J. Vallance-Owen

Insulin and atheroma.

New information on carbohydrate and lipid metabolism has resulted in reappraisal of ideas of the underlying abnormalities in diabetes and atherosclerosis. It is noted that the incidence of diabetic arteriopathy has increased in spite of control of hyperglycemia and ketosis by insulin and that many nondiabetic persons with coronary artery disease have abnormalities or carbohydrate and lipid metabolism similar to those found in diabetics. Some patients secrete abnormally large amounts of insulin in response to dietary carbohydrate; these people have a particularly high incidence of vascular disease. Physicial excercise lowers insulin requirements. Synalbumin increased serum lipids in the forms of cholesterol triglycerides and the endogenous type of hyperlipidemia induced by dietary carbohydrate have been related to the incidence of coronary artery disease. The insulin response produced by the carbohydrate diet is related to the hepatic-triglyceride-secretion rate and is considered to be the primary cause of elevated serum-triglyceride. A similar mechanism is assumed for serum-cholesterol regulation. Hyperinsulinism is found in obesity in patients with hypertension and in some women who have been taking oral contraceptives for more than 1 year. These women also show elevated triglycerides and pre-beta-lipoprotein levels. It has been reported that these women also have an increased risk of vascular diseas e. The evidence incriminating insulin and carbohydrate is considered strong and would link atherosclerosis with diabetes obesity hyperlipidemia lack of physical exercise and possibly hypertention and use of contraceptive drugs.

The relationship of arterial disease and glucagon metabolism in insulin-treated chickens

Abstract Thirty twelve-week old chickens were divided into two equal groups. One group was treated with insulin zinc suspension (lente) for 19 weeks and the other group, which served as control, received the vehicle solution only. All the birds were fed ad libitum from one source of ordinary chicken feed. The chickens were sacrificed after 19 weeks. The aortas from the insulin-treated birds contained significantly more lipid in the intima and adjacent media than the controls. Blood taken at 19 weeks showed no difference in the sugar content between the two groups, but cholesterol, triglyceride and immunoreactive glucagon were all elevated in the insulin-treated group. Plasma glucagon showed a negative correlation with both cholesterol and triglyceride in the control birds. This correlation was lost in the insulin-treated birds, which did however show a negative correlation between blood sugar and plasma glucagon. It is concluded that hyperinsulinism in chickens is associated with excessive lipid deposition in the aorta and elevation of blood lipids, and would be consistent with the hypothesis that elevated insulin levels may play a part in the development of human vascular disease. The results suggest that glucagon has a role in lipid metabolism in chickens, and extension of such studies of lucagon to man would be of interest.

Neuroleptic malignant syndrome successfully treated with amantidine.

Sir, I recently had occasion to review the literature on the association between sarcoidosis and lymphoma. This has been a topic for discussion in your journal in the recent past (Brennan et al., 1983). Due to the paucity of cases with both conditions, it is difficult to substantiate the theory that sarcoidosis predisposes to lymphoma (Romer, 1980, 1982). It has been proposed that it is the steroid treatment, rather than sarcoidosis itself, which is responsible for precipitating steroid sensitive lymphomas. This would not account for the predominance of Hodgkins disease, as opposed to other lymphomas, in reported cases. It would support the average latent period of 2 years between discovery of the sarcoidosis and the lymphoma, but is less credible in those cases exhibiting a more prolonged interval. Up to 17 years has been previously recorded (Brincker, 1972). My interest was aroused by recently encountering a patient who developed a B cell lymphoma of the caecum 33 years after treatment for pulmonary sarcoidosis. This further strengthened my view that any such association between the two conditions is purely coincidental. P.D. McInerney Department of Surgery, Clatterbridge Hospital, Bebington, Wirral, Merseyside L63 4JY, UK.

VARIATIONS IN SYNALBUMIN INSULIN ANTAGONISM DURING GLUCOSE-TOLERANCE TESTS

Abstract Albumin was extracted from plasma taken during oral glucose-tolerance tests in twenty healthy volunteers and tested at a concentration of 2·5 g. per 100 ml. for insulin antagonism on the rat diaphragm in vitro. With two exceptions, a significant fall in insulin antagonism was observed after 30 and/or 60 minutes. Three intravenous tests showed that the fall in antagonism started after 5-15 minutes. The extracts had no effect on the glucose uptake of the rat diaphragm in the absence of insulin. These results may explain earlier reports that a normal glucose-tolerance curve can be obtained in the absence of increased insulin secretion.

IN-VIVO EFFECTS OF THE SYNALBUMIN INSULIN ANTAGONIST AND OF B-CHAIN ALBUMIN

Abstract Synalbumin and albumin to which an insulin B-chain has been attached have been tested in vivo for insulin antagonistic activity by an intraperitoneal injection method. Both inhibit the effect of insulin on the rat diaphragm, but not on the epididymal fat pad. These findings are similar to those reported in vitro. The results are compatible with the hypothesis that the synalbumin insulin antagonist is the same as the B-chain of the insulin molecule.

Insulin antagonism of normal and diabetic albumin after liver perfusion

Summary Albumin prepared from diabetic patients and healthy controls was allowed to become non-antagonistic to insulin by storage. After perfusion, with insulin, through the isolated rat liver, diabetic albumin became antagonistic to that hormone when tested at 0·8% on the isolated rat diaphragm, whereas normal albumin remained non-antagonistic at this concentration. This suggests that diabetic and normal albumin differ in their ability to bind insulin B-chain.

MATERNAL SYNALBUMIN ANTAGONISM AND LARGE BABIES

Abstract Of 23 women with a history of having delivered an infant weighing 9·5 1b. or over, 15 (65%) showed increased synalbumin antagonism as against 26 (36%) of 72 age-matched control subjects. Increased maternal synalbumin antagonism may account for fetal islet-cell hypertrophy, hyperinsulinism, and increased birth-weight.

AN INTEGRATED FINAL MB EXAMINATION

SIR,-We were interested in the comments made on our May 15 paper by Professor Hobbs (May 29, p. 1246). We did not in that paper elaborate on our progressive assessment which we, like the Royal Free Hospital School of Medicine, consider very important for identifying weak students and helping them. Each department has its own type of assessment-for example, surgery bases its assessment on reports from the teachers, the submission of essays based upon case-reports, and a viva examination held at the end of each clinical attachment. Other departments have multiple choice assessments but all departments have the sanction of requiring a student who has performed unsatisfactorily to repeat an assessment and, ultimately, to be refused admission to the final examination. We do not, however, find the issue as clear cut as seems to be the case at the Royal Free. The sanction of refusing a student permission to sit the final examination has never been exercised and we do not feel that the few students who fail the examination come to harm by doing so and repeating part of the course for a re-sit examination in

Precipitin reactions between insulin, proinsulin, insulin chains and insulin antibody.

SummaryInsulin antibody was produced in guinea pigs and the precipitins tested by double diffusion in agarose gel. Pork, beef and monocomponent insulin produced precipitin lines. Proinsulin also produced a precipitin line with these antisera but no lines appeared with either the A-chain or the B-chain of insulin. There was good correlation between the precipitin titre and the radioimmunoassay titre.

EFFECT OF SYNALBUMIN ON LIPOLYSIS

Abstract Serum-albumin from healthy individuals strongly antagonises the antilipolytic effect of insulin on rat adipose tissue. It also possesses insulin-like activity in a glucose-free medium. Both these effects are increased with albumin prepared from diabetic patients.