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ADRENALINE RESPONSE TO HYPOGLYCAEMIA AND INSULIN SPECIES
1332 DISTRIBUTION BY SUBSITE OF COLORECTAL CANCER FOUND AT NECROPSY AND (A) RECOGNISED AS UNDERLYING CAUSE OF DEATH OR (B) UNRELATED TO PRIMARY CAUSE OF DEATH (NON-FATAL)
I
Numbers of cases
on
Distribution bv site (%)
I
latent cancers of the right colon were in people older than 70. This
(eg, complete colonoscopy and double contrast X-ray) in old people and by a less aggressive attitude by clinicians. The prevalence of unsuspected colorectal cancer in our series was 9-6per 1000, increasing among men from 3-9 in the age group 40-49 to 15-9 per 1000 in those aged over 80 and among women from 3 7 to 14-3 per 1000, respectively. The prevalences we found are lower than the 20-3 per 1000 reported2 for Hawaiian Japanese over 65 (to 10-2 per 1000 in our series for those aged 60 plus). For those over 40 the prevalence we found is only slightly less than that reported by Berg et aP(12’8 per 1000) in a large series of necropsies in Los Angeles county between 1953 and 1959. Our results are also lower than those reported by Lee3 among Chinese in Singapore (13-1for all over age 14 and 27-6 for those aged 60 plus). Differences in the prevalence of latent cancers found at necropsy probably reflect real differences in the frequency of the lesion among populations as well as differences in the methods of ascertainment of malignant lesions. Institute of Anatomy and Histopathology, University of Tneste, 34125 Trieste, Italy
MAURO DELENDI DANIELA GARDIMAN
Unit of Analytical Epidemiology, International Agency for Research on Cancer, 69372 Lyon, France
ELIO RIBOLI ANNIE J. SASCO
Berg JW, Downing A, Lukes RJ. Prevalence of undiagnosed cancer of the large bowel
found at autopsy Cancer 1970; 25: 1076-80. 2. Stemmermann GN. Unsuspected cancer in elderly Hawaiian Japanese Hum Pathol 1982; 13: 1039-44. 3. Lee YS. Incidental carcinoma of the colorectum at autopsy and its effects on the incidence and future trends of colorectal cancers in Singapore. Cancer 1988; 61: 1059-64. 4. Berrino F, Vigano G, Gatta G, Crosignani P, Pisani P, Macaluso M. In. Muir C, Waterhouse J, Mack T, Powell J, Whelan S, eds. Cancer incidence in five continents: vol V (IARC Sci Publ no 88) Lyon: International Agency for Research on Cancer, 1987: 560-65.
ADRENALINE RESPONSE TO HYPOGLYCAEMIA AND INSULIN SPECIES
Siram baffled that Dr Kerr and his colleagues should believe their one case report (April 15, p 836) to "suggest that adrenaline secretion in response to hypoglycaemia may be affected by the
species of insulin". They give too few details of their investigations of January, 1989, for valid comparison with the two previous studies. Were the initial glucose levels at the start of the studies similar, or were fructosamine levels similar? The glucose threshold at which adrenaline "secretion" is triggered is strongly influenced by metabolic (certainly glycaemic) control, but the published evidence, as well as common sense, indicates a period much less than the six weeks or more for which glycated haemoglobin concentrations give a notion of average glycaemia. Yet their only evidence of "metabolic control" comes from the three haemoglobin Al percentages. In the absence of measurement of insulin antibodies we may that their patient had substantial concentrations of these antibodies, raised by use of bovine ultralente (Novo) in 1985-86, assume
at age:
which estimates are based are shown in parentheses
may be explained by difficulty with extensive diagnostic procedures
1.
Prevalence (Der 1000 necronsies)
(FATAL)
and perhaps reactivated by beef soluble and protamine-like insulins in 1989. Hence, many insulin variables may have been quite different between the two clamp studies-in particular, the free insulin concentrations, the rates of insulin disposal, and the rates of change in both free insulin and, especially, glucose concentrations in the 5 or 10 minutes before the adrenaline determination (plasma adrenaline concentration has a short half-life). Hypoglycaemia is not the only stimulus that increases plasma adrenaline concentration. Anxiety and other emotions may do so, and apparently while there was no increase in pulse rate in August, 1988, despite a six-fold increase in plasma adrenaline, heart rate did change (presumably upwards) in January, 1989. The question of
the symptomatic response to hypoglycaemia is complicated by its tendency to disappear with increasing duration of diagnosed diabetes. What is certain is that upsets in glycaemic control (especially hypoglycaemia) will continue to occur if patients are switched from notably antigenic insulins to those much less so (such as the highly purified porcine and human insulins) without reduction in dose, at least initially-as surprisingly was done by Kerr et al in August, 1986. Difficulties caused by antibody formation can be complicated by alterations in formulation. With as empirical a business as individual glycaemic control, there may be patients who fare better on beef and porcine insulin than on human, and on impure rather than pure insulin preparations. But it would prima facie seem a sound policy to aim to replace defective human insulin secretion by insulin preparations of the same or closely similar structures (and as little contaminated as possible); and thus reduce and retard the generation of insulin antibodies. This would seem especially useful for patients starting treatment with insulin, even if such a policy might not bear much fruit for several years. Adrenaline secretion may vary with the rate and extent of decrease in glycaemia, and with the initial blood-glucose
concentration, but there is nothing in Kerr and colleagues’ report to
give any substantial reason to believe that the species of insulin itself either alters the adrenaline response or is a cause of hypoglycaemic unawareness.
Sheikh Rashid Diabetes Unit, Radcliffe Infirmary, Oxford OX2 6HE
T. D. R. HOCKADAY
NEONATAL HYPOGLYCAEMIA
SIR,-Your editorial (April 22, p 882) suggests that the blood glucose be kept above 2-5 mmol/1 in newborn infants. The results of Koh et al,’ cited in the editorial, are only partly relevant because only five of their patients were newborn (gestational ages not reported) and a neurophysiological effect of a blood glucose as high as5 mmol/1 was found in only one of them. We have studied nine preterm infants who had a blood glucose below 1.7 mmol/lin the first hours of life, and no effect of hypoglycaemia was found in visual evoked potentials in amplitude integrated EelsWe did, however, find an increase in cerebral blood flow at a blood glucose below 17 mmolll, reflecting a compensatory mechanism and, possibly, stress.
I
Numbers of cases
on
Distribution bv site (%)
I
latent cancers of the right colon were in people older than 70. This
(eg, complete colonoscopy and double contrast X-ray) in old people and by a less aggressive attitude by clinicians. The prevalence of unsuspected colorectal cancer in our series was 9-6per 1000, increasing among men from 3-9 in the age group 40-49 to 15-9 per 1000 in those aged over 80 and among women from 3 7 to 14-3 per 1000, respectively. The prevalences we found are lower than the 20-3 per 1000 reported2 for Hawaiian Japanese over 65 (to 10-2 per 1000 in our series for those aged 60 plus). For those over 40 the prevalence we found is only slightly less than that reported by Berg et aP(12’8 per 1000) in a large series of necropsies in Los Angeles county between 1953 and 1959. Our results are also lower than those reported by Lee3 among Chinese in Singapore (13-1for all over age 14 and 27-6 for those aged 60 plus). Differences in the prevalence of latent cancers found at necropsy probably reflect real differences in the frequency of the lesion among populations as well as differences in the methods of ascertainment of malignant lesions. Institute of Anatomy and Histopathology, University of Tneste, 34125 Trieste, Italy
MAURO DELENDI DANIELA GARDIMAN
Unit of Analytical Epidemiology, International Agency for Research on Cancer, 69372 Lyon, France
ELIO RIBOLI ANNIE J. SASCO
Berg JW, Downing A, Lukes RJ. Prevalence of undiagnosed cancer of the large bowel
found at autopsy Cancer 1970; 25: 1076-80. 2. Stemmermann GN. Unsuspected cancer in elderly Hawaiian Japanese Hum Pathol 1982; 13: 1039-44. 3. Lee YS. Incidental carcinoma of the colorectum at autopsy and its effects on the incidence and future trends of colorectal cancers in Singapore. Cancer 1988; 61: 1059-64. 4. Berrino F, Vigano G, Gatta G, Crosignani P, Pisani P, Macaluso M. In. Muir C, Waterhouse J, Mack T, Powell J, Whelan S, eds. Cancer incidence in five continents: vol V (IARC Sci Publ no 88) Lyon: International Agency for Research on Cancer, 1987: 560-65.
ADRENALINE RESPONSE TO HYPOGLYCAEMIA AND INSULIN SPECIES
Siram baffled that Dr Kerr and his colleagues should believe their one case report (April 15, p 836) to "suggest that adrenaline secretion in response to hypoglycaemia may be affected by the
species of insulin". They give too few details of their investigations of January, 1989, for valid comparison with the two previous studies. Were the initial glucose levels at the start of the studies similar, or were fructosamine levels similar? The glucose threshold at which adrenaline "secretion" is triggered is strongly influenced by metabolic (certainly glycaemic) control, but the published evidence, as well as common sense, indicates a period much less than the six weeks or more for which glycated haemoglobin concentrations give a notion of average glycaemia. Yet their only evidence of "metabolic control" comes from the three haemoglobin Al percentages. In the absence of measurement of insulin antibodies we may that their patient had substantial concentrations of these antibodies, raised by use of bovine ultralente (Novo) in 1985-86, assume
at age:
which estimates are based are shown in parentheses
may be explained by difficulty with extensive diagnostic procedures
1.
Prevalence (Der 1000 necronsies)
(FATAL)
and perhaps reactivated by beef soluble and protamine-like insulins in 1989. Hence, many insulin variables may have been quite different between the two clamp studies-in particular, the free insulin concentrations, the rates of insulin disposal, and the rates of change in both free insulin and, especially, glucose concentrations in the 5 or 10 minutes before the adrenaline determination (plasma adrenaline concentration has a short half-life). Hypoglycaemia is not the only stimulus that increases plasma adrenaline concentration. Anxiety and other emotions may do so, and apparently while there was no increase in pulse rate in August, 1988, despite a six-fold increase in plasma adrenaline, heart rate did change (presumably upwards) in January, 1989. The question of
the symptomatic response to hypoglycaemia is complicated by its tendency to disappear with increasing duration of diagnosed diabetes. What is certain is that upsets in glycaemic control (especially hypoglycaemia) will continue to occur if patients are switched from notably antigenic insulins to those much less so (such as the highly purified porcine and human insulins) without reduction in dose, at least initially-as surprisingly was done by Kerr et al in August, 1986. Difficulties caused by antibody formation can be complicated by alterations in formulation. With as empirical a business as individual glycaemic control, there may be patients who fare better on beef and porcine insulin than on human, and on impure rather than pure insulin preparations. But it would prima facie seem a sound policy to aim to replace defective human insulin secretion by insulin preparations of the same or closely similar structures (and as little contaminated as possible); and thus reduce and retard the generation of insulin antibodies. This would seem especially useful for patients starting treatment with insulin, even if such a policy might not bear much fruit for several years. Adrenaline secretion may vary with the rate and extent of decrease in glycaemia, and with the initial blood-glucose
concentration, but there is nothing in Kerr and colleagues’ report to
give any substantial reason to believe that the species of insulin itself either alters the adrenaline response or is a cause of hypoglycaemic unawareness.
Sheikh Rashid Diabetes Unit, Radcliffe Infirmary, Oxford OX2 6HE
T. D. R. HOCKADAY
NEONATAL HYPOGLYCAEMIA
SIR,-Your editorial (April 22, p 882) suggests that the blood glucose be kept above 2-5 mmol/1 in newborn infants. The results of Koh et al,’ cited in the editorial, are only partly relevant because only five of their patients were newborn (gestational ages not reported) and a neurophysiological effect of a blood glucose as high as5 mmol/1 was found in only one of them. We have studied nine preterm infants who had a blood glucose below 1.7 mmol/lin the first hours of life, and no effect of hypoglycaemia was found in visual evoked potentials in amplitude integrated EelsWe did, however, find an increase in cerebral blood flow at a blood glucose below 17 mmolll, reflecting a compensatory mechanism and, possibly, stress.