bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Interpretation of Plasma Glucose Values
Authors: Tustison Winston A , Bowen Angela J , Crampton Joseph H 
Published: December 2014

The use of plasma instead of whole blood for glucose determinations has become increasingly frequent. Since the values obtained differ significantly, it is necessary to establish new standards for the interpretation of plasma glucose levels.
Both whole blood and plasma glucose concentrations were determined simultaneously on 480 blood samples from 120 glucose tolerance tests. From these determinations, a mathematical formula for the interconversion of plasma and whole blood glucose values was established: Whole blood glucose equals .0925 + .8543 plasma glucose. From this formula, normal upper limits were derived for the interpretation of the oral glucose tolerance test using plasma glucose values: 185 mg. per 100 ml. at one hour and 140 nig. per 100 ml. at two hours. Applying these levels, interpretations from simultaneous plasma and whole blood glucose values of the 120 glucose tolerance tests were compared and the results agreed well.
Pregnancy in the Diabetic
Authors: Drury M I 
Published: December 2014

A study of 300 pregnancies in 156 Irish diabetics is presented. Thirty per cent of the pregnancies were fifth or later, and the mean maternal age was thirty years. The abortion rate was 11 per cent, and the loss of viable infants was 10 per cent. There was no maternal death.
Control of diabetes was strict, and this is reflected in the occurrence of hypoglycemic coma on twenty-one occasions. Diabetic ketosis occurred in twelve cases—all of whom were unbooked emergency admissions. The influence of these complications on fetal survival is contrasted.
Pre-eclamptic toxemia and hydramnios in the mother, and respiratory-distress syndrome in the infant contributed heavily to infant loss.
Of recent years the aim has been to deliver at thirtyeight weeks in uncomplicated cases—usually by the vaginal route. The cesarean section rate for the whole series was 22 per cent, and for primigravidae was 29 per cent. A plea is made for a more dynamic approach to vaginal delivery.
Effect of Diet on the Glucose Tolerance and Plasma Insulin Levels of the Sand Rat (Psammomys Obesus)
Authors: Hackel Donald B , Frohman L , Mikat E , Lebovitz H E , Schmidt-Nielsen K , Kinney T D 
Published: December 2014

When sand rats were switched from their usual all vegetable diet to laboratory chow or to a synthetic diet, most developed glycosuria, a marked decrease in glucose tolerance, and elevated plasma insulin. Some animals (all males) had a fulminating reaction with markedly decreased glucose tolerance, low plasma insulin levels and death within three weeks. Others were more resistant and did not show glycosuria at any time although their glucose tolerance tests were abnormal and their plasma insulin levels were high. Still others had an intermediate reaction with early appearance of glycosuria, decreased glucose tolerance, and elevated plasma insulin; then a gradual decrease in these diabetic signs; and finally a reappearance of abnormal glucose tolerance tests with death from severe diabetes mellitus.
Since the plasma insulin level was high in most diabetic animals despite a high blood glucose level and decreased glucose tolerance, it is probable that the basic defect in these animals is not an inability to produce insulin, but rather a decrease in peripheral effectiveness of the hormone. However, the few animals that had a fulminating response were apparently unable to synthesize and release an adequate supply of insulin.
Sand rats maintained on an all vegetable diet did not show these same marked signs of diabetes mellitus. However, occasional decreases in glucose tolerance were observed which, in some cases, were apparently precipitated by severe jaw infections.
The caloric intake of the sand rats fed laboratory chow or the synthetic diet was significantly higher than that of the animals fed only vegetables, although the weight gained by animals on chow or synthetic food was only slightly greater or no greater than that gained by animals on all vegetables.
The Vallance-Owen (“Synalbumin”) Insulin Antagonist: Reproducibility and Reliability of Results in Nondiabetic and Diabetic Humans
Authors: Sherman Lawrence 
Published: December 2014

Cellulose acetate, starch gel, and immunoelectrophoresis of human serum “albumin” extracts were performed. TCA/ethanol extraction altered the albumin so that polymers were present in addition to normal monomer albumin. Alpha1globulin was also present in the extracts, proving them to be heterogeneous in nature.
Nevertheless, extracts from nondiabetic and diabetic sera demonstrated insulin antagonism when measured on rat hemidiaphragms in physiologic serum concentration (4.0 per cent). Reduced concentration (1.25 per cent) of diabetic extracts still demonstrated insulin antagonism; normal extracts did not. These results, consistently found, support the idea that a difference exists between nondiabetic and diabetic humans in quantity of insulin antagonist associated with circulating protein. Extracts of the same blood sample, or of blood from the same subject on different days, gave reproducible results from one observation to another.
Despite constancy of insulin concentration in hemi-diaphragm preparations, biologic effect of insulin (glucose uptake increase) varied. At all levels of insulin effect diabetic extracts significantly antagonized insulin compared to nondiabetic extracts. To show differences in effect among individual extracts, comparison was made between per cent change from basal uptake produced by extract-plus-insulin and that produced by insulin alone. In twenty-seven of thirty-three nondiabetic subjects (82 per cent) change in glucose uptake produced by insulin-plus-extract was over 60 per cent of that produced by insulin alone; in six (18 per cent) the change lay between 50 per cent and 60 per cent. In all thirty-nine diabetic subjects change from basal uptake was less than 60 per cent of that produced by insulin alone.
Long-standing Diabetes Mellitus: A Case Report
Authors: Gray P A , Blackbourne Brian 
Published: December 2014

The case is reported of a patient who survived the preinsulin era and lived a total of forty-eight years after the diagnosis of diabetes mellitus had been made. Although he was never strictly controlled, from a purely chemical point of view, his diet and insulin requirement remained fairly constant.
He suffered only slightly from diabetic glomerulosclerosis and less from diabetic retinopathy. In the later years of his life, paralysis agitans became an outstanding feature of his case. Occlusive vascular disease of the extremities also presented problems in management. He suffered two episodes of coronary occlusion without chest pain. Death was finally attributed to coronary artery disease, which was, in turn, part of the generalized arteriosclerotic problem. At autopsy no beta cells could be identified in the islets of Langerhans.
Insulin Response to Ingested Protein in Diabetes
Authors: Berger Sheldon , Vongaraya Nori 
Published: December 2014

The ingestion of protein by normal human subjects has been shown recently to represent a stimulus to the secretion of insulin. This response is probably related to the postprandial rise in plasma amino acid concentration.
Since disordered protein synthesis may contribute to the pathogenesis of diabetes and its complications, the insulin response to ingested protein (casein or gelatin, 50-100 gm.) was compared in twenty-eight normals and ten maturity-onset diabetics. Insulin response (microunits-minutes, μU.-min.) was considered to be the area included by that portion of the plasma insulin response curve above projected basal insulin secretion. Following protein ingestion the diabetics showed a mean insulin response (± S.E.M.) of 3,425 ± 367 μU.-min., compared with 1,005 ± 136 in the normals, a 3.4-fold difference (p &lt; 0.01). In neither group were there significant or consistent changes in plasma glucose concentration. The fall in free fatty acids was comparable and no difference was seen in the plasma amino acid nitrogen curves.
These data indicate that the insulin response to ingested protein is excessive in diabetes. The mechanism of the hyperresponse would seem to lie within the beta cell since no abnormality of the presumed amino acid stimulus was demonstrated.
Effect of Pancreatic Proteins on Insulin Assay Systems
Authors: Pruitt Kenneth M , Boshell Buris R , Kreisberg Robert A 
Published: December 2014

The following proteins were analyzed for insulin-like behavior in the rat hemidiaphragm, rat fat pad, and two antibody immunoassay systems: ribonuclease A, deoxyribo-nuclease I, alpha-chymotrypsin, chymotrypsinogen A, tryp-sin, and trypsinogen. Chymotrypsin stimulated glucose uptake in the rat hemidiaphragm and behaved like insulin in the immunoassay system when the enzyme concentration was 7 × 10-6 M. No similar activity was found for any of the other proteins. Chymotrypsin was inactive at lower concentrations.
The stimulation of glucose uptake in the rat hemidiaphragm by chymotrypsin was not prevented by the presence of guinea pig anti-insulin serum. This and other evidence suggests that the enhanced uptake of sugar is not due to insulin contamination and is probably a result of partial proteolysis of cell membrane with resulting increase in permeability.
Mixtures of chymotrypsin with guinea pig anti-insulin serum and 1-131-labeled insulin under the conditions of the immunoassay were analyzed electrophoretically, and the results indicate partial hydrolysis of the labeled insulin. This hydrolysis probably accounts for the apparent insulin response produced by chymotrypsin in the two antibody immunoassay system.
Effects of Diazoxide Administration on Plasma Glucose, Insulin, and Lipids in Von Gierke's Disease
Authors: Spergel Gabriel , Bleicher Sheldon J 
Published: December 2014

A twelve-year old boy with proven type 1 glycogen storage disease and accompanying hypoglycemia and hyperlipemia was treated with diazoxide. Increase of 30 to 70 mg. per 100 ml. in postprandial plasma glucose levels and decrease in oral glucose tolerance occurred. Skin xanthomata disappeared during diazoxide treatment despite an increase of over 1,700 mg. per 100 ml. in plasma triglycerides. Treatment of the patient had to be discontinued after seventeen days because of a diffuse petechial eruption, presumably due to drug sensitivity.
The mechanism(s) by which hyperglycemia is induced with diazoxide are not yet established. Glycogenolysis would appear to be excluded in this patient by virtue of the enzymatic deficiency present. Inhibition of plasma insulin response to glucose was demonstrated.
Support for a third mechanism is presented, based on analysis of serial oral glucose tolerance tests. It is suggested that diazoxide, directly or indirectly, inhibits hepatic glucose uptake.
Studies of the Metabolic Effects of Acute Insulin Deficiency: I. Mechanism of Impairment of Hepatic Fatty Acid and Protein Synthesis
Authors: Kalkhoff R K , Kipnis D M 
Published: December 2014

(1) Acute insulin deficiency was produced in rats by the intravenous administration of potent anti-insulin guinea pig serum. Plasma glucose and nonesterified fatty acid (NEFA) levels rapidly increased to an excess of 350 mg. per cent and 1,200 μEq/L. respectively, and were kept elevated by repeated injections of anti-insulin serum.
(2) Hepatic fatty acid synthesis was determined by measuring the incorporation of acetate-1-C-14, acetyl-1-C-14 CoA, and malonyl-1,3-C-14 CoA into fatty acid by cell-free liver homogenates. Within 90 min. after the induction of acute insulin deficiency, acetate and acetyl CoA incorporation were markedly decreased, but malonyl CoA conversion to fatty acids was unaffected, indicating a block in lipogenesis at the acetyl CoA carboxylase step.
(3) The acute inhibition of carboxylase appeared to be a feedback mechanism since significant increases in hepatic tissue NEFA were observed when fatty acid synthesis decreased, and similar patterns of inhibition could be reproduced in normal rat liver homogenates by addition of either palmitate or palmityl CoA.
(4) Hepatic protein synthesis, measured by the incorporation of lysine-U-C-14 did not become impaired until three hours after the induction of acute insulin deficiency. The delayed onset of inhibition and the failure to observe impairment of protein synthesis following the in vitro addition of palmitate, suggest that the factor(s) responsible for impaired hepatic protein synthesis following acute insulin deprivation differ from those causing impaired lipogenesis under similar conditions.
(5) In contrast to previous reports using chronically insulin deprived animals (alloxan diabetes), the protein synthesizing activity of both soluble and microsomal fractions was impaired following acute insulin deprivation.
Glucoregulatory Hormones in Health and Disease: A Teleologic Model
Authors: Unger Roger H 
Published: December 2014

A teleologic model, based upon currently available knowledge of the glucoregulatory hormones, insulin, glucagon and growth hormone, has been presented in an effort to simplify understanding of their physiologic importance. The approach employed in this conceptual “repackaging” stresses in evolutionary terms the contribution of these hormones to the solution of critical problems of energy storage and supply, which, in their absence, would block phylogenetic progress.
Clinical disorders of glucoregulatory hormone secretion, both real and theoretical, are classified and briefly discussed.
Hypoglycemia Due to Intrapancreatic Infusion of Leucine
Authors: Colwell Arthur R 
Published: December 2014

Introduction of L-leucine (0.2 gm.) in saline into the pancreatic artery in anesthetized dogs pretreated with chlorpropamide caused a marked peripheral venous hypoglycemia. Intraportal administration of leucine to sensitized dogs failed to produce the effect, as did injection of leucine or tolbutamide separately into the pancreas in the absence of pretreatment. Fall in blood glucose caused by infusion of leucine and tolbutamide concurrently into the pancreatic artery was not significantly different from that due to infusion into the portal vein.
The hypoglycemia is most likely due to insulin secretion from pancreatic islets sensitized by action of chlorpropamide to the stimulating effect of leucine. Intraportal infusion of tolbutamide and leucine produced a greater fall in venous blood glucose than a doubled amount of tolbutamide alone. This might support the idea of a second action of leucine that might enhance the effect of endogenous insulin on the liver.
Diabetes Mellitus in Rabbits Immunized with Insulin
Authors: Grodsky Gerold M , Feldman Robert , Toreson Wilfred E , Lee John C 
Published: December 2014

Normal rabbits immunized with bovine insulin in adjuvant produce circulating autoantibodies that bind large amounts of endogenous insulin (measured by an immunoassay which distinguishes endogenous and exogenous insulin). In a series of nine immunized animals, two not only produced autoantibody but also, as a result of the autoimmune phenomenon, became acutely diabetic. Their blood sugar, circulating antibody, endogenous insulin bound to antibody and morphologic lesions in the islets of Langerhans observed by light and electron microscopy were compared to those of immunized but nondiabetic rabbits for a period of sixty-five weeks.
Diabetes was characterized by weight loss, lipemia and blood sugar levels maintained at 350 to 600 mg. per 100 ml. throughout an experimental period of twenty-one weeks after immunization with insulin. Although circulating antibody levels were unusually high in the diabetic animals, little antibody-bound insulin was evidenced in contrast to the nondiabetic immunized rabbits whose bound endogenous insulin ranged fiom 390 to 2,340 μU. per ml.
Histologic examination by light and electron microscopy at twenty-one weeks revealed absence of beta cell granules and severe damage to the beta cells. Lymphocytic infiltration of the islets was noted in the less severe diabetic in which some beta cells remained, but neither lymphocytes nor beta cells could be detected in the most severely diabetic animal. Alpha cells in each rabbit were normal. Significantly, the nondiabetic immunized rabbits also showed specific changes in their beta cells detectable by electron microscopy.
The surviving, less severely diabetic rabbit remained diabetic and had detectable antibody until sacrificed fourteen months after immunization. Improvement of the animal at this time was indicated by a blood sugar level of 174 mg. per 100 ml., an increase in antibody-bound endogenous insulin, extractable pancreatic insulin in an amount two thirds of normal, and demonstrable granules in most of the beta cells.
It was concluded thai an autoimmune diabetes that closely resembles the early juvenile form can be created in rabbits by immunization with insulin. The possibility that autoimmunity can not only contribute to the diabetic state in insulin-treated subjects but may prove important as an underlying cause in some forms of diabetes is discussed.
Inhibitory Effects of “Bound” Insulin on Insulin Uptake by Isolated Tissues
Authors: Antoniades Harry N , Gershoff Stanley N 
Published: December 2014

“Bound” insulin preparations obtained from pooled human sera inhibited the uptake of crystalline insulin by isolated rat muscle (hemidiaphragm) and epididymal adipose tissue. When crystalline insulin alone was incubated with isolated tissues, its concentration in the incubating medium declined gradually, as shown by immunoassay of samples obtained at various intervals during the incubation. Addition of “bound” insulin preparations into the incubation medium greatly reduced the rate of disappearance of the crystalline insulin, “bound” insulin inhibiting the uptake of insulin by the tissues. The inhibition of insulin uptake by muscle, caused by “bound” insulin, was accompanied by inhibition of the biologic activity of insulin on this tissue.
Preincubation of the isolated tissues with “bound” insulin, with whole fasting human sera from maturity-onset diabetics, or with crystalline insulin, prior to the addition of crystalline insulin, also resulted in significant inhibition of insulin uptake by these tissues.
Synalbumin preparations obtained from fasting human sera by acid-ethanol extraction, as described by Vallance-Owen and collaborators, also inhibited the uptake of crystalline insulin by isolated muscle and adipose tissue and the biologic activity of insulin on muscle. Like “bound” insulin, the synalbumin extracts were inactive on isolated muscle and unreactive with anti-insulin antisera but exerted insulin-like activity on isolated adipose tissue. Their action when injected intraperitoneally into intact rats was similar to that of “bound” and crystalline insulin on the muscle and the adipose tissue. It is suggested that the synalbumin preparations obtained from sera by acid-ethanol extraction may contain the bulk of the serum “bound” insulin which contributes, at least in part, to the insulin inhibitory properties of these preparations.
Periodontal Changes and Dental Caries in Experimental Prediabetes
Authors: Borghelli Ricardo F , Devoto Francisco C H , Foglia Virgilio G , Erausquin Jorge 
Published: December 2014

The prevalence, activity and rate of progression of dental caries, as well as the periodontal histopathology (presence or absence of pathological pockets, structure and thickness of the osseous alveolar crest, and width of the marginal periodontal ligament) in prediabetic and diabetic white rats were studied.
The observations of caries activity (within the prediabetic period) were made on rats sacrificed forty-five days after being 95 per cent and 80 per cent pancreatectomized. A significant increment of caries activity was found in all aspects investigated in both groups of experimental animals with respect to normal and sham operated controls.
The histopathology of the periodontium of 95 per cent pancreatectomized rats sacrificed ten months after the operation with diabetes of several months and varying degrees of hyperglycemia showed morphological alterations of the osseous alveolar crest, with significant thickening of the marginal periodontal ligament. This process could be observed very early in prediabetes in rats with normal blood sugar, no glycosuria, and normal diuresis and body weight, sacrificed three months after the operation.
Even though it seems to be indisputable that alterations of carbohydrate metabolism in diabetic rats have an aggravating effect, changes in prediabetes suggest that the observed caries and lesions of the periodontium start very early and independently of the diabetic changes in carbohydrate metabolism.
The Banting Memorial Lecture 1967: Angiopathy in Diabetes: An Unsolved Problem
Authors: Marble Alexander 
Published: December 2014

Vascular disease, exceedingly common in persons with long-term diabetes and affecting both large and small blood vessels, presents the greatest problem and challenge in diabetes today. Large vessel involvement is responsible for a frequency of cerebrovascular, coronary and peripheralvascular disease which is significantly greater in diabetic than nondiabetic individuals. However, most characteristic of diabetes is microangiopathy which, although widespread in the body, is seen most forcibly in the eyes (diabetic retinopathy) and kidneys (intercapillary glomerulosclerosis). Since treatment of fully developed complications is unsatisfactory, exploration of ways of prevention offers the best hope for the future. This leads the investigator and clinician alike into the origins of diabetes itself and the relationship of the metabolic defect (insulin deficiency) to vascular disease.
That the tendency to diabetes is inherited is commonly accepted but knowledge is lacking as to exactly what the diabetic inherits. Environmental factors such as overnutrition, pregnancy, infections, steroid administration, etc., favor the emergence of the tendency to a state clinically recognizable. Special studies and clinical experience suggest that in the early stages of the diabetic state (“prediabetes” and “chemical diabetes”) there exists a fluid, dynamic condition in which not only progression but also remission are possible, therein affording hope for the eventual discovery of means of halting progression of the metabolic defect.
Microvascular disease may be demonstrable (in the form of thickening of the basement membrane of small blood vessels) even in the early stages of the diabetic state. However, present knowledge does not warrant the conclusion that the tendency to vascular disease is inherited as a separate trait which develops independently of the tendency to the metabolic defect. On the contrary, there is increasing evidence to suggest that even in prediabetes the pancreatic release of insulin in response to glucose given intravenously may be subnormal, delayed or inappropriate in relation to the level of blood glucose at the time. With information currently available it is unwarranted to assume that vascular disease in its origin and development is unrelated to the metabolic defect.
These considerations lead naturally into the matter as to whether the degree of control of diabetes, i.e., to which insulin deficiency is met, has any influence on the frequency, degree and time of appearance of the vascular sequelae. Evidence is presented from studies in nonhereditary diabetes both in man and animals, from general clinical experience and from special clinical studies, to support the view that there is, indeed, such a relationship and that by careful and consistent control of diabetes, complications may be lessened or delayed.