Martin G. Goldner

The effect of potassium on the imparired glucose tolerance in chronic uremia

Abstract The glucose intolerance of 4 patients with chronic uremia was studied. All patients were shown to have low values for total exchangeable body potassium (K E ), and abnormal oral glucose tolerance tests. Although plasma urea nitrogen values fell during the period of potassium replacement there was no apparent improvement in renal function as plasma creatinine concentrations did not significantly change. When K E was raised by oral potassium supplementation, the glucose tolerance tests returned toward normal. Following potassium the response of endogenous insulin was more prompt and reached higher values than during the control period. Delayed insulin release apparently contributes to the abnormal oral glucose tolerance found in the uremic state.

Electrolyte-activated lipolysis in vitro: modifying effect of calcium.

In vitro experiments, employing rat epididymal fat tissue, have shown spontaneous lipolysis to be induced by Cafree media containing high K concentrations. Electrolyte-activated lipolysis proceeds linearly over a 2 hour incubation period and is not affected by omission of albumin from incubation media. Inclusion of 2.5 mEq./L. Ca in the medium sensitizes adipose tissue to low concentrations of K but results in a biphasic response, wherein lipolysis in all-K media is less than in mixed Na/K media. Neither Mg nor buffer anions were found to play any role in the response, except that in all-PO 4 buffers lipolysis developed at lower K concentrations than in Ca-free Cl-HCO 3 buffers; a similar effect was achieved by adding EDTA to Cl-HCO 3 buffer. Cysteine did not modify the response to Ca. Although the response to Na/K buffers in the presence of Ca is not specific, in that similar effects were achieved in mixed Na/choline buffers, extrapolation to the in vivo state suggests that Na/K flux may play a role in regulating the basal state of adipose tissue, in modifying the capacity to respond to lipolytic stimuli, and serve in orienting the tissue in generally anabolic or catabolic directions.

Effect of caloric restriction on cholesterol atherogenesis in the rabbit.

Summary 1. Rabbits on severe caloric restriction were fed cholesterol and showed significantly increased blood cholesterol, fatty acids, lipoproteins and phospholipids. The degree of these biochemical changes and of the atherosclerosis was greater than that of a control group fed similar amounts of cholesterol in addition to a normal diet. 2. Therefore, severe caloric restriction does not protect, but enhances cholesterol induced atherosclerosis in rabbits. This effect of weight loss should be taken into consideration in experiments on atherosclerosis.

History of Insulin

Excerpt To the editor: The editorial in the November issue, Insulin: Fifty Years Ago, clarifies the roles played by Macleod and by Collip in the work initiated and conducted by Banting and Best. ...

Failure of protein to protect against cholesterol atherogenesis in underfed rabbits.

Summary 1. Study of effect of protein on development of experimental atherosclerosis on blood lipids and lipoproteins, in underfed rabbits with supplementary cholesterol, was performed. 2. Cholesterol fed rabbits on a limited intake of standard laboratory food lost approximately one-fourth of their body weight. A marked degree of atherosclerosis, increased blood lipids and lipoproteins was produced. 3. Cholesterol-fed rabbits on a limited intake of a relatively high protein diet, who lost equivalent amounts of weight, developed approximately the same degree of atherosclerosis, increase in blood lipids and lipoproteins.

The UGDP and Insulin Therapy: A Reply

The UGDP and Insulin Therapy: A Reply An author of an editorial has, of course, the right to pass judgment on the topic under discussion in addition to reporting on it, but he also has the k obligation to base his judgment on the facts at hand. What facts are there in the UGDP report on insulin treatment (J.A.M.A. 240: 37-42, 1978) to suggest that the authors have made unjustified or irresponsible extrapolations of the results, as was stated in the editorial The UGDP and Insulin Therapy? The UGDP authors clearly described their results as follows: Thus, over the time period studied with an average follow-up of 12 years, insulin used in fixed dosage or used in a variable dosage to normalize blood glucose levels was no better than diet alone (plus placebo tablets or capsules) in prolonging life or in preventing the vascular complications considered in this report in the adult-onset, non-ketosis-prone diabetic Is the author of the editorial justified in ignoring that key statement and presenting instead a sentence out of context—a sentence that was qualified as to its significance and its limitation in the preceding paragraph? Should the action of the editorial writer not be considered unjustified, if not irresponsible, if he condemns the UGDP investigators for the widespread public dissemination of the unjustified conclusions . . . in the lay press and broadcast media, when in fact, the UGDP investigators have never used the nonprofessional media and have published their reports only in peer review journals? The UGDP has not been the perpetrator but rather the target of a deplorable and vicious campaign mostly in nonprofessional media by critics of the study. Why does the editorial writer accuse the UGDP of having applied their results relative to tolbutamide to other sulfonylureas not studied when in the report on the tolbutamide findings there was the following statement: It should be noted that any conclusion reached in this study pertains only to the type of patient studied and to the specific hypoglycemic agents and dosage schedules used. Extrapolation of findings obtained in the UGDP to other dosage schedules of the same drug or to other chemically related hypoglycemic agents not included in this study must be made on a judgmental and nonstatistical basis? The reports on the phenformin and insulin results contain similar cautionary statements. Two other points of the editorial require correction. While it is correct that the observation period of patients was a minimum of nine years, the majority (460 of 612 patients) had been followed for 11 or more years—a time span adequate for the development of diabetic microangiopathy and well beyond the 10 years that the editorialist thought is necessary. With regard to the diabetic patients under study in the UGDP, the editorial writer conveys the impression that only patients with the mild type of disease were included in the UGDP and thus the UGDP patients are not representative of the population with non-ketosis-prone diabetes. While many of the UGDP patients showed only moderately elevated fasting blood glucose levels, the disease was sufficiently severe to cause microvasculopathy in the retina in roughly 60% of the patients. The editorial writer might also have taken into consideration the significant increase in daily dosage required for patients in the insulin variable group as evidence of the natural worsening of the diabetic state over the period of observation. As stated in the UGDP report, the range in daily dosage at the first quarter for patients in the insulin variable group was 5 to 40 U and the mean was equal to 11 U; after 9A years the range was 5 to 240 U and the mean was 47 U. These dosage ranges are indeed those which are used for a substantial portion of the population of adult-onset diabetic patients. Finally, it is rather puzzling that the editorial writer objects to publication of UGDP reports in a general medical journal, such as the Journal of the American Medical Association, when the problems concerning the management of the nonketotic, stable, maturity-onset diabetic patient belong in a journal that is easily accessible to the general