bluuebunny/crossref_metadata_2025 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.
Effects of Severe Protein-Calorie Deficiency on the Endocrine Control of Carbohydrate Metabolism
Authors: Heard C R C
Published: December 2014

Severe protein-calorie deficiency resembling human syndromes (e.g., marasmus and kwashiorkor) has been produced in young pigs by manipulation of dietary protein and carbohydrate levels. These animals show impaired glucose tolerance; increased insulin sensitivity, including hypoglycemia nonresponsiveness; accumulation of glycogen in the liver and deficiency of hepatic glucose-6-phosphatase; normal or raised excretion of urinary corticosteroids. Tissue water content is elevated but fat accumulates only in animals receiving extra carbohydrate. It is suggested that a deficiency of insulin and of thyroid and growth hormones and a consequent relative excess of adrenocortical hormones is characteristic of severe protein-calorie deficiency in humans and experimental animals and explains many of the biochemical changes.
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.
A Survey for Unknown Diabetics in a Mental Hospital: II. Men from Age Fifty
Authors: Waitzkin Leo
Published: December 2014

A 100 gm. two-hour oral glucose tolerance test was administered to an institutional group of 213 mentally ill men who were fifty to eighty-eight years old and without known diabetes. Thereafter, the test was selectively repeated. In thirty-two cases results were interpreted, in association with other data, as consistent with previously unknown, unsuspected diabetes — an incidence of 15 per cent. Discovery of this high incidence is attributed to universal employment of the glucose tolerance test. The influence of phenothiazine therapy on carbohydrate metabolism was partially examined with inconclusive results and requires further study.
Diabetes Mellitus Treated with Chlorpropamide and Tolbutamide: A Four-year Clinical Study
Authors: Powell T , Howells Leonard
Published: December 2014

The findings in 676 patients treated with tolbutamide and chlorpropamide for periods of up to four years are presented. Only small differences between the results obtained with the two drugs were found. In twenty patients treatment was discontinued because of intercurrent disease or because of side effects. There were sixty-seven primary failures (10 per cent). Of the remaining 589, there were sixty-six secondary failures (11 per cent), fifty-eight achieved fair control (10 per cent) and 465 good control (79 per cent). Satisfactory results were obtained most often in patients weighing between 85 per cent and 115 per cent of their standard weight, in those over forty-five years of age, and in those who had not previously required insulin. The mean body weight of the patients increased by 1.3 per cent while they were receiving sulfonylureas. Needle core liver biopsies were obtained from eight patients. Four of these were normal, three showed focal collections of chronic inflammatory cells, and one showed early portal cirrhosis.
Insulin-binding Index in Juvenile Diabetes
Authors: Marks James F , Wolfson Jerome H , Hamlin Marie , Freeman Betty
Published: December 2014

The insulin binding index was studied in a group of growth-onset diabetic children. There was a significant difference between diabetic children and normal adults and children. No statistical distinctions could be drawn between the diabetic children on the basis of (1) insulin dosage in the range studied (6 to 75 U.), and (2) duration of disease.
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 < 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.
Spontaneous Diabetes Mellitus in Tree Shrews, Urogale Everetti
Authors: Rabb G B , Getty R E , Williamson W M , Lombard L S
Published: December 2014

Two tree shrews with bilateral cataracts, a male and a female from a colony of six in captivity for more than a year, were found to have diabetes mellitus. The male died before his condition was controlled with insulin and restrictive diet. A fairly satisfactory state of balance of the female was maintained for two and a half months on a relatively high dosage of insulin. Microscopic examination of the pancreatic tissue of the male revealed degranulation and vacuolation of the islet cells, with probable absence of beta cells. In the female there was diffuse fibrosis with replacement of nearly all of the islet cells.
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.
Uric Acid Excretion in Diabetic Ketoacidosis
Authors: Healey L A , Wheaton E A , Cutler R E , Demartini F E
Published: December 2014

Renal clearance studies in five patients during and after an episode of diabetic ketosis showed that there was decreased uric acid excretion and consequent elevation of the serum level. This was due to altered tubular handling of urate. Similar renal changes were produced by the infusion of beta-hydroxybutyrate in three normal subjects.
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.
Diabetic Vascular Complications in Long-standing Panhypopituitarism with Diabetes: A Case Report
Authors: Ewing Carol , Zorrilla Eduardo , Hernandez Alfredo , Berris Robert
Published: December 2014

A case presenting severe hypoplasia of islets of Langer hans and diffuse diabetic glomerulosclerosis is described in which panhypopituitarism due to craniopharyngioma prevented the overt manifestation of diabetes.
Age Effect on Insulin Action in Rat Adipose Tissue
Authors: Dobrzanski Tadeusz
Published: December 2014

In a study on thirty-seven Wistar rats the effect of Crystalline Insulin in a concentration of 0.1 units per milliliter of incubation medium on glucose uptake by both epididymal and perinephric isolated rat adipose tissue has been found to decrease with the age of the rat. This is a very little difference in the pattern shown by samples of epididymal or perinephric fat.
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.
Cerebrospinal Fluid Lipids in Diabetes Mellitus
Authors: Gregory R Frederick , Mills Gordon C , Gregory Raymond L , Lee Nancy
Published: December 2014

Abnormalities in cerebrospinal fluid (CSF) lipids have been found in certain diseases and have correlated with direct biochemical measurements of lipids in nervous system tissue. In the present study, total and free cholesterol, total lipid, and total phospholipid were determined by micro-analytic technics in the serum and CSF of thirty subjects: eight normal controls, seven diabetic subjects with polyneuropathy, eight diabetic subjects without neuropathy, and seven patients with other neurological diseases. An elevation of free cholesterol (p < 0.02) was found in the CSF of all diabetics regardless of neurological involvement and independent of any simultaneous abnormality of serum. Phospholipid was probably elevated. The abnormality of CSF free cholesterol could be related to neurological dysfunction in the diabetic patient and to ganglion cell abnormality.
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.
Changes in the Islets of Langerhans in Cows Injected with Heterologous and Homologous Insulin
Authors: LeCompte Philip M , Steinke Jurgen , Soeldner J Stuart , Renold Albert E
Published: December 2014

The histopathological findings in a group of cows injected with homologous or heterologous insulin in adjuvant are described. The essential features in the most severely affected cows (including two which received only bovine insulin) were lymphocytic infiltration of the islets of Langerhans with destruction of beta cells and fibrosis. The surviving beta cells showed signs of over-activity. The findings, which are regarded as having the characteristics of an “autoimmune” response, are discussed in relation to similar pathologic findings in human juvenile diabetes of recent onset.
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.
Some Factors Affecting Insulin Antibody Production in Guinea Pigs
Authors: Wright Peter H , Norman Laurance L
Published: December 2014

Repeated injections of insulin in an adjuvant containing heavy mineral oil and lanolin produces very variable effects on antibody production in guinea pigs. Incorporation of H. pertussis vaccine in the adjuvant used for initial injections raises the proportion of active producers of antibodies and rapidly increases the levels of insulin antibodies in their serum. This adjuvant appears to be more effective than the conventional Freund's adjuvant but results in high mortality if given frequently. Using a simple method of antibody assay, it is possible to segregate nonproductive animals at an early stage and so increase the yield of highly active anti-insulin serum.
Enzyme Strip Method of Blood Glucose Determination
Authors: Hollister Leo E , Helmke Elizabeth , Wright Agnes
Published: December 2014

Determinations of blood glucose levels by an enzyme strip test and the AutoAnalyzer were compared in 542 samples. The enzyme strip test tended to overestimate glucose values in the lower ranges and underestimate them in the upper ranges. Although agreement between the methods was reasonably good in the 60 to 130, and 130 to 200 mg. per 100 ml. ranges, underestimation of values by the strip test occurred in 10 per cent of the samples at the latter range. A study of the sources of variability of the enzyme strip test revealed that the color-matching step was most likely the source of most of the technical error. The latter was high for the test, the coefficient of variation of blind independent determinations on ten samples by four technicians being 27.5 per cent. The clinical usefulness of the test is limited, and it should not be employed if other methods of determining glucose levels are easily available.
Light and Electron Microscopy of Lesions in Rats Rendered Diabetic with Streptozotocin
Authors: Arison R N , Ciaccio E I , Glitzer M S , Cassaro J A , Pruss M P
Published: December 2014

Light and electron microscopic examination of organs of rats rendered hyperglycemic with streptozotocin revealed the following: (1) rapid degranulation of beta cells without necrosis; (2) development of cataracts in four months after injection of 65 mg. per kilogram of the drug; (3) accumulation of glycogen in the proximal convoluted tubules of the kidney after 65 mg. per kilogram; (4) lesions in the exocrine cells of the pancreas after 100 mg. per kilogram; and (5) persistence of small, possibly secretory, granules in the Golgi zone of beta cells in diabetic rats. The significance of these findings is discussed.
Radioimmunoassay of the A-chain of Insulin
Authors: Blackard William G
Published: December 2014

A radioimmunoassay for isolated A-chain is described. The immunospecificity of A-chain is shown to vary depending on the variation in structure about the cysteine residues. The presence of one or two intrachain disulfide bonds alters the immunoreactivity greatly in a system in which A-chain with all four cysteine residues carboxymethylated is the homologous antigen. Species specificity is also suggested by differences in the immunoreactivity of the cleaved products of bovine and porcine insulin. Further attempts to assay A-chain in human plasma by immunological methods must take these two factors into consideration.
Unknown Diabetes Mellitus Among Apparently Healthy Men With “Nonspecific” T Wave Abnormalities—in a Mental Hospital
Authors: Waitzkin Leo
Published: December 2014

A group of 117 psychiatric male inpatients under age fifty, physically healthy, without known diabetes or manifest heart disease or electrocardiographic evidence of myo-cardial infarction, were given a 100-gm., two-hour oral glucose tolerance test because their electrocardiograms showed inverted or isoelectric T waves. These men were compared with a similarly studied control group of 303 who did not have such nonspecific abnormalities. Significantly more diabetes was discovered in the former group among those aged forty to forty-nine. At that age, then, abnormal T waves were significantly associated with previously unknown diabetes. Results suggest there is an unusually high prevalence of undetected diabetes among apparently healthy men in their forties who have these nonspecific T wave abnormalities.
Observations on the Ultrastructure of a Metastasizing Beta Cell Islet Tumor
Authors: Joker Cyril
Published: December 2014

Reported ultrastructural studies of beta cell islet tumors have related to lesions confined within the pancreatic substance. Electron microscopy of a metastatic deposit from a nonfunctioning beta cell tumor is now presented. The investigation has revealed a highly complex and relatively orderly cytoplasmic structure—in conformity with the low grade of clinical malignancy exhibited by these lesions. Beta granules were present within many cells, but were usually sparse. They resembled the beta granules which have been described within both normal and neoplastic beta cells. The granules differed from alpha granules in the configuration, structure, relative size and electron density, of the central core. Characterization of islet cell tumors by virtue of the ultrastructure of their specific granules can now be achieved through the application of established criteria.
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.
Organ Cultures of Pancreases of Fetuses from Diabetic Rats: Effects of High-glucose Media upon the Granulation of the Beta Cells and upon the Insulin Content of the Media
Authors: Wells Lemen J , Lazarow Arnold
Published: December 2014

Forty pregnant rats were made diabetic by injecting alloxan intravenously on day 11.5 of pregnancy. On day 19.5 or day 21.5 the mothers were killed and their fetuses obtained for study. Pieces of fetal pancreases were grown in organ cultures on liquid media containing varying amounts of glucose for two to four days. At the time of the explantation, the beginning control pancreases contained virtually no granulated beta cells.

In cultures grown on the standard media (about 175 mg. of glucose per 100 ml.), the pancreatic islets had acquired many granulated beta cells. In those grown on the highglucose media (about 350, 500 and 1,000 mg. per 100 ml.) the islets had either few granulated beta cells or none. These observations complement our previous findings in pancreatic cultures from normal rat embryos.

The insulin content of the media after incubation was within the range of the insulin concentration in the blood of normal fed rats. The insulin content in the media after days 3-4 of culture was considerably greater than that after 1-2. The high-glucose levels in the media did not cause an increase in the insulin content of the media. Our studies suggest that the high-glucose levels in the media inhibited the synthesis (and/or storage) of insulin in the pancreatic culture.
Some Metabolic Effects of Phenformin in Rat Adipose Tissue
Authors: Pereira J N , Jangaard N O , Pinson E R
Published: December 2014

In rat adipose tissue, phenformin (5 × 10−4M) inhibited the oxidation of C1 and C6 of glucose to CO2, blocked the stimulatory effect of insulin (32 μU./ml.) on Ct oxidation, inhibited lipogenesis from C1 and C6 of glucose, and abolished the stimulatory effect of acetate on glucose oxidation and lipogenesis. These effects were accompanied by lactate accumulation. Such inhibitory effects suggest that phenformin interrupts the pentose shunt and lipogenesis, both of which are pyridine nucleotide-linked processes. Phenformin was shown, by inhibition of oxidation of pyruvate C1, to interfere with the sequence at the point of pyruvate decarboxylation, since acetate incorporation was not affected. Both pyruvate decarboxylation and oxidation of acetate in the tricarboxylic acid cycle were blocked, presumably by interference with electron transport. This effect of phenformin on pyruvate decarboxylation is sufficient to explain the observed reduction in pentose shunt activity and lipogenesis as well as the increased lactate accumulation.
The Natural History of Diabetes: I. Mortality
Authors: Hirohata Tomio , MacMahon Brian , Root Howard F
Published: December 2014

Survival data are presented for five groups of diabetic patients seen at the Joslin Clinic, Boston, between 1939 and 1959. Patients were white, Massachusetts residents, and diagnosed diabetic within twelve months of first visit to the Clinic. The data are analyzed in terms of crude survival rates, relative survival ratios and mortality “attributable” to diabetes after the elimination of competing causes.

The excess mortality rate experienced by diabetic patients increases with duration of diabetes. While persons with juvenile onset experience virtually no excess mortality in the first fifteen years of the disease, between the fifteenth and the twenty-fourth year they have an excess death rate of 1 to 1.5 per cent per year. In the older age groups the excess is larger and appears earlier.

The mortality attributable to diabetes increases with increasing age of onset. Females have higher attributable mortality rates than males, particularly among cases with onset after forty years of age.

Patients first seen in 1944 had substantially better survival rates than those first seen in 1939. However, between 1944 and 1959 no further improvement has been evident. This leveling off in the former decline in diabetes mortality has occurred at a point when diabetic patients still experience an excess mortality of approximately 30 per cent within the first twenty-five years of their disease.
Morphological Observations on Spontaneous Pancreatic Islet Changes in Rats
Authors: Hajdu Andrew , Rona George
Published: December 2014

A spontaneous lesion of the islet of Langerhans characterized by fibrosis and enlargement is described in the aging albino rat, occurring almost exclusively in males. Further studies are in progress to define the histogenesis, endocrine aspect and functional significance of this lesion.
Effect of Alloxan on the Mouse Pancreas during and after Recovery from Diabetes
Authors: Bunnag Srichitra C , Warner Nancy E , Bunnag Sirotma
Published: December 2014

Temporary diabetes was produced in mice by the intravenous injection of alloxan, 75 mg. per kilogram of body weight. The beta cells were degranulated within 6 hrs., but changes in microcirculation did not occur until 24 hrs., and did not appear to play arole in initiating damage to the beta cells. The total number of islets was decreased markedly within one week, but cellular proliferation of ducts and islets began as early as two weeks as indicated by in vivo study and radioautography. Improvement in the diabetic state, manifested by lowered blood glucose, coincided with restoration of a number of the islets. Although the total number of islets was not restored completely, the blood glucose values returned to normal, indicating that the new islets were functioning adequately. Replacement of the insular cells occurred solely by budding of new islets from the ducts,and no evidence of acino-insular transformation, or transformation of centro-acinar cellsinto beta cells, was found.
Intravenous Glucose Tolerance Test in an Industrial Population: Controls, Subjects with Coronary Heart Disease and Relatives of Diabetics
Authors: Ryan Will G , Economou Peter G , Schwartz Theodore B
Published: December 2014

Intravenous glucose tolerance was measured in a population of industrial workers who were participating in a prospective study to assess the importance of various factors contributing to the development of coronary heart disease. No significant differences in intravenous glucose tolerance could be detected between groups of control subjects, subjects with a close diabetic relative, or subjects with coronary heart disease.
Diabetic Amyotrophy: Light and Electron Microscopic Investigation
Authors: Bloodworth J M B , Epstein Murray
Published: December 2014

An elderly male with recent onset of mild diabetes mellitus developed diabetic amyotrophy. There were muscle atrophy and pain in the thighs without sensory changes. Multiple biopsies were made over a fourteen-month period and studied with light and electron microscopy. The changes of individual muscle fiber atrophy, typical of this disease, are described.
Ultrastructure of Dermal Capillaries of Africans in South Africa
Authors: Yodaiken Ralph E , Seftel Harold C , Rubenstein Arthur N
Published: December 2014

A “blind” study on the ultrastructure of the dermal capillaries of Africans in Johannesburg, South Africa, is reported. None of the patients had a family history of diabetes mellitus, and all were normotensive. A group of African, nondiabetic, normotensive ward patients with normal glucose tolerance curves acted as controls. As a corollary, a small group of Indian (Asiatic) and white patients were included in the sample to determine if any capillary changes could be related to ethnic group, diet, or other circumstances. The results indicate that thickening of the basal lamina (basement membrane) in the dermal capillaries of Africans is not specific for diabetes mellitus, and that no significant ultrastructural differences exist among the diabetics of the three major ethnic groups. However, it appears that the capillary lesion is commoner in diabetics than in nondiabetics, and the role of the pericyte in the possible pathogenesis of the lesion is discussed.
Effect of Intravenous Tolbutamide in Juvenile Diabetes Mellitus
Authors: Belle Ross De , Belmonte Mimi M , Colle Eleanor
Published: December 2014

Intravenous tolbutamide was administered to three groups of children with diabetes mellitus: (A) those with newly diagnosed disease, (B) those diabetic for less than two and one-half years, and (C) those diabetic for more than three years. Children in Groups A and B were found to respond to tolbutamide with a drop in blood glucose which differed from the response of normal children in that it was slow in onset and persisted throughout a three-hour period of observation. Children in Group C were unresponsive to tolbutamide. Children in Groups A and B showed an interference with the expected starvation-induced rise in nonesterified fatty acids over the period of observation, while children in Group C showed gradually increasing levels. The effect of tolbutamide on nonesterified fatty acids was less striking and showed more individual variation than did the effect on blood glucose. A few children with early diabetes mellitus developed hypoglycemia which appeared resistant to the usual counter-regulatory mechanisms. The fall in blood glucose was not accompanied by increased levels of insulin in peripheral blood.
Effects of Exogenous Insulin and Alloxan Diabetes on Rat Placenta
Authors: Powell Elinor D U , Caulfield James B , Field Richard A
Published: December 2014

Cell disruption with vacuolization of the third trophoblast layer and increased glycogen deposition in the second layer of the rat placental labyrinth have been found following insulin administration throughout pregnancy. These changes were also seen to a lesser extent in alloxan-diabetic animals treated with insulin, but not in a diabetic animal which survived without insulin treatment. It is suggested that abnormalities with these characteristics seen in the placentas of diabetic patients may be a consequence of insulin administration rather than due to the primary carbohydrate disorder.
Fatty Metabolism and Ketogenesis after Liver Denervation or Bilateral Thoracolumbar Sympathectomy in Pancreatectomized Dogs
Authors: Houssay Bernardo A , Rietti Giro T , Ashkar Edmundo , Castillo Enrique J Del , Galli María Elisa , Roldán Alicia , Urgoiti Enrique J
Published: December 2014

Bilateral extirpation of sympathetic chains from Tl to L6, including stellate ganglia and splanchnic nerves in totally pancreatectomized dogs, induces in blood: no changes in the diabetic hyperglycemia or cholesterolemia, but decrease of fatty acid mobilization from adipose tissue (lower values of FFA and lipemia), and a striking diminution of the diabetic ketonemia. In the liver, as in pancreatectomized dogs, there is less increase of total lipids (and triglycerides) but high values of cholesterol.

Acute hepatic denervation in pancreatectomized dogs does not change the mobilization of fatty acids from adipose tissue (the high levels of hyperlipemia and FFA are similar to those of pancreatectomized controls), but the increase of the ketonemic level is markedly depressed. Glycemia and cholesterolemia are increased as in the pancreatectomized dogs. In the denervated liver there is less increase of total lipids, triglycerides and cholesterol as compared with the pancreatectomized controls.

In the pancreatectomized dogs with chronic hepatic denervation the blood changes are similar to those of the pancreatectomized dogs. There is no attenuation of ketonemia. In the liver the cholesterol content is strikingly diminished as compared with the pancreatectomized controls. The diabetic hyperglycemia is high after pancreatectomy either after sympathectomy or hepatic denervation.