ostexercise Late-Onset Hypoglycemia in Insulin ... - Diabetes Care

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hypoglycemia occurred in 48 of ~300 diabetic type I patients who were ... hypoglycemia were not using significant amounts of insulin that peaked at night.
ostexercise Late-Onset Hypoglycemia in Insulin-Dependent Diabetic Patients MICHAEL J. M A C D O N A L D , MD

A new clinical entity that is prevalent in young type I (insulin-dependent) diabetic patients, postexercise late-onset (PEL) hypoglycemia, is described. A prospective case-finding study suggested that PEL hypoglycemia occurred in 48 of ~300 diabetic type I patients who were diagnosed as diabetic before age 20 yr and who were monitored for up to 2 yr. Typically, hypoglycemia was nocturnal and occurred 6—15 h after the completion of unusually strenuous exercise or play. In more than half the cases the hypoglycemia resulted in loss of consciousness or seizures and necessitated treatment with subcutaneous glucagon or intravenous glucose and/or attendance by a health professional. The hypoglycemia was not limited to patients in good or excellent metabolic control and often occurred after a single bout of exercise in patients unaccustomed to exercise or in athletic patients who were making the transition from an untrained to a trained state. Surprisingly, 12 of the patients who experienced nocturnal PEL hypoglycemia were not using significant amounts of insulin that peaked at night. Type I diabetic patients should be made aware of the possibility of PEL hypoglycemia to enable them to make adjustments in their management plans in anticipation of unusually strenuous exercise, so that they may attempt to minimize or avoid late-onset hypoglycemia. Diabetes Care 10:584—88, 1987

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lmost all diabetic individuals are aware of the effect of exercise on blood glucose and take precautions to prevent hypoglycemia during exercise. For this reason, and possibly because of some immediate hyperglycemic effect of strenuous exercise (1), hypoglycemia during exercise or 1-2 h after exercise seems to be relatively uncommon in diabetes. By contrast, in our clinic population, hypoglycemia occurring in patients 6-15 h after unusually strenuous exercise or play seems to be relatively common. Because the phenomenon of late-onset hypoglycemia after exercise or play does not seem to be widely recognized among physicians and is at best only mentioned in passing in the diabetes literature, a study was undertaken to learn more about the circumstances surrounding postexercise late-onset (PEL) hypoglycemia and to obtain a rough estimate of its prevalence in pediatric patients. A prospective 2-yr case study of 300 children and teenagers with type I (insulin-dependent) diabetes indicated that 48 of them experienced PEL hypoglycemia. The characteristics of these subjects and the situations associated with the episodes of hypoglycemia are briefly summarized, and precautions for minimizing or avoiding this type of hypoglycemia are mentioned. 584

SUBJECTS AND METHODS

In May 1982, a 2-yr prospective study of PEL hypoglycemia among ~300 type I diabetic patients who were diagnosed before age 20 yr and who attended the Pediatric Diabetes Clinic was begun. Most of the patients were seen every 3— 4 mo for routine care and were questioned about PEL hypoglycemia. PEL hypoglycemia was defined as hypoglycemia occurring >4 h after the end of exercise. The time of the onset of hypoglycemia was defined as the time it was noticed by the patient or someone else. Newly diagnosed patients, newly referred patients first seen during the 2-yr period, and patients who had been followed for many years were included in the study. Glycosylated hemoglobin (HbAj) was determined by ionexchange chromatography with a kit from Bio-Rad (Richmond, CA) by the University Hospital Clinical Laboratory. An HbA, value was measured in each patient within a few weeks of the episode(s) of PEL hypoglycemia. This value was compared with the mean (±SD) HbA] values obtained at 3- to 4-mo intervals and up to 2 yr before and/or after the episode of PEL hypoglycemia. The mean of 209 determinations in 35 nondiabetic subjects over 18 mo was 6.37 ± 0.52% (range 5.3-7.6%).

DIABETES CARE, VOL. 10 NO. 5, SEPTEMBER-OCTOBER 1987

POSTEXERCISE LATE-ONSET HYPOGLYCEMIA/M. J. M A C D O N A L D

Brief Case Histories Subject 2. This 9-yr-old boy (with diabetes of 4-mo duration) experienced low blood glucose on Mondays after Sundays on which he skied. This occurred three times in one winter. Blood glucose was usually normal or higher than normal during the day and evening on days when he skied. His usual daily insulin dose was 3 U regular and 6 U NPH insulin administered before breakfast and 1 U of each type of insulin before supper. However, on 1 day on which he went skiing, he received only 2 U regular and 4 U NPH insulin before breakfast, and the insulin doses usually given before supper were omitted. The next morning (Monday) at 0700 h, his blood glucose was slightly less than 40 mg/dl, and he experienced moderate symptoms of hypoglycemia, then became disoriented and briefly lost consciousness. Despite continuing to use the lower insulin doses and increasing food intake, his blood glucose remained ~40 mg/dl until evening. HbA, was 10.0% at the time of the hypoglycemia; this value was slightly lower than the mean (11.5 ± 1.2%, n = 8) of values obtained before and after the episodes of hypoglycemia. Subject 24. This 15-yr-old girl (with diabetes of 9-yr duration) became limp and unconscious and had a seizure at 0800 h after swimming vigorously (playing a tag game in the water) from 1900 to 2200 h the previous evening. She had even eaten much more than usual at a potluck dinner before swimming, and she snacked after swimming until midnight. She was taken to a hospital emergency ward, where she regained consciousness after receiving glucose intravenously. Her usual daily insulin dose included very little insulin given in the evening. At the time of the hypoglycemic episode, she was routinely using 34 U lente insulin before breakfast and 4 U lente insulin before supper (0.7 U • kg"1 body wt • day"1) and was not using short-acting insulin. Mean (±SD) HbA, at the time of the hypoglycemia was 10.2%, which was a typical value (10.3 ± 0.9, n = 7). Subject 41. This 4-yr-old boy was diagnosed as diabetic 10 mo before a severe hypoglycemic episode occurred during a vacation at a lake resort. On the day before the hypoglycemia, he was very active. In his parents' words, he "swam all day, would not come out of the water, ran around, and was very active." He weighed 15.7 kg, and his usual daily dose of insulin was 6.5 U NPH and 0.5 U regular insulin before breakfast and 4 U NPH insulin before supper. However, while on vacation, his insulin doses were lowered because of the expected increased activity. He received only 0.5 U regular and 4 U NPH insulin each morning and no insulin in the evening on the 3 days before the hypoglycemia occurred. On the morning after the exercise, he began convulsing intermittently at ~0430 h. He was given some orange juice and was taken to a hospital emergency ward, where his blood glucose was 43 mg/dl. He was given glucose intravenously. HbA, was 9.4% (mean ± SD 10.1 ± 0.7, n = 4). Subject 43. This 15-yr-old boy was diagnosed as diabetic at age 9 and had been using continuous subcutaneous insulin infusion (CSII) for 1 yr. The basal rate was 1.5 U/h with boluses of ~ 11 U for each meal and 3 U before the bedtime snack (1.2 U • kg"1 body wt • day"1). The boy began a pro-

gram of running 3 miles/day. After 5 days of this program, he experienced a severe hypoglycemic reaction at 0530 h, with loss of consciousness and convulsions. The hypoglycemia was treated with glucagon at home and then with glucose intravenously in a hospital emergency ward. There had been no change in his insulin plan, and there was a slight increase in food intake after the program of running was started. HbA, was 9.2%, compared to a mean value of 9.8 ± 0.9% (n = 9). RESULTS

Forty-eight out of ~300 patients monitored for 2 yr reported moderately severe or severe PEL hypoglycemia. Table 1 shows various characteristics of these patients and some of the circumstances surrounding the hypoglycemia. Hypoglycemia occurred 3-31 h after the end of exercise (mean ± SD 9.9 ± 3.7 h, excluding the 31-h value). Most of the patients had hypoglycemia between 6 and 15 h after exercise. Eighteen patients had 2-5 episodes of hypoglycemia, and one patient had >10 episodes, possibly due to her erratic pattern of exercise. The hypoglycemia was defined as severe if a patient lost consciousness, had a seizure, was taken to an emergency ward, or was given glucose intravenously. According to these criteria, 32 patients had severe hypoglycemia. Sixteen subjects were classified as having experienced moderately severe hypoglycemia characterized by weakness, shakiness, disorientation, mild confusion, and/or a headache. In four of these cases, there was near loss of consciousness, and glucagon administration was thought to be necessary. The age range of the patients (4-24 yr) reflected that of a pediatric diabetes clinic population. Duration of diabetes ranged from 1 mo to 12 yr. The total daily insulin dose ranged from 0.2 to 2.0 U/kg body wt and did not appear to be excessive for any patient based on age, size, pubertal status, or duration of diabetes. Thirty-two of the patients used regular insulin in combination with NPH or lente insulin and injected the insulin before both breakfast and supper. Three of the patients used CSII via an insulin pump. Two patients used ^ 3 insulin injections/day. Interestingly, 11 of the patients routinely used insulin plans that provided little or no coverage with exogenous insulin in the evening and at night. Each of these patients experienced severe hypoglycemia between 0200 and 0800 h. Five of these 11 subjects used regular and NPH insulins only before breakfast, and 3 of them used both of these insulins at breakfast but only regular insulin before supper. One patient (subject 24) routinely used a large amount of lente insulin before breakfast and an insignificant amount of the same insulin before supper and did not use a short-acting insulin at all. Another patient used only NPH insulin before breakfast. Another patient usually received short- and intermediate-acting insulin before breakfast and supper. However, because he was vacationing with his family at a lake resort and was expected to be very active, he was given insulin only in the morning during the week in which PEL hypoglycemia occurred (subject 41).

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POSTEXERCISE LATE-ONSET HYPOGLYCEMIA/M. J. MACDONALD

TABLE 1 Summary of characteristics of 48 patients who experienced late-onset hypoglycemia after play or exercise Characteristic

Comments

Age (yr) Duration of diabetes (yr) Total daily insulin dose (U/kg body wt) Interval between end of exercise and hypoglycemia (h) HbA, at time of hypoglycemia (%) Sex distribution Time of day exercise ended Time of day of hypoglycemia

Mean ± SD 12.15 ± 4.67, median 13, range 4-24 Mean ± SD 5.1 ± 3.7, median 5, range 0.1-14Mean ± SD 0.98 ± 0.37, median 0.9, range 0.2-2.0 Mean ± SD 9.9 ± 3.7, median 11, range 3-31 Mean ± SD 9.9 ± 1.5 (n = 46), median 9.9, range 6.9-14.2 26 boys, 22 girls Between 1500 and 2000 h (n = 47) Between 2000 h and midnight in 10 patients, between 0100 and 0800 h in 36 patients, and after 0800 h in 2 patients Moderate in 16 patients; stupor, coma, and/or seizure in 32 patients 22 patients received glucagon, 17 were treated in a hospital emergency room, and 11 received intravenous glucose Vigorous playing (15), basketball (6), swimming (6), running (5), bicycling (4), roller or ice skating (4), skiing (2), dancing (2), football (2), garden work (2), walking (2), hiking (2), sledding (1), baseball (1), cutting wood (1), ice fishing (1), jumping rope (1), shoveling snow (1), riding a horse (1), calisthenics (1), sailing (1), and tennis (1); many activities were combined with others 32 patients used morning and evening short- and intermediate-acting insulin, 11 patients used little or no evening and night insulin coverage, 3 patients used subcutaneous insulin infusion, and 2 patients used S3 injections/day Recent improvement in metabolic control or tight control did not explain hypoglycemia; HbA, was judged as excellent (