bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypophysectomy in Diabetic Retinopathy: The Relationship Between the Degree of Pituitary Ablation and Ocular Response
Authors: Adams Donald A , Rand Robert W , Roth Nathan H , Dashe Alfred M , Gipstein Robert M , Heuser Gunnar
Published: December 2014

Cryohypophysectomy was performed twenty-nine times in twenty-eight critically selected insulin-dependent diabetic subjects who exhibited progressive proliferative diabetic retinopathy. The procedure was safe, relatively free of significant complications, and medical management was not difficult. Various endocrine parameters of pituitary function were studied before and after surgery with emphasis on growth hormone activity. Seventeen of the twenty-eight patients demonstrated evidence of “complete” pituitary ablation with twenty (71.4 per cent) patients showing a favorable ocular response after an average follow-up of forty-three months. Fourteen (82 per cent) of the seventeen patients with “complete” pituitary ablation had a favorable ocular response.

Five patients had transsphenoidal microsurgical pituitary ablation, but this procedure was not as satisfactory as cryoablation in our hands.

Growth hormone ablation appeared to be a common factor in most of the cases who had favorable results, particularly illustrated by a few patients who improved only after repeat surgery ablated growth hormone that had not been eliminated by their initial operation.

Our data suggest that there is a positive relationship between the degree of pituitary ablation and successful ocular response and support the hypothesis that growth hormone may play a causal role in diabetic retinopathy.
Insulin Extractable from the Pancreas and Islet Cell Histology: Comparative Studies in Spontaneous Diabetes in Dogs and Human Subjects
Authors: Wrenshall Gerald A , Hartroft W Stanley , Best Charles H
Published: December 2014

The characteristics of diabetes mellitus in man have long been compared, either directly or by inference, with those of diabetes produced in animals by experimental means. From the earliest studies in this field by von Mering and Minkowski1, in the work leading to the discovery of insulin2 (1921), and in many later investigations, the dog has occupied a prominent and productive place amongst experimental animals. In recent years, special aspects of the spontaneous diabetes of dogs have come under study in this laboratory and in that of Professor Henry Ricketts in Chicago.

It is the purpose of this paper to examine the available data to determine the degree to which the spontaneous and the experimentally induced diabetes mellitus of dogs correspond with each other and with the spontaneous diabetes mellitus of man, in terms of the insulin extractable from the pancreas and the histological state of the islands of Langerhans. The relationship of these factors to the diabetic state with which they are associated will also be considered.
Coronary Artery Disease in the Diabetic
Authors: Marble Alexander
Published: December 2014

More than half of the deaths in the United States today are due to cardiovascular renal diseases, and chief among these is coronary heart disease. Among diabetics this complication is particularly common. Of 3,499 deaths among patients of the Joslin Clinic between Jan. I, 1944, and Apr. 27, 1951, 2,456, or 70.2 per cent, were considered by the attending physician to be due to arteriosclerotic cardiovascular-renal disease. Of the total deaths 1,627, or 46.5 Per cent, were ascribed to arteriosclerotic heart disease. Of 656 deaths during the period 1950 to 1952, 496, or 75.6 per cent, were due to arteriosclerotic cardiovascular-renal disease; 312 or 47.6 per cent, were of cardiac origin.
A Comparison of Obese and Nonobese Diabetic Subjects
Authors: Murray Ian , Wang Ian
Published: December 2014

From the clinical aspect the obese, lipoplethoric diabetic differs in many respects from the nonobese insulindeficient patient, as has been pointed out by Lawrence. Nevertheless, published statistics with regard to diabetes do not generally take cognizance of such differences, and it appeared that it might be of interest to investigate the characteristics of these two groups separately. Accordingly we undertook a study of 1,000 patients all of whom had been diabetic for at least one year and who were attending the diabetic clinic at the Victoria Infirmary in Glasgow.
Importance of Outpatient Supervision in the Prognosis of Juvenile Diabetes Mellitus: A Cost/Benefit Analysis
Authors: Deckert Torsten , Poulsen Jacob E , Larsen Mogens
Published: December 2014

The object of this study was to investigate whether outpatient follow-up visits to a subspecialized clinic have a favorable effect upon length of life of juvenile diabetic patients, and to evaluate whether the cost of suchoutpatient supervision is in reasonable proportion to the benefit obtained. The study comprises 180 insulin-dependent diabetic patients in whom a diagnosis had been made before 1933, and before they were 31 years of age. The patients had been admitted to the Steno Memorial Hospital before their fifteenth year of diabetes. Sixteen patients could not be traced after forty years of diabetes, while the others were followed until death or until their fortieth year with diabetes. Seventy-seven patients never attended follow-up in the outpatient clinic, while the others attended one to 145 times in thecourse of their first twenty years of diabetes. From the results it is apparent that the duration of diabetes correlated with increased frequency of outpatient follow-up. With 4.4 annual outpatient follow-up visits, the duration of diabetes was prolonged by 11.9 years. The cost of this was estimated at $10,468 per patient over forty years. The benefit per patient over the entire forty years was $100,656. These findings suggest that outpatient supervision of diabetes in a subspecialized clinic is beneficial for patients and involves relatively little cost.
Ineffectiveness of SMS 201-995 in Severe Hyperinsulinemia
Authors: Boden Guenther , Ryan Isabel G , Shuman Charles R
Published: December 2014

The long-acting somatostatin analogue SMS 201–995 has been used with impressive success in the treatment of certain endocrine disorders, including acromegaly (1-4), the Verner-Morrison syndrome (5,6), and the carcinoid syndrome (7,8). There is less information with respect to the effectiveness of this drug in the treatment of organic hyperinsulinism (β-cell adenomas, carcinomas, hyperplasia, and nesidioblastosis). We report two cases with severe hyperinsulinism caused by islet cell adenomas. In both cases, protracted hypoglycemia and hyperinsulinemia were not improved by SMS 201–995.
Eye Disease and Nephropathy in NIDDM
Authors: Herman William H
Published: December 2014

Diabetic eye disease and diabetic nephropathy are major causes of morbidity among the elderly. Herein, I focus on the epidemiology, prevention, and treatment of diabetic eye and kidney disease in people with noninsulin-dependent diabetes mellitus (NIDDM) and identify some of the major gaps in our knowledge about these conditions.
Circulation in Lower Extremities and Sympathetic Function in Diabetic Patients: Significance of Age
Authors: Christensen Niels Juel
Published: December 2014

Circulation in the lower extremities and sympathetic function have been studied extensively in long-term type I (insulin-dependent) diabetic patients. Arterial lesions are demonstrable in these patients, but clinical vascular disease (e.g., ischemic gangrene) manifests itself mainly in elderly diabetic patients, suggesting important interactions between vascular effects of aging and diabetes mellitus. Sympathetic denervation reduces spontaneous variability in resting blood flow in the foot. This abnormality impairs thermoregulation and contributes to the development of orthostatic hypotension in diabetic patients. Cardiovascular function may already be impaired in the elderly due to a reduced cardiovascular responsiveness to catecholamines. The addition of sympathetic denervation may further decrease sympathetic function in the elderly. Impaired vasomotor control and hypotension due to autonomic dysfunction can potentially magnify perfusion problems due to vascular disease, thereby increasing the risk of clinically significant ischemia.
Health-Care Communication and Selected Psychosocial Correlates of Adherence in Diabetes Management
Authors: Anderson Lynda A
Published: December 2014

Meeting the needs of older adults with diabetes mellitus requires understanding the multiple factors that interact to influence patient adherence to the prescribed regimen and adjustment to the disease. Herein, we propose a conceptual framework to explain patient adherence and to discuss practical strategies for enhancing adherence. The conceptual framework is based on the cycle of care and is expanded to incorporate major theories in health-behavior change. Based on this review, numerous factors were identified that can affect patient adherence. First, features of the regimen, such as complexity, duration, and extent of behavioral change, can negatively influence patient adherence. Second, psychosocial and environmental barriers to patient adherence are described. A major area of importance is patient-provider relationships. Specifically, patients' and professionals' attitudes, beliefs, communication processes, and subsequent reactions to the consultation can affect adherence. Suggestions are made regarding strategies to enhance adherence, including the need to assess and monitor the patient's beliefs and practices, enhance the communicative skills of health-care professionals and patients, and develop programs specifically targeted at promoting professional and patient problem-solving skills. The problem of generalizing from current research is that few empirical studies have focused on diabetes management among older adults.
Metabolic Effects of Combination Glipizide and Human Proinsulin Treatment in NIDDM
Authors: Pasmantier RoseMarie , Chaiken Rochelle L , Hirsch Sondra R , Lebovitz Harold E
Published: December 2014

The effects of 3 mo of treatment with a combination of glipizide and human proinsulin were studied in a small group of closely monitored patients. The patients had non-insulin-dependent diabetes mellitus (NIDDM) and poor glucose regulation, despite maximal sulfonylurea therapy. This was a randomized double-blind placebocontrolled trial in which there were three treatment groups who received either 20 mg glipizide given 30 min before breakfast and dinner and human proinsulin given subcutaneously at bedtime (n = 5), glipizide and human proinsulin placebo (n = 5), or glipizide placebo and human proinsulin (n = 5). Glycemic regulation was assessed by measurements of 24-h plasma glucose profiles and glycosylated hemoglobin. Our observations demonstrate that the combination of glipizide plus human proinsulin was more effective than either agent alone in controlling overall glycemia in patients with NIDDM. The data support the concept of use of an agent during the day that has its major effects postprandially and another agent at bedtime that is relatively hepatospecific.
Renal Factors Influencing Blood Pressure Threshold and Choice of Treatment for Hypertension in IDDM
Authors: Mogensen Carl Erik , Hansen Klavs W , Pedersen Margrethe M , Christensen Cramer K
Published: December 2014

In this article, we analyze the blood pressure (BP) threshold for the start of antihypertensive treatment in insulin-dependent diabetes mellitus (IDDM) patients, with particular emphasis on those with persistent microalbuminuria or proteinuria (incipient and overt nephropathy, respectively). In such individuals, there is a clear increase in the prevalence of hypertension and in actual measured BP values that is not observed in normoalbuminuric patients. In 94 young healthy adults (<45 yr of age), average mean ± SD arterial pressure (MAP; diastolic + 1/3 pulse pressure) was ∼90.0 ± 8.1 mmHg, closely corresponding to large population studies. In microalbuminuric IDDM patients, MAP values between ∼105 and ∼95 mmHg have been found in different studies, and the level has progressively decreased in various studies between 1984 and 1990 with similar BP-measuring techniques. Somewhat higher values are seen in patients with proteinuria, who are also consistently characterized by reduced glomerular filtration rate (GFR). A clear correlation is found between MAP plotted against the increased rate of microalbuminuria (%/yr) in incipient nephropathy and against fall rate of GFR (ml · min−1 · mo−1) in proteinuric patients. In the natural history of renal disease, different cutoff points in MAP for start of progression are observed: >95 mmHg for the start of progression of microalbuminuria and >105 mmHg for the decrease in GFR. During antihypertensive treatment, there is reduction or no progression in microalbuminuria with MAP of ∼90−95 mmHg and only a limited fall in GFR with MAP of ∼100 mmHg. However, certain antihypertensive drugs (angiotensin-converting enzyme inhibitors) may have specific renoprotective actions, reducing microalbuminuria at rather low BP levels or even independent of BP reduction. The optimal way of monitoring BP may be by 24-h ambulatory recording.
Diabetes in American Indians and Alaska Natives
Authors: Gohdes Dorothy , Bennett Peter H
Published: December 2014

Diabetes in American Indians and Alaska Natives was the focus of a conference that resulted in a unique interchange among tribal leaders, health-care providers, and medical scientists with particular interests in diabetes mellitus and its complications. The conference, which was held in Mesa, Arizona, 14–17 November 1989, was sponsored by the Indian Health Service: and the National Institute of Diabetes and Digestive and Kidney Diseases, in collaboration with the Intertribal Council of Arizona.
Diabetes in American Indians: Reflections and future directions
Authors: Kuller Lewis H
Published: December 2014

The two goals of the next generation of diabetes research should be to reduce the incidence of diabetes mellitus and to decrease the risk of complications from the disease. The prevention of diabetes will require a better understanding of the interaction of genetic and host-environmental factors, especially energy balance, diet and exercise, and specific nutrients. The prevention of weight gain should probably be of highest priority. The prevention of complications needs to focus on hyperinsulinemia, hyperglycemia, blood pressure, smoking, and lipoproteins. Clinical trials are needed to evaluate objectively the benefits of specific interventions. Such trials should be closely linked to community health programs to maximize the health status of the population.
Research, Development, Production, and Safety of Biosynthetic Human Insulin
Authors: Chance Ronald E , Frank Bruce H
Published: December 2014

This paper provides some historical aspects on the research and development of Humulin® (rDNA origin), the first human health-care product derived from rDNA technology more than a decade ago. Also referred to as biosynthetic human insulin, Humulin® is currently produced via the human proinsulin route, using an Escherichia coli fermentation process. The authenticity, high purity, and safety of BHI has been investigated and verified by a complex battery of analytical and physicochemical methods. The daily treatment of more than two million diabetic patients worldwide with this rDNA human insulin not only demonstrates the value of rDNA technology in providing an important medical product, it is assurance that diabetic patients will have unlimited supplies of this vital hormone as well as potential analogue refinements.
New Directions in Drug Development: Mixtures, Analogues, and Modeling
Authors: Galloway John A
Published: December 2014

Success in modern medical research is acheived when basic and clinical information about a given disorder converges, either intentionally or fortuitously, with the availability of technology or other means to design and apply interventions for the disorder in question. A prime example is the discovery of insulin and its replacement in patients with IDDM in 1923. Seven decades later, the focus of diabetes management is on improvement in metabolic control to forestall the chronic complications of the disease and improve the quality of life of patients with the disease. Metabolic control is being addressed through the development of insulin analogues using sophisticated techniques to understand the chemistry of insulin and to modify it using rDNA technology. The objective of these efforts is to simulate normal insulin secretion with subcutaneously injected agonists. Quality-of-life needs are being addressed with delivery devices, insulin mixtures, and insulin analogues. Although none of these improvements parallel the discovery of insulin, they do provide an optimistic outlook for patients with diabetes mellitus.
Glucose Clamp Investigations: The ups and downs
Authors: Boyle Patrick J
Published: December 2014

With the results of the Diabetes Control and Complications Trial (DCCT) now known (1), health-care providers are faced with the task of implementing more strict glucose control in diabetic patients. Yet, the methodology on the safest way to complete this change in health-care delivery is far from crystallized. Epidemiological data from the DCCT strongly suggest that hypoglycemia begets hypoglycemia (2). Over half of the severe hypoglycemie episodes occurred without warning signs. The importance of understanding the pathophysiological mechanisms behind this disturbing excess of morbidity is clear.
High—Monounsaturated Fat Diet for Diabetic Patients: Is it time to change the current dietary recommendations?
Authors: Garg Abhimanyu
Published: December 2014

The study by Rasmussen et al. (1) and studies by Campbell et al. (2, this issue) and Lerman-Garber et al. (3, this issue) report on the beneficial effects of high-monounsamrated fat diets in comparison with high-carbohydrate diets in patients with non-insulin-dependent diabetes mellims (N1DDM). The study by Rasmussen et al. (1) reported improvement of glycemie control and lowering of blood pressure (BP) with a high-monounsaturated fat diet. Campbell et al. (2) describe practical ways to prescribe a high-monounsaturated fat diet to NIDDM patients for use at home and report improvement in glycemie control and plasma triglyceride levels. Lerman-Garber et al. (3) report lowering of plasma triglyceride levels with an avocado-based high-monounsaturated fat diet. These data generally confirm the results of previous studies (4-9) and further support the use of high-monounsaturated fat diets in diabetic patients.
Diabetes, Health Insurance, and Health-Care Reform
Authors: Herman William H , Dasbach Erik J
Published: December 2014

In this issue of Diabetes Care (p. 585–591), Harris, Cowie, and Eastman analyze results from the 1989 National Health Interview Survey, and they describe health insurance coverage for U.S. adults ≥18 years of age. Of all people with diabetes, 13.5% of those 18–64 years of age and 1.2% of those ≥65 years of age report having no health insurance. The former is a national tragedy. The latter clearly reflects a success of Medicare. Before Medicare's enactment in 1965, 44% of the elderly in the U.S. had no hospital insurance (1). Although the authors do not comment on people with diabetes who are <18 years of age, the 1988 National Health Interview Survey on Child Health fou d that 17% of U.S. children and adolescents were not covered by a health insurance plan (2). As has been described by others, the authors found only small differences in rates of coverage between people with and without diabetes (3). They did, however, describe important differences in types of coverage. People with diabetes who were 18–64 years of age were more likely than those without diabetes to report coverage through Medicaid and Medicare, and were less likely to report having private insurance. having some other type of health insurance.
Exercise in Individuals With IDDM
Authors: Wasserman David H , Zinman Bernard
Published: December 2014

The greater energy requirements that accompany exercise necessitate an increase in fuel mobilization from sites of storage and a subsequent increase in the oxidation of thesefuels within the working muscle. A precise endocrine response controls the needed increment in fuel metabolism. The importance of the endocrine system is readily apparent in individuals with insulin-dependent diabetes mellitus (IDDM) in whom the normal endocrine response to exercise is lost. When a person with IDDM exercises with too little insulin in the circulation, an excessive counterregulatory hormone response may ensue, and the alreadyelevated blood glucose and ketone body levels can become even greater. On the other hand,if too much insulin is present, the exercise-induced increase in substrate mobilization can be attenuated or completely blocked and, as a result, hypoglycemia may ensue. Insulin therapy must be modified in anticipation of exercise to avoid states of under- or overinsulinization, and/or carbohydrate ingestion must be adjusted to compensate for the potential glycemic effects of inappropriate insulin levels. The presence of advanced diabetic complications can further accentuate the difficulty of exercise for those with IDDM. The purpose of this review is to provide the scientific information necessary to assess therationale for recommending regular exercise to individuals with IDDM and to develop guidelines for integrating daily exercise with insulin treatment and dietary management.
Glucagon and its Family Revisited
Authors: Lefèbvre Pierre J
Published: December 2014

Considered for decades as a contaminant of insulin preparations, gluca-gon was among the very first hormones to be isolated, purified, sequenced, and synthesized during the late 1950s. The field of glucagon research exploded after R.H. Unger and his colleagues in Dallas, TX, described a method permitting its measurement in the plasma by radioimmunoassay. Such assay made it possible to firmly establish the basic principles of glucagon physiology and to discover its pathophysiology. More recently, important progress has been made in exploring the molecular biology of this hormone: the glucagon gene and the glu-cagon-receptor gene have been identified and their expression investigated. Furthermore, the processing of the glucagon gene product has been elucidated and the function of the members of the glucagon family has been clarified. Finally, current investigations are in progress to develop glucagon agonists and antagonists and to identify new modes of administration of the hormone. These various topics will be considered in this review.
A Case of Myocarditis Associated With IDDM
Authors: Mokuno Takehiko , Sawai Yoshikuni , Oda Naohisa , Mano Toshiki , Hayakawa Nobuki , Kato Ritsuko , Itoh Yasutoshi , Shimazaki Keiko , Kotake Motoko , Nakai Akira , Hiramitsu Shinya , Itoh Mitsuyasu , Morimoto Shinichiro , Nagasaka Akio
Published: December 2014

We report a case of diabetic ketoacidosis (DKA) complicated by acute myocarditis, which was confirmed by cardiac biopsy. A 26-year-old man was hospitalized with severe DKA. On admission, nonspecific ST-T change was noted on the electrocardiogram (ECG). The patient's levels of creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase were slightly elevated, but he did not complain of chest discomfort or symptoms of heart disease. On the first day after admission, ST-T elevation was noted on ECG during treatment of DKA. By cardiac angiography and cardiac biopsy, coronary heart disease was ruled out and postmyocarditic change was histologically confirmed. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient suffered from viral-induced myocarditis and consequent development of IDDM. This possibility was confirmed by the clinical course of ECG change, with elevated CPK and lactate dehydrogenase and a slightly elevated antibody titer for echovirus.
Recommendations on the Standardization of Methods and Reporting of Tests for Diabetes and Its Microvascular Complications in Epidemiologic Studies
Authors: Bennett Peter H
Published: December 2014

This paper emphasizes the need and importance of standardization of methods and reporting in the epidemiology of diabetes and suggests methods for determination of glucose tolerance and for reporting data on such characteristics as history, obesity, and presence of microangiopathy
Diabetes in America: Epidemiology and Scope of the Problem
Authors: Harris Maureen I
Published: December 2014

Epidemiological studies performed over the past 40 years have shown that the prevalence of diagnosed diabetes has increased dramatically in the U.S. and that a substantial proportion of the population has undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance. Diabetes is most prevalent in minority populations, such as African-Americans, Native Americans, and Mexican Americans. Increasing prevalence of diabetes has led to increases in microvascular complications such as blindness, end-stage renal disease, and lower limb amputations. Poor glycemic control contributes to the high incidence of these complications, yet community-based studies of diabetic patients show their mean fasting plasma glucose concentration is generally >180 mg/dl compared with 100 mg/dl for nondiabetic individuals. In people with diabetes, risk factors for cardiovascular disease including elevated fasting plasma glucose, blood pressure, total cholesterol, triglycerides, and obesity partly explain the high proportion of deaths (60–70%) caused by cardiovascular disease in people with diabetes. More intensive diabetes management and improved glycemic control could minimize long-term complications of the disease and would be expected to reduce the morbidity, mortality, and costs associated with diabetes.
The Effects of Treatment on the Direct Costs of Diabetes
Authors: Herman William H , Eastman Richard C
Published: December 2014

Treatment of diabetic complications consumes health care resources. Intensive therapy was shown by the Diabetes Control and Complications Trial (DCCT) to avert complications. Economic analyses and models have been used to evaluate the cost-effectiveness of intensive therapy for people with type 1 and type 2 diabetes. An economic analysis of the DCCT estimated the cost of intensive therapy to be two to three times greater than that of conventional therapy. In contrast, an economic model predicts that intensive therapy, as compared with conventional therapy, could reduce blindness from 34 to 20% or by 41%, end-stage renal disease from 24 to 7% or by 71%, and lower-extremity amputations from 7 to 4% or by 43%. Although intensive therapy is more expensive, when the costs of complications are factored in, it becomes cost-effective for treatment of type 1 diabetes. Similarly, a model to evaluate the cost-effectiveness of intensive therapy for people with type 2 diabetes found that the lifetime costs of general and diabetes-related medical care would be approximately two times greater. However, the reduction in lifetime costs of complications, which would produce substantial reductions in costs of treatment, largely offsets the difference. Intensive therapy for type 1 and type 2 diabetes may be more expensive than conventional therapy, but from an economic perspective, it is comparable in cost to pharmacological therapies for people with hypertension and hypercholesterolemia. From a health system viewpoint, intensive therapy represents a fruitful long-term financial investment.
Epidemiology of Type 2 Diabetes: Risk Factors
Authors: Haffner Steven M.
Published: December 2014

A number of cross-sectional and prospective studies that compared the insulin sensitivity of various national and ethnic populations within the U.S. to the total U.S. population were analyzed to find possible risk factors for the development of type 2 diabetes. It was found that the risks for diabetes in African-Americans, Hispanics, and Native Americans are approximately 2, 2.5, and 5 times greater, respectively, than in Caucasians. Studies of the prevalence of type 2 diabetes in Mexican Americans and non-Hispanic whites in San Antonio showed that there is an inverse relationship between socioeconomic status and the prevalence of diabetes. It also appears that cultural effects lead to an increased incidence of obesity in these populations, which may lead to insulin resistance. Genetic factors may also be a contributing factor. A 5-year, prospective study of insulin resistance in Pima Indians showed a relationship between impaired glucose tolerance and subsequent development of type 2 diabetes. In a 7-year study in Mexican Americans, those subjects who had both high insulin secretion and impaired insulin sensitivity had a 14-fold increased risk of developing type 2 diabetes. Regardless of cultural and ethnic factors, the San Antonio Heart Study, which compared Mexican Americans and non-Hispanic whites, showed that in both groups, the strongest predictors of developing type 2 diabetes are elevated fasting insulin concentrations and low insulin secretion.
Self-Monitoring of Blood Glucose During Pregnancy in Women with Juvenile Diabetes
Authors: Karp Moshe , Flexer Zipora , Faiman Gila , Topper Eithan , Neeman Hana , Laron Zvi
Published: December 2014

Eight pregnant patients with insulin-dependent juvenile diabetes were persuaded to start self-monitoring of blood glucose between the 10th to the 20th week of gestation. One patient with two children discontinued this effort after a short period. Four patients are still on a regimen of self-monitoring during their pregnancy, and three have delivered normal infants. The latter three patients were all able to achieve almost normal blood glucose levels during the pregnancies. These observations, in addition to those of others, lead to the conclusion that self-monitoring of blood glucose can be an useful tool in the management of diabetes, particularly in pregnant women, who have a high degree of motivation to achieve good Control.
continuous Subcutaneous Insulin Infusion in the Treatment of Diabetes Mellitus
Authors: Pickup J C , Keen H , Viberti G C , White M C , Kohner E M , Parsons J A , Alerti K G M M
Published: December 2014

Low-volume, dual-rate, continuous subcutaneous insulin infusion (CSII) creates long periods of nearnormalization of blood glucose and major intermediary metabolites in most insulin-requiring diabetic patients. The technology and strategy of the system are discussed. We have observed encouraging clinical and fluorescein angiographic improvement in severe diabetic retinopathy after 3 mo of outpatient CSII; in the kidney, glomerular capillary permeability (microalbuminuria) is reduced or normalized in long-standing diabetic patients after a few days of CSII-induced strict control. Reduction in insulin dose during CSII treatment of newly diagnosed ketonuric diabetic patients may indicate improved B-cell function in this group. Although CSII must remain a research tool, undertaken only under close medical supervision, it is increasingly likely that the technique affords the conditions for testing the hypothesis that metabolic near-normalization of diabetes slows, arrests, or reverses the course of the microvascular disease associated with the syndrome.
Quantitative Estimation of Systemic Glucose Production in Normal and Diabetic Pregnancy
Authors: Kalhan Satish C , Adam Peter A J
Published: December 2014

Fasting during pregnancy is accompanied by a decline in plasma glucose and glycogenic amino acid concentration and an early recruitment of alternate fuel by mobilizing fatty acids from adipose tissue stores. Systemic glucose production rates were measured in normal, gestationally diabetic, and juvenile-onset diabetic subjects using (1-13C)glucose and (6,6-2H2)glucose tracers according to the constant-rate infusion technique. Even though the plasma glucose concentration during normal pregnancy had declined after an overnight fast, as compared with the nonpregnant subject (P < 0.0005), the systemic glucose production rate was 16% greater, a rate sufficient to provide the glucose requirement of the fetus at term gestation. The decline in glucose concentration could be the result of an increase in apparent volume of distribution of glucose. Systemic glucose production rates in well-regulated gestationally diabetic and insulin-dependent diabetic subjects were similar to those in normal pregnant subjects. These data suggest that the early disturbance in diabetes is the inability to assimilate exogenously administered glucose and other nutrients. Hormonal-fuel relationship during pregnancy suggests that during fasting, the insulin/glucagon molar ratio is maintained similar to that in nonpregnant subjects. Adrenal catecholamines do not appear to play a significant role in the regulation of hepatic glucose production. However, their role may be important in the early recruitment of alternate fuels.
Quantitative and qualitative changes in the early insulin response to glucose in subjects with impaired carbohydrate tolerance
Authors: Ratzmann Klaus Peter , Schulz Bernd , Heinke Peter , Michaelis Dietrich
Published: December 2014

To investigate changes in the sensitivity of early insulin repsonse to glucose, a pulse stimulation of 1.0, 2.5, and 5.0 g glucose was carried out at intervals of 30 min in 73 nonobese subjects suspected of having an impaired carbohydrate tolerance (CHT) and 24 body-weight and sex-matched healthy controls without a family history of diabetes. CHT was characterized by means of a 2-h glucose infusion test (GIT; 12 mg/kg-min), primed by an initial injection of 0.33 g/kg. Subjects suspected of having an impaired CHT (glucosuria in all subjects, 49 of whom exibited a borderline or pathologic 50-g standard oral glucose tolerance test and 27 of whom had a family history of diabetes) were classified as having a normal, borderline, and pathologic CHT according to the result of GIT. Compared with controls the early insulin response (∆IRI area, 0–5 min) during GIT was significantly reduced in subjects with normal, borderline, and pathologic CHT. During staircase glucose stimulation, a dose-dependent significant increase of the ∆max IRI response was observed in controls, whereas this strong relationship was lacking in all other groups studied. In subjects with normal, borderline, and pathologic CHT, ∆max IRI responses revealed by pulse stimulation of 1.0, 2.5, and 5.0 g glucose were significantly reduced compared with controls. Besides quantitative differences in early insulin response among all groups studied, a shift of the glucoseinsulin dose-response curve to the right was found in subjects with normal, borderline, and pathologic CHT. Our results provide further evidence of a reduced sensitivity of the pancreatic beta-cells to glucose during development of carbohydrate intolerance. The staircase glucose stimulation enables both a quantitative evaluation of the early insulin response to glucose and a characterization of the glucose-insulin dose-response relationship. For this reason the test seems to be a useful tool in studying the sensitivity of the pancreatic beta-cells to glucose.
Algorithms and Diet
Authors: Kaufman Ellen
Published: December 2014

I found the recent paper describing insulin dose adjustment during self-monitoring of blood glucose extremely interesting and helpful.1
Immunologic Improvement Resulting from the Transfer of Animal Insulin–treated Diabetic Subjects to Human Insulin (recombinant DNA)
Authors: Edwin Fineberg S , Galloway John A , Fineberg Naomi S , Rathbun Mary Jo
Published: December 2014

To study the immunologic effects of transfer of patients from animal insulins to human insulin (recombinant DNA), a double-blind comparative trial was begun in over 300 patients. Preliminary results are reported in 116 individuals. After maintenance on purified pork or mixed beef-pork insulins (PPI or MBP) for a minimum of 6 mo, 116 patients were either switched to human insulin or maintained on their previous insulin. Antibody levels were assessed at a baseline visit and then monthly. In PPI-maintained individuals as well as those switched to human insulin there was a significant decrease in qualitative antibody binding as indicated by species-specific binding of 125I beef and human insulins (SBB and SBH), both P < 0.005. Quantitative binding, as indicated by bound insulin levels, decreased to a much greater extent in patients switched to human insulin, 52% versus 31%, P < 0.005. Parameters derived from formal antibody titration did not change. In patients maintained on MBP, bound insulin decreased (− 36% at 6 mo, P < 0.002). When switched from MBP to human insulin, there was a marked reduction in all parameters of binding, both qualitative and quantitative: SBP, −68%; SBH, −61%; SBB, −57%; bound insulin, −67% (all P < 0.001) and decreases in high- and low-affinity binding capacities (P < 0.02). Thus, for patients treated previously with nonhomologous insulins, transfer to human insulin may result in significant immunologic improvement in anti-insulin antibody levels.
Human Insulin (recombinant DNA) in the Treatment of Patients with Newly Diagnosed Insulin-dependent Diabetes Mellitus (IDDM)
Authors: Lotz Norbert , Bachmann Werner , Mehnert Hellmut
Published: December 2014

Human insulin (recombinant DNA) was administered subcutaneously to 16 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM), whereas a control group of 11 patients received highly purified pork insulin (PPI). The control group was only available for the inpatient period, while the HI-treated patients could be observed monthly afterward. For metabolic control, basal and postprandial blood glucose, plasma C-peptide, and HbA1 were measured. During the outpatient period, blood glucose self-monitoring was also performed. Within 6 days of therapy, blood glucose levels were lowered to normal without any statistical differences between the HI and PPI groups. Mean insulin requirement was 35 U/day in both groups. Plasma C-peptide levels were not different at any time. In the human insulin group, HbA1 values were continuously lowered from the initial 13% to the normal range within 2–3 mo and remained normal after 6 mo of therapy. No allergic reaction and no other side effects could be seen. The results suggest that in the first period of treatment, the metabolic situation of patients with IDDM could be well controlled by human insulin as well as by PPI. Human insulin has been proven to be an effective and safe insulin.
Intradermal Desensitization with Human Insulin (recombinant DNA) in a Patient with Severe Allergic Skin Reaction due to Insulin
Authors: Bachmann Werner , Hasche Helmut , Mehnert Hellmut
Published: December 2014

This is a case report of a 70-yr-old female patient with a severe allergic skin reaction (necroses) due to insulin injections. Because of insulin dependency, desensitization to insulin was mandatory. For desensitization, a schedule with intradermal injections of increasing insulin concentrations (from 0.02 to 2 U per injection) at time intervals of 3 h was used. With highly purified pork insulin, the concentration limit of 0.04 U was reached in spite of 75 injections. After changing to human insulin (recombinant DNA), a rapid desensitization could be performed at the same concentration. Desensitization resulted not only to human insulin but also to highly purified pork insulin, as shown by intradermal testing 6 mo later.
Time-Action Profile of Zinc Human Insulin (recombinant DNA) in Young Volunteers as Compared with Zinc Porcine Insulin (Monotard)
Authors: Hoogen F H J Vander , Hulst S G Th , Zweens J
Published: December 2014

Zinc human insulin (recombinant DNA) or zinc PPI (Monotard) 20 U was injected subcutaneously to study the time-action profile in six healthy volunteers. During the test period they received a 10-g biscuit containing 3% moisture, 7% protein, 10% fat, 80% carbohydrate, and 30 ml of water every hour. The onset of action with zinc human insulin occurred earlier than with zinc PPI. Also, the intensity of the blood sugar-lowering effect was more pronounced 3 and 4 h after administration of insulin. No other statistically significant differences were detected between the two blood glucose curves. The results show that it is possible to develop a zinc human insulin formulation with a duration of the blood sugar-lowering effect equal to a zinc PPI formulation.
Comparative Studies on Intermediary Metabolism and Hormonal Counterregulation Following Human Insulin (recombinant DNA) and Purified Pork Insulin in Man
Authors: Rosak C , Althoff P-H , Enzmann F , Schöffling K
Published: December 2014

Human insulin (recombinant DNA) and purified pork insulin (PPI) were administered intravenously at a dosage of 0.075 U/kg in eight healthy men. Both insulins exerted the same hypoglycemic effect with the same restoration pattern to normal glucose levels at the end of the test. Differences were found with respect to a stronger antilipolytic and antiketogenic effect of human insulin; also the reactive rise of both compounds at the end of the test is less under human insulin in comparison with PPI. In spite of the same glucose nadir, the pattern of hormonal counterregulation is different under human insulin in comparison with PPI. There was less epinephrine and glucagon and practically no prolactin secretion following human insulin. Growth hormone secretion is augmented under human insulin. The clinical significance of these results under long-term treatment with human insulin has to be assessed.
The Incidence of Insulin-dependent Diabetes Mellitus in Israeli Children and Adolescents 0–20 Years of Age: A Retrospective Study, 1975–1980
Authors: Laron Zvi , Karp Moshe , Modan Michaela
Published: December 2014

A survey of the entire population of Israel revealed 392 newly diagnosed type I diabetic children and adolescents aged 0–20 for the period of 1975–80. The mean annual age specific incidence of type I (insulin-dependent) diabetes mellitus was 3.8/105 for the age group 0–14 yr and 4.2/105 for the age group 0–20 yr. The incidence among the Jews of Ashkenazi origin was 6.8 × 105 and that for Jews of non-Ashkenazi origin was 4.3 × 105, whereas that for the Arabs was 1.2 × 105. The overall incidence is lower than that reported for similar populations in most European countries, the USA, Canada, and New Zealand; similar to that reported for Arabs in Kuwait; and higher than only that found in Japan. The relative importance of environmental and genetic factors in the interpopulation differences in incidence of type I diabetes remains to be established.
Changing Concepts of the Epidemiology of Insulin-dependent Diabetes
Authors: Bennett Peter H
Published: December 2014

Recent epidemiologic studies of the determinants and natural history of IDDM using HLA typing and detecting islet cell antibodies have shown that HLA-identical siblings of probands with IDDM are at extremely high risk of developing IDDM, and that islet cell antibodies and glucose intolerance usually appear long before clinical manifestations. Thus, the disease often has a long latent period. The epidemiologic characteristics of the disease, in particular relating to variation in age of onset and seasonal variation, must now be reinterpreted in the light of these observations. It appears that the variation in seasonal onset and the age distribution probably reflect the effects of factors that precipitate clinical manifestations of the disease rather than those that are directly responsible for initiating pancreatic β- cell destruction. The ability to identify individuals at high risk of developing IDDM now allows investigations designed to identify factors responsible for initiating pancreatic β-cell destruction, and many ultimately result in the application of preventive measures for the disease.
Medical Care Patterns at the Onset of Insulin-dependent Diabetes Mellitus: Association with Severity and Subsequent Complications
Authors: Hamman Richard F , Cook Magdalena , Keefer Sharon , Young Walter F , Finch Jack L , Lezotte Dennis , Mclaren Beth , Orleans Miriam , Klingensmith Georgeanna , Peter Chase H
Published: December 2014

The hospitalization of a child at the onset of insulin-dependent diabetes mellitus (IDDM) has become routine in many parts of the world, although controversy exists about its necessity. We examined the patterns of medical care use and the prognosis for acute complications after diagnosis for children with newly diagnosed IDDM in Colorado from 1978 to 1982. We reasoned that if children cared for entirely in outpatient settings at diagnosis had no more frequent acute complications after diagnosis than hospitalized children, we would be encouraged to further explore other potential benefits of outpatient care at onset. Twelve percent of 305 children studied statewide received only outpatient care during the first 2 wk after diagnosis, and, prognostically, their subsequent hospitalization and ketoacidosis rates were 2–3.7 times lower than those of children who received any inpatient care. No differences were noted for severe insulin reaction rates. Children classified as “severe” at onset, or with parents of lower education and income, or aged 10–14 yr at onset, regardless of care setting, had 2–4 times higher subsequent acute complication rates after onset than children without these characteristics. These findings, together with data on nights hospitalized and average length of stay in hospital at onset, suggest that a 42% reduction in total nights hospitalized could occur if children with “mild” or “normal” severity at onset were treated largely in the outpatient setting.
PSO Based Optimal Location and Sizing of SVC for Novel Multiobjective Voltage Stability Analysis during N – 2 Line Contingency
Authors: Mangaiyarkarasi S.P. , Raja T. Sree Renga
Published: December 2014

In this paper voltage stability is analysed based not only on the voltage deviations from the nominal values but also on the number of limit violating buses and severity of voltage limit violations. The expression of the actual state of the system as a numerical index like severity, aids the system operator in taking better security related decisions at control centres both during a period of contingency and also at a highly stressed operating condition. In contrary to conventional N – 1 contingency analysis, Northern Electric Reliability Council (NERC) recommends N – 2 line contingency analysis. The decision of the system operator to overcome the present contingency state of the system must blend harmoniously with the stability of the system. Hence the work presents a novel N – 2 contingency analysis based on the continuous severity function of the system. The study is performed on 4005 possible combinations of N – 2 contingency states for the practical Indian Utility 62 bus system. Static VAr Compensator is used to improve voltage profile during line contingencies. A multi- objective optimization with the objective of minimizing the voltage deviation and also the number of limit violating bus with optimal location and optimal sizing of SVC is achieved by Particle Swarm Optimization algorithm.
Validation of Finite Element Solutions of Nonlinear, Periodic Eddy Current Problems
Authors: Plasser René , Bíró Oszkár
Published: December 2014

An industrial application is presented to validate a finite element analysis of 3-dimensional, nonlinear eddy-current problems with periodic excitation. The harmonic- balance method and the fixed-point technique are applied to get the steady state solution using the finite element method. The losses occurring in steel reinforcements underneath a reactor due to induced eddy-currents are computed and compared to measurements.