bluuebunny/crossref_metadata_2025 huggingface dataset:
Steatorrhea Complicating Diabetes Mellitus with Neuropathy: Report of Cases without Apparent External Pancreatic Insufficiency
Authors: Berge Kenneth G , Wollaeger Eric E , Scholz Donald A , Rooke E Douglas , Sprague Randall G
Published: December 2014

Disturbances of gastrointestinal function have frequently been observed in association with diabetes mellitus. The disorders which have been reported include gastric atony and dilatation, postprandial abdominal cramping, severe constipation, and intractable diarrhea characterized by watery stools, nocturnal exacerbations and fecal incontinence. These disturbances have been attributed by many investigators to alterations in gastrointestinal motility secondary to visceral diabetic neuropathy. The purpose of the present report is to call attention to a group of patients with diabetes mellitus and neuropathy who exhibited diarrhea and steatorrhea which apparently could not be attributed to external pancreatic insufficiency.
Tautologous Diabetic Coma—A Behavior Syndrome: Multiple Unnecessary Episodes of Diabetic Coma
Authors: Peck Franklin B , Peck Franklin B
Published: December 2014

The occurrence in a single patient of almost 50 repetitive instances of severe diabetic coma within 8 years of onset of the disease at age 12 is unique. Multiple comas of reasonable number are not unusual, but we know of no reported case having so many. The term tautologous has not been previously applied to diabetic coma. It is usually employed rhetorically, but in this instance it seems especially apropos, signifying as it does “needless repetition.” The development of this behavior pattern is of special interest in relation to the effect of stressful situations on the control of diabetes and the influence of subsequent poor control on the development of vascular complications.
The Banting Memorial Lecture 1956: Recent Advances In Insulin Research
Authors: Stadie William C
Published: December 2014

Dr. Ricketts, Members of the Association and Guests: I am indeed highly honored that this Society has selected me, one who long since abandoned the bedside for the laboratory, to give the Banting Lecture. I am happy to join with this Association to pay tribute to a great physician whose discovery of insulin has done so much to diminish suffering in man. Outstanding discoveries in the field of medical therapy are rare. We count surgical asepsis, anesthetics, and antibiotics among the important ones. The imperishable studies of Banting and Best added insulin to these. Its discovery generated problems in many areas of medicine and these have aroused the imagination and stimulated the activities of scientists all over the world. Driven by insatiable intellectual curiosity, they have labored indefatigably to search out the mode of action of insulin upon mammalian metabolism. Although obscurity still darkens the field, these researches reveal a pattern which begins to have meaning. I have undertaken the task in this hour to describe this pattern as I see it.
Massive Insulin Hypoglycemia and Capillary Vascular Physiology in Man
Authors: Lovet Doust John W , Salna Maria E
Published: December 2014

The vascular responses attending major insulin hypoglycemic reactions in man have been reviewed by Kalinowsky and Hoch, Bellak, and others, but the special role of the capillary and other small vessels has received little attention. The importance of this role is implied in the investigations made on the influence of insulin in coma-provoking doses in regard to brain metabolism, the literature on which has been reviewed by Himwich, and since the capillary system is the final common path by which energy is transferred between blood elements and tissue cells.

This paper is concerned with the acute responses of the minute vasculature of two nondiabetic human subjects receiving massive doses of insulin five times weekly, over a three-month period. The more chronic vascular effects of this sequential experience of hypoglycemia are reported elsewhere.
Carl H. von Noorden 1858-1944
Authors: Porges Otto
Published: December 2014

Carl H. von Noorden was born in Bonn, Germany, Sept. 13, 1858. His father, C. v. Noorden, was professor of history at German universities. After an excellent education in different schools (“Gymnasiums”) in Germany the son pursued university studies, first in philosophy, mathematics and law; but he soon changed over to medicine at the universities of Tubingen, Leipzig and Freiburg. He was graduated a doctor of medicine from Leipzig. He became an assistant at the physiological institute of the University of Kiel, later assistant at the medical clinics of the universities in Tübingen (Professor Jurgensen), Giessen (Professor Riegel) and finally in Berlin (Professor Gerhardt).
Diabetes Mellitus and Pregnancy
Authors: Mintz Daniel H , Skyler Jay S , Chez Ronald A
Published: December 2014

Proper therapy in pregnancy complicated by diabetes mellitus affords the physician an opportunity that is unparalleled in immediate impact and over-all therapeutic dimension for his or her patient. The immediate survival of the mother can be virtually assured and that of the unborn child brought close to that of the child of the nondiabetic gravida. Further, the benefit of this care extends considerably beyond these traditional clinical targets. Such relatively remote events as intellectual and psychologic performance in offspring from these pregnancies may be jeopardized by inadequate attention to details of medical management during pregnancy. Lastly, an opportunity is presented to both physician and patient to beneficially influence future diabetes therapy. The intense motivation of the mother, together with her positive experiences, can be channeled to promote an enduring attitudinal and behavioral approach to future
Diabetes Mellitus and Its Degenerative Complications: A Prospective Study of 4,400 Patients Observed Between 1947 and 1973
Authors: Pirart Jean
Published: December 2014

This article was originally published in French in Diabete et Metabolisme (vol. 3: 97–107, 173–182, 245–256; 1977). The Editors of DIABETES CARE thank the author, and the editors and publisher of Diabete et Metabolisme for granting permission for us to print this English translation. The paper was translated by Marjorie Levin of Miami, Florida.

Part I of this translation appeared in the May–June issue of DIABETES CARE (vol. I: 168–188).
Report of the American Diabetes Association's Task Force on Nutrition: Introduction
Authors: Vinik Aaron
Published: December 2014

Writing in the sixteenth century B.C., the Egyptians described diabetes as the dissolving of flesh in urine and promoted its treatment with diets high in carbohydrate as a means of combating the loss of fuels. Early in the first century, Aretaeus of Cappadocca endorsed these suggestions, recommending a diet of milk, cereals, and starch. By the early twentieth century, the whimsical rice, potato, and oatmeal diets had evolved from these beginnings and reached the apex of their popularity. The noted physician Willis—possibly more famous for the description of a circle of blood vessels at the base of the brain—endorsed such diets on the basis of the appearance of sweetness of the urine. Thus, many a medical student was obliged to taste urine before the advent of more advanced technology. Now a more sophisticated method is employed in which a treated strip of paper inserted in the urine is transposed, to a degree proportional to the quantity of glucose present, into one of the colors of the rainbow—a facility not generally endowed to the human taste bud.
Glycemic Effects of Beer in IDDM Patients: Studies With Constant Insulin Delivery
Authors: Spraul Maximilian , Chantelau Ernst , Schönbach Anna-Maria , Berger Michael
Published: December 2014

There are many factors influencing the glycemic response to carbohydrate (CHO) foods in humans, with several divergent reports in the literature (1-13). Part of the variability is probably due to methodological inadequacies, such as those recently pointed out by Gannon and Nuttall (14). To control for one of the most important variables affecting postprandial glycemia in subjects with endogenous insulin secretion, i.e., the meal-induced insulin response, we investigated the glycemic properties of alcoholic beverages with and without CHO in insulin-dependent diabetic (IDDM) patients connected to a constant intravenous insulin infusion according to the method of Brodows et al. (15) and Hermansen et al. (16,17).
Validity of Serum Fructosamine as Index of Short-Term Glycemic Control in Diabetic Outpatients
Authors: Cefalu William T , Parker Trudy B , Johnson Carolyn R
Published: December 2014

The glycosylated hemoglobin (HbA1c) assay has become the standard by which clinicians have assessed long-term glycemic control in patients. Due to the relatively long half-life of the erythrocyte, the assay is not suited to monitor glycemic control over several weeks. In recent years, the measurement of serum glycosylated proteins with half-lives ranging from 17 to 20 days have been postulated to be more sensitive than the HbA1c in detecting intermediate glycemic control (1–3). Several methods have been used to measure serum protein glycosylation such as the 5-hydroxymethyl-2-furfural colorimetric assay and affinity chromatography on boronate-agarose gels (1–4). However, these assays are time consuming and are not readily available in commercial laboratories for widespread clinical application. The fructosamine assay is a new colorimetric assay designed to measure serum glycosylated protein concentration.
What Diabetologists Should Know About Elderly Patients
Authors: Minaker Kenneth L
Published: December 2014

New challenges face the diabetologist from the enlarging elderly population with its increased prevalence of diabetes mellitus. Health-care utilization increases with both age and diabetes mellitus. The ways in which the elderly enter and respond to the healthcare system have changed significantly. Aging exerts a variable and recognizable influence on the way illnesses develop and how patients perceive their symptoms. The most important interaction of aging and disease is increased vulnerability to the development of severe diabetic complications. The techniques of history and physical examination are modified with age. An overall assessment of function becomes an important technique that assists in both diagnosis and management of elderly patients. Several important geriatric syndromes including delirium, urinary incontinence, falls, systolic hypertension, and polypharmacy are particularly common in elderly diabetic patients. Approaches to these prevalent conditions in the elderly are discussed.
Diabetes Education: What Should Health-Care Providers In Long-Term Nursing Care Facilities Know About Diabetes?
Authors: Tonino Richard P
Published: December 2014

Herein, I focus on three areas: 1) the context of diabetes in nursing homes, 2) the effectiveness of educational programs, and 3) recommendations for future directions. The 15% prevalence of diabetes in nursing homes is twice the rate in the general population. These patients have more macro- and microvascular comorbidity compared with nondiabetic nursing home residents and require 31% more hospitalizations. Targeted educational programs have been shown to improve patient care and reduce the number of hospital days by 28%. Guidelines for implementation of these educational programs take into account the special strengths and weaknesses of nursing homes. National and state initiatives should be made to increase diabetes education for health-care providers in long-term nursing care facilities.
Role of the Diabetes Educator for Older Adults
Authors: Funnell Martha Mitchell
Published: December 2014

Patient education is an essential component in the care of patients with diabetes. Older adults often have particular educational needs due to the effects of aging, concomitant illnesses, and the complications of diabetes. Because of the necessity for appropriately trained patients, the role of health-care professionals as diabetes educators is of paramount importance to the health-care team. The diabetes educator is able to assume responsibility for all aspects of the education process, including assessment, teaching, and follow-up, and take into account the individual needs presented by the older adult patient with diabetes.
Mechanisms of Age-Related Glucose Intolerance
Authors: Jackson Rodwin A
Published: December 2014

The influence of aging on the kinetic response to glucose ingestion and the mechanisms underlying age-related glucose intolerance are described. Despite delayed absorption of the ingested glucose load, impaired glucose tolerance develops with age. This impairment is multifactorial, being characterized by delays in glucose-induced insulin secretion, insulininduced suppression of hepatic glucose output, and a rise in insulin-mediated glucose uptake. The major disturbance appears to be impaired insulin-mediated glucose uptake, with skeletal muscle the principal site of this defect. Because insulin receptors are unchanged with age, the impairment in insulin action is primarily due to a postreceptor defect. Possible mechanisms associated with the age-related impairment in glucose uptake by muscle include 1) decreased muscle mass, 2) increasing obesity, 3) decreased physical activity, 4) poor diet, and 5) increased plasma free-fatty acid levels. However, evidence from recent research suggests that none of these factors plays a significant role in this regard. The principal postreceptor defect in insulin action may comprise a decreased maximum velocity of glucose transport due to a decreased number of glucose transporters, although each transporter functions normally. Conceivably, the transport defect may be due to a depletion of the intracellular pool of transporters, which may ultimately reflect insulin resistance at the level of glucose-transporter mRNA and/or defective insulin internalization and intracellular metabolism. However, an age-related impairment in intracellular glucose metabolism may be present in addition to any changes in the glucose-transport system. The phenomenon of age-related glucose intolerance is the result of defects specific for the aging process and distinct and separate from those characterizing obesity and non-insulin-dependent diabetes; their distinguishing features are discussed.
Factors Influencing Threshold and Choice of Treatment for Hypertension in NIDDM: Cardiovascular Factors
Authors: Yudkin John S
Published: December 2014

In nondiabetic populations, there is an ∼40% increase in stroke risk and a 25% increase in coronary heart disease (CHD) risk with every 6-mmHg increase above 75mmHg in usual diastolic blood pressure. Diabetesincreases the risk of both conditions by two- to threefold, and in diabetic patients, hypertension further increases these risks. The benefits of lowering blood pressure in nondiabetic subjects have been subjected to metaanalysis, which has demonstrated benefits equivalent to 100% reversal of the excess risk for stroke but with only ∼50% of CHD risk reversible after 2–3 yr of treatment. In these analyses, the benefit of treating diastolic blood pressure is similar at all levels >90 mmHg. If these results are extrapolated to diabetic patients, possible benefits of therapy for mild hypertension could be two to three times greater than in nondiabetic subjects, but this could still correspond to 300 person-yr of treatment to prevent one nonfatal stroke and 2500 person-yr oftreatment to prevent one CHD death, with treatment that may deleteriously affect quality of life in 36% of all diabetic patients. There may also be risks in treating patients with mild hypertension who have existing CHDor left ventricular hypertrophy, which are more common in diabetes. Despite the theoretical risk of deleterious changes in several cardiovascular risk factors with thiazides or β-blockers, most of the newer agents have not yet been demonstrated to produce similarbenefits to the large prospective studies in which the aforementioned agents have been used. It is only with prospective studies in high-risk diabetic populations that the treatments can be compared and the possible risks of a J-shaped curve assessed.
Insulin Pump Therapy: Indication, Method, Technology
Authors: Paterson K R
Published: December 2014

The last decade, with the introduction and increasing technical sophistication of portable insulin-infusion pump systems, has seen insulin-infusion therapy introduced, gain limited popularity as a treatment option, and, in many countries, fall from favor with the move to multiple injection regimens and pen injection devices. The time is right for an appraisal of the true role of insulin-pump treatment, synthesizing the many anecdotal reports and few controlled studies into useful guidelines for the safe and effective use of this demanding form of insulin delivery. Unfortunately, this book fails to meet the requirement for a critical and analytical review, and its usefulness is thus severely limited.
Hyperinsulinemia—How Innocent a Bystander?
Authors: Zimmet Paul Z
Published: December 2014

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
User Error in Blood Glucose Monitoring: The National Steering Committee for Quality Assurance Report
Authors: Nettles Anne
Published: December 2014

Since the invention of patient-operated blood glucose testing devices, professionals have expressed concern about the accuracy of the results (1). In part, their concern relates to the impact of patient results on diabetes management decisions. Numerous authors and investigators have examined potential sources of error ranging from the devices themselves to deterioration in operator technique (2–5).
Finding the Right Fit for Meal Planning
Authors: Franz Marion J
Published: December 2014

Nuttall (this issue, F.Q. Nuttall, p. 1039–42) is to be congratulated on articulating a constant CHO meal-planning approach that can be used by medical professionals and individuals with diabetes. Central to this approach is determining the usual amount of CHO eaten at meals and/or snacks by the person with diabetes, keeping that amount constant, and covering with the appropriate amount of insulin.
Quality Control in Patient Self-Monitoring of Blood Glucose
Authors: Greyson Jerome P
Published: December 2014

The American Diabetes Association (1), the National Committee for Clinical Laboratory Standards (2), the Canadian Association of Pathologists (3), and the conferees of the Consensus Development Conference on SMBG (4) have all published recommendations, guidelines, or position statements on the practice of SMBG in hospital settings that call for, among other things, enhanced personnel training and establishment of quality control programs. However, no formal quality control or educational guidelines have yet been developed for patient use of SMBG devices.
The Potential Role of Diabetes Guidelines in the Reduction of Medical Injury and Malpractice Claims Involving Diabetes
Authors: Clark Charles M , Kinney Eleanor D
Published: December 2014

Little is known about the nature of the medical injuries that give rise to malpractice claims. Also little is known about the degree to which clinical practice guidelines would apply to the medical conditions and associated medical treatment in malpractice claims.
Recommendations for Desirable Features of Adaptive Diabetes Self-Care Equipment for Visually Impaired Persons
Authors: Williams Ann S
Published: December 2014

The Task Force on Adaptive Diabetes Education for Visually Impaired Persons (ADEVIP) met at Cleveland Sight Center on 23–25 April 1993 for a consensus development meeting (1). This project brought together a multidisciplinary group of professionals who have expertise in working with visually impaired people who have diabetes. Building on the work of the 1988 National Task Force on Diabetes and Vision Impairment, the Task Force on ADEVIP addressed a number of issues that affect diabetes care for people who live with both diabetes and visual impairment. In the U. S., between 15,000 and 39,000 people with diabetes become blind each year (2). One recent estimate was as high as 47,000 (R. Brechner, unpublished observation). With numbers of this magnitude, these concerns are not of trivial significance.
Epidemiologic Methods in Diabetic Macrovascular Disease
Authors: Rose Geoffrey , Keen Harry , Jarrett John
Published: December 2014

This paper covers the important factors in making valid comparisons in epidemiologic studies, including case definition, validity and repeatability of measurements, and quality control
The Public Health Burden of Diabetes and the Reality of Limits
Authors: Vinicor Frank
Published: December 2014

Improvements in diabetes surveillance, diagnosis, and treatment have, in recent years, heightened awareness of the burden of diabetes and aroused concern about the amount of health care resources that will be necessary to manage this disease effectively in the future. Examination of diabetes from the twin perspectives of economics and public health challenges basic notions of the health care tradition in the Western world: the real-world combination of finite resources and the growing need/demand for health services forces the consideration of limits in the provision of health care. The growing need to rationally allocate limited health care resources poses emotional, potentially divisive questions of science, politics, economics, and ethics that patients and physicians must each address.
Diabetes and the Promise of Managed Care
Authors: McDonald Robert C
Published: December 2014

The term managed care has a positive connotation to many people and a negative connotation to others. It implies a systematic approach to the provision of care supported by a managed care organization, the underlying values of which are efficiency in care delivery and continuous health improvement of the population being served. The recent advances in knowledge surrounding the treatment of diabetes, the codification of these advances into treatment guidelines, and the significant gap between recommended and real-world treatment patterns all suggest that there is an opportunity for managed care organizations to play a beneficial role in improving the treatment of people with diabetes. Typical strategies used by managed care organizations include dissemination of treatment guidelines and information feedback to providers and patients to suggest diagnostic measures or therapeutic interventions that should be repeated with regularity to maintain or improve the health of people with diabetes. Improvements in population-level measurement of health care quality will increase the focus on preventable long-term complications of diabetes and other chronic diseases and may establish increasingly quantitative quality metrics that should improve real-world treatment patterns. Models exist for a multifaceted approach to improve the care of people with diabetes through such mechanisms; this article reviews the experience of one health plan with such undertakings.
The Burden of Chronic Hyperglycemia
Authors: Clark Charles M
Published: December 2014

Diabetic complications constitute the principal clinical and economic burdens of diabetes. Available evidence indicates that sustained reduction in hyperglycemia (as measured by HbA1c) reduces the incidence of diabetic complications, including microvascular and neurological disease, and will likely reduce the risk of macrovascular disease. In the U.S., targeting interventions to aged and ethnic subpopulations, which are currently receiving suboptimal care, and increasing efforts to lower the average HbA1c concentrations one or two percentage points in people with diabetes would be a more cost-effective goal than aiming for a theoretical HbA1c threshold below which the risk of complications is negligible. Other risk factors for diabetic complications, such as obesity, hypertension, cigarette smoking, and hypercholesterolemia, must also be addressed to reduce the burden of diabetes.
Alternate Routes of Insulin Delivery
Authors: Irsigler Karl , Kritz Harrald
Published: December 2014

The relative merits of intraperitoneal (i.p.) and subcutaneous (s.c.) insulin delivery compared with intravenous (i.v.) delivery were investigated in seven diabetic patients using a combination of glucosecontrolled closed-loop (Biostator) and portable open-loop (Siemens minipump) insulin infusion systems. With appropriate algorithms for feedback-controlled insulin infusion, it could be shown that each of the three approaches was able to achieve satisfactory blood glucose levels. After glucose challenge, i.p. administration required almost twice as much insulin and twice as much time as i.v. to return to normal blood glucose (BG) levels. When the insulin dosage profile determined with Biostator feedback control is transformed to a simpler program consisting of basal rate and rectangularly shaped supplementary profiles for the open-loop system, good control was achieved during observation periods of about 1 wk with both s.c. and i.p. delivery. Subcutaneous infusion with the minipump was also carried out for a period of 70 days in one patient on an outpatient basis. In this long-term study s.c. infusion was not superior to twice-daily s.c. injections with frequent monitoring of BG and self-adjustment of insulin dosage by the patient. The optimal method of delivery appeared to be i.v., with i.p. and s.c. in second and third place. Intraperitoneal delivery seems to be a viable alternative that might help to solve some problems in the development of implantable devices. Further investigations should be carried out.
Role of Liver in Glucose Homeostasis
Authors: Sherwin Robert S
Published: December 2014

The liver has a unique role in regulation of blood glucose in the postabsorptive state, after ingestion of glucose-containing meals, and in circumstances of glucopenia. It is soley responsible for the delivery of glucose to the bloodstream in the fasted state, thereby maintaining blood glucose concentration for the ongoing needs of body tissues, particularly the brain. An equally important role is played by the liver in the maintenance of normal glucose tolerance in response to carbohydrate ingestion. The liver is the principal site of glucose deposition after glucose feeding, while muscle and adipose tissue represent relatively minor sites of disposal of ingested glucose. In addition, the rise in glucose and insulin caused by glucose ingestion inhibits endogenous hepatic glucose production, which serves to minimize postprandial elevations in blood glucose. When blood glucose is reduced by small increments in circulating insulin, a rebound increase in glucose output from the liver is the initial or principal mechanism counteracting the fall in blood glucose concentration. Studies in juvenile-onset diabetes indicate that the liver is capable of altering its release of glucose in response to changes in blood glucose concentration when small, physiologic doses of insulin are infused. These findings may provide an explanation for the efficacy of preprogrammed insulin delivery systems in the treatment of diabetes.
Glucagon Responses to Hypoglycemia in Type I Diabetic Men After 24-hour Glucoregulation by Glucose-controlled Insulin Infusion
Authors: Ensinck John W , Kanter Robert A
Published: December 2014

To determine if the attenuated glucagon response to insulin-induced glucopenia characteristic of type I diabetic patients might be restored to normal by optimizing glucose “control,” four type I diabetic men were studied after precise glucoregulation by means of a glucose-controlled insulin infusion system (GCIIS). Plasma glucose and immunoreactive glucagon (IRG) levels were measured before and after an intravenous bolus of insulin, and the results were compared with those in six healthy young men and in five healthy, type I diabetic patients who were receiving conventional insulin therapy. In comparison to the augmented secretion of IRG in the normals after glucopenia, the conventionally treated diabetic subjects had a trivial increase in IRG levels despite similar decrements in plasma glucose levels. In four diabetic men, plasma glucose levels were maintained within euglycemic ranges by GCIIS throughout 24 h, and, immediately thereafter, their IRG responses to insulin-evoked hypoglycemia were quantitatively indistinguishable from the type I diabetic patients who had not been treated by GCIIS. These observations contrast to evidence that A-cell responses to signals such as glucose or amino acids are partially or completely restored by short- or long-term insulin administration. It is inferred that this abnormality reflecting a possible defect in A-cell glucose recognition may be a persistent abnormality in patients with type I diabetes.
New Devices and Methods for Long-term Vascular Access for Blood Sampling and Insulin Infusion
Authors: Bahoric A , Filler R M , Perlman K , Jackman W S , Albisser A M
Published: December 2014

Studies aimed at quantifying the benefits of infused rather than injected insulin have been impeded by the unavailability of suitable methods for continuous vascular access. We have developed indwelling catheters suitable for the long-term blood sampling as well as insulin infusion. A typical catheter consists of a silicone rubber tube, which terminates with a blunt-point needle. Internal or external reinforcement as well as a removable strain relief fitting protect the area of insertion of the needle. Anchoring of the implanted extravascular portion of the catheter is important and is achieved by special grommets that prevent motion without obstructing the lumen. Methods of catheter assembly as well as implantation in the jugular and portal veins of dogs and jugular veins of humans are described. A total of 34 blood sampling catheters were implanted in 26 beagle dogs: 74% were uncomplicated with a duration of implantation of 18–576 days while 15% and 11%, respectively, failed due to infection or physical damage after an average of 200 days. Thirteen portal infusion catheters were implanted: 62% were functional a mean of 100 days (14–166 days) after implantation while 35% became covered with an endothelial sleeve and had to be removed. Thirty-two peripheral infusion catheters were implanted in dogs: one infection occurred, two catheters were physically damaged, and three were plugged. There were no catheter-related complications in the five adolescent diabetic subjects with such jugular venous catheters studied for an average of 19.5 days and three adult diabetic subjects in whom catheters remained patent for 150–270 days. It is the inherent characteristics of the silicone rubber material as well as the new methods of catheter construction and implantation that virtually eliminate catheter-related problems and that now provide an ideal route of access for long-term intravascular insulin infusion in diabetes mellitus.
Comparison of Biologic Potency of Human Insulin (recombinant DNA) and Purified Porcine Insulin (PPI) on the Rat and Human Adipocyte Lipogenesis Model
Authors: Khokher M A , Dandona P
Published: December 2014

To assess whether human insulin (recombinant DNA) is superior to porcine insulin, we compared the biologic effect of these two insulin preparations on rat and human adipocyte lipogenesis in vitro. The biologic potency of these two insulin preparations was similar on both human and rat adipocytes. Iodination of human and porcine insulin with 125I at A14 position led to a significant but similar loss of potency of both insulin preparations.
Receptor Binding Properties of Human Insulin (recombinant DNA) and Human Proinsulin and Their Interaction at the Receptor Site
Authors: Prager Rudolf , Schernthaner Guntram
Published: December 2014

The binding properties of human insulin (recombinant DNA) and human proinsulin were compared in seven healthy volunteers. Specific cell binding of human proinsulin was significantly lower compared with the human insulin receptor binding with an approximately 100-fold lower average affinity (3.71 mol−1 × 108 for human insulin versus 0.042 mol−1 × 108 for human proinsulin). Native human proinsulin at low concentrations had no significant effect on specific human insulin receptor binding. Only at high hormone concentrations human proinsulin could displace human insulin from the insulin receptor. We conclude that in vivo proinsulin-insulin interactions at the receptor do not possess major clinical relevance.
Absorption Kinetics of Semisynthetic Human Insulin and Biosynthetic (recombinant DNA)Human Insulin
Authors: Kemmer F W , Sonnenberg G , Cüppers H J , Berger M
Published: December 2014

Absorption kinetics of subcutaneously injected human insulin (recombinant DNA) and semisynthetic human regular insulin were investigated and compared to the respective porcine insulin preparations in normal volunteers. The absorption of all regular human insulin preparations tested was accelerated as compared to porcine insulins. The clinical relevance of these findings in regard to the treatment of diabetes mellitus appears to be doubtful. As for mixtures of porcine regular and intermediate-acting insulin preparations, the absorption of human regular insulin is not altered when mixed with intermediate-acting human insulin.
Plasma Insulin and C-Peptide After Subcutaneous and Intravenous Administration of Human Insulin (recombinant DNA) and Purified Porcine Insulin in Healthy Men
Authors: Pickup John C , Bilous Rudolf W , Viberti Gian Carlo , Keen Harry , John Jarrett R , Glynne Alan , Cauldwell Joan , Root Mary , Rubenstein Arthur H
Published: December 2014

We have compared the plasma profiles of C-peptide, human insulin (recombinant DNA), and purified porcine insulin of pancreatic origin (PPI) in six nondiabetic men after low-dose (4.8 U) or high-dose (9.6 U) subcutaneous injection and low-rate (1.0 U/h) or high-rate (1.7 U/h) intravenous infusion. There was no significant difference in plasma C-peptide or glucose levels when human insulin was compared with PPI at either dose level for subcutaneous injection or intravenous infusion. Thus, there was equal suppression of endogenous insulin by the two species of exogenous insulin. For low-dose subcutaneous injection there was no significant difference between plasma insulin levels of the two species at single time points or when areas were compared. For high-dose subcutaneous injection mean plasma insulin levels were higher after human insulin than after PPI (20–300 min); this serial difference reached conventional statistical significance at 50 min (P < 0.05) and 90 min (P < 0.01). For the area under plasma insulin profiles between 0 and 90 min after high-dose s.c. injection, human insulin was higher than PPI (P = 0.06). There was no significant difference between insulin concentrations after human insulin and PPI given by either low- or high-dose intravenous infusion, except that highdose PPI values (55–110 min) were slightly but significantly higher after high-dose intravenous infusion. Further comparisons of the pharmacokinetics of human and other species of insulin are, therefore, justified in larger numbers of subjects and particularly in diabetic individuals.
Insulin Concentrations and Time-Action Profiles of Three Different Intermediate-acting Insulin Preparations in Nondiabetic Volunteers Under Glucose-controlled Glucose Infusion Technique
Authors: Bottermann P , Gyaram H , Wahl K , Ermler R , Lebender A
Published: December 2014

This study describes the pharmacokinetics of three intermediate-acting insulin preparations, NPH porcine insulin, NPH human insulin (recombinant DNA), and “Depot-A” insulin, a mixture of 20% regular and 80% NPH human insulin from Eli Lilly and Company. Metabolic healthy normal weight volunteers were selected for the study. After overnight fasting, each test person received 0.4 U of each insulin per kg body weight injected subcutaneously in the triceps area of the arm. To prevent severe hypoglycemia, the test persons were connected to a “GCIIS Biostator” with blood glucose clamp at the 60 mg/dl level. Peripheral blood was sampled at regular intervals for glucose, insulin, and C-peptide determination. More elevated insulin levels were measured after application of both NPH human insulin and “Depot-A” insulin than after NPH porcine insulin. A more rapid decrease in the blood glucose concentration was observed after injection of both human insulin preparations than after porcine insulin. The dextrose output of the “GCIIS Biostator” was more pronounced in both human insulins than after the porcine preparation. After the injection of NPH human and NPH porcine insulin, significant differences were calculated between the concentrations of these two insulins in the blood, from the 2nd to the 10th hour (P < 0.05-P < 0.005) and between the dextrose output of the “GCIIS Biostator” from the 3rd to the 8.5th hour (P < 0.05). The fall of the C-peptide concentration to the lower detection limit of the assay reflects suppression of the endogenous B-cell secretion and confirms the measure of peripheral insulin concentrations as a result of the exogenously applied insulin. Although all investigations were performed under identical experimental conditions and equal dosages of each insulin were injected, higher insulin concentrations and a stronger biologic effect, shown by larger amount of dextrose delivered, were observed in both human insulins than in porcine insulin. Why this phenomenon occurs is as yet unclear. The clamp technique used with the “GCIIS Biostator” enables establishment of the biologic profile of any insulin, and thus represents a valuable tool in comparative studies.
Comparative Study of NPH Human Insulin (recombinant DNA) and Pork Insulin in Diabetic Subjects: Preliminary Report
Authors: Mirouze J , Monnier L , Richard J L , Gancel A , Soua K B
Published: December 2014

Continuous blood glucose monitoring in six insulin-dependent diabetic patients shows that the biologic action of NPH human insulin (recombinant DNA) and pork insulin is similar. Nevertheless, the activity of NPH human insulin seems faster and more pronounced since minimal glycemia is lower and more rapidly reached after human insulin. The speed of glycemic increase is slightly lower and the decrease is faster with NPH human insulin; thus the area under the NPH human insulin-induced glycemic curve is less wide, but differences are not significant. Our data favor a faster and more potent effect of NPH human insulin.
Comparative Study of NPH Human Insulin (recombinant DNA) and NPH Bovine Insulin in Diabetic Subjects
Authors: Marre M , Tabbi-Anneni A , Tabbi-Anneni H , Assan R
Published: December 2014

The hypoglycemic potencies of human insulin (recombinant DNA) and bovine NPH insulin were compared in insulin-dependent diabetic subjects. The same dosages of the two preparations were alternately injected, for two successive 5-day periods, on a twice-a-day schedule. Blood glucose profiles were monitored by finger pricking 6 times/day. Slight but significant differences in glucose time appeared, suggesting that human NPH insulin acts faster than bovine NPH, and for a shorter time.
The Therapeutic Efficacy of Human Insulin (recombinant DNA) in Patients with Insulin-dependent Diabetes Mellitus: A Comparative Study with Purified Porcine Insulin
Authors: Howey Daniel C , Edwin Fineberg S , Nolen Phyllis A , Stone Margaret I , Gibson Reid G , Fineberg Naomi S , Galloway John A
Published: December 2014

The therapeutic efficacy of human insulin (recombinant DNA) was compared with that of purified porcine insulin (PPI) in seven male subjects with previously treated insulin-dependent diabetes mellitus. In a random crossover design the patients received either PPI or human insulin during one of two consecutive 7-day periods of intensive insulin therapy. Control was evaluated on days 6 and 13. Tissue sensitivity and responsiveness to the study insulins were determined by insulin dose-response studies performed using the euglycemic glucose clamp on days 7 and 14. Insulin dose and all measures of control on days 6 and 13 were not statistically different between treatments. When the insulin dose-response studies during each treatment were compared there were no differences between them. Thus, in previously treated patients with insulin-dependent diabetes, undergoing brief but intensive insulin therapy with continuous subcutaneous insulin infusion, human insulin is as clinically efficacious as PPI. Furthermore, insulin sensitivity and responsiveness, as assessed by dose-response studies during the euglycemic glucose clamp were equivalent for both insulins.
Geographic Differences in the Risk of Insulin-dependent Diabetes Mellitus: The Importance of Registries
Authors: LaPorte Ronald E , Tajima Naoko , Åkerblom Hans K , Berlin Nina , Brosseau James , Christy Morten , Drash Allan L , Fishbein Howard , Green Anders , Hamman Richard , Harris Maureen , King Hilary , Laron Zvi , Neil Andrew
Published: December 2014

There are marked geographic differences in the incidence of insulin-dependent diabetes mellitus (IDDM); for example, children in countries such as Finland are over 35 times more likely to develop IDDM than children in Japan. An understanding of the reasons for the geographic differences is likely to be important for understanding and, hopefully, preventing IDDM. There are problems, however, because of the lack of registries with adequate standardization. The major needs for the future studies include (1) to clarify the definition of IDDM for epidemiologic study, (2) to establish a standardized approach for IDDM registries, (3) to use registries to evaluate viral, immunologic, and genetic differences in order to explain differential risks across populations, and (4) to encourage the development of new population-based registries worldwide.
Thyroid, Gastric, and Adrenal Autoimmunities Associated with Insulin-dependent Diabetes Mellitus
Authors: Maclaren Noel K , Riley William J
Published: December 2014

Thyroid microsomal, gastric parietal, and adrenocortical autoantibodies were sought in 1456 Caucasian and 240 black patients with insulin-dependent diabetes mellitus (IDDM), in 1467 of the Caucasian patients' immediate family members, and in 1519 normal Caucasian control subjects. Positive clinical significances and predictive values of these autoantibodies for associated gland dysfunctions were found. In all groups, thyroid and gastric autoantibodies were more common in female subjects. In the control group, thyroid and gastric autoantibodies were more frequent with advancing age, affecting more than one-third of Caucasian women after age 60 yr. This age-augmented increase occurred very prematurely in patients with IDDM and their relatives. Among the patients with IDDM and thyroid and gastric autoantibodies, these autoantibodies appeared by the time of onset of IDDM in the large majority of cases; however, they were more common among patients with later ages of onset of IDDM. Occurrence of thyroid and gastric autoantibodies in 404 siblings of patients with IDDM was not affected by their degree of HLA-haplotype sharing with their diabetic sibling, suggesting that the inherited predisposition to thyroid and gastric autoimmunity is not HLA-related. In light of this, the increased frequencies of these antibodies in patients with IDDM and their relatives suggest that “thyroid and gastric autoimmunity genes” may also predispose to IDDM.
Speed Control of Multiphase Cage Induction Motors Incorporating Supply Sequence
Authors: Drozdowski Piotr
Published: December 2014

The subject of this paper is the control possibility of the multiphase cage induction motors having number of phases greater than 3. These motors have additional properties for speed control that distinguish them from the standard 3 phase motors: operation at various sequences of supplying voltages due to the inverter control and possible operation with few open-circuited phases. For each supply sequence different no load speeds at the same frequency can be obtained. This feature extends the motor application for miscellaneous drive demands including vector or scalar control. This depends mainly on the type of the stator winding for a given number of phases, since the principle of motor operation is based on co-operation of higher harmonics of magnetic field. Examples of operation are presented for a 9-phase motor, though general approach has been discussed. This motor was fed by a voltage source inverter at field oriented control with forced currents. The mathematical model of the motor was reduced to the form incorporating all most important physical features and appropriate for the control law formulation. The operation was illustrated for various supply sequences for “healthy” motor and for the motor operating at one phase broken. The obtained results have shown that parasitic influence of harmonic fields interaction has negligible influence on motor operation with respect to the useful coupling for properly designed stator winding.