Erika Bruck

Posthypoglycemic hyperglycemia in diabetic children.

Posthypoglycemic hyperglycemia was suspected in eight diabetic children who had excessive glycosuria while taking large doses of insulin. The cases of two brothers with diabetes since infancy are reported as examples. Rapid changes in levels of blood glucose with episodes of hypoglycemia were suspected; therefore glucose in blood was measured every half hour for 48 hours while the patients received their customary insulin dosage and diet. Urine was collected in two-hourly portions for measurements of glucose and tests for ketones. Hypoglycemic episodes were documented repeatedly. They lasted between one and 22 hours, occurred at varying times, and were usually followed by abrupt rises of blood sugar; blood sugar often rose or fell by 200 to 300 mg. per 100 ml. within two to four hours. Hyperglycemic phases lasted from several hours to several days. Conventional spot tests of urine and “fasting” or “postprandial” blood sugar values often failed to detect the hypoglycemia.

Acute Diabetic Ketoacidosis in Children: Role of the Stress Hormones

Summary: Twenty-five cases of acute ketoacidosis, occurring in insulin-treated diabetic children in previous good health, were studied close to the onset of illness and throughout the first 24 hr of therapy. In most patients, symptoms of illness and ketonuria had been present for less than 12 hr; in 9 subjects, they had been present for less than 4 hr. Initial plasma glucose concentrations ranged from 252 to 849 mg/dl. The first pH values in 21 cases were less than 7.27, and in the remaining 4 studies, the CO2 was less than 14 mEq/liter. Identifiable sources of stress, such as infections or emotional arousal, preceded the development of ketoacidosis in 20 cases.Serial measurements were made of plasma glucocorticoid, growth hormone, and glucagon concentrations as well as urinary excretion of epinephrine and norepinephrine to assess the role of these hormones in acute ketoacidosis and to evaluate their relationship to the abnormalities in glucose and electrolyte homeostasis. Excessive urinary excretion of epinephrine was a frequent and striking phenomenon. Output was greater than 4 S.D. above the mean in 20 of 23 cases in the first 2 hr of the study. In 15 cases, the values fell into the normal range by approximately 14.5 hr, but in seven patients, epinephrine overproduction persisted for the entire study. Cortisol hypersecretion was present in 24 of 25 patients and persisted for 6 to 8 hr or longer before gradually subsiding. Initial growth hormone concentrations were elevated in seven patients (20 ng/ml or above), but the highest values (20 to 160 ng/ml) were observed after insulin administration. At the outset, plasma glucagon concentrations were less than 200 pg/ml in 11 patients; in 11 others, it ranged between 250 and 1250 pg/ml. The elevated values usually were transient. Of 22 cases in whom all five hormones were measured at the start of the study, 21 exhibited increased production of at least three of the stress hormones.We conclude that some diabetic children who have received their usual dose of insulin develop hyperglycemia, dehydration, and acidosis within a few hr of experiencing stress because large amounts of counterregulatory hormones, especially catecholamines and cortisol, are released.Speculation: Acute onset of ketoacidosis in previously healthy insulin-treated diabetic children occurs because their daily dose of insulin is insufficient to offset the effects of the counterregulatory hormones produced in response to stress (catecholamines, cortisol, glucagon, and growth hormone). Hyperglycemia, dehydration, and acidosis result from the glycogenolytic, lipolytic, and ketogenic action of the stress hormones.

Interaction of Endogenous Growth Hormone, Cortisol, and Catecholamines with Blood Glucose in Children with Brittle Diabetes Mellitus

Extract: Hormonal balance was studied in eight insulin-treated diabetic children who had excessive glycosuria. Glucose, growth hormone, and cortisol in plasma were determined every 0.5 hr for 48 hr. Total catecholamines and glucose were measured and tests for ketones done in 2-hourly collections of urine.Intermittent hypoglycemia as low as 20 mg/100 ml and swings of the blood sugar curve by 200–300 mg/100 ml within 2–4 hr were documented in most patients.Peaks of growth hormone concentration in plasma (8–78 ng/ml) followed almost every sharp fall in blood glucose; these peaks were usually followed by abrupt rises of glucose and prolonged hyperglycemia.Cortisol concentration was usually within the high normal range; there was no consistent relationship to the concentration of glucose.Urinary excretion of catecholamines in most patients was between 1 and 6 μg/hr; three patients excreted up to 8–23 μg/hr during short periods and up to 190 μg in 24 hr. The causes for the high excretion of catecholamines are unknown and may not have included hypoglycemia.Speculation: Excessive production of growth hormone and possibly other hormonal antagonists of insulin may be provoked by hypoglycemia and other physiologic stresses in diabetic children. The resulting hyperglycemia may prompt the administration of increasing doses of insulin which, in turn, contribute to a vicious cycle of hypoglycemia alternating with hyperglycemia.

Water in expired air: Physiology and measurement

Summary The physiology of insensible water loss and the methods of measuring this loss are reviewed. Because of the multiple sources of potential artifacts, only few reliable data for total insensible loss are available in the literature, especially in that of the last 25 years. Values for insensible losses through skin and respiratory passages obtained from the literature since 1906 are tabulated. Those data which were obtained with reasonably precise methods, usually on healthy, well-nourished individuals under basal conditions, indicate that under these conditions the total insensible weight loss amounts to approximately 25 ml. per square meter of body surface per hour. This total insensible weight loss includes the weight of carbon dioxide produced minus that of oxygen consumed as well as the weight of water evaporated from the skin and respiratory passages. Between one third and one half of the total amount may represent water lost with the expired air. Water loss through respiration is thought to be determined by the volume of minute ventilation and by the temperature and humidity of inspired air, probably also by body temperature. Expired air has a lower temperature than the interior of the body and may or may not be saturated with water vapor at that temperature. Although low absolute humidity of the inspired air (e.g., in winter) would be expected to enhance the water loss through respiration, the available experimental data are not sufficient to evaluate the importance of this factor, especially in sick children. Respiratory water loss may vary greatly in pathologic conditions; such variations have been suspected as the cause of disturbances of the total water balance of the body but have not been measured accurately in children.

Water in expired air: II. Gravimetric determination of water content of timed and measured samples of expired air collected from infants and children***

Expired air is collected through a nasal valve. It is passed through a heat exchangerpacked in dry ice in which the water contained in the expired air is precipitated by freezing and can be measured by weighing. After passing through the heat exchanger, the expired air is collected in a polyvinyl bag, its volume and composition are then measured by classical methods. Timed collections are made over periods of a few minutes. The procedure is easily performed at the bedside and well tolerated by young infants and children.

Renal function studies in acute glomerulonephritis in children.

Summary 1. Acute glomerulonephritis resultsin disruption of the renal functional pattern. G.F.R. and F.F. are significantly reduced in the early stages of the disease, with few exceptions, and may remain so for several months, often after albumin and red blood cells have disappeared from the urine. 2. Functioning tubular mass, asmeasured by Tm pah , is considerably reduced in about half the patients. In an occasional patient with significantly reduced Tm pah the G.F.R. remains within normal limits, indicating a greater degree of tubular than glomerular dysfunction. 3. Hyperemia of the kidney tissueas measured by the R.P.F./Tm pah ratio was observed in those cases with a significantly reduced Tm pah . Ischemia of the kidney tissue as measured by a low value of the above ratio is not a part of the pattern of acute glomerulonephritis. It, therefore, does not appear to be a factor in the hypertension noted in half of our patients studied early in their disease. 4. With clinical recovery there is a return toward normal of renal function as measured by the tests used. Functional recovery is frequently delayed beyond clinical recovery.

Hormonal aspects of post-hypoglycemic hyperglcemia (Somogyieffect) in diabetie children

The cause of hyperglycemia and acetonuria which may alternate with hypoglycemia in diabetic children are poorly understood. To evaluate the hormaonla basis of the “Somogyi effect” in 3 “brittle” diabetic children, glucose, growth hormone (HGH) and cortisol levels in blood were measured hourly or half-hourly, and urinary catecholamine excretion in 2-hourly collections, for several 24–28 hour periods. Profound hypoglycemi (7–40 mg%) alternating with prolonged hyperglycemia was demonstrated at unpredictabel times, even though fasting glucose was normal or elevated. HGH levels increased sharply, sometimes to as much as 30–75 mμg/ml, with hypoglycemia or following every sharp fall in glucose, even when the latter remained in the hyperglycemic range. These peaks of HGH were usually followed by marked hyperglycemia. Plasma cortisol levels varied errastically without consistent relationship to glucose levels. Rises in catecholamine excretion (to 4–12 μg/hr) occurred following hypoglycemia and also independently of it, but did not always cause elevation of glucose. With gradual reduction of insulin dosage, the control of the diabetes improved, and in one patient who was profoundly stuporous, the mental state improved dramatically. These studies emphasize the importance of determining blood sugar concentration at frequent intervals since hypoglycemia may go unrecognized for years if the standard sampling times are adhered to. The hormonal data support the concept that growth hormone release in response to hypoglycemia in the diabetic is an important factor in producing hyperglycemia and insulin resistance.

Laboratory Tests in the Analysis of States of Dehydration

In an otherwise healthy child with acute dehydration known to be due to diarrhea or vomiting, the amount of deficit can best be estimated by accurate weight. Total serum protein and hematocrit provide a rough estimate of reduction in circulating blood volume, but calculation from these data will usually underestimate the deficit. Determination of urea nitrogen concentration helps to detect reduced glomerular filtration rate. Acid-base disturbances, most commonly metabolic acidosis, are detected by measuring pH and CO2 content (or base excess). Blood glucose should be measured to rule out diabetes mellitus, even in the absence of a suggestive history. Determination of potassium in serum is most important in the diagnosis of adrenal or renal insufficiency and in the post-acidotic phase after dehydration. Osmolality of body fluids is estimated by measuring [Na+]. Since osmolality of body fluids is normally maintained at the expense of fluid volume by the kidney and the hormones governing renal excretion of water and sodium, abnormal osmolality indicates a serious condition which has to be interpreted with the help of clinical data. In cases of abnormal renal function or of abnormal losses, as with removal of gastrointestinal fluids by suction, or excessive and prolonged diarrhea, measuring volume and composition of excreta may be essential. Because of cumulative deficits, patients with prolonged losses or inability to regulate oral intake by thirst cannot be treated without continual careful interpretation of the reports from a good laboratory.

STRESS HORMONES IN DIABETIC KETOACIDOSIS

The aim of this study was to define the role of “stress hormones” in the pathogenesis of acute diabetic ketoacidosis. Hourly plasma levels of glucose, growth hormone (GH), cortisol (C) and glucagon (G) and urinary norepinephrine (NE) and epinephrine (E) were measured for the first 24 hours in 20 children, ages 2-21 years who presented on 25 occasions with ketoacidosis of a few hours duration despite their usual insulin therapy.In 23/25 studies, E excretion was >4 S.D. (in 7 studies > 10 S.D.) above the normal mean during the first hour while NE was within or slightly above 2 S.D. of the normal mean in 21. Plasma C was above 25 μg/dl in 16/25 and often remained elevated for several hours. Ten patients with an initial C level > 40 μg/dl excreted > 1 μg/M2 of E (normal < 0.3) per hour. The mean admission GH was 13.7 ng/ml (range 1-39.6). It rose sharply after high or low dose insulin injections in 19/25. The mean peak for all patients was 34 ng/ml (range 6.7-160), independent of a fall of glucose. 7/20 cases had glucagon levels > 200 pg/ml on admission, 3 of these > 1000 pg/ml. No correlation was noted between initial G and any of the other hormones, including E.The data suggest endogenous E production in response to stress is the trigger event in acute ketoacidosis in insulin-treated Juvenile diabetics. High or inappropriate secretion of glucocorticoids, GH and glucagon also is present in many patients with this disorder.