Adrenergic Symptoms Research Articles

Suspected postprandial hypoglycemia is associated with beta-adrenergic hypersensitivity and emotional distress.

Suspected postprandial (reactive or idiopathic) hypoglycemia is characterized by predominantly adrenergic symptoms appearing after meals rich in carbohydrates and by their rare association with low blood glucose level (< 2.77 mmol/L). We studied heart rate, blood pressure, plasma insulin, C-peptide, and catecholamine responses during a 5-h oral glucose tolerance test in eight patients with suspected postprandial hypoglycemia and eight age-, sex-, and body mass index-matched healthy controls. We also evaluated beta-adrenergic sensitivity by using the isoproterenol sensitivity test. Psychological profile was assessed by the Symptom Checklist (SCL-90R) self-report symptom inventory. Patients with suspected postprandial hypoglycemia had higher beta-adrenergic sensitivity (defined as the dose of isoproterenol required to increase the resting heart rate by 25 beats/min) than controls (mean +/- SEM, 0.8 +/- 0.13 vs. 1.86 +/- 0.25 microgram isoproterenol; P = 0.002). After administration of glucose (75 g) blood glucose, plasma C-peptide, plasma epinephrine, and plasma norepinephrine responses were identical in the two groups, but plasma insulin was higher in the patients (group effect, P = 0.02; group by time interaction, P = 0.0001). Both heart rate and systolic blood pressure were significantly higher (but remained in the normal range) after glucose administration in patients with suspected postprandial hypoglycemia than in controls (group by time interactions, P = 0.004 and 0.0007, respectively). After glucose intake, seven patients had symptoms (palpitations, headache, tremor, generalized sweating, hunger, dizziness, sweating of the palms, flush, nausea, and fatigue), whereas in the control group, one subject reported flush and another palpitations, tremor, and hunger. Analysis of the SCL-90R questionnaire revealed that patients had emotional distress and significantly higher anxiety, somatization, depression, and obsessive-compulsive scores than controls. We may conclude that patients with suspected postprandial hypoglycemia have normal glucose tolerance, increased beta-adrenergic sensitivity, and emotional distress.

The USA experience with the clonidine transdermal therapeutic system

Cardiovascular diseases are the leading causes of death in the United States, with hypertension being amongst the most prevalent of the cardiovascular risk factors. Improvement of hypertension management has, in consequence, received much attention. Extensive pre- and post-marketing experience with the transdermal formulation of clonidine marketed in the USA in the mid-1980s has now been accumulated. Transdermal clonidine is effective as monotherapy in mild-moderate hypertension, and in combination with diuretics, calcium antagonists and ACE inhibitors in more resistant cases. It controls blood pressure throughout the 24-h circadian cycle. It is effective and generally well-tolerated in adolescents, the elderly, blacks, diabetics, and subjects with chronic renal insufficiency. It has been used perioperatively and for suppression of adrenergic symptoms in subjects withdrawing from addicting substances. In comparison with oral clonidine, transdermal clonidine reduces the incidence and severity of such symptomatic side-effects as dry mouth, drowsiness, and sexual dysfunction. Minor skin reactions occur at the site of application of the transdermal patch with moderate frequency. Adherence to transdermal clonidine therapy is high, and patients commonly prefer it to oral therapy. Transdermal administration of clonidine is a useful therapeutic advance in the long-term management of hypertension.

Paroxysmal Dyskinesia Associated with Hypoglycemia

The association of movement disorders with hypoglycemia has been rarely noted in the past. We recently observed 2 patients with documented hypoglycemia and paroxysmal dyskinesias. One patient had evidence of an insulin-secreting tumor. The other patient had insulin-dependent diabetes, and also experienced recurrent episodes of hypoglycemic hemiparesis. Classical adrenergic symptoms of hypoglycemia were absent in both patients. Our observations support the concept that the development of neuroglycopenic symptoms cannot be predicted from blood glucose measurements alone, but must depend on other factors controlling the availability or metabolism of glucose in the brain.

The impact of recent advances in diagnostic technology on the clinical presentation of phaeochromocytoma.

To examine the impact of recent advances in diagnostic technology on the spectrum of clinical and biochemical features of patients presenting with a new diagnosis of phaeochromocytoma. A retrospective review of the clinical and biochemical features of patients diagnosed by our laboratory as having phaeochromocytoma within a 27-month period up to December, 1990. Noradrenaline, adrenaline and dihydroxyphenylglycol were assayed in 24-hour urine specimens (19 patients) or plasma (1 anuric patient) by gas chromatography/mass spectrometry. A tertiary level chemical pathology department. Twenty patients with a new diagnosis of phaeochromocytoma. The classic, episodic adrenergic symptoms traditionally associated with phaeochromocytoma were absent in 9 of the 20 patients (45%). "Atypical" phaeochromocytoma presented as a mass on computed tomography imaging (6 patients, 30%), "phaeochromocytoma crisis" (4 patients, 20%) or family screening (1 patient, 5%). Excessive adrenaline production was found in 11 patients (55%) and six (30%) had predominantly adrenaline-secreting tumours. The urinary noradrenaline:dihydroxyphenylglycol ratio was raised in all nine patients with predominantly noradrenaline-secreting tumours but was not raised in nine out of ten patients with adrenaline-secreting phaeochromocytoma. Adrenaline excretion was significantly correlated with tumour size (r = 0.8; P less than 0.05). Advances in diagnostic technology, particularly specific adrenaline assays and computed tomography, have made possible the early diagnosis of patients with phaeochromocytoma presenting in ways previously thought to be uncommon. All patients with adrenal masses noted incidentally on CT scan should be investigated for phaeochromocytoma. Adrenaline-secreting tumours are common and both noradrenaline and adrenaline should be assayed in all patients investigated for phaeochromocytoma.

Doxepin therapy for postprandial symptomatic hypoglycaemic patients: neurochemical, hormonal and metabolic disturbances

1. Three oral glucose tolerance tests were performed in each of 32 symptomatic postprandial hypoglycaemic patients (before placebo, before doxepin therapy and after doxepin therapy). Plasma neurotransmitters were determined in parallel with assays of plasma insulin and glucose levels. 2. Three different types of patients were distinguished. Type I showed a low noradrenaline/adrenaline ratio, high dopamine levels and low platelet 5-hydroxytryptamine (serotonin) levels during basal periods. After a glucose load, late peaks of dopamine and free 5-hydroxytryptamine, which coincided with the symptoms but not with the nadir of plasma glucose, were observed. Type II showed a low basal plasma noradrenaline/adrenaline ratio. After a glucose load, progressive increases in adrenaline and decreases in glucose were seen. Adrenergic symptoms coincided with the nadir of glucose. Although type III patients showed hyperinsulinaemia after a glucose load similar to the other types of patient, they did not show hyperglycaemia, but rather exhibited a sustained and progressive reduction in plasma glucose. These patients were characterized by a high basal plasma noradrenaline/adrenaline ratio, high basal plasma levels of 4-hydroxy-3-methoxyphenylethyleneglycol and high basal levels of platelet 5-hydroxytryptamine, all of which increased after a glucose load. Systolic and diastolic blood pressure decreases paralleled reductions in heart rate and glucose. The nadir of plasma glucose occurred simultaneously with the appearance of symptoms (weakness, heartburn, oppressive chest pain, tension headache, abdominal cramps, dizziness, etc.). Therapy with doxepin led to disappearance of the symptoms within 3-4 weeks. Normalization of all other disordered variables (cardiovascular, metabolic and neurochemical, and the clonidine test) paralleled the disappearance of the symptoms. 3. Symptoms varied in the three types of patients and we conclude that they are related to hypoglycaemia-induced disorders of plasma neurotransmitters, rather than to hypoglycaemia per se. We postulate that an uncoping stress situation (type I and II patients) and depression (type III patients) underlie the physiopathological mechanisms.

Hypoglycaemic episodes during intensified insulin treatment: increased frequency but no effect on cognitive function

Ninety-seven patients with insulin dependent diabetes mellitus (IDDM) were randomized to intensified conventional treatment (ICT, n = 44) or regular treatment (RT, n = 53). The mean HbA1c level (+/- SEM) was reduced from 9.5 +/- 0.2% to 7.4 +/- 0.1% in the ICT group (P less than 0.001), and from 9.4 +/- 0.2% to 9.0 +/- 0.2% (P less than 0.01) in the RT group. The difference between the groups was significant (P less than 0.001). During a period of 3 years, 57% of the ICT patients (95% confidence interval 44-73%) and 23% of the RT patients (95% CI, 11-34%) (P less than 0.001) had at least one episode of serious hypoglycaemia, with the need for third-party assistance or resulting in coma. Eighteen of the 32 ICT patients who initially had adrenergic symptoms during hypoglycaemia changed to predominantly neuroglycopenic symptoms. This was the case with only 8 of 38 RT patients (P less than 0.01). The change in symptoms was related to the increased frequency of serious hypoglycaemia, but neither symptoms nor frequency of hypoglycaemia bor any relationship to insulin dose, body mass index, duration of diabetes or autonomic nerve function. The results of several neuropsychological tests did not differ between the groups at baseline, and did not change during the study. There were no signs of deteriorating cognitive function in the patients with serious hypoglycaemic episodes.

Sucrose and Delinquency: Oral Sucrose Tolerance Test and Nutritional Assessment

Claims that juvenile delinquency may be associated with reactive hypoglycemia or nutritional deficiencies have received widespread attention but little objective evaluation. To assess the validity of these claims, nutritional and psychological indices of juvenile delinquents have been measured. Serum glucose and insulin profiles during an oral sucrose tolerance test were measured in 137 delinquent and 41 nondelinquent male adolescents aged 14 to 19. In addition, nutritional status of both populations was assessed by anthropometry (height, weight, arm circumference, triceps skin fold) and biochemical measures (hematocrit, red-blood cell thiamin, and serum copper, ferritin, and zinc). Delinquent subjects had slightly but significantly lower serum glucose values at four of six time points (fasting, 60 minutes, 120 minutes, 180 minutes) and higher serum insulin values at one time point (30 minutes) compared with nondelinquent subjects. Changes in glucose from fasting levels indicate that these subjects were regulating serum glucose adequately, but doing so at lower values; changes in insulin from fasting levels indicate that black delinquents initially secreted more insulin than either white subject group. There were no significant associations between excursions in serum glucose or insulin and any adrenergic signs or symptoms of low blood glucose levels. Nutritional status of incarcerated delinquents did not differ from that of nonincarcerated subjects on most measures. Although the significantly lower serum glucose levels and higher serum insulin levels are intriguing, no support is offered by results of this study for allegations that sucrose ingestion causes reactive hypoglycemia in juvenile delinquents or that delinquent male adolescents are at greater risk nutritionally than male adolescents of the same age who are not delinquent.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycemic Control and Neuropsychologic Function during Hypoglycemia in Patients with Insulin-Dependent Diabetes Mellitus

To evaluate counterregulatory hormone secretion and neuropsychologic function during hypoglycemia in two groups of patients with insulin-dependent diabetes mellitus: those with good and those with poor glycemic control. Cross-sectional physiologic and neuropsychologic evaluation. Clinical research unit of a referral-based diabetes clinic. Eight patients with well controlled diabetes (glycosylated hemoglobin [HgbA1], 8.0% +/- 0.2%), nine patients with poorly controlled diabetes (HgbA1, 11.8% +/- 0.4%), and ten healthy persons. The insulin clamp technique was used to produce a stepwise decline in plasma glucose from 5.0 to 2.2 mmol/L over 3 hours. Tests of attention, memory, visual-spatial skills, visual-motor skills, and global cognition; a symptom survey; and counterregulatory hormone measurements were done at glucose decrements of 0.6 mmol/L. Patients with well controlled diabetes did not differ statistically from those with poorly controlled diabetes regarding the median glucose threshold for dysfunction in visual-spatial skills, visual-motor skills, or global cognition. In contrast, glycemic thresholds for an increase in adrenergic symptoms and release of epinephrine, norepinephrine, cortisol, and growth hormone were lower in patients with well controlled diabetes than in those with poorly controlled diabetes (P less than 0.05 to 0.005). Despite alterations in the glucose levels at which adrenergic symptoms of hypoglycemia occur and counterregulation begins, there is no statistically detectable change in the glucose threshold at which cognitive deterioration occurs in diabetic persons with strict glycemic control. This dissociation of neuropsychologic function and counterregulatory hormone secretion suggests that diabetic patients with good glycemic control are at increased risk for developing cognitive impairment before the onset of adrenergic symptoms during hypoglycemia.

Catecholamine-thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism

The spectrum of classic symptoms of hyperthyroidism suggests that in addition to the effects of increased thyroid hormone, affecting various organ systems, there is also a hyperadrenergic state. Despite this clinical impression, direct measures of serum levels of catecholamines and their urinary metabolites demonstrate values that are equal to or less than normal. In contrast, the hypothyroid patient who clinically manifests signs or decreased adrenergic stimulation can be expected to have increased levels of epinephrine, norepinephrine, and its metabolites. This review discusses possible mechanisms to explain this seeming paradox. Treatment of hyperthyroidism includes the rapid reversal of many of the adrenergic symptoms with use of β-blocking drugs. Return to a clinically and chemically euthyroid state, however, requires antithyroid therapy accomplished over a longer period of time. A knowledge of the interaction of the cardiovascular and extracardiovascular manifestations of hyperthyroidism and the role of the adrenergic nervous system is important in the rational management of these patients.

Arginine Vasopressin Response to Insulin-Induced Hypoglycemia in Insulin-Dependent Diabetics with Asymptomatic Hypoglycemia

Insulin-induced hypoglycemia causes an increase in plasma vasopressin (AVP) in healthy subjects but the response in diabetics is not established. We investigated the effect of insulin-induced hypoglycemia on ten insulin-dependent diabetics with asymptomatic hypoglycemia, and compared the results with those for seven healthy subjects. The lack of adrenergic symptoms of hypoglycemia in insulin dependent diabetics being attributed to a diminished beta-adrenergic sensitivity, the effect of isoprenaline infusion was investigated as control. Insulin-induced hypoglycemia resulted in both populations in significant increase (P less than 0.01) in AVP in addition to significant increases in heart rate, plasma epinephrine (E), norepenephrine (NE) and cortisol (COR). Effective osmolality and mean arterial blood pressure did not vary. Diabetics showed smaller increase in AVP (P less than 0.01) and heart rate (P less than 0.05) than controls. Maximal E, NE and COR values did not differ between the two populations. Isoprenaline infusion resulted in increase in heart rate and plasma renin activity, but AVP and COR did not vary in the two populations. In conclusion, insulin-induced hypoglycemia released AVP in diabetics with asymptomatic hypoglycemia, but the response was weaker than in healthy subjects. A causal hypothalamic alteration of beta-adrenergic or glycopenia sensitivity is discussed.

Unawareness of Hypoglycemia by Insulin-Dependent Diabetics

After several years of insulin therapy, about 20% of insulin-dependent diabetics have little or no perception of hypoglycaemia because of a loss of the adrenergic warning symptoms. This defect, poorly correlated with the presence of autonomic neuropathy, has been classically explained by a defect in the catecholamine secretion. We compared the hormonal counterregulation during hypoglycaemia induced by subcutaneous injection of insulin in 7 insulin-dependent diabetics with poor perception of hypoglycaemia and experiencing repeated episodes of severe hypoglycaemia (group A) and 7 insulin-treated diabetics with very good perception of hypoglycaemia and not experiencing severe hypoglycaemia (group B). Groups A and B were similar in terms of age, duration of diabetes, HbA1c level and degenerative complications. The glucagon levels were identical and non-reactive in the two groups. The basal levels and secretion peaks of adrenaline, noradrenaline, growth hormone and cortisol were similar between the two groups, but there was a significant delay in secretion in group A with a blood glucose threshold of adrenergic secretion of between 3.1 +/- 0.5 and 1.6 +/- 0.2 mmoles/l in group A and between 4.6 +/- 0.3 and 3.2 +/- 0.2 mmoles/l in group B (P less than 0.05). This delayed secretion could be explained by desensitisation of the hypothalamic glucostat and could be due to the frequency and/or severity of hypoglycaemic episodes.

Hypoglycemia in children.

Hypoglycemia, although rare in childhood beyond the newborn period, remains a vexing problem for the pediatrician. First, the symptoms may be vague and nonspecific, thus making diagnosis particularly dependent on a high index of suspicion. Second, the pathogenic mechanisms that result in hypoglycemia are as numerous and complicated as the physiologic mechanisms that maintain euglycemia. Finally, although most patients have no permanent sequelae, a catastrophic episode of hypoglycemia can cause neurologic deficit and mental retardation. In this brief review, the most common cause for hypoglycemia, namely, insulin-dependent type I diabetes mellitus, will not be considered. Instead, we will focus on those metabolic disorders that result directly in a loss of the ability to maintain normal serum glucose concentrations.SYMPTOMSIn the older infant (older than 2 months), child, and adult, a rapid decrease in blood glucose to levels less than 40 mg/dL (2.2 mmol/L) may produce hunger and trigger an excessive release of epinephrine, causing weakness, anxiety, cold sweat, inward trembling and tachycardia. These adrenergic symptoms tend to occur in persons with postprandial hypoglycemia. In contrast, fasting hypoglycemia generally is progressive and gradual and produces neuroglycopenic symptoms which include headache, mental dullness, fatigue, confusion, abnormal behavior or psychosis, amnesia or other neurologic deficit, seizures, or frank coma.

Hypoglycemia in Children

Hypoglycemia, although rare in childhood beyond the newborn period, remains a vexing problem for the pediatrician. First, the symptoms may be vague and nonspecific, thus making diagnosis particularly dependent on a high index of suspicion. Second, the pathogenic mechanisms that result in hypoglycemia are as numerous and complicated as the physiologic mechanisms that maintain euglycemia. Finally, although most patients have no permanent sequelae, a catastrophic episode of hypoglycemia can cause neurologic deficit and mental retardation. In this brief review, the most common cause for hypoglycemia, namely, insulin-dependent type I diabetes mellitus, will not be considered. Instead, we will focus on those metabolic disorders that result directly in a loss of the ability to maintain normal serum glucose concentrations. SYMPTOMS In the older infant (older than 2 months), child, and adult, a rapid decrease in blood glucose to levels less than 40 mg/dL (2.2 mmol/L) may produce hunger and trigger an excessive release of epinephrine, causing weakness, anxiety, cold sweat, inward trembling and tachycardia. These adrenergic symptoms tend to occur in persons with postprandial hypoglycemia. In contrast, fasting hypoglycemia generally is progressive and gradual and produces neuroglycopenic symptoms which include headache, mental dullness, fatigue, confusion, abnormal behavior or psychosis, amnesia or other neurologic deficit, seizures, or frank coma.

Beta-adrenergic blockade does not prevent hypoglycemia awareness in non-diabetic humans.

This study's purpose was to test whether beta-adrenergic blockade reduces awareness of hypoglycemia. Six non-diabetic human adults received six experimental sessions each, one with each combination of intravenous propranolol (0.0, 0.05, and 0.15 mg/kg) followed by intravenous regular insulin (2 and 4 units). Physiological, biochemical, and symptom variables, and choice (was an active or an inactive substance administered?) were measured at 15, 30, and 45 min after insulin. Insulin dose and time after insulin administration significantly influenced choice, but propranolol did not significantly influence choice. Adrenergic symptoms were not prominent. These results may or may not apply to individuals with disorders of adrenergic function such as diabetic autonomic neuropathy.

In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer

Miniature, amperometric glucose sensors were constructed for implantation in the subcutaneous tissue of normal and insulin-dependent diabetic subjects. To minimise dependence on fluctuating tissue oxygen tension, we employed the technology of mediated electron transfer, with 1,1'-dimethylferrocene acting as the redox shuttle between immobilized glucose oxidase and a platinum base electrode. In 6 normal subjects, the subcutaneous sensor responses mirrored the simultaneously-measured changes in blood glucose concentration after a 75 g oral glucose load and after intravenous injection of 0.15 U/kg short-acting insulin, though increases and decreases in the sensor output were slower than the glycaemic changes. The mean peak delay in sensor response after the oral glucose was 40 min (range 0-45 min) and the delay in the hypoglycaemic nadir was 4 min (range 0-15 min). In 5 insulin-dependent diabetic subjects, spontaneous and induced hypoglycaemia was detectable by the implanted sensor. In addition, marked and frequent oscillations in the sensor current occurred in several normal and diabetic individuals as the blood glucose fell below about 1.9 mmol/l. These oscillations were present in a diabetic subject who had lost adrenergic warning symptoms to hypoglycaemia. Continuous metabolic monitoring in diabetes, particularly the detection of hypoglycaemia, may be possible with implanted sensors based on this technology.

Lack of hypoglycemic symptoms and decreased beta-adrenergic sensitivity in insulin-dependent diabetic patients.

Plasma epinephrine, norepinephrine, and dopamine responses were studied in insulin-dependent diabetic patients at rest, on standing and during insulin-induced hypoglycemia. beta-Adrenergic sensitivity was evaluated by the isoproterenol sensitivity test. Five men who had adrenergic symptoms during hypoglycemia and no severe hypoglycemic accidents (coma, seizures) (group A) and five men who had repeated severe hypoglycemic accidents but lack of adrenergic symptoms of hypoglycemia (group B) were studied. The mean resting plasma epinephrine was lower in group B (147 +/- 22 pmol/L, SEM) than in group A (398 +/- 98 pmol/L, P less than 0.02). On standing plasma epinephrine increased significantly in both groups. During hypoglycemia blood glucose decreased identically in the two groups; plasma epinephrine and norepinephrine increased significantly and to the same extent in both groups; the mean maximal heart rate was significantly greater in group A than in group B. Isoproterenol sensitivity (defined as the dose of isoproterenol required to increase heart rate by 25 beats/min) was lower in group B (5.87 +/- 1.12 micrograms) than in group A (2.37 +/- 0.22 micrograms, P less than 0.01). The group B patients had significantly fewer hypoglycemic symptoms during insulin-induced hypoglycemia than did group A patients. We conclude that decreased beta-adrenergic sensitivity contributes to the lack of adrenergic symptoms of hypoglycemia in insulin-dependent diabetic patients.

Hypoglycemia in the elderly.

Fifty three elderly hypoglycemic patients seen at Tokyo Metropolitan Geriatric Hospital during last 4 years were reviewed, and these data suggest that clinical characteristics of hypoglycemic patients in the elderly are as follows: 1) Non-diabetics without any hypoglycemic drugs seem to take relatively large part in hypoglycemic patients; 2) malnutrition due to chronic disease, and liver dysfunction may be important predisposing factors in development of hypoglycemia; 3) they are often lacking in adrenergic symptoms and do not tend to present symptoms until their plasma glucose levels decrease at extremely low levels, moreover in such cases, they tend to manifest neuroglycopenia in the beginning of their hypoglycemic attacks. Therefore, it is noteworthy that impaired subjective recognition may increase the risk of hypoglycemia and hypoglycemia should be one of the important considerations in differential diagnosis of stupor and coma in the elderly patients, even though they have not been administered any hypoglycemic agents.

Symptoms of insulin-induced hypoglycemia in normal subjects

In order to better characterize the psychobiology of hypoglycemic symptom production, six normal subjects had physiological/biochemical and symptom ratings at 20, 30 and 40 min after six different doses of intravenous regular insulin (0.0, 0.5, 1.0, 2.0, 3.0 and 4.0 units, in a Latin-square design); subjects also indicated after each dose whether they believed they had received an active or an inactive substance. Choice response switched from inactive to active substance when plasma glucose fell to the mid to high 50s mg/dl (i.e. whole blood glucose of approximately 50), and plasma epinephrine levels rose to between 100 and 200 pg/ml. Adrenergic symptoms and ‘weakness’ were most strongly associated with choice; other symptom variables had weaker associations. Symptoms were more strongly correlated with epinephrine than glucose levels, but anxiety was not strongly correlated with the epinephrine increases.

Hypoglycemic symptoms and decreased beta-adrenergic sensitivity in insulin-dependent diabetic patients.

Thirty-seven insulin-dependent diabetic patients were tested for symptoms of hypoglycemia, cardiac autonomic neuropathy (i.e., heart rate variation during deep breathing, Valsalva maneuver, immediate heart rate response to standing), and isoproterenol sensitivity (defined as the dose of isoproterenol required to increase heart rate by 25 beats/min: I25). Tests of cardiac autonomic neuropathy showed no relation to hypoglycemic symptoms. On the contrary, a clear relationship could be established between isoproterenol sensitivity and adrenergic symptoms of hypoglycemia. Diabetic patients with decreased response to isoproterenol had fewer adrenergic symptoms, perceived hypoglycemia at a lower blood glucose level, and had more hypoglycemic accidents. Symptoms most related to isoproterenol sensitivity were tremor, sweaty palms, and hunger. With the isoproterenol-sensitivity test a distinction could be made between the groups at high (I25 greater than 3 micrograms) and low (I25 less than 3 micrograms) risk for hypoglycemic accidents. We suggest that the isoproterenol-sensitivity test could be used to identify diabetic patients at increased risk for hypoglycemia.

Reversing severe hypoglycemia during pregnancy with glucagon therapy.

Glucagon therapy has been used to reverse severe hypoglycemia-induced unconsciousness, but no known study exists which reports its use during pregnancy. Pregnant diabetic women were eligible if they had either a prior hypoglycemic episode requiring intravenous glucose administration or had repeated capillary blood glucose determinations less than 40 mg/dl without any warning adrenergic symptoms. Of 51 insulin-dependent diabetic women, 16 were candidates for glucagon use during a recent 3 1/2-year period. Seven of these 16 persons required an injection on 12 occasions, and an immediate reversal of unconsciousness was encountered in 11 circumstances. No apparent short- or long-term maternal adverse effects were present. We conclude that glucagon therapy is needed infrequently for diabetic women during pregnancy but is helpful in reversing acute episodes of severe hypoglycemia.