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PLASMA-INSULIN LEVELS DURING ORAL GLUCOSE LOADS IN PREDIABETIC SUBJECTS
1182
PLASMA-INSULIN LEVELS DURING ORAL GLUCOSE LOADS IN PREDIABETIC SUBJECTS SiR,-While it is generally agreed that diabetic patients with raised fasting blood-glucose levels have a delayed initial release of endogenous insulin, much controversy still exists about the plasma-insulin response in prediabetes and chemical diabetes. Dr Cerasi and his colleagues,1.2 in their enthusiasm for proving that " a low insulin response to glucose is characteristic of the prediabetic state ", argue in a circle. They demonstrate a reduced insulin response to intravenously administered glucose in prediabetics, but the so-called prediabetics were deemed to be prediabetics on the basis of a low insulin response after intravenous glucose. Cerasi et al. now have extended their studies and found that healthy subjects with a low insulin response to intravenous glucose infusion also demonstrate a decreased insulin response to oral glucose. It is hardly revolutionary or surprising that people if selected as having a low insulin response to glucose do have a low insulin response. Elliott P. Joslin Research
Laboratory, Harvard Medical School, 170 Pilgrim Road, Boston 02215, Massachusetts, U.S.A.
KLAUS
JOHANSEN.
*
** We showed Dr Johansen’s letter to Dr Cerasi and his colleagues, whose reply follows.-ED. L.
prediabetics for this group such as increased family history of diabetes or cortisone-glucose testing.1 Secondly, they found diminished absolute insulin responses to oral glucose in the mild diabetic subjects. This finding is in agreement with previous work2 but at odds with the bulk of studies of chemical diabetic patients,3--8 as well as of genetic prediabetics.9-12 The authors attempt to reconcile the discrepancy by reasoning that calculating insulin-glucose ratios or dose-response curves would uncover diminished insulin responses in the previous reports. Even if one assumes, as many do not, that plasmainsulin levels normally relate to peripheral plasma-glucose and not the glucose load, the majority of the previous reports show " normal " insulin/glucose ratios for chemical diabetics. 3-6 More likely, the relatively lower insulin responses of the chemical diabetic subjects in the present report may simply reflect population variation or may be explained in part by the fact that the diabetic group was 20 of
years older than the control group,
responders (" prediabetics ")
Department of Endocrinology and Metabolism, Karolinska Sjukhuset, 104 01 Stockholm, Sweden.
EROL CERASI SUAD EFENDIĆ ROLF LUFT.
School of Medicine, P.O. Box 875,
Biscayne Annex, Miami, Florida 33152,
solely on the basis of their reduced insulin response. The authors cite no additional independent characteristics
of Sonksen et al.13 suggest the use of small amounts of insulin to correct severe ketoacidotic coma. Both reports agree that slow infusions of small amounts of insulin intravenously may provide a rational approach to insulin administration. However, patients with severe acidosis are relatively refractory to the actions of insulin. Patients with severe acidosis, profound coma, and plasma acetones of 4+ are usually treated quite vigorously to restore normal protein, fat, and carbohydrate metabolism. The emergency treatment consists of large doses of regular insulin, given subcutaneously and intravenously. As the acidosis is corrected, an increase to insulin sensitivity is seen, and the dosage is decreased. The use of insulin in intravenous infusions to treat patients has been reported previously. 14,15 However,
3. 4.
5. 6. 7. 8. 9.
10. 11. 12.
group 1. 2. 3.
Cerasi, E., Luft. R., Efendić, S. Diabetes, 1972, 21, 224. Cerasi, E., Luft, R., Efendić, S. Lancet, April 14, 1973, p. 794. Cerasi, E., Luft, R. Acta endocr. 1967, 55, 305.
ANDREW L. TAYLOR.
INSULIN INFUSION IN DIABETIC COMA SiR,—Dr Menzel’s letter (April 14, p. 830) and the work
1. 2.
SIR,-Some of the interpretations of the data presented by Dr Cerasi and his colleagues on insulin response to glucose in normal and mild diabetic subjects appear misleading. First, it is simple tautology to conclude that " the insulinreleasing potency of glucose is reduced " in prediabetic subjects, since they had defined prediabetics by low insulin responses to glucose. Similarly, it is unwarranted to conclude a progressive reduction of sensitivity of the P-cell to glucose from normal to prediabetic to diabetic subjects, when the prediabetic group was selected from the control
that the low-insulin excluded from the
controls. There is a consensus that diminished insulin release to glucose is characteristic of overt diabetes in normal-weight subjects, but the enigma remains, undiminished by the findings of Dr Cerasi and his colleagues, whether the insulinopenia is the primary defect or secondary to peripheral or humoral changes.
U.S.A.
SiR,-Dr Johansen seems to be unaware of the number of papers stating that the insulin response to oral glucose is not reduced in mild maturity-onset diabetes or chemical diabetes (for references see our original paper). As to the prediabetics, he may read in one of our papers3 our description of low-insulin response to oral glucose. The present report*demonstrates that normal insulin response can be elicited in these subjects provided that the hyperglycsemic stimulus is raised sufficiently. Furthermore, we are astonished by the confidence Dr Johansen shows in excluding a priori the possible role of intestinal factors in modulating the final insulin response under physiological circumstances in these subjects. We had not the boldness to draw such a conclusion without the appropriate experimental evidence. Finally, we recommend the re-reading of our discussion which may, we hope, deserve attention for some interesting, albeit non-revolutionary, aspects of P-cell dysfunction in diabetes.
or
were
13. 14. 15.
Cerasi, E., Luft, R. Acta endocr. 1967, 55, 278. Floyd, J. C., Jr., Fajans, S. S., Conn, J. W., Thiffault, C., Knopf, R., Guntsche, E. J. clin. Endocr. Metab. 1968, 28, 266. Levin, S. R., Reed, J. W., Ching, K. N., Davis, J. W., M. R., Forsham, P. H. Diabetes, 1973, 22, 194. Jackson, W. P. V., Keller, P. Hormones, 1972, 3, 361. Reaven, G. M., Shen, S. W., Silvers, A., Farquhar, J. W. Dibaetes, 1971, 20, 416. Chiles, R., Tzagournis, M. ibid. 1970, 19, 458. Seltzer, H. S., Allen, W. E., Herron, A. L., Jr., Brennen, M. T. J. clin. Invest. 1967, 46, 323. Yalow, R. S., Berson, S. A. ibid. 1960, 39, 1157. Soeldner, J. S., Gleason, R. E., Williams, R. F., Garcia, M. J., Beardwood, D. M., Marble, A. Diabetes, 1968, 17, 17. Siperstein, M. D., Unger, R. H., Madison, L. L. J. clin. Invest. 1968, 47, 1973. Ricketts, H. T., Cherry, R. A., Kirsteins, L. Diabetes, 1966, 15, 880. Grodsky, G. M., Karam, J. H., Pavlatus, F. Ch., Forsham, P. H. Lancet, 1965, i, 290. Sonksen, P. H., Srivastava, M. C., Tompkins, C. V., Nabarro, J. D. N. Lancet, 1972, ii, 155. Galloway, J. A., Shuman, C. R. Am. J. Med. 1963, 34, 177. Oppenheimer, H. E. Diabetes Mellitus: Diagnosis and Treatment; chap. XXXI, p. 151. 1964.
PLASMA-INSULIN LEVELS DURING ORAL GLUCOSE LOADS IN PREDIABETIC SUBJECTS SiR,-While it is generally agreed that diabetic patients with raised fasting blood-glucose levels have a delayed initial release of endogenous insulin, much controversy still exists about the plasma-insulin response in prediabetes and chemical diabetes. Dr Cerasi and his colleagues,1.2 in their enthusiasm for proving that " a low insulin response to glucose is characteristic of the prediabetic state ", argue in a circle. They demonstrate a reduced insulin response to intravenously administered glucose in prediabetics, but the so-called prediabetics were deemed to be prediabetics on the basis of a low insulin response after intravenous glucose. Cerasi et al. now have extended their studies and found that healthy subjects with a low insulin response to intravenous glucose infusion also demonstrate a decreased insulin response to oral glucose. It is hardly revolutionary or surprising that people if selected as having a low insulin response to glucose do have a low insulin response. Elliott P. Joslin Research
Laboratory, Harvard Medical School, 170 Pilgrim Road, Boston 02215, Massachusetts, U.S.A.
KLAUS
JOHANSEN.
*
** We showed Dr Johansen’s letter to Dr Cerasi and his colleagues, whose reply follows.-ED. L.
prediabetics for this group such as increased family history of diabetes or cortisone-glucose testing.1 Secondly, they found diminished absolute insulin responses to oral glucose in the mild diabetic subjects. This finding is in agreement with previous work2 but at odds with the bulk of studies of chemical diabetic patients,3--8 as well as of genetic prediabetics.9-12 The authors attempt to reconcile the discrepancy by reasoning that calculating insulin-glucose ratios or dose-response curves would uncover diminished insulin responses in the previous reports. Even if one assumes, as many do not, that plasmainsulin levels normally relate to peripheral plasma-glucose and not the glucose load, the majority of the previous reports show " normal " insulin/glucose ratios for chemical diabetics. 3-6 More likely, the relatively lower insulin responses of the chemical diabetic subjects in the present report may simply reflect population variation or may be explained in part by the fact that the diabetic group was 20 of
years older than the control group,
responders (" prediabetics ")
Department of Endocrinology and Metabolism, Karolinska Sjukhuset, 104 01 Stockholm, Sweden.
EROL CERASI SUAD EFENDIĆ ROLF LUFT.
School of Medicine, P.O. Box 875,
Biscayne Annex, Miami, Florida 33152,
solely on the basis of their reduced insulin response. The authors cite no additional independent characteristics
of Sonksen et al.13 suggest the use of small amounts of insulin to correct severe ketoacidotic coma. Both reports agree that slow infusions of small amounts of insulin intravenously may provide a rational approach to insulin administration. However, patients with severe acidosis are relatively refractory to the actions of insulin. Patients with severe acidosis, profound coma, and plasma acetones of 4+ are usually treated quite vigorously to restore normal protein, fat, and carbohydrate metabolism. The emergency treatment consists of large doses of regular insulin, given subcutaneously and intravenously. As the acidosis is corrected, an increase to insulin sensitivity is seen, and the dosage is decreased. The use of insulin in intravenous infusions to treat patients has been reported previously. 14,15 However,
3. 4.
5. 6. 7. 8. 9.
10. 11. 12.
group 1. 2. 3.
Cerasi, E., Luft. R., Efendić, S. Diabetes, 1972, 21, 224. Cerasi, E., Luft, R., Efendić, S. Lancet, April 14, 1973, p. 794. Cerasi, E., Luft, R. Acta endocr. 1967, 55, 305.
ANDREW L. TAYLOR.
INSULIN INFUSION IN DIABETIC COMA SiR,—Dr Menzel’s letter (April 14, p. 830) and the work
1. 2.
SIR,-Some of the interpretations of the data presented by Dr Cerasi and his colleagues on insulin response to glucose in normal and mild diabetic subjects appear misleading. First, it is simple tautology to conclude that " the insulinreleasing potency of glucose is reduced " in prediabetic subjects, since they had defined prediabetics by low insulin responses to glucose. Similarly, it is unwarranted to conclude a progressive reduction of sensitivity of the P-cell to glucose from normal to prediabetic to diabetic subjects, when the prediabetic group was selected from the control
that the low-insulin excluded from the
controls. There is a consensus that diminished insulin release to glucose is characteristic of overt diabetes in normal-weight subjects, but the enigma remains, undiminished by the findings of Dr Cerasi and his colleagues, whether the insulinopenia is the primary defect or secondary to peripheral or humoral changes.
U.S.A.
SiR,-Dr Johansen seems to be unaware of the number of papers stating that the insulin response to oral glucose is not reduced in mild maturity-onset diabetes or chemical diabetes (for references see our original paper). As to the prediabetics, he may read in one of our papers3 our description of low-insulin response to oral glucose. The present report*demonstrates that normal insulin response can be elicited in these subjects provided that the hyperglycsemic stimulus is raised sufficiently. Furthermore, we are astonished by the confidence Dr Johansen shows in excluding a priori the possible role of intestinal factors in modulating the final insulin response under physiological circumstances in these subjects. We had not the boldness to draw such a conclusion without the appropriate experimental evidence. Finally, we recommend the re-reading of our discussion which may, we hope, deserve attention for some interesting, albeit non-revolutionary, aspects of P-cell dysfunction in diabetes.
or
were
13. 14. 15.
Cerasi, E., Luft, R. Acta endocr. 1967, 55, 278. Floyd, J. C., Jr., Fajans, S. S., Conn, J. W., Thiffault, C., Knopf, R., Guntsche, E. J. clin. Endocr. Metab. 1968, 28, 266. Levin, S. R., Reed, J. W., Ching, K. N., Davis, J. W., M. R., Forsham, P. H. Diabetes, 1973, 22, 194. Jackson, W. P. V., Keller, P. Hormones, 1972, 3, 361. Reaven, G. M., Shen, S. W., Silvers, A., Farquhar, J. W. Dibaetes, 1971, 20, 416. Chiles, R., Tzagournis, M. ibid. 1970, 19, 458. Seltzer, H. S., Allen, W. E., Herron, A. L., Jr., Brennen, M. T. J. clin. Invest. 1967, 46, 323. Yalow, R. S., Berson, S. A. ibid. 1960, 39, 1157. Soeldner, J. S., Gleason, R. E., Williams, R. F., Garcia, M. J., Beardwood, D. M., Marble, A. Diabetes, 1968, 17, 17. Siperstein, M. D., Unger, R. H., Madison, L. L. J. clin. Invest. 1968, 47, 1973. Ricketts, H. T., Cherry, R. A., Kirsteins, L. Diabetes, 1966, 15, 880. Grodsky, G. M., Karam, J. H., Pavlatus, F. Ch., Forsham, P. H. Lancet, 1965, i, 290. Sonksen, P. H., Srivastava, M. C., Tompkins, C. V., Nabarro, J. D. N. Lancet, 1972, ii, 155. Galloway, J. A., Shuman, C. R. Am. J. Med. 1963, 34, 177. Oppenheimer, H. E. Diabetes Mellitus: Diagnosis and Treatment; chap. XXXI, p. 151. 1964.