Jenkins AB, Chisholm DJ, James DE, Ho. KY, Kraegen EW: Exercise-induced he- patic glucose output is precisely sensitive to the rate of systemic glucose ...
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Glycemic Responses to Exercise in IDDM After Simple and Complex Carbohydrate Supplementation cemic effects of carbohydrate supplements for exercise. Importantly, Nathan et al. (6) examined the glycemic responses during exercise in five intensively treated IDDM subjects with three different carbohydrate snacks but did not include glucose administration or a nonexercise conOBJECTIVE — Subjects with IDDM should take carbohydrate before exercise to avoid hy- trol. We felt it was of interest to compare poglycemia. However, there is little information on the glycemic effect of recommended supple- exercise and nonexercise responses bementation. This study is aimed to determine the glycemic effects of oral glucose or bread (30 g cause the absorption of solid complex carbohydrate) before 45 min of moderate exercise. carbohydrate foods such as bread could possibly be altered by decreases in gastroRESEARCH DESIGN A N D METHODS— Nine subjects with uncomplicated IDDM did 45 min of bicycle ergometer exercise at 60% Vo 2max in the morning before insulin injection intestinal motility (7) and blood (low (8) on three occasions: 1) with no carbohydrate supplement, 2) with 30 g glucose in water at —5 during exercise. Therefore, the aim of our study min, and 3) with 30 g carbohydrate as white bread with water at —20 min. The glycemic responses were determined. The glycemic responses to glucose and bread were also determined was to investigate the effects of two forms without exercise in six subjects. of carbohydrate supplement (liquid glucose and bread) on glycemia during exerRESULTS — Without carbohydrate, exercise caused a small fall (—1.2 ± 0.6 mmol/1, mean ± cise in IDDM subjects and to compare SH) in plasma glucose (PG). With either glucose or bread, PG rose (the change in plasma glucose these profiles with those in the resting relative to basal [APG] = 5.1 ± 0.8 and 2.6 ± 0.8, respectively). The rise was greater (P < 0.01) state. without exercise (APG = 6.9 ± 0.7 and 4.5 ± 0.7, respectively). During exercise, glucose increased PG levels more than bread increased glucose levels (P < 0.05). RESEARCH DESIGN A N D CONCLUSIONS — Before morning insulin injection, the fall in PG during moderate exer- METHODS— Exercise and resting cise in IDDM subjects is generally small or absent. The glycemic effects of complex carbohydrate studies were performed. Nine subjects are slightly less than glucose before exercise. Under these circumstances, the usually recom- with uncomplicated IDDM participated mended amount of carbohydrate tends to cause an unwanted elevation of PG; thus, IDDM in the exercise studies; six of these subsubjects should anticipate reducing or even omitting carbohydrate supplementation after mon- jects also took part in the resting studies. itoring their individual glycemic response. Clinical data are presented in Table 1. The nature, object, and possible risks involved in the studies were explained to each subne of the challenges in the manage- inhibiting hepatic glucose output; hence, ject, and informed consent was obtained. ment of IDDM is ensuring that in- a fall in blood glucose levels is likely. The research protocol was approved by dividuals are able to participate To lessen the risk of exercise- the St. Vincent's Hospital Research Ethics fully in the activities of their peers, includ- induced hypoglycemia in IDDM, current Committee. ing the ability to exercise safely. Hypogly- practice is to advise a reduction in insulin cemia during physical activity or in the dose before long-duration exercise or in- Protocol hours following is a well-recognized risk. crease preexercise carbohydrate intake All studies were performed in the mornAmong factors implicated in this phe- for short-duration activity. For unantici- ing after an overnight fast and before the nomenon are the inability to decrease cir- pated exercise, increasing preexercise car- subjects' morning insulin dose. Each subculating insulin levels during exercise and bohydrate is the only approach available ject was studied with exercise on three accelerated insulin absorption secondary (3-5). occasions: 1) after no supplementation to increased muscle blood flow during acWhile general guidelines are (control), 2) after complex carbohydrate tivity (1,2). These conditions promote available for IDDM patients, there is a rel- supplement, or 3) after simple carbohyhigh skeletal muscle glucose uptake while ative deficiency of knowledge on the gly- drate supplement. In the resting studies, subjects were studied twice after ]) complex carbohydrate or 2) simple carbohydrate. The studies for each individual I'rom the Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia. were performed at least 2 days apart in Address correspondence and reprint requests to D.J. Chisholm, FRACP, Garvan Institute of Medical random order. Each subject was blinded Research, Si. Vincent's Hospital, Sydney NSW 2010, Australia. to the order of studies until presentation. Received for publication 19 October 1995 and accepted in revised form 25 January 1996. Subjects were asked to maintain an idenPG, plasma glucose; APG, the change in plasma glucose relaiive to basal.
KARF.N SOO, BSC STUART M. FURLER, PHD KATHERINE SAMARAS, MB, BS
ARTHUR B.JENKINS, PHD LESLEY V. CAMPBELL, FRCP DONALD J. CHISHOLM, FRACP
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DIABIIIS CARE, VOLUME 19, NUMBER 6, JUNE 1996
575
Carbohydrate with exercise in IDDM
Table 1—Clinical data
Subject
Age (years)
1
40
2
30
3
IDDM duration (years)
Sex
BMI
M
22.3
1
M
21.7
22
6
F
24.4
4
24
21
M
23.3
5
16
1.5
M
21.1
6
17
4
M
22.3
7
24
5
M
21.6
8
29
10
M
23.4
9
30
9
M
24.8
concentrations were assayed by a doubleantibody radioimmunoassay, as previously described (14). Insulin antibodies were removed by precipitation with polyethylene glycol (15) to isolate free insulin.
Daily insulin dose 13 UR 14 UI 1UR 21 UI 12 UR 46 UI 48 UM 6UR 7UR 13 UI 32 UL 16 UR 52 UI 55 UR 35 UI 9UR 36 UI 30 UR 40 UI
Subjects ar 9 participated in both exercise and resting studies. UR, units regular insulin; UI, iects 1, 3, 4, 6, 8, and units isophane; UM, units premixed (30% regular insulin, 70% isophane); UL, units lente.
tical diet, exercise, and medication routine between the studies, especially on the day before each study. In subjects who regularly experienced relatively low fasting blood glucose levels, a 1- to 2-unit reduction in their evening intermediate acting insulin and/or increased food intake the evening before the studies were suggested to avoid having to abort the control study because of hypoglycemia. Such adjustments were maintained across the three studies. On the morning of each study, an intravenous catheter was inserted into an antecubital vein 20 min before exercise (t ~ — 20 min). Blood samples for analysis of basal plasma glucose and free insulin concentrations were taken at this time. In the non-control studies, 30 g of carbohydrate were ingested either as 80 ml of liquid glucose (followed immediately by 50 ml of water) at — 5 min or two slices of white bread (with 100 ml of water) at — 20 min (immediately after cannulation). The amount of complex carbohydrate and timing of ingestion is in accordance with current recommendations (3,9). The difference in timing of liquid glucose ingestion and bread was to adjust for the expected differences in timing of blood glucose elevation due to the different carbohydrate forms (10). After blood 576
sampling at 0 min, subjects exercised or remained at rest for 45 min, followed by a 60-min recovery period. Blood samples were taken at 15-min intervals during exercise or rest and during the recovery period. Exercise was at 50% heart rate maxreserve on an electrically braked upright cycle ergometer (Lode, Holland). The exercise intensity was estimated by the following formula: training heart rate = 0.5 (maximum heart rate — resting heart rate) + resting heart rate. Maximum heart rate = 220 — age in nonobese individuals (11,12). This intensity is approximately equal to 70% maximum heart rate or 60% Vo 2max (13). Exercise intensity was adjusted using a heart rate monitor (Polar Electro, Finland) to maintain the target heart rate. Blood glucose was measured immediately on a portable reflectance photometer (Reflolux S, Boehringer Mannheim, Germany) to ensure that hypoglycemia or severe hyperglycemia did not occur. Analytical methods Plasma glucose was determined by an automated immobilized glucose oxidase method (YSI 23A glucose analyzer, Yellow Springs, OH). Insulin and glucagon
Statistical analysis To isolate the response to carbohydrate and exercise, plasma glucose at each time point was expressed as the change in plasma glucose (PG) relative to basal (APG). The maximum (over the 45-min study period) of the plasma glucose excursion above or below basal (APGmax) was used to characterize and contrast the plasma glucose responses. For the exercise-only studies, APGmax was typically negative; for the meal studies, APGmax was positive. Data were analyzed using commercially available software (16). The APGmax values were initially examined for an overall effect of supplement type by a one-factor repeated measures analysis of variance. After a significant overall effect had been established, a series of post-hoc tests (Scheffe's) was used to investigate specific comparisons. The 2 X 2 data subset (n = 6), which included the four combinations of carbohydrate type (glucose versus bread) and activity state (rest versus exercise), was analyzed for differences using a two-factor analysis of variance. Unless stated otherwise, results are presented as mean ± SE. RESULTS— Each subject reached, then maintained his or her individual training heart rate for each of the three exercise periods (range 119-144, mean 132 ± 3 beats per minute). There were no significant differences in mean exercise workload between each exercise condition (control 71.3 ± 4.3 W, bread 73.3 ± 5.4 W, glucose 71.6 ± 5.1 W). Basal PG concentrations for the exercise and nonexercise studies are shown in Table 2. There were no significant differences between the exercise and resting studies or between carbohydrate supplement types. Mean APG for the exercise studies over time are shown in Fig. 1, and those for the resting studies are given in Fig. 2. There was a large variation in responses between subjects. For the exercise studies (Fig. 1), the range (n = 9) in APG at t = 45 min was -4.2-1.6, - 1 . 1 7.1, and 0.5-9.5 mmol/1 for no supplementation, bread supplementation, and
DIABETES CARE, VOLUME 19,
NUMBER 6, JUNE
1996
Soo and Associates
Table 2—Basal plasma glucose concentrations (mmol/l) No. supplement
Bread
Glucose
13.0 ± 1.5
11.8 ± 1.5 12.2 ± 1.8 12.0 ± 2 . 0
11.6 ± 1.7 12.7 ± 1.5 9.2 ± 1.7
lixercise lixercise Rest Data are mean ± SE.
6 (mmol/L
Study type
8 -|
12 Q.
10- • fasting o bread • glucose
feet was not significant (P = 0.08); the elevation of PG was sustained for the 60 min after exercise. There was no tendency toward an interactive effect between carbohydrate type and exercise (P = 0.92). The APGmax values at rest and exercise in those subjects (n = 6) who participated in both phases of the study are shown in Fig. 3. Basal free insulin levels for the exercise studies were 14 ± 3 mU/1. There was no significant correlation between the basal free insulin level and glycemic response. Glucagon levels in the exercise studies rose from a mean of 163 ± 17 to 175 ± 20 at 30 min and declined to 155 ± 22 (ng/1) by 105 min (60 min after completion of exercise); glucagon levels also did not correlate significantly with the glycemic response.
exercise
a
rest
T
4 -
a glucose supplementation, respectively. For the resting studies (Fig. 2), the corresponding ranges (n = 6) were 2.6-6.6 and 4.6-8.7 mmol/l for bread supplementation and glucose supplementation, respectively. No episodes of symptomatic hypoglycemia occurred during the exercise or resting studies. The lowest plasma glucose observed was 3.6 mmol/l, which occurred during the control exercise study of one subject. An overall difference (P < 0.0005) between groups for APGmax in the exercised state was established. Post-hoc testing showed that all groups differed from each other (control: —1.2 ± 0.6 mmol/l vs. bread: 2.6 ± 0.8 mmol/l vs. glucose: 5.1 :t 0.8 mmol/l; P < 0.05). Analysis of the ?. X 2 data subset (the four combinations of exercise state and carbohydrate type) indicated a significant lowering effect of exercise on PG (bread + exercise: 3.1 :t 1.1 mmol/l vs. bread + rest: 4.5 ± 0.7 mmol/l; glucose + exercise: 5.5 ± 0.5 mmol/l vs. glucose + rest: 6.9 ± 0.7 mmol/l; P < 0.01). Across exercised and nonexercised groups, there was a tendency for liquid glucose to produce a higher APGmax than bread, but with this analysis (and smaller group sizes), the ef-
•
0 -2 -
J• control
b
glucose
Figure 3—APG n i a x during exercise and rest for the control study and for each carbohydrate meal type. Results are expressed as mean ± SE for n r 6.
study has clarified the glycemic effects of two forms of carbohydrate supplement with exercise performed before the morning insulin injection. In addition, we compared the effects of carbohydrate intake before exercise with those in the resting state. The study of exercise before the morning insulin injection was undertaken because not only is this a time of day chosen by a number of IDDM subjects for exercise, but the different glycemic responses could be more easily differentiCONCLUSIONS— The glycemic re- ated without the confounding effects of a sponse to exercise in IDDM is expected to preceding meal. vary according to factors such as duration The first clinically important findand intensity of exercise, initial blood gluing was the variability of the APG in the cose level, and time since previous insulin control study. The mean fall in PG due to dose. Thus, formulating recommendaexercise in the fasted state was small, contions for insulin dose and carbohydrate sistent with previous research (17), but intake adjustment for exercise is clearly there was substantial variability in PG redifficult. Nevertheless, starting guidelines sponses, with a range in APG of —4.2-1 .6 need to be offered to patients who wish to by the completion of exercise. With no begin an exercise program, to which indisupplementation, PG decrements were vidual adjustments can be made. This observed in four out of the nine subjects (APG range: - 0 . 9 to -4.2 mmol/l). One subject's PG nadir was 3.6 mmol/l. 10o bread The risk of exercise-induced hy• glucose poglycemia has been reported as being 6H lowest in the morning before the morning insulin dose and breakfast because of the low circulating insulin levels at this time Q. < 2of day (18). Postprandial exercise, a time of higher insulin levels, commonly results oin PG levels below fasting (19) and can -2 result in hypoglycemia if measures to 30 60 90 120 counter the effect of exercise are omitted minutes Figure 2—APG relative to basal during the (17). However, we have shown that even resting studies. Sampling began at —20 min (bas- under fasting conditions in the morning, a al), and each point represents the change from this significant fall in PG can occur during acstarting value. Results arc expressed as mean ± tivity, carrying with it the risk of hypoglySEforn = 6 (0-45min)andn = 5 (45-105min). cemia. These results highlight the impor-
II
a.
