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PHENYLKETONURIA
1040 PHENYLKETONURIA
SIR,-Letters from Mr. Clough and Dr. Johnston (March 26) and Dr. Scott (April 16) have drawn attention to the inadequacy of the ’Phenistix’ test for the early detection of all infants suffering from phenylketonuria. At present this is the method recommended by the Ministry of Health, and by its use a number of affected children have been diagnosed early enough to benefit from treatment. Despite the known fallacies, until this technique can be generally replaced by a better one the useful work now being done by large numbers of health visitors should not be discouraged. Other methods of mass screening, all requiring laboratory facilities and posing greater problems of administration and financial support, are being investigated at various centres. Until it is possible to implement such measures on a permanent basis, as Dr. Scott appears to be well on the way to doing in Scotland, there is no alternative to the phenistix test, and its use must be actively encouraged. We would not, however, accept a negative phenistix test as adequate before an adoption. Facilities for assay of bloodphenylalanine levels are now fairly generally available, and a specimen can be obtained for this test when blood is being taken to exclude syphilis. Blood-testing is also essential in the investigation of siblings of known nhenvlketonurics.
E. G. HALL F. P. HUDSON.
Alder Hey Children’s Hospital,
Liverpool
12.
GLUCAGON-STIMULATED INSULIN RELEASE SIR,-Elrick et al.," and since them others, have reported that glucagon induces an increase in the peripheral arterio-
glucose concentration, and an increase in the arterial-venous index ŇŇ,which is considered a measure A venous
of
differences in
glucose
utilisation.
The
early discharge of endogenous
A-V
Effect of total pancreatectomy on influence of index of blood-glucose in the dog. (p < 0-05.)
glucagon
on
A
insulin after glucagon administration, to which Samols et awl.2 and Crockford et a1.3 have drawn attention, as well as the insulin release from isolated pancreas in vitro under the influence of glucagon, J ; are to be considered when studying the effects of insulin on the peripheral metabolism of glucose. This is illustrated by the accompanying figure which shows that pancreatectomy significantly reduces the striking rise in the A—V —
index observed in the first 15 minutes after intravenous
A
injection, in the dog, of glucagon (100 g. per kg.). During that time, insulin-plasma levels are notably increased in the dog as we have observed, and this confirms the finding of Samols et al.2 1. 2. 3. 4.
5.
Elrick, H., Hlad, C. J., Jr., Witten, T. J. clin. Invest. 1955, 34, 1830. Samols, E., Marri, G., Marks, V. Lancet, 1965, ii, 415. Crockford, P. M., Porte, D., Jr., Wood, F. C., Jr., Williams, R. H. Metabolism, 1966, 15, 114. Vecchio, D., Luyckx, A., Zahnd, G. R., Renold, A. E. in Proceedings of the Conference on Problems Connected with the Preparation and Use of Labelled Proteins in Tracer Studies. Pisa, 1966 (in the press). Euratom, Brussels, 1966. Turner, D. S., McIntyre, N. Lancet, Feb. 12, 1966. p. 351.
We think that this early discharge of insulin could contribute, at least in part, to the increase of peripheral glucose uptake observed after glucagon iniection or infusion. Department of Clinical Medicine and Pathology, PIERRE LEFEBVRE Institute of Medicine, ALFRED LUYCKX. Hôpital de Bavière, Liège, Belgium.
AGE. GLUCOSE TOLERANCE. AND INSULIN SIR,-The preliminary communication by Dr. Crockford and his colleagues (Feb. 26) on the influence of age on intravenous glucose tolerance and serum immunoreactive insulin (I.R.I.) levels prompts us to comment on our recent survey of postprandial glycaemia in 456 members of the general population to evaluate the response to a new glucose-gelatin preparation (’ Geladex ’ Uni-Tech Chemical Manufacturing Company, Sun Valley, California). For this evaluation, members of a suburban community were invited to attend a series of diabetes-detection clinics held in a local hospital. Only healthy individuals were encouraged to participate-those with knowledge of suspected or diagnosed diabetes mellitus were excluded from the investigation. All participants were requested to fast for at least 4 hours before attending the clinic, where they received 225 ml. of cherryflavoured gelatin, containing 100 g. of glucose, which was chilled to a semi-solid consistency before serving. Participants were encouraged to eat the mixture within 5 minutes, and were asked to complete a brief questionary on their subjective impressions of the test meal. In almost all cases, the participants considered the preparation to be palatable and similar to a fruit-flavoured gelatin often used for desserts or salads. Blood was collected from the subjects 2 hours after ingestion of the glucose challenge. In one session of the clinic, bloodspecimens were drawn before, as well as at, the 2-hourpostprandial period. After blood-collection, the participants were individually asked a uniform group of questions designed to reveal any possible symptoms related to diabetes mellitus, or a familial history of the disease. Serum was separated from all samples within 30 minutes, and assayed for " true " glucose in a ’Technicon Autoanalyzer ’ by a modified glucose oxidase method. Analysis of specimens collected from 91 patients before the test meal disclosed only 3 individuals with serum levels of " true" glucose that exceeded 110 mg. per 100 ml.-our upper normal limit for the fasting state. These individuals exhibited initial values of 120, 135, and 225 mg. per 100 ml., which, at the 2-hour-sampling period, rose to concentrations of 125, 450, and 400 mg. per 100 ml., respectively. It therefore appeared reasonable to assume that a high proportion of the participants in the other clinics were probably also in the post-absorptive state before ingestion of the test dose of glucose. Tabulation of the 2-hour serum-glucose levels of the entire study group disclosed a surprisingly high incidence of apparent" glucose intolerance. For example, serum-levels of " true glucose of 32% of the males and 36% of the females were in excess of 140 mg. per 100 ml. at the 2-hour-postprandial period. The hyperglycaemic tendency became more conspicuous with increasing age in both sexes, but particularly in the females. Thus 40 out of 57 males (70%) under 50 years of age had serumvalues of " true " glucose below 110 per 100 ml. Levels below this limit were exhibited by only 52 out of 110 females (47%) in this age-group. Out of 93 males and 196 females over 50 years of age, 62% and 61%, respectively, showed 2-hourglucose values exceeding 110 mg. per 100 ml. The reason for the apparent difference in glucose tolerance between males and females less than 50 years of age remains to be determined. It is tempting to speculate, however, that the prevalence of glucose intolerance in premenopausal females may be related to hormonal mechanisms. Possibly the stress associated with pregnancy during the child-bearing years may tax the endocrine pancreas of females to a significant extent. Review of the questionaries showed that 39-4% of the females and 30-8° of the males in the studv 1.
sroun
had
Saifer, A., Gerstenfeld, S. J. Lab. clin. Med. 1958, 51,
a
familial
448.
SIR,-Letters from Mr. Clough and Dr. Johnston (March 26) and Dr. Scott (April 16) have drawn attention to the inadequacy of the ’Phenistix’ test for the early detection of all infants suffering from phenylketonuria. At present this is the method recommended by the Ministry of Health, and by its use a number of affected children have been diagnosed early enough to benefit from treatment. Despite the known fallacies, until this technique can be generally replaced by a better one the useful work now being done by large numbers of health visitors should not be discouraged. Other methods of mass screening, all requiring laboratory facilities and posing greater problems of administration and financial support, are being investigated at various centres. Until it is possible to implement such measures on a permanent basis, as Dr. Scott appears to be well on the way to doing in Scotland, there is no alternative to the phenistix test, and its use must be actively encouraged. We would not, however, accept a negative phenistix test as adequate before an adoption. Facilities for assay of bloodphenylalanine levels are now fairly generally available, and a specimen can be obtained for this test when blood is being taken to exclude syphilis. Blood-testing is also essential in the investigation of siblings of known nhenvlketonurics.
E. G. HALL F. P. HUDSON.
Alder Hey Children’s Hospital,
Liverpool
12.
GLUCAGON-STIMULATED INSULIN RELEASE SIR,-Elrick et al.," and since them others, have reported that glucagon induces an increase in the peripheral arterio-
glucose concentration, and an increase in the arterial-venous index ŇŇ,which is considered a measure A venous
of
differences in
glucose
utilisation.
The
early discharge of endogenous
A-V
Effect of total pancreatectomy on influence of index of blood-glucose in the dog. (p < 0-05.)
glucagon
on
A
insulin after glucagon administration, to which Samols et awl.2 and Crockford et a1.3 have drawn attention, as well as the insulin release from isolated pancreas in vitro under the influence of glucagon, J ; are to be considered when studying the effects of insulin on the peripheral metabolism of glucose. This is illustrated by the accompanying figure which shows that pancreatectomy significantly reduces the striking rise in the A—V —
index observed in the first 15 minutes after intravenous
A
injection, in the dog, of glucagon (100 g. per kg.). During that time, insulin-plasma levels are notably increased in the dog as we have observed, and this confirms the finding of Samols et al.2 1. 2. 3. 4.
5.
Elrick, H., Hlad, C. J., Jr., Witten, T. J. clin. Invest. 1955, 34, 1830. Samols, E., Marri, G., Marks, V. Lancet, 1965, ii, 415. Crockford, P. M., Porte, D., Jr., Wood, F. C., Jr., Williams, R. H. Metabolism, 1966, 15, 114. Vecchio, D., Luyckx, A., Zahnd, G. R., Renold, A. E. in Proceedings of the Conference on Problems Connected with the Preparation and Use of Labelled Proteins in Tracer Studies. Pisa, 1966 (in the press). Euratom, Brussels, 1966. Turner, D. S., McIntyre, N. Lancet, Feb. 12, 1966. p. 351.
We think that this early discharge of insulin could contribute, at least in part, to the increase of peripheral glucose uptake observed after glucagon iniection or infusion. Department of Clinical Medicine and Pathology, PIERRE LEFEBVRE Institute of Medicine, ALFRED LUYCKX. Hôpital de Bavière, Liège, Belgium.
AGE. GLUCOSE TOLERANCE. AND INSULIN SIR,-The preliminary communication by Dr. Crockford and his colleagues (Feb. 26) on the influence of age on intravenous glucose tolerance and serum immunoreactive insulin (I.R.I.) levels prompts us to comment on our recent survey of postprandial glycaemia in 456 members of the general population to evaluate the response to a new glucose-gelatin preparation (’ Geladex ’ Uni-Tech Chemical Manufacturing Company, Sun Valley, California). For this evaluation, members of a suburban community were invited to attend a series of diabetes-detection clinics held in a local hospital. Only healthy individuals were encouraged to participate-those with knowledge of suspected or diagnosed diabetes mellitus were excluded from the investigation. All participants were requested to fast for at least 4 hours before attending the clinic, where they received 225 ml. of cherryflavoured gelatin, containing 100 g. of glucose, which was chilled to a semi-solid consistency before serving. Participants were encouraged to eat the mixture within 5 minutes, and were asked to complete a brief questionary on their subjective impressions of the test meal. In almost all cases, the participants considered the preparation to be palatable and similar to a fruit-flavoured gelatin often used for desserts or salads. Blood was collected from the subjects 2 hours after ingestion of the glucose challenge. In one session of the clinic, bloodspecimens were drawn before, as well as at, the 2-hourpostprandial period. After blood-collection, the participants were individually asked a uniform group of questions designed to reveal any possible symptoms related to diabetes mellitus, or a familial history of the disease. Serum was separated from all samples within 30 minutes, and assayed for " true " glucose in a ’Technicon Autoanalyzer ’ by a modified glucose oxidase method. Analysis of specimens collected from 91 patients before the test meal disclosed only 3 individuals with serum levels of " true" glucose that exceeded 110 mg. per 100 ml.-our upper normal limit for the fasting state. These individuals exhibited initial values of 120, 135, and 225 mg. per 100 ml., which, at the 2-hour-sampling period, rose to concentrations of 125, 450, and 400 mg. per 100 ml., respectively. It therefore appeared reasonable to assume that a high proportion of the participants in the other clinics were probably also in the post-absorptive state before ingestion of the test dose of glucose. Tabulation of the 2-hour serum-glucose levels of the entire study group disclosed a surprisingly high incidence of apparent" glucose intolerance. For example, serum-levels of " true glucose of 32% of the males and 36% of the females were in excess of 140 mg. per 100 ml. at the 2-hour-postprandial period. The hyperglycaemic tendency became more conspicuous with increasing age in both sexes, but particularly in the females. Thus 40 out of 57 males (70%) under 50 years of age had serumvalues of " true " glucose below 110 per 100 ml. Levels below this limit were exhibited by only 52 out of 110 females (47%) in this age-group. Out of 93 males and 196 females over 50 years of age, 62% and 61%, respectively, showed 2-hourglucose values exceeding 110 mg. per 100 ml. The reason for the apparent difference in glucose tolerance between males and females less than 50 years of age remains to be determined. It is tempting to speculate, however, that the prevalence of glucose intolerance in premenopausal females may be related to hormonal mechanisms. Possibly the stress associated with pregnancy during the child-bearing years may tax the endocrine pancreas of females to a significant extent. Review of the questionaries showed that 39-4% of the females and 30-8° of the males in the studv 1.
sroun
had
Saifer, A., Gerstenfeld, S. J. Lab. clin. Med. 1958, 51,
a
familial
448.