Blood glucose in intoxicated chronic alcoholics P. Kallas,*
sc; E. M.
Sellers,
frcp[c] Summary: Chronic alcoholics may Frequent clinical reports document the 1973 were included in this study, as association of alcohol ingestion with were patients who were drowsy, comapresent with hyperglycemia or hypoglycemia. Because alcohol induces hypoglycemia in both adults and chil¬ tose or had seizures. The study group dren.1"5 In adults hypoglycemia typically initially comprised 208 chronic alco¬ glycogenolysis, chronic alcoholics occurs in chronic alcoholic patients usually have higher blood glucose holics and 201 age- and sex-matched values than do nonalcoholic subjects. with a history of poor dietary intake.4"6 nonalcoholic controls, staff members of In a prospective study of blood glucose Children are also susceptible to alcohol- the Addiction Research Foundation concentration in 201 chronic alcoholics, induced hypoglycemia because of their and volunteers from the Red Cross blood alcohol concentration, sex, normally low glycogen stores. In blood donor clinic. weight, type of beverage consumed and chronic alcoholics who are hypogly¬ On admission of each patient a time since last eating were not generally cemic, liver biopsies reveal depletion 20-ml blood sample was immediately associated with lower blood glucose of glycogen stores.3 The mechanism of drawn; none ate before the sample of values. The b
infrequency
md, ph d,
hypoglycemia ethanol-induced alterations in blood
was taken. Blood samples were also drawn from the control subjects. Con¬ centrations of blood alcohol, blood
in ambulatory chronic alcoholics may reflect the relatively ready availability
glucose concentration is complex but well understood.7"12 If hepa¬ reasonably of hostels, detoxification centres tic glycogen stores are adequate, the and hospitals in large cities. It is, combination of alcohol-induced glyco¬ however, important to be aware of and decreased glucose uptake genolysis the possible occurrence of hypoglycemia into muscles may result in an elevation in chronic alcoholics, particularly in blood glucose concentration.8"11 Once when community facilities for the stores are depleted, hypogly¬ glycogen chronic alcoholic are not available. cemia may develop because of impair¬ ment of gluconeogenesis by ethanol.8 Hypoglycemia can occur even after Resume: La glycemie chez des alcohol is no longer detectable in the alcooliques chroniques en 6tat d'6briete blood if glycogen stores are not replenished.6 Les alcooliques chroniques peuvent Chronic alcoholics are frequently presenter de I'hyperglycemie ou de to hospital emergency wards brought donne Etant que I'hypoglycemie. with altered mental status consistent I'alcool provoque la glycogenolyse, with that due to hypoglycemia. Recur¬ les alcooliques chroniques ont rent hypoglycemia can cause progres¬ d'ordinaire une glycemie plus elevee sive dementia not unlike the altered que les nonalcooliques. Une etude mental status and early-onset dementia prospective de la glycemie chez
201 alcooliques chroniques, de la concentration d'alcool dans le sang, du sexe, du poids, du genre d'alcool consomme et du laps de temps ecoule depuis le dernier repas, a permis de conclure a la rarete relative de I'hypoglycemie. Cette rarete chez des alcooliques chroniques ambulatoires peut s'-expliquer par la facilite relative de trouver dans les grandes villes des hdtels, des centres de desintoxication et des hopitaux. II est neanmoins important de garder presente a I'esprit la possibilite d'un episode d'hypoglycemie chez des alcooliques chroniques, particulierement dans les endroits depourvus des commodites
glucose,
serum
albumin,
serum
of chronic alcoholics.13,14 Because the incidence of, and the risk factors pre¬ disposing to, hypoglycemia in "skidrow" chronic alcoholics is unknown, we attempted to determine the pattern of blood glucose abnormalities and the prevalence of hypoglycemia in such a group of chronic alcoholics.
ysis.
When the alcoholic subjects were sober a detailed account was obtained of the amount and type of food eaten daily; the type of alcohol consumed daily during the past week; the usual frequency and history of alcoholic con¬ sumption; the usual daily alcoholic consumption; and a past history of light-headedness, seizures, blackouts and dizziness. Daily caloric intakes from food and the various alcoholic beverages were calculated. The data were analysed by a mul¬ tiple linear regression program on a IBM/370 computer.
Methods and materials All intoxicated male and female seen in the emergency room of the Addiction Research Founda¬ tion's Clinical Institute or at the Detoxication Centre, 410 Dundas St., Toronto, between June 1 and July 31,
patients
prementionnees. From the Clinical Institute, Addiction Research Foundation and The Toronto Western Hospital and departments of medicine and pharmacology, University of Toronto ?Supported in part by RODA Summer Use of Scholarship from the Non-Medical Directorate, Health and Welfare Drugs Canada Reprint requests to: Dr. E.M. Sellers, Clinical pharmacology program, Clinical Institute, Addiction Research Foundation, 33 Russell St.. Toronto, Ont. M5S 2S1
Table I.Comparison of mean values* of clinical and laboratory variables in male chronic alcoholics and normal male subjects Controls (n 131) Alcoholics (n 131) Variable 44.1 ± 15.1 (18-64) 11.6 47.5 ± (25-78) Age (yr) 78.8 ± 10.5 (55-114) 72.6 ± 12.0 (41-109) Weight (kg) 91.2 ± 15.6 (59-149) 104.3 ± 38.4 (42-199) Blood glucose (mg/dl) 11.6 ± 4.3 (5-30) 6.9 ± 3.6(0.5-21) BUN (mg/dl) 17.2 ± 9 6(10-28) 37.3 ± 36.9 (8-326) SG0T(IU/l) ?Results are expressed as mean ± standard error, with range of values indicated in parenthesis.
590 CMA JOURNAL/MARCH 8, 1975/VOL. 112
gluta-
mic oxaloacetic transaminase, blood urea nitrogen and psychoactive and analgesic drugs were determined on each sample by standard laboratory techniques. At the same time the blood sample was taken, information was re¬ corded for each patient regarding age, sex, weight, mental state, level of consciousness, usual alcoholic beverage and elapsed time since last consumption of food. Repeat samples from the same in¬ dividual and samples with blood al¬ cohol values of less than 0.3 g/1 were excluded from further analysis. The number of males investigated further was therefore 131. Because only 14 female chronic alcoholic subjects were studied, samples from these patients were also excluded from further anal¬
=
=
Results Table I summarizes the characteris¬ tics of the 131 alcoholics and 131 controls. The mean ages and blood glucose values were not different be¬ tween the groups. In the chronic alco¬ holics, BUN values and weights were significantly lower and SGOT values higher than in the controls (P < 0.05), though the range of SGOT values in chronic alcoholics was greater. At the time of entry into the study, mean al¬ cohol concentration in the males was 2.51 ± 0.95 g/1 (range, 0.30 to 4.53
g/1).
The wide range and distribution of blood alcohol values at the time of admission of the 131 male alcoholics are shown in Fig. 1. There was no relation between blood alcohol con¬ centration and type of beverage con¬
hyperglycemia. Larger alcohol intakes and longer durations of fasting (> 24 (P < 0.05). h) are associated with a greater degree Table III shows the distribution of of hypoglycemia. These biphasic effects types of beverage consumed in this of ethanol on blood glucose concentra¬ group of alcoholics. The higher alco¬ tion reflect initial stimulation of glycohol content of spirits/ is not associated genolysis and subsequent impairment with a decreased random blood glucose of gluconeogenesis from lactate by al¬ In both control and alcoholic subjects, blood glucose value increased with age
value.
Discussion Administration of 150 ml of whisky subjects results in an increase in blood glucose concentration in 30 to 60 minutes. The concentration then decreases more rapidly than in control subjects not receiving alcohol.8"10 Over¬ night fasting can decrease the initial to human
Table II.Characteristics of two
"hypoglycemic" alcoholics
sumed.5
2 shows the distribution of random blood glucose values in the 131 male subjects and 131 controls. The distribution is skewed to the right in chronic alcoholics to a greater ex¬ tent than in the normals. A chi-square test indicates that a significantly greater number of alcoholics have blood glu¬ cose values of > 110 mg/dl (P < 0.05). There are no differences in distribu¬ tion of blood glucose values of < 80 mg/dl between alcoholic and control subjects. Two "hypoglycemic" alcohol¬ ics with blood glucose values of 42 and 57 mg/dl were detected in the 131 male patients included in the analysis (Table II). Both patients were asympto¬ matic. Multiple regression analysis showed that there was no significant influence of weight, sex, SGOT, BUN, time since last meal, blood alcohol value, caloric intake from food, and type of beverage consumed (e.g. spirits, wine or beer) on blood glucose values.
cohol.4'*40 Alterations in insulin con¬ centration do not account for the rela¬ tive hypoglycemia because the insulin concentration decreases promptly as the blood glucose concentration decreases.12 The elevated blood glucose value observed in many of the alcoholics in this study reflects glycogenolysis in the presence of adequate caloric intake. Only two chronic alcoholics had blood glucose values of less than 60 mg/dl,
Patient A
Fig.
Patient B
*For nine other subjects full data were not available. fPredominant beverage consumed.
0.3 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 BLOOD ALCOHOL g/1
V: '^-^
FIG. 1.Distribution of blood alcohol concentrations on admission in 131 male chronic alcoholics.
,T\
¦¦¦¦'¦¦
"".:.-,
..-¦
-'
¦¦¦
^BLOOD
GLUGC&&i&iMK
FIG. 2.Distribution of random blood control subjects and chronic alcoholics.
glucose values in
131 male
age-matched
CMA JOURNAL/MARCH 8, 1975/VOL. 112 591
the lowest being 42 mg/dl. The patient with this value was neuropathologically normal. The reasons for the relative rarity of hypoglycemia in this group of patients are complex. In part, the ready availability of hostels, detoxification centres and hospitals, and the relative affluence of society, suggests that these chronic alcoholics seldom go without food for more than 24 hours. In addition, in the alcoholics we studied, alcohol was present in the blood at the time of blood glucose determination. Alcohol inhibition of peripheral glucose utilization may prevent the appearance of hypoglycemia." It is unfortunate that no previous comparable prospective studies were done before the introduction of detoxification centres in Toronto to assess the influence of these supportive facilities on the occurrence of hypoglycemia in the homeless alcoholic. Studies are needed in more remote parts of Canada without these community resources in order to define the prevalence of hypoglycemia and possible contribution of recurrent episodes to the early occurrence of dementia in chronic alcoholics.'4 The failure to confirm an increased risk of hypoglycemia due to liver disease,3 duration of fasting,9"0 intake of other drugs,. decreased weight9 or drinking'0 may reflect in part the difficulty in getting reliable historical information from these patients and, more important, the inability to control adequately the interdependent variables in each patient. Even though hypoglycemia in the chronic alcoholic seems to be rare, awareness of its possible occurrence is important. The high blood alcohol concentrations measured in these subjects emphasizes the difficulty in predicting whether a change in level of consciousness is due to alcoh.A or hypoglycemia, for subjects can drift from alcoholic stupor to hypoglycemic coma. It is judicious to assume that hypoglycemia occurs frequently enough in chronic alcoholics that all such individuals presenting to emergency rooms with seizures or altered mental status should have their blood glucose routinely determined. Except in the comatose patient administration of glucose can usually await the results of the chemical analysis. Glucagon will not be effective if glycogen stores are depleted.8'9 It is important in the clinical management of the chronic alcoholic with symptomatic hypoglycemia to recall that hypoglycemia can recur after admission to hospital. To prevent this, initial treatment of the patient with 50% glucose should be followed by
an infusion of 10% glucose for 24 hours. Chronic alcoholics with severe liver disease, renal disease or adrenal insufficiency, who require tolbutamide or who ingest excess salicylate, will have an increased risk of developing hypoglycemia.5 Chronic alcoholic patients with true diabetes will be more liable to wide fluctuations in blood glucose concentration if they continue to drink,15 and the diagnosis of diabetes can be made in error if patients have been drinking recently. We thank Mrs. J. Keck and Mrs. K. Chater and the nursing staffs of the clinical investigation unit and emergency room of the Clinical Institute, and the staff of the clinical chemistry laboratory and the Detoxication Centre for their cooperation and assistance. The donation of blood samples by Clinical Institute staff and Red Cross donors and the assistance of Mr. A. Kornaczewski in analysing these data are gratefully acknowledged. References 1. BROWN IM, HARVEY AM: Spontaneous hypoglycemia in "smoke" drinkers. JAMA 117: 12, 1941 2. TUCKER H ST G, PORTZR WB: Hypoglycemia following alcoholic intoxication. Am I Med Sd 204: 559, 1942 3. HED R, NYGREN A: Alcohol-induced hypoglycemia in chronic alcoholics with liver disease. Acta Med Scand 183: 507, 1968 4. H.wcsNs RD, KALANT H: The metabolism of ethanol and its metabolic effects. Pharmacol Rev 24: 68, 1972 5. SELTZER HS: Drug-induced hypoglycemia. Diabetes 21: 955, 1972 6. MARKs V, MEDD WE: Alcohol-induced hypoglycemia. Br I Psychiatry 110: 228, 1964 7. Han R: Clinical studies in chronic II. Carbohydrate metabolism in coholics with particular reference and insulin tolerances. Acta Med
alcoholism. chronic alto glucose Scand 162:
195, 1958 GE: Studies on the mechanism of ethanol-induced hypoglycemia. I Clin Invest 42: 497, 1963 9. FItEINKEL N, SINGER DC, ARKY RA, et al: Alcohol hypoglycemia. I. Carbohydrate metabolism of patients with clinical alcohol hypoglycemia and the experimental reproduction of the syndrome with pure ethanol. Ibid, p 1112 10. FREINKEL N, Aixy RA: Effects of alcohol on carbohydrate metabolism in man. Psychosom Med 28: 551, 1966 11. LOCHNER A, Wuu'F 3, MADIsoN LL: Ethanol8. FIELD JB, WILLIAMS HE, MORTIMORE
induced hypoglycemia. I. The acute effects of ethanol on hepatic glucose output and peripheral glucose utilization in fasted dogs.
Metabolism 16: 1, 1967 12. BAGDADE 3D, BIERMAN EL, PORTE D: Counterregulation of basal insulin secretion during ethanol hypoglycemia in diabetic and normal subjects. Diabetes 21: 65, 1972 13. RYBACK RS: Alcohol amnesia. Q I Stud Alcohol 31: 616, 1970 14. RANKIN JG, SCHMIDT W, POPHAM RE DE LINT J: Epidemiology of alcoholic liver disease: insights and problems, in Symposium on
Alcoholic Liver Pathology. Addiction Research Foundation, October 1973 (in press)
15. ARKY RA, VEYERBRANTS E, ABRAMSON EA:
Irreversible hypoglycemia: a complication of alcohol and insulin. JAMA 206: 575, 1968
592 CMA JOURNAL/MARCH 8, 1975/VOL. 112
new .Stemetil 'Spansule' Capsules 10 mg for continuous, dependable anti-emetic action Indication: nausea and vomiting due to stimulation of the chemoreceptor trigger zone. Dosage: one or two 10 mg 'Spansule' Capsules every twelve hours. This dosage may be increased as required by increments of 10 mg every 2 or 3 days until symptoms are controlled. For maintenance therapy the dosage should be reduced to the minimum effective dose. Because of the lower pediatric dosage requirements, the 'Spansule' Capsules are not intended for use in children. ContraIndications: Comatose or deeply depressed states of the CNS due to hypnotics, analgesics, narcotics, alcohol, etc.; hypersensitivity to phenothiazines; blood dyscrasias; bone marrow depression; liver damage.
Warnings and precautions: etiology of vomiting should be established before using the drug as its antiemetic action may mask symptoms of intracranial pressure or intestinal obstruction. Patients with a history of convulsive disorders should be given an appropriate anticonvulsant while on therapy. Tardive dyskinesia may occur in patients on long-term therapy. If used with CNS depressants, the possibility of an additive effect should be considered. Use with great caution in patients with glaucoma or prostatic hypertrophy. The drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, especially during the first few days of therapy. Keep in mind that all medications should be used cautiously in pregnant patients, especially during the first trimester. Side effects: extrapyramidal reactions, disturbed temperature regulation and seizures have been encountered. Other side effects due to phenothiazine derivatives should be borne in mind; for complete list, see product monograph. Overdosage: no specific antidote; symptomatic treatment. If a pressor agent is required, norepinephrine may be given (not epinephrine as it may further depress the blood pressure).
Complete information upon request MEMBER
EEEJ
sc; E. M.
Sellers,
frcp[c] Summary: Chronic alcoholics may Frequent clinical reports document the 1973 were included in this study, as association of alcohol ingestion with were patients who were drowsy, comapresent with hyperglycemia or hypoglycemia. Because alcohol induces hypoglycemia in both adults and chil¬ tose or had seizures. The study group dren.1"5 In adults hypoglycemia typically initially comprised 208 chronic alco¬ glycogenolysis, chronic alcoholics occurs in chronic alcoholic patients usually have higher blood glucose holics and 201 age- and sex-matched values than do nonalcoholic subjects. with a history of poor dietary intake.4"6 nonalcoholic controls, staff members of In a prospective study of blood glucose Children are also susceptible to alcohol- the Addiction Research Foundation concentration in 201 chronic alcoholics, induced hypoglycemia because of their and volunteers from the Red Cross blood alcohol concentration, sex, normally low glycogen stores. In blood donor clinic. weight, type of beverage consumed and chronic alcoholics who are hypogly¬ On admission of each patient a time since last eating were not generally cemic, liver biopsies reveal depletion 20-ml blood sample was immediately associated with lower blood glucose of glycogen stores.3 The mechanism of drawn; none ate before the sample of values. The b
infrequency
md, ph d,
hypoglycemia ethanol-induced alterations in blood
was taken. Blood samples were also drawn from the control subjects. Con¬ centrations of blood alcohol, blood
in ambulatory chronic alcoholics may reflect the relatively ready availability
glucose concentration is complex but well understood.7"12 If hepa¬ reasonably of hostels, detoxification centres tic glycogen stores are adequate, the and hospitals in large cities. It is, combination of alcohol-induced glyco¬ however, important to be aware of and decreased glucose uptake genolysis the possible occurrence of hypoglycemia into muscles may result in an elevation in chronic alcoholics, particularly in blood glucose concentration.8"11 Once when community facilities for the stores are depleted, hypogly¬ glycogen chronic alcoholic are not available. cemia may develop because of impair¬ ment of gluconeogenesis by ethanol.8 Hypoglycemia can occur even after Resume: La glycemie chez des alcohol is no longer detectable in the alcooliques chroniques en 6tat d'6briete blood if glycogen stores are not replenished.6 Les alcooliques chroniques peuvent Chronic alcoholics are frequently presenter de I'hyperglycemie ou de to hospital emergency wards brought donne Etant que I'hypoglycemie. with altered mental status consistent I'alcool provoque la glycogenolyse, with that due to hypoglycemia. Recur¬ les alcooliques chroniques ont rent hypoglycemia can cause progres¬ d'ordinaire une glycemie plus elevee sive dementia not unlike the altered que les nonalcooliques. Une etude mental status and early-onset dementia prospective de la glycemie chez
201 alcooliques chroniques, de la concentration d'alcool dans le sang, du sexe, du poids, du genre d'alcool consomme et du laps de temps ecoule depuis le dernier repas, a permis de conclure a la rarete relative de I'hypoglycemie. Cette rarete chez des alcooliques chroniques ambulatoires peut s'-expliquer par la facilite relative de trouver dans les grandes villes des hdtels, des centres de desintoxication et des hopitaux. II est neanmoins important de garder presente a I'esprit la possibilite d'un episode d'hypoglycemie chez des alcooliques chroniques, particulierement dans les endroits depourvus des commodites
glucose,
serum
albumin,
serum
of chronic alcoholics.13,14 Because the incidence of, and the risk factors pre¬ disposing to, hypoglycemia in "skidrow" chronic alcoholics is unknown, we attempted to determine the pattern of blood glucose abnormalities and the prevalence of hypoglycemia in such a group of chronic alcoholics.
ysis.
When the alcoholic subjects were sober a detailed account was obtained of the amount and type of food eaten daily; the type of alcohol consumed daily during the past week; the usual frequency and history of alcoholic con¬ sumption; the usual daily alcoholic consumption; and a past history of light-headedness, seizures, blackouts and dizziness. Daily caloric intakes from food and the various alcoholic beverages were calculated. The data were analysed by a mul¬ tiple linear regression program on a IBM/370 computer.
Methods and materials All intoxicated male and female seen in the emergency room of the Addiction Research Founda¬ tion's Clinical Institute or at the Detoxication Centre, 410 Dundas St., Toronto, between June 1 and July 31,
patients
prementionnees. From the Clinical Institute, Addiction Research Foundation and The Toronto Western Hospital and departments of medicine and pharmacology, University of Toronto ?Supported in part by RODA Summer Use of Scholarship from the Non-Medical Directorate, Health and Welfare Drugs Canada Reprint requests to: Dr. E.M. Sellers, Clinical pharmacology program, Clinical Institute, Addiction Research Foundation, 33 Russell St.. Toronto, Ont. M5S 2S1
Table I.Comparison of mean values* of clinical and laboratory variables in male chronic alcoholics and normal male subjects Controls (n 131) Alcoholics (n 131) Variable 44.1 ± 15.1 (18-64) 11.6 47.5 ± (25-78) Age (yr) 78.8 ± 10.5 (55-114) 72.6 ± 12.0 (41-109) Weight (kg) 91.2 ± 15.6 (59-149) 104.3 ± 38.4 (42-199) Blood glucose (mg/dl) 11.6 ± 4.3 (5-30) 6.9 ± 3.6(0.5-21) BUN (mg/dl) 17.2 ± 9 6(10-28) 37.3 ± 36.9 (8-326) SG0T(IU/l) ?Results are expressed as mean ± standard error, with range of values indicated in parenthesis.
590 CMA JOURNAL/MARCH 8, 1975/VOL. 112
gluta-
mic oxaloacetic transaminase, blood urea nitrogen and psychoactive and analgesic drugs were determined on each sample by standard laboratory techniques. At the same time the blood sample was taken, information was re¬ corded for each patient regarding age, sex, weight, mental state, level of consciousness, usual alcoholic beverage and elapsed time since last consumption of food. Repeat samples from the same in¬ dividual and samples with blood al¬ cohol values of less than 0.3 g/1 were excluded from further analysis. The number of males investigated further was therefore 131. Because only 14 female chronic alcoholic subjects were studied, samples from these patients were also excluded from further anal¬
=
=
Results Table I summarizes the characteris¬ tics of the 131 alcoholics and 131 controls. The mean ages and blood glucose values were not different be¬ tween the groups. In the chronic alco¬ holics, BUN values and weights were significantly lower and SGOT values higher than in the controls (P < 0.05), though the range of SGOT values in chronic alcoholics was greater. At the time of entry into the study, mean al¬ cohol concentration in the males was 2.51 ± 0.95 g/1 (range, 0.30 to 4.53
g/1).
The wide range and distribution of blood alcohol values at the time of admission of the 131 male alcoholics are shown in Fig. 1. There was no relation between blood alcohol con¬ centration and type of beverage con¬
hyperglycemia. Larger alcohol intakes and longer durations of fasting (> 24 (P < 0.05). h) are associated with a greater degree Table III shows the distribution of of hypoglycemia. These biphasic effects types of beverage consumed in this of ethanol on blood glucose concentra¬ group of alcoholics. The higher alco¬ tion reflect initial stimulation of glycohol content of spirits/ is not associated genolysis and subsequent impairment with a decreased random blood glucose of gluconeogenesis from lactate by al¬ In both control and alcoholic subjects, blood glucose value increased with age
value.
Discussion Administration of 150 ml of whisky subjects results in an increase in blood glucose concentration in 30 to 60 minutes. The concentration then decreases more rapidly than in control subjects not receiving alcohol.8"10 Over¬ night fasting can decrease the initial to human
Table II.Characteristics of two
"hypoglycemic" alcoholics
sumed.5
2 shows the distribution of random blood glucose values in the 131 male subjects and 131 controls. The distribution is skewed to the right in chronic alcoholics to a greater ex¬ tent than in the normals. A chi-square test indicates that a significantly greater number of alcoholics have blood glu¬ cose values of > 110 mg/dl (P < 0.05). There are no differences in distribu¬ tion of blood glucose values of < 80 mg/dl between alcoholic and control subjects. Two "hypoglycemic" alcohol¬ ics with blood glucose values of 42 and 57 mg/dl were detected in the 131 male patients included in the analysis (Table II). Both patients were asympto¬ matic. Multiple regression analysis showed that there was no significant influence of weight, sex, SGOT, BUN, time since last meal, blood alcohol value, caloric intake from food, and type of beverage consumed (e.g. spirits, wine or beer) on blood glucose values.
cohol.4'*40 Alterations in insulin con¬ centration do not account for the rela¬ tive hypoglycemia because the insulin concentration decreases promptly as the blood glucose concentration decreases.12 The elevated blood glucose value observed in many of the alcoholics in this study reflects glycogenolysis in the presence of adequate caloric intake. Only two chronic alcoholics had blood glucose values of less than 60 mg/dl,
Patient A
Fig.
Patient B
*For nine other subjects full data were not available. fPredominant beverage consumed.
0.3 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 BLOOD ALCOHOL g/1
V: '^-^
FIG. 1.Distribution of blood alcohol concentrations on admission in 131 male chronic alcoholics.
,T\
¦¦¦¦'¦¦
"".:.-,
..-¦
-'
¦¦¦
^BLOOD
GLUGC&&i&iMK
FIG. 2.Distribution of random blood control subjects and chronic alcoholics.
glucose values in
131 male
age-matched
CMA JOURNAL/MARCH 8, 1975/VOL. 112 591
the lowest being 42 mg/dl. The patient with this value was neuropathologically normal. The reasons for the relative rarity of hypoglycemia in this group of patients are complex. In part, the ready availability of hostels, detoxification centres and hospitals, and the relative affluence of society, suggests that these chronic alcoholics seldom go without food for more than 24 hours. In addition, in the alcoholics we studied, alcohol was present in the blood at the time of blood glucose determination. Alcohol inhibition of peripheral glucose utilization may prevent the appearance of hypoglycemia." It is unfortunate that no previous comparable prospective studies were done before the introduction of detoxification centres in Toronto to assess the influence of these supportive facilities on the occurrence of hypoglycemia in the homeless alcoholic. Studies are needed in more remote parts of Canada without these community resources in order to define the prevalence of hypoglycemia and possible contribution of recurrent episodes to the early occurrence of dementia in chronic alcoholics.'4 The failure to confirm an increased risk of hypoglycemia due to liver disease,3 duration of fasting,9"0 intake of other drugs,. decreased weight9 or drinking'0 may reflect in part the difficulty in getting reliable historical information from these patients and, more important, the inability to control adequately the interdependent variables in each patient. Even though hypoglycemia in the chronic alcoholic seems to be rare, awareness of its possible occurrence is important. The high blood alcohol concentrations measured in these subjects emphasizes the difficulty in predicting whether a change in level of consciousness is due to alcoh.A or hypoglycemia, for subjects can drift from alcoholic stupor to hypoglycemic coma. It is judicious to assume that hypoglycemia occurs frequently enough in chronic alcoholics that all such individuals presenting to emergency rooms with seizures or altered mental status should have their blood glucose routinely determined. Except in the comatose patient administration of glucose can usually await the results of the chemical analysis. Glucagon will not be effective if glycogen stores are depleted.8'9 It is important in the clinical management of the chronic alcoholic with symptomatic hypoglycemia to recall that hypoglycemia can recur after admission to hospital. To prevent this, initial treatment of the patient with 50% glucose should be followed by
an infusion of 10% glucose for 24 hours. Chronic alcoholics with severe liver disease, renal disease or adrenal insufficiency, who require tolbutamide or who ingest excess salicylate, will have an increased risk of developing hypoglycemia.5 Chronic alcoholic patients with true diabetes will be more liable to wide fluctuations in blood glucose concentration if they continue to drink,15 and the diagnosis of diabetes can be made in error if patients have been drinking recently. We thank Mrs. J. Keck and Mrs. K. Chater and the nursing staffs of the clinical investigation unit and emergency room of the Clinical Institute, and the staff of the clinical chemistry laboratory and the Detoxication Centre for their cooperation and assistance. The donation of blood samples by Clinical Institute staff and Red Cross donors and the assistance of Mr. A. Kornaczewski in analysing these data are gratefully acknowledged. References 1. BROWN IM, HARVEY AM: Spontaneous hypoglycemia in "smoke" drinkers. JAMA 117: 12, 1941 2. TUCKER H ST G, PORTZR WB: Hypoglycemia following alcoholic intoxication. Am I Med Sd 204: 559, 1942 3. HED R, NYGREN A: Alcohol-induced hypoglycemia in chronic alcoholics with liver disease. Acta Med Scand 183: 507, 1968 4. H.wcsNs RD, KALANT H: The metabolism of ethanol and its metabolic effects. Pharmacol Rev 24: 68, 1972 5. SELTZER HS: Drug-induced hypoglycemia. Diabetes 21: 955, 1972 6. MARKs V, MEDD WE: Alcohol-induced hypoglycemia. Br I Psychiatry 110: 228, 1964 7. Han R: Clinical studies in chronic II. Carbohydrate metabolism in coholics with particular reference and insulin tolerances. Acta Med
alcoholism. chronic alto glucose Scand 162:
195, 1958 GE: Studies on the mechanism of ethanol-induced hypoglycemia. I Clin Invest 42: 497, 1963 9. FItEINKEL N, SINGER DC, ARKY RA, et al: Alcohol hypoglycemia. I. Carbohydrate metabolism of patients with clinical alcohol hypoglycemia and the experimental reproduction of the syndrome with pure ethanol. Ibid, p 1112 10. FREINKEL N, Aixy RA: Effects of alcohol on carbohydrate metabolism in man. Psychosom Med 28: 551, 1966 11. LOCHNER A, Wuu'F 3, MADIsoN LL: Ethanol8. FIELD JB, WILLIAMS HE, MORTIMORE
induced hypoglycemia. I. The acute effects of ethanol on hepatic glucose output and peripheral glucose utilization in fasted dogs.
Metabolism 16: 1, 1967 12. BAGDADE 3D, BIERMAN EL, PORTE D: Counterregulation of basal insulin secretion during ethanol hypoglycemia in diabetic and normal subjects. Diabetes 21: 65, 1972 13. RYBACK RS: Alcohol amnesia. Q I Stud Alcohol 31: 616, 1970 14. RANKIN JG, SCHMIDT W, POPHAM RE DE LINT J: Epidemiology of alcoholic liver disease: insights and problems, in Symposium on
Alcoholic Liver Pathology. Addiction Research Foundation, October 1973 (in press)
15. ARKY RA, VEYERBRANTS E, ABRAMSON EA:
Irreversible hypoglycemia: a complication of alcohol and insulin. JAMA 206: 575, 1968
592 CMA JOURNAL/MARCH 8, 1975/VOL. 112
new .Stemetil 'Spansule' Capsules 10 mg for continuous, dependable anti-emetic action Indication: nausea and vomiting due to stimulation of the chemoreceptor trigger zone. Dosage: one or two 10 mg 'Spansule' Capsules every twelve hours. This dosage may be increased as required by increments of 10 mg every 2 or 3 days until symptoms are controlled. For maintenance therapy the dosage should be reduced to the minimum effective dose. Because of the lower pediatric dosage requirements, the 'Spansule' Capsules are not intended for use in children. ContraIndications: Comatose or deeply depressed states of the CNS due to hypnotics, analgesics, narcotics, alcohol, etc.; hypersensitivity to phenothiazines; blood dyscrasias; bone marrow depression; liver damage.
Warnings and precautions: etiology of vomiting should be established before using the drug as its antiemetic action may mask symptoms of intracranial pressure or intestinal obstruction. Patients with a history of convulsive disorders should be given an appropriate anticonvulsant while on therapy. Tardive dyskinesia may occur in patients on long-term therapy. If used with CNS depressants, the possibility of an additive effect should be considered. Use with great caution in patients with glaucoma or prostatic hypertrophy. The drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, especially during the first few days of therapy. Keep in mind that all medications should be used cautiously in pregnant patients, especially during the first trimester. Side effects: extrapyramidal reactions, disturbed temperature regulation and seizures have been encountered. Other side effects due to phenothiazine derivatives should be borne in mind; for complete list, see product monograph. Overdosage: no specific antidote; symptomatic treatment. If a pressor agent is required, norepinephrine may be given (not epinephrine as it may further depress the blood pressure).
Complete information upon request MEMBER
EEEJ
