) when compared with 75% ( n = 6 ) and full ( n = 6 ) .
the total number of patients experiencing hypoglycemia and the total number of hypoglycemic episodes during the postlaboratory period during the postlaboratory period , total energy consumed ( full , 1,588  234 ; 75% , 1,769  275 ; 50% , 1,731  141 kcal ; p = 0.836 ) , with contribution from carbohydrate ( full , 55  4 ; 75% , 47  5 ;
50% , 48  4% ; p = 0.516 ) , fat ( full , 30  4 ; 75% , 31  4 ; 50% , 34  4% ; p = 0.916 ) , and protein ( full , 16  2 ; 75% , 22  6 ; 50% , 18  2% ; p = 0.827 ) , was similar between conditions .
moreover , there were no differences in the total amount of insulin administered or in the insulin to carbohydrate ratio ( p > 0.05 ) .
no differences were observed in activity patterns during the 24-h postexercise period , with similar steps recorded ( full , 5,341  95 ; 75% , 4,786  87 ; 50% , 5,543  108 steps ; p = 0.877 ) across conditions .
patients displayed similar glycemic control during the 24 h before arriving to the laboratory , with similar mean ( full , 8.6  0.4 ; 75% , 7.7  0.5 ; 50% , 8.1  0.6 mmol  l ; p = 0.451 ) and total interstitial glucose area under the curve ( full , 12,389  705 ; 75% , 10,986  765 ; 50% ,
11,385  791 mmol  l  min ; p = 0.400 ) across trials . during this time , dietary patterns were similar , with no differences in total energy intake ( full , 2,249  110 ; 5% , 2,290  178 ; 50% , 2,130  128 kcal ; p = 0.750 ) , with percentage contribution from carbohydrate ( full , 52  3 ; 75% , 49  4 ; 50% , 49  4% ; p = 0.844 ) , fat ( full , 29  3 ; 75% , 30  3 ; 50% , 33  3% ; p = 0.958 ) , and protein ( full , 18  2 ; 75% , 21  3 ; 50% , 18  2% ; p = 0.843 ) similar between conditions .
no differences were observed in activity patterns with similar total steps recorded across conditions ( full , 7,507  124 ; 75% , 8,028  119 ; 50% , 8,056  138 steps ; p = 0.627 ) .
1 . there was a significant time effect ( p < 0.001 , partial- = 0.643 ) and a significant condition  time interaction for absolute blood glucose concentrations ( p < 0.001 , partial- = 0.290 ) .
fasting blood glucose concentrations were similar between conditions ( full , 7.2  0.9 ; 75% , 7.1  0.7 ; 50% , 7.1  0.6 mmol  l ; p = 0.594 ) .
after the ingestion of the breakfast meal and reduced rapid - acting insulin dose , blood glucose peaked at 60 min and was similar across conditions ( fig .
there were no differences in fasting serum insulin ( p = 0.989 ) or -hydroxybutyrate ( p = 0.962 ) concentrations across conditions ( table 1 ) .
pre - exercise serum insulin and -hydroxybutyrate responses were similar across conditions ( p > 0.05 ) ( table 1 ) .
transparent sample point within a condition indicates significant difference from premeal concentrations ( p  0.05 ) . * significantly different from full ( p  0.05 ) ; * * significantly different from full and 75% ( p  0.05 ) .
thatched area indicates exercise , and vertical dashed line break indicates postexercise intervention . note that test meal and insulin were administered immediately after rest and 60-min postexercise sample points .
serum insulin and -hydroxybutyrate responses during the trials there were no differences in exercising rates of % vo2peak ( full , 73.8  0.01 ; 75% , 72.8  0.01 ; 50% , 70.8  0.01% ; p = 0.575 ) or peak heart rate ( full , 80  2 ; 75% , 79  3 ; 50% , 79  1% ; p = 0.631 ) .
the decline in blood glucose with exercise was similar across conditions ( full ,  = 6.8  0.03 ; 75% ,  = 6.9  0.03 ; 50% ,  = 6.2  0.03 mmol  l ; p = 0.891 ) ; moreover , patients elicited similar peak lactates immediately postexercise ( full , 3.7  0.6 ; 75% , 3.8  0.5 ; 50% , 3.7  0.5 mmol  l ; p = 0.965 ) .
there were no incidences of hypoglycemia during exercise , with all patients completing the exercise protocol on each occasion .
after the postexercise meal and rapid - acting insulin dose , total serum insulin area under the curve was significantly lower under 50% ( 21,748  4,799
pmol  l  min , p = 0.004 ) and 75% ( 33,351  5,634
individual peak serum insulin concentrations were lowest under 50% ( 83  29 pmol  l  min ) compared with 75% ( 196  42 pmol  l  min , p = 0.017 ) and full ( 229  44 pmol  l  min , p = 0.020 ) .
blood glucose concentrations decreased under full and 75% ; however , under 50% , blood glucose was preserved , eliciting similar concentrations to premeal ( fig .
1 ) . during this time , five patients experienced hypoglycemia under full and two under 75% , whereas under 50% , all patients were protected .
furthermore , some participants experienced multiple bouts of hypoglycemia , with total episodes across each trial greatest under full ( full , n = 9 ; 75% , n = 6 ; 50% , n = 0 ) . on average , blood glucose concentrations were 2.8  0.2 mmol  l before receiving carbohydrate supplementation . upon leaving the laboratory on 180 min postmeal ,
blood glucose concentrations were greater under 50% when compared with full and 75% ( fig .
1 ) . there were no conditional differences in blood lactate responses ( p = 0.996 ) or serum -hydroxybutyrate ( p = 0.076 ) ( table 1 ) .
50% prevented hypoglycemia for a further 4 h , meaning the first hypoglycemic episode under 50% occurred at 8 h postexercise . during the evening ( fig .
2 ) , total interstitial glucose area under the curve was significantly greater under 50% ( 2,709  245 mmol  l  min ) when compared with full ( 1,706  247 mmol  l  min , p <
0.001 ) and 75% ( 1,860  244 mmol  l  min , p < 0.001 ) .
data presented as mean ( sem error bars have been removed for reader clarity ) .
black line , full ; blue line , 75% ; red line , 50% . *
* interstitial glucose area under the curve is significantly different from full and 75% ( p  0.05 ) .
vertical dashed line breaks indicate evening , nocturnal , or morning periods . by 9 h postexercise ,
glycemia under 50% had decreased over time , with concentrations lower than those elicited upon leaving the laboratory ( fig .
, interstitial glucose concentrations became comparable across conditions and were lowest during the night ( fig .
all patients experiencing hypoglycemia during the laboratory period also experienced further hypoglycemic episodes during sleep .
the total number of hypoglycemic episodes during the postlaboratory phase was lowest under 50% ( table 2 ) . of the total hypoglycemic episodes across all trials
, 82% occurred nocturnally ( table 2 ) . additionally , the number of patients who self - corrected blood glucose to prevent further declines in glycemia was less under 50% ( n = 2 ) when compared with 75% ( n = 6 ) and full ( n = 6 ) . the total number of patients experiencing hypoglycemia and the total number of hypoglycemic episodes during the postlaboratory period during the postlaboratory period , total energy consumed ( full , 1,588  234 ; 75% , 1,769  275 ; 50% , 1,731  141 kcal ; p = 0.836 ) , with contribution from carbohydrate ( full , 55  4 ; 75% , 47
 5 ; 50% , 48  4% ; p = 0.516 ) , fat ( full , 30  4 ; 75% , 31  4 ; 50% , 34  4% ; p = 0.916 ) , and protein ( full , 16  2 ; 75% , 22  6 ; 50% , 18  2% ; p = 0.827 ) , was similar between conditions .
moreover , there were no differences in the total amount of insulin administered or in the insulin to carbohydrate ratio ( p > 0.05 ) .
no differences were observed in activity patterns during the 24-h postexercise period , with similar steps recorded ( full , 5,341  95 ; 75% , 4,786  87 ; 50% , 5,543  108 steps ; p = 0.877 ) across conditions .
the aim of this study was to examine the acute and 24-h glycemic responses to reductions in postexercise rapid - acting insulin dose , when the recommended pre - exercise insulin reductions were used , in patients with type 1 diabetes .
the results demonstrate that despite a large reduction in the pre - exercise , rapid - acting insulin dose , it is important that the postexercise dose is also heavily reduced .
we have demonstrated that a reduction in postexercise rapid - acting insulin of 50% best preserves glycemia and provides the greatest protection against hypoglycemia early after exercise ( 8 h ) .
however , beyond this time , this strategy becomes less effective . a potential mechanism explaining the late fall in glycemia could be the administration of further unchanged doses of rapid - acting insulin and/or unchanged circulating basal insulin concentrations during a second period of elevated glucose uptake ( 22 ) .
all patients completed a bout of moderate - intensity aerobic exercise ( 73% vo2peak ) , running at a velocity of 9.3  0.3 km  h and expending 708  16 kcal , with no incidences of hypoglycemia during exercise .
this complements the recommendations of prior literature ( 1012 ) and emphasizes the importance of reducing the rapid - acting insulin dose before exercise .
furthermore , patients were , on average , within euglycemic ranges for 60 min after exercise , suggesting this strategy exposes patients to only transient periods of hyperglycemia prior to exercise ( fig .
was best preserved with a 50% reduced rapid - acting insulin dose , which protected all patients from hypoglycemia throughout the postexercise meal period , whereas blood glucose concentrations declined under both full and 75% doses ( fig .
moderate - intensity running exercise requires a contribution from muscle glycogen ( 27,28 ) , of which the replenishment is of a high metabolic priority ( 21 ) , with muscle glycogen depletion suggested to have a role in the development of postexercise hypoglycemia ( 29 ) .
after exercise , glycogen synthesis is increased dramatically , thought to be driven primarily by depleted glycogen ( 30,31 ) , an upregulation of insulin signaling pathways ( 32 ) , and a prolonged increase in the permeability of the muscle cell membrane to glucose ( 33 ) .
taken together , an increased rate of glucose transport into the muscle and an increased capacity to convert glucose to glycogen results in a window where there is likely an increased potency of the administered rapid - acting insulin ( 34 ) . to suggest that the glycemic responses of our patients under full and 75% are solely due to depleted muscle glycogen stores is difficult , as large carbohydrate boluses ( 1.0 g carbohydrate  kg bm ) were ingested before and after exercise , which would have helped supplement glycogen reserves ( 21 ) .
however , additional explanations for why hypoglycemia was experienced during the full and 75% conditions may be that the administration of larger doses of rapid - acting insulin created a milieu of relative hyperinsulinemia , in turn suppressing hepatic glucose production and enhancing glucose uptake ( 34 ) , potentially into nonexercised tissue ( 27 ) .
irrespective of the mechanisms at play , we have demonstrated the importance of reducing the dose of rapid - acting insulin administered with the meal after exercise .
in contrast to current recommendations that advocate a reduction of 30% ( 35 ) , we found a 50% reduction was necessary to prevent falls in blood glucose early after exercise .
although serum -hydroxybutyrate throughout the postmeal period was , on average , greatest under 50% ( table 1 ) , these concentrations were of little clinical significance , with concentrations well below those deemed hyperketonemic ( > 1.0 mmol ) ( 36 ) . from a clinical viewpoint , a 50% reduction in rapid - acting insulin after exercise , when the pre - exercise dose was also heavily reduced , does not increase ketone body concentrations .
interstitial glucose concentrations revealed a preservation of glycemia under 50% for a further 4 h after leaving the laboratory , meaning patients had been protected against hypoglycemia for 8 h postexercise .
however , patients were exposed to hyperglycemia during this time . in comparison , glycemia during the evening ( between 4 and 9 h postexercise ) ( fig .
2 ) was significantly lower under both full and 75% conditions , with patients experiencing further hypoglycemic episodes under these conditions .
however , at 7 h postexercise , there was a decline in interstitial glucose concentrations under 50% , such that at 9 h postexercise , glycemia was similar between conditions .
patients replicated dietary habits ( i.e. , meal composition , time of consumption , and rapid - acting insulin dose ) , and their basal insulin regimen was standardized across trials .
type 1 diabetic patients face particular difficulty in avoiding hypoglycemia 711 h postexercise , as the requirement for glucose to maintain euglycemia is increased ( 26,37 ) .
considering that increased insulin sensitivity may persist for > 48 h after exercise , an additional strategy could be to reduce the basal insulin dose .
however , this strategy requires planning exercise in advance and offers little flexibility regarding the timing of exercise ; if unforeseen circumstances prevent planned exercise from taking place , the patient is likely to be exposed to prolonged periods of hyperglycemia ( 38 ) .
therefore , it may be more appropriate to further adjust the rapid - acting insulin dose during this time . of the total number of hypoglycemic episodes experienced across all trials during the postlaboratory period , 82% occurred nocturnally .
therefore , sleep may be a contributing factor to the increased incidence of hypoglycemia during the night ( 3 ) . as well as recent exercise ( 5 , 20 ) , antecedent hypoglycemia ( 6 ) may blunt symptomatic and autonomic responses to hypoglycemia later in the day , particularly during sleep ( 39 ) .
this is important , as those patients who experienced hypoglycemia in the laboratory eliciting blood glucose concentrations <3 mmol  l also experienced hypoglycemia again during sleep .
these data suggest that if patients experience hypoglycemia early after exercise , there is potential that they are at an increased risk of blood glucose falling again during the night .
although only 18% of patients experienced nocturnal hypoglycemia under 50% , the late fall in glycemia means the risk , albeit less , may still be present for patients despite the large reductions in pre- and postexercise rapid - acting insulin dose .
experiencing hypoglycemia during sleep is a real fear for type 1 diabetic patients ( 39 ) , which is likely to be exacerbated when exercise is performed during the day .
therefore , there is a need to further refine current exercise recommendations for type 1 diabetic patients such that patients can engage in regular exercise with a reduced risk , and fear , of postexercise nocturnal hypoglycemia .
sport and recreational activities vary greatly in terms of their physiological demands and metabolic responses .
the effects of changing the intensity , duration , or mode of exercise may therefore necessitate manipulating the rapid - acting insulin dose accordingly to account for these changes .
moreover , the feeding pattern used in this study ( 60 min before and after exercise ) may not be typical of the normal dietary habits of exercising patients .
worthy of note , the patients examined in this study were in good glycemic control ( hba1c 7.7  0.3% , 61  3.4 mmol / mol ) and had a good level of aerobic fitness ( vo2peak 53  1 ml  kg  min ) .
thus , there is potential that the glycemic response to pre- and postexercise rapid - acting insulin reductions may differ with patient age , fitness , and glycemic control .
although it was not possible to address these issues within this study , this should not detract from the clinical application of our findings . to our knowledge
, we are the first to investigate postexercise rapid - acting insulin dose reductions after running exercise in patients with type 1 diabetes , when using the recommended pre - exercise insulin dose reductions . we have demonstrated the importance of large reductions in the pre- and postexercise rapid - acting insulin dose in preserving glycemia early after exercise and , through investigation under free - living conditions , further highlight that the difficulties related to delayed and , in particular , nocturnal postexercise hypoglycemia are still existent despite the application of large rapid - acting insulin dose reductions before and after exercise .
therefore , future research should further investigate strategies to normalize glycemia in the late postexercise period , preventing late - onset hypoglycemia . in summary
, the results of the current study suggest that a 50% reduction in postexercise rapid - acting insulin dose , when combined with a large pre - exercise rapid - acting insulin reduction , preserves glycemia and prevents hypoglycemia for 8 h after exercise .
however , patients should be made aware that they may be exposed to periods of hyperglycemia , but not hyperketonemia , after the postexercise meal , and there is still a risk of developing late - onset hypoglycemia .
patients are therefore recommended to refine these strategies according to their own individual exercise routine and glycemic responses .
 objectiveto examine the acute and 24-h glycemic responses to reductions in postexercise rapid - acting insulin dose in type 1 diabetic patients.research design and methodsafter preliminary testing , 11 male patients ( 24  2 years , hba1c 7.7  0.3% ; 61  3.4 mmol / mol ) attended the laboratory on three mornings . 
 patients consumed a standardized breakfast ( 1 g carbohydrate  kg1 bm ; 380  10 kcal ) and self - administered a 25% rapid - acting insulin dose 60 min prior to performing 45 min of treadmill running at 72.5  0.9% vo2peak . at 60 min postexercise 
 , patients ingested a meal ( 1 g carbohydrate  kg1 bm ; 660  21 kcal ) and administered a full , 75% , or 50% rapid - acting insulin dose . 
 blood glucose concentrations were measured for 3 h postmeal . 
 interstitial glucose was recorded for 20 h after leaving the laboratory using a continuous glucose monitoring system.resultsall glycemic responses were similar across conditions up to 60 min postexercise . 
 after the postexercise meal , blood glucose was preserved under 50% , but declined under full and 75% . 
 thence at 3 h , blood glucose was highest under 50% ( 50% [ 10.4  1.2 ] vs. full [ 6.2  0.7 ] and 75% [ 7.6  1.2 mmol  l1 ] , p = 0.029 ) ; throughout this period , all patients were protected against hypoglycemia under 50% ( blood glucose 3.9 ; full , n = 5 ; 75% , n = 2 ; 50% , n = 0 ) . 
 fifty percent continued to protect patients against hypoglycemia for a further 4 h under free - living conditions . 
 however , late - evening and nocturnal glycemia were similar ; as a consequence , late - onset hypoglycemia was experienced under all conditions.conclusionsa 25% pre - exercise and 50% postexercise rapid - acting insulin dose preserves glycemia and protects patients against early - onset hypoglycemia ( 8 h ) 
 . however , this strategy does not protect against late - onset postexercise hypoglycemia . 
RESEARCH DESIGN AND METHODS
Patients
Prelaboratory phase
CGMS
Diet and activity replication
Testing procedure
Postlaboratory period
Data analysis
RESULTS
Prelaboratory phase
Laboratory phase
Postexercise intervention
Postlaboratory phase
CONCLUSIONS