George V. Mann

Serum Lipoproteins and Cholesterol Levels in Normal Subjects and in Young Patients with Diabetes in Relation to Vascular Complications

The present study is concerned with the lipoprotein and cholesterol content of the blood serum in relation to diabetes of long duration and its characteristic complications. It has become increasingly evident that although young diabetic patients may survive under insulin treatment for 10 to 15 years without difficulty, thereafter generalized vascular disease, particularly with lesions in the eyes and kidneys, becomes distressingly frequent. These patients offer an unusual opportunity for the study of the nature of arteriosclerosis, uncomplicated by other chronic diseases frequently present in older subjects. A long-term study designed to assess the relationship between the degree of control of diabetes by means of insulin and diet and the frequency or severity of these complications, has been in progress in this clinic for several years. Since the observations by

Bile acid excretion by the rat: nutritional effects.

Abstract A modification of several published procedures for bile acid determinations has been developed, and this procedure has been applied to the 24-hr, biliary excretions of rats prepared for 15 days on a series of dietary regimens. It has been established that: 1. 1. Cholesterol supplementation of the basal synthetic diet or of Purina Chow resulted in significantly increased biliary bile acid and cholesterol excretion. 2. 2. The levels of vegetable fat did not influence the biliary excretion of bile acids and cholesterol. 3. 3. The feeding of a commercial diet (Purina Rat Chow) resulted in a much higher bile acid excretion with a higher proportion as cholic acid than did any synthetic diet tested. 4. 4. The substitution of egg albumin for casein in the synthetic diet resulted in an increased bile acid excretion; however, the addition of methionine, cystine, or taurine did not produce a significant increase. 5. 5. The addition of brewers yeast or desiccated liver to the diet or the administration of parenteral vitamin B 12 was without significant effect. 6. 6. Fasting decreased the bile acid excretion of rats previously fed Purina Chow but increased the excretion of rats fed the basal (sucrosecontaining) diet. The substitution of starch for sucrose in the basal dict resulted in a larger biliary excretion of bile acids and a larger proportion as cholic acid. Dextrose substituted for sucrose was without effect. 7. 7. Increasing the levels of Cellu-flour in the basal diet also resulted in an increased biliary bile acid excretion. The conclusion was drawn that sucrose and dextrose are inhibitors of biliary bile acid excretion in the rat.

The Importance of Sex in the Variability of the Cholesteremic Response of Rabbits Fed Cholesterol

Cholesterol feeding studies revealed that the wide variability of cholesteremic response of rabbits is in part sex determined. Male rabbits display lower cholesterol levels both before and after cholesterol feeding. Estradiol treatment of selected rabbits fed cholesterol augmented their cholesteremic response; testosterone treatment had an opposite effect. Ovariectomy lowered while orchidectomy augmented the cholesteremic response of rabbits fed cholesterol; castration tended to diminish the wide variability of cholesteremic response previously observed among intact rabbits.

Clinical manifestations of intercapillary glomerulosclerosis in diabetes mellitus

Abstract 1.1. The records of all patients with urinary tract disease admitted over a period of one year to a hospital medical service specializing in diabetes have been studied and the types of renal disease classified. 2.2. The incidence of a characteristic syndrome consisting of proteinuria, edema, hypertension and retinitis occurring in young people with diabetes of long duration, is determined. Although the prognosis in the past has been grave, hope for future improvement by better control of diabetes and its complications is well founded. 3.3. A group of forty-three patients exhibiting this renal complication of diabetes has been studied and the usual course of the disease described. 4.4. The correlation of these clinical manifestations with the distinctive anatomic lesions often seen in the renal glomeruli of diabetic patients is discussed.

The Effects of Diabetic Acidosis and Coma Upon the Serum Lipoproteins and Cholesterol

The disturbances of lipid metabolism induced by diabetic acidosis have been studied repeatedly since the pioneering work of Bloor. Within the limitations of the chemical methods used, most workers have agreed that diabetic acidosis is generally characterized by chemical lipemia consisting principally of neutral fat, by hypercholesterolemia, and by a variable degree of lactescence of the separated serum. A preoccupation with the lipid metabolism of diabetic subjects is produced by three hypotheses. First, the conspicuous predilection of diabetic subjects to atherosclerosis, as well as other forms of arteriosclerosis, may be a consequence of transitory or continuing disorders of lipid metabolism. Second, the defect in lipid metabolism in diabetes mellitus may be even more ba°ic to the disease than is generally appreciated. Third, the extreme deviations of lipid metabolism sometimes seen in diabetic acidosis may afford a profitable opportunity to investigate the physological mechanisms for the transport of neutral fat or other lipids. The collaborative efforts of our laboratories have been directed primarily toward the first of these considerations. The lipids in the blood are carried in the form of lipid-protein complexes. Gofman and his associates studied some of these lipoproteins by an ultracentrifugal technic and found that they could be separated into various classes or bands, designated as Sf o-n, 12-20, etc., depending upon the density of the molecule. The measurement of the kind and quantity of these lipoprotein classes in the serum gives an indication of the state of lipid metabolism.

Bile acids in blood: Methods and their application to studies of experimental atherosclerosis in monkeys☆

Abstract 1. 1. A method for assay of blood sera for cholic, deoxycholic, and “chenodeoxycholic” acids was described. 2. 2. The values for cholic acid and for deoxycholic acid in human hypercholesteremic sera did not differ statistically from the values for these bile acids in normal sera. The value for the measurement designated as “chenodeoxycholic acid” was significantly elevated in human hypercholesteremic sera. 3. 3. Hypercholesteremia and hyper-β-lipoproteinemia were produced in Cebus monkeys by feeding diets containing α-protein with and without added sodium cholate and in monkeys fed casein diets with added cholate. The monkeys fed α-protein and those fed casein with added sodium cholate had levels of cholic acid and deoxycholic acid in the sera which were not elevated above the levels in normal cholesteremic monkeys fed a casein diet without added sodium cholate. The measurement designated “chenodeoxycholic acid” was, however, elevated in the hypercholesteremic monkeys. 4. 4. An evaluation of the vascular lesions revealed significant aortic atherosclerosis in all hypercholesteremic animals. The degree of involvement was, at least, as great in the animals fed casein and cholic acid as in those animals fed α-protein.

Metabolism of the Serum Lipids in Diabetes and in Arteriosclerosis

As an experimentalist interested in arteriosclerosis, I look upon diabetes mellitus as a natural experiment in atherogenesis. This narrow view may distress clinicians engaged in the management or prevention of diabetes, but they should agree that progress in the prevention of atherosclerosis will benefit diabetic human beings most of all. In 1947 I began a laboratory study of the effect of experimental diabetes on the development of vascular disease in animals. The premise that the presence of diabetes aggravates the vascular disease is so attractive that even after five years of fruitless work it is sometimes tempting to try again. It was not possible to demonstrate that this was a valid hypothesis. Although certain capillary lesions were demonstrated in diabetic rats, no evidences of major vessel disease were produced in either rats, dogs, or monkeys, whether fed cholesterol or not. A second hypothesis concerning atherogenesis has been studied and contested for almost half a century and yet has eluded the critical experiment which will properly evaluate its verity. In simple terms this hypothesis states that atherosclerosis, a variant of arteriosclerosis, is a consequence of abnormal lipid metabolism. The immediate problems posed are those of describing the kind and extent of abnormal lipid metabolism necessary for this consequence, a description of the contribution or weight of abnormal lipid metabolism in this effect, and finally a description of the mechanism by which the lipid abnormality develops. There is now a great deal of acceptable information on these points, but for the present I shall consider some evidence that my associates and I have obtained in studies of diabetic human subjects. If from the relation of these observations, any suggestions or implications are made for the management of diabetes, they are fortuitous.

The serum cholesterol and lipoprotein levels in mongolism

Summary A comparison of the serum total cholesterol levels and certain classes of serum beta-lipoprotein levels among fifty-four mongoloid subjects, fifty-four institutional controls, and 1,039 well subjects has failed to reveal consistent differences. Such evidence of higher serum lipid levels as was found among the mongoloids appears to be explained by a greater prevalence of obesity in those subjects. Mongolism is not characterized by unusual serum lipid patterns.

The need of fat in intravenous feeding

SummaryFat emulsions satisfactory for intravenous administration have an important role to play in parenteral nutrition. They offer an opportunity to provide adequate calories in a limited fluid volume. Fat emulsions given intravenously are utilized for energy requirements for growth and maintenance and are helpful in maintaining a positive nitrogen balance. They have been given successfully to man. They should play an important role in supportive and preventive therapy in pre-and post-operative care and in any disease characterized by serious weight loss or emaciation.

Survey of serologic evidence for syphilis among the Masai of Tanzania.

T HE MASAI PEOPLE of East Africa are Nilo-Hamitic pastoralist,s who occupy a large highland area along the eastern limb of the Rift Va,lley. They have maintained their traditional way of life while giving ground steadily to surrounding agriculturists who have been aided in this land pressure by foreign colonists. It is often said in East Africa that the Masai are heavily infected with venereal disease, although there is little documentation to support this opinion. The belief may be a kind of slander arising from the truculent, haughty, and superior manner which the Masai typically assume and which has complicated the social interaction of this East African tribe with others. If indeed the Masai are heavily infected with venereal disease this must constitute a public health problem deserving attention. During studies of the behavior of cardiovascular disease among the Masai, an opportunity was available for investigation of the prevalence of venereal disease among them. When the cardiovascular study was arranged, a bargain was made with the leaders of the tribe. In return for submitting to physical examination and the drawing of blood specimens, the tribesmen were to be examined and treated, if necessary, for venereal disease. Accordingly, the clinical and serologic evidence for venereal disease in 406 Masai living in South Masailand of Tanzania (Tanganyika at that time) was investigated during two cardiovascular field surveys in 1962 and 1963. The customs of the Masai are relevant to the behavior of venereal disease among them. The society is patriarchal and polygamous. A warrior class, called murran, serves both to protect the tribe and to obtain cattle and women from surrounding tribes. This class is formed at age 12 to 15 years when the boys are initiated into the rites of manhood. These youths then assume responsibilities for defending the clan and the cattle and they acquire certain privileges, Dr. Mann and Dr. Sandstead are with the division of nutrition, School of Medicine, Vanderbilt University, Nashville, Tenn. Dr. Anderson is at Meharry Medical College, Nashville. Dr. Shafller was associated with the African Medical and Research Foundation, Nairobi, Kenya. Technical assistance was provided by Mrs. Virginia Falcone and Dr. M. Brittain Moore, Jr., Venereal Disease Research Laboratory, Public Health Service, Atlanta, Ga.; H. Prendergast of the African Medical and Research Foundation; and S. Moitanik, J. 01 Monah, S. M. Isaac, and 0. H. Msangi of the Tanzanian Ministry of Health, Dar es Salaam, Tanzania. The studies were supported by grants from the National Livestock and Meat Board, the American Heart Association, and the National Heart Institute of the Public Health Service. Dr. Mann is a career investigator of the National Heart Institute (K6-HE-8288) .