325 intestinal resection. Fasting blood-samples were taken and lipoprotein concentrations were determined by preparative ultracentrifugation and compared with values for ageadjusted, randomly selected controls.4 Total serum triglycerides and triglycerides in the very-low-density lipoproteins (V.L.D.L.) were not significantly different in patients and controls. In the low-density lipoprotein (L.D.L.) fraction the cholesterol concentration of the patients was about half that of the controls. There was a negative correlation between L.D.L. cholesterol concentration and the length of the resected intestine (see figure). There was no absolute reduction in mean H.D.L. cholesterol concentration but concentrations were negatively correlated with the length of the resected small intestine. No correlation was observed between v.L.D.L. triglycerides and H.D.L. cholesterol. There was no significant correlation between body-weight and H.D.L. cholesterol concentration, indicating that the nutritional state of the patients was not a major determinant of their H.D.r.. cholesterol. The finding of a lower L.D.L. cholesterol concentration in patients with the most extensive resections accord with corresponding reductions found in patients operated on for massive obesity with jejunoileal bypass. The negative correlation between H.D.L. cholesterol and length of small-intestinal resecsuggests the possibility of an intestinal secretion of H.D.L. in man. The finding of unchanged H.D.L. cholesterol concentrations in shunt-operated obese patients, in whom the small intestine is intact although bypassed,s lends indirect support for such a hypothesis.
tion particles
an average period of 6.3 weeks (range 3-13 weeks) all patients received insulin injections, while the oral drugs were omitted. Throughout this period the diet remained the same. Each patient thus served as his own control. Glucose was measured by an automated method. Cholesterol, triglycerides, and lipoprotein concentrations were measured as previously described.4.5 H.D.L.-cholesterol was measured after precipitation of the lowdensity lipoproteins in the fraction with density > 1-006 g/ml. Treatment with insulin did not significantly alter the H.D.L. level as measured by its cholesterol content (see table). In the 9 patients on oral hypoglycaemic agents, the H.D.L.-cholesterol level was also unchanged-1.01+0.32 mmol/1 during oral therapy, 1-04+0-32 during insulin therapy (means ± S.D.). Our results are at variance with those of Bar-On et al. and suggest that the conclusions of the University Group Diabetes Program are not explained by the lowering of H.D.L. levels by
oral therapy.
C. JOHANSSON S. RÖSSNER G. WALLDIUS
S-104 01 Stockholm 60, Sweden
HIGH-DENSITY-LIPOPROTEIN AND MATURITY-ONSET DIABETES
SIR,-A low level of high-density lipoprotein (H.D.L.) in seems to accelerate the development of atheroscleroSiS.l.2 Bar-On et a1.3 found that H.D.L. and cholesterol in serum from 11 elderly patients on oral therapy were lower than in 12 diabetics on insulin and suggested that this might explain the University Group Diabetes Program conclusion that treatment with oral hypoglycaemic agents (tolbutamide and phenformin) increases cardiovascular mortality. However, Bar-On et al. studied two different groups of patients with an unequal sex ratio. This and other discrepancies between the groups could explain the difference in lipoprotein levels. We measured plasma-lipoprotein before and after treatment with insulin in a group of patients (8 males, 7 females, mean age 58 years, range 51-67 years) with maturity-onset diabetes and type iv hyperlipoproteinaemia. They had been treated for several years with diet alone (6 patients) or diet and oral hypoglycaemic agents sulphonylureas 8, phenformin 1. During
plasma
4. Carlson, K. J. clin. Path. 1973, 26, suppl. 5, p. 32. 5. Rössner, S. Hallberg, D. Acta med. scand. (in the press). 1. Miller, G. J., Miller, N. E. Lancet, 1975, i, 16. 2. Berg, K., Børresen, A. L., Dahlen, G. ibid. 1976, i, 499. 3. Bar-On, H., Landau, D., Berry, E. ibid. 1977, i, 761.
University of Nijmegen, Nijmegen, Netherlands
EXOGENOUS ŒSTROGENS AND OVARIAN CANCER
SIR, -Dr Annegers and his colleagues’ suggest that the data in
our
preliminary communication2"do
=
=
not
point
as
strongly
with exogenous oestrogen use" as we suggested. They note that the "expected" values calculated for ovarian cancer did not take into account the proportion of women in the general population who are not at risk-namely, those with surgically removed ovaries. By adjusting for the 10% prevalence-rate’ of bilateral oophorectomy prevailing in the Mayo Clinic population, they estimate that our expected numbers for oestrogen-treated women are 11 % too low, and that two of the three relative risks values are not statistically significant. In case others may have been misled by our paper, we would like to emphasise the following points: (1) We did not claim that ovarian cancer was associated with the use of exogenous oestrogens generally, but rather with specific oestrogen, diethylstilboestrol (D.E.S.). We tried to stress this by entitling the paper Stilboestrol (Diethylstilboestrol) and the Risk of Ovarian Cancer. (2) The relative risk (R.R.) for the association between D.E.s. use and ovarian cancer was 30.0 (confidence interval, 6.2-87-7). These values are not changed by adjusting for the prevalence of oophorectomy in the general population, whether one uses the Mayo Clinic oophorectomy prevalencerate or makes the extreme assumption that every woman in the general population with a hysterectomy has also undergone bilateral oophorectomy, (3) Our most conservative estimate of the R.R. for all
increased risk of ovarian
cancer
4.
Demacker, P.
2.
Hoover, R., Gray, L. A., Sr, Fraumeni, J. F., Jr ibid. p. 533.
N. M., v. Oppenraay, J., Baadenhuysen, H., Jansen, A. P. Clin. chim. Acta, 1975, 64, 45. 5. Demacker, P. N. M., Vos-Janssen, H. E., Jansen, A. P., van ’t Laar, A. Clin. Chem. 1977, 23, 1238. 1. Annegers, J. F., O’Fallon, W., Kurland, L. T. Lancet, 1977, ii, 869 (see also
p. 1188).
PLASMA-LIPOPROTEINS DURING ORAL THERAPY AND INSULIN THERAPY
Results are means < S.D. Student’s t test for paired data. *L.D.L. low-density lipoprotein. V.L.D.L. very-low-density lipoprotein.
P. N. M. DEMACKER J. A. LUTTERMAN A. VAN ’T LAAR
Department of Medicine,
to an
Department of Internal Medicine and King Gustaf V Research Institute, Karolinska Hospital,
A. F. H. STALENHOEF
tion particles
an average period of 6.3 weeks (range 3-13 weeks) all patients received insulin injections, while the oral drugs were omitted. Throughout this period the diet remained the same. Each patient thus served as his own control. Glucose was measured by an automated method. Cholesterol, triglycerides, and lipoprotein concentrations were measured as previously described.4.5 H.D.L.-cholesterol was measured after precipitation of the lowdensity lipoproteins in the fraction with density > 1-006 g/ml. Treatment with insulin did not significantly alter the H.D.L. level as measured by its cholesterol content (see table). In the 9 patients on oral hypoglycaemic agents, the H.D.L.-cholesterol level was also unchanged-1.01+0.32 mmol/1 during oral therapy, 1-04+0-32 during insulin therapy (means ± S.D.). Our results are at variance with those of Bar-On et al. and suggest that the conclusions of the University Group Diabetes Program are not explained by the lowering of H.D.L. levels by
oral therapy.
C. JOHANSSON S. RÖSSNER G. WALLDIUS
S-104 01 Stockholm 60, Sweden
HIGH-DENSITY-LIPOPROTEIN AND MATURITY-ONSET DIABETES
SIR,-A low level of high-density lipoprotein (H.D.L.) in seems to accelerate the development of atheroscleroSiS.l.2 Bar-On et a1.3 found that H.D.L. and cholesterol in serum from 11 elderly patients on oral therapy were lower than in 12 diabetics on insulin and suggested that this might explain the University Group Diabetes Program conclusion that treatment with oral hypoglycaemic agents (tolbutamide and phenformin) increases cardiovascular mortality. However, Bar-On et al. studied two different groups of patients with an unequal sex ratio. This and other discrepancies between the groups could explain the difference in lipoprotein levels. We measured plasma-lipoprotein before and after treatment with insulin in a group of patients (8 males, 7 females, mean age 58 years, range 51-67 years) with maturity-onset diabetes and type iv hyperlipoproteinaemia. They had been treated for several years with diet alone (6 patients) or diet and oral hypoglycaemic agents sulphonylureas 8, phenformin 1. During
plasma
4. Carlson, K. J. clin. Path. 1973, 26, suppl. 5, p. 32. 5. Rössner, S. Hallberg, D. Acta med. scand. (in the press). 1. Miller, G. J., Miller, N. E. Lancet, 1975, i, 16. 2. Berg, K., Børresen, A. L., Dahlen, G. ibid. 1976, i, 499. 3. Bar-On, H., Landau, D., Berry, E. ibid. 1977, i, 761.
University of Nijmegen, Nijmegen, Netherlands
EXOGENOUS ŒSTROGENS AND OVARIAN CANCER
SIR, -Dr Annegers and his colleagues’ suggest that the data in
our
preliminary communication2"do
=
=
not
point
as
strongly
with exogenous oestrogen use" as we suggested. They note that the "expected" values calculated for ovarian cancer did not take into account the proportion of women in the general population who are not at risk-namely, those with surgically removed ovaries. By adjusting for the 10% prevalence-rate’ of bilateral oophorectomy prevailing in the Mayo Clinic population, they estimate that our expected numbers for oestrogen-treated women are 11 % too low, and that two of the three relative risks values are not statistically significant. In case others may have been misled by our paper, we would like to emphasise the following points: (1) We did not claim that ovarian cancer was associated with the use of exogenous oestrogens generally, but rather with specific oestrogen, diethylstilboestrol (D.E.S.). We tried to stress this by entitling the paper Stilboestrol (Diethylstilboestrol) and the Risk of Ovarian Cancer. (2) The relative risk (R.R.) for the association between D.E.s. use and ovarian cancer was 30.0 (confidence interval, 6.2-87-7). These values are not changed by adjusting for the prevalence of oophorectomy in the general population, whether one uses the Mayo Clinic oophorectomy prevalencerate or makes the extreme assumption that every woman in the general population with a hysterectomy has also undergone bilateral oophorectomy, (3) Our most conservative estimate of the R.R. for all
increased risk of ovarian
cancer
4.
Demacker, P.
2.
Hoover, R., Gray, L. A., Sr, Fraumeni, J. F., Jr ibid. p. 533.
N. M., v. Oppenraay, J., Baadenhuysen, H., Jansen, A. P. Clin. chim. Acta, 1975, 64, 45. 5. Demacker, P. N. M., Vos-Janssen, H. E., Jansen, A. P., van ’t Laar, A. Clin. Chem. 1977, 23, 1238. 1. Annegers, J. F., O’Fallon, W., Kurland, L. T. Lancet, 1977, ii, 869 (see also
p. 1188).
PLASMA-LIPOPROTEINS DURING ORAL THERAPY AND INSULIN THERAPY
Results are means < S.D. Student’s t test for paired data. *L.D.L. low-density lipoprotein. V.L.D.L. very-low-density lipoprotein.
P. N. M. DEMACKER J. A. LUTTERMAN A. VAN ’T LAAR
Department of Medicine,
to an
Department of Internal Medicine and King Gustaf V Research Institute, Karolinska Hospital,
A. F. H. STALENHOEF
