bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose Kinetics During Oral Glucose Tolerance Test in Normal, Methylprednisolone-Treated and Alloxan Diabetic Dogs
Authors: Issekutz Bela , Issekutz Thomas B , Elahi Dariush
Published: December 2014

Using 2-3H-glucose as tracer, glucose turnover was measured (primed constant rate infusion) on dogs with indwelling arterial and venous catheters. Normal, methylprednisolone(MP)-treated (three days, 3 to 3.2 mg.'kg.) and alloxan diabetic dogs were given 2 gm.'kg. glucose (in 200 ml. water) containing 2.3 μCi.'gm. of 14C-glucose (U) to drink. The rate of absorption of glucose was calculated from the course of the specific activity of 14C-glucose in the plasma. In normal and MP-treated dogs, the cumulative absorption of glucose could be described as a linear function of time for t < 120 minutes. The glucose absorption in alloxanized dogs showed an early peak with a subsequent decline. In all three types of dogs a single exponential function described the glucose absorption for t > 90 minutes with an asymptotic value of about 2 gm.'kg. In normal and glucocorticoid-treated dogs, the glucose load decreased the hepatic glucose output by 50 and 70 per cent, respectively. The metabolic clearance rate (MCR) of glucose was greatly increased in both groups. There was a log-to-log correlation between MCR and immunoreactive insulin in the plasma. In alloxan diabetes the low glucose tolerance was due to two factors: (a) the glucose drink failed to suppress the hepatic glucose output, and (b) it increased the clearance rate of glucose (the sum of MCR and renal clearance) very little.
Role of Insulin and Glucagon in Obesity
Authors: Schade D S , Eaton R Philip
Published: December 2014

To investigate the hormonal balance in obesity with respect to insulin and glucagon secretion and to assess their effect at the substrate level, we compared ten obese subjects with an equal number of normal weight controls. No subject was diabetic by USPHS criteria.

Aminogenic hormonal secretion was measured after arginine was given intravenously at a rate of 1 gm.'min. for thirty minutes. Changes in the hormonally sensitive substrates, glucose and free fatty acids, were examined in relation to the hormonal secretion.

Our obese population was characterized by increased insulin and decreased glucagon secretion. At the substrate level, these hormonal differences were reflected in changes of serum glucose but not in free fatty acids.
Phytohemagglutinin Transformation and Circulating Lymphocyte Subpopulations in Insulin-dependent Diabetic Patients
Authors: MacCuish A C , Urbaniak S J , Campbell C J , Duncan L J P , Irvine W J
Published: December 2014

The lymphocyte transformation response to the mitogen phytohemagglutinin (PHA) was determined in forty well controlled insulin-dependent diabetics, forty matched normal subjects and fourteen poorly controlled insulin-dependent diabetics. There was no significant difference in the PHA responses of normal subjects and well controlled diabetics, but poorly controlled diabetics showed a marked depression of lymphocyte transformation.

Peripheral blood T and B lymphocyte subpopulations were also measured in fifteen normal subjects, fifteen well controlled diabetics and ten poorly controlled diabetics. The results showed no significant difference between normal and diabetic subjects, whether well or poorly controlled.

The depressed PHA response in poorly controlled diabetics would seem to reflect inadequately corrected metabolic disturbance rather than an inherent, genetically determined immunologic abnormality.
Influence of Diet on Intestinal Cell DNA Synthesis in the Diabetic Rat
Authors: Nakayama Hidetaka , Iju Morimasa , Nakagawa Shoichi
Published: December 2014

The incorporation of thymidine methyl-3H (3H-TdR) into deoxyribonucleic acid (DNA) was measured in the intestine of diabetic rats. Animals were allowed food ad libitum or were pair-fed. Diabetes was induced with streptozotocin. In the pair-feeding experiment, there was a decrease in 3H-TdR incorporation into DNA in the intestine of diabetic rats, and the mucosal weight did not differ significantly from controls. However, when diabetic rats were allowed food ad libitum, there was a significant increase in DNA synthesis in the intestine. The mucosal weight of the diabetic animal was 62 per cent greater in the jejunum and 31 per cent greater in the ileum than in the control segments. It is concluded that a decrease in proliferative cellular activity occurs in the intestinal mucosa of diabetic rats but hyperphagia leads to a compensatory increase in DNA synthesis in these animals.
Prevention of Vascular Disease in the Diabetic
Authors: Kinsell Laurance W
Published: December 2014

In view of the present state of our knowledge, the title of this paper is ambitious. I may begin with the unequivocal statement that neither my associates nor I have any magic formula which predictably will prevent vascular disease in the diabetic. However, I should like to consider with you some of the observations of others, and some observations of our own which bear upon this subject.

In our own thinking, diabetes mellitus is divided into two diseases: the form that occurs typically in middle age, which, from a functional standpoint, we consider as presenting essentially a problem in hypoinsulinism with associated metabolic abnormalities; and juvenile diabetes, which represents a combined problem of hyperpituitarism and hypoinsulinism.

In both groups one deals with two vascular problems. One, atherosclerosis, is identical with that which afflicts the average nondiabetic member of the American population, if he lives sufficiently long. Statistically, the onset of this vascular disease in the diabetic is earlier and the progress more rapid. The other is a rather specific disease, in which characteristic changes occur in the retinal and glomerular capillaries. This latter problem is most distressing in the juvenile diabetic, because of its occurrence at an early age.

Atherosclerosis in Association With Diabetes With the possible exception of cancer, no field of clinical investigation is receiving more attention than that of degenerative vascular disease. Since atherosclerosis in the diabetic appears earlier and progresses more rapidly than in the nondiabetic, and since we have some knowledge of the endocrine and metabolic abnormalities which occur in diabetes and which, at least in part, are presumably related to the pathogenesis of the vascular disease, it seems logical to conclude that the answer to the over-all problem of atherosclerosis might very well be found more readily in the diabetic than in the nondiabetic population.
The Distribution and Metabolism of Insulin Labeled with Radioactive Iodine (I131) in Normal and Diabetic Subjects
Authors: Welsh George W , Henley Elaine D , Williams Robert H , Elgee Neil J
Published: December 2014

To investigate possible differences in the distribution and metabolism of insulin in diabetics and normals, insulin labeled with radioactive iodine (I131) was given intravenously to 40 diabetics of varying type and severity, 15 healthy controls, and 11 other nondiabetics with various illnesses. The labeled insulin was given in tracer amounts (50 to 100 microcuries) and test doses varied between 0.5 and 5.0 units of insulin. The dose was diluted in normal physiologic saline solution and injected slowly into fasting subjects over a two-minute period. In most cases therapeutic insulin had been withheld from diabetics for 24 to 96 hours. Plasma samples were drawn at predetermined times, and the amount of protein-bound radioactivity was determined by precipitation with trichloroacetic acid (TCA).

Since labeled insulin is virtually completely precipitated with TCA, the protein-bound radioactivity was assumed to represent undegraded labeled insulin, whereas the TCA-soluble radioactivity was assumed to be comprised of the degradation products of the labeled hormone. Total urinary radioactivity, of which an average of 95 per cent is TCA-soluble, was also measured during the test period. In some subjects surface measurement of radioactivity over various organ areas, such as the thyroid, liver, kidney, and muscle masses, was made.
Level of Plasma Amino Acids in Eviscerate Rats Given Glucose and Fructose with and without Insulin
Authors: Ingle Dwight J , Flores Violeta , Torralba Gloria
Published: December 2014

This is one of a series of studies on the effect of hormones upon protein metabolism in the eviscerate rat. Insulin causes a temporary decrease in the level of plasma amino acids (PAA) in the eviscerate rat and suppresses the rate of increase in PAA. HOW do this and other effects of insulin upon protein metabolism relate to the action of insulin upon carbohydrate utilization? If the changes in protein metabolism are secondary to a primary action of insulin upon the utilization of carbohydrate it should be possible to suppress the rise in PAA in the eviscerate rat by enhancing the utilization of carbohydrate by other means. There is some evidence that fructose is well utilized in the absence of insulin, and it is commonly believed that insulin does not affect the utilization of fructose. In the present experiments we have tested the hypothesis that fructose might suppress the rise in PAA following evisceration. The results are negative.
Pancreatic Extracts in The Treatment of Diabetes Mellitus
Authors: Banting F G , Best C H , Collip J B , Campbell W R , Fletcher A A
Published: December 2014

Since the year 1889, when von Mering and Minkowski produced severe and fatal diabetes by total removal of the pancreas in dogs, many investigators have endeavoured to obtain some beneficial effect in diabetes mellitus, either by feeding pancreas, or by administration of pancreatic extracts.
Teaching the Diabetic Patient
Authors: Beaser Samuel B
Published: December 2014

SUMMARY: Education about diabetes does not consist simply in presenting the basic facts to patients. Rather, it should be directed to a real understanding of the disease and a proper attitude toward its care by both patient and physician. A more precise definition of the area for which the patient is responsible will prevent both his overstepping the bounds or, even worse, ending up completely outside medical supervision. It is entirely reasonable to propose that good medical care of each hospitalized diabetic regardless of the cause of admission is not complete until he has been educated in self-care. The responsibility for this program in the hospital should properly rest upon both the administrative and professional staffs, with the understanding that patient education is a vital facet of the minimum standards of medical care in their institution.
A Newer Pathway Of Carbohydrate Metabolism; The Pentose Phosphate Pathway
Authors: Marks Paul A
Published: December 2014

In the past thirty years a vast body of information has been compiled relating to carbohydrate metabolism. Nevertheless, it is becoming increasingly evident that the elucidation of the metabolic disturbance in diabetes mellitus requires an even more complete knowledge than is presently available of the complex chemical routes followed by glucose in its conversions and interactions with other cell components. In this area of carbohydrate metabolism most gratifying progress has been made with the demonstration of previously unsuspected pathways of glucose utilization. Until rather recently, it was generally believed that the primary, if not the sole, route of glucose breakdown by mammalian tissue was via the Embden-Meyerhof or anaerobic-glycolytic pathway involving the conversion of glucose to pyruvate and lactate and its subsequent oxidation to co2 by the citric acid cycle. Evidence has now accumulated to indicate the existence of at least one new pathway of glucose metabolism, referred to as the pentose phosphate pathway, or the hexose monophosphate oxidative shunt, which may often supplement significantly the anaerobic-glycolytic scheme. Before turning to some of the details and possible significance of this alternate pathway, a brief review of the reactions of glycolysis and the citric acid cycle is desirable.
The Prediabetic State in Man: Definition, Interpretation and Implications
Authors: Conn Jerome W
Published: December 2014

It is with pride, humility and a sense of important responsibility that I begin the presentation of a Banting Memorial Lecture.

The problem which I have chosen to discuss today is one with which my group has been concerned during the past eleven years. It has to do with the effect of ACTH and glucocorticoids upon carbohydrate tolerance of normal people. Before proceeding further I wish to point out that today I act as spokesman for the various past and present members of my research staff who have contributed their ideas and efforts to this long-term project.
Diabetic Retinopathy: A General Survey
Authors: Blankenship George W , Skyler Jay S
Published: December 2014

Diabetic retinopathy has become one of the major causes of legal blindness and can cause a degree of visual loss that prevents independent ambulation and even total blindness. It-is now the second leading cause of new blindness in the United States and the leading cause in adults under age sixty-five.1–2 The tragedy of this is even more greatly magnified when one considers that those blinded by diabetes are often quite young, in their twenties or thirties. Fortunately, most patients with diabetic retinopathy do not have visual impairment. The prevalence of diabetic retinopathy is strongly and positively associated with duration of diabetes.3–5 Retinopathy is seen after a shorter duration of diabetes in older patients than in younger patients, but prevalence figures for all ages seem to merge after ten years duration of diabetes.3 Thus, the overall prevalence of clinically detectable retinopathy in patients under age thirty at diagnosis is less than 10% if the duration of the disease is less than ten years, while the prevalence for patients over age 60 at diagnosis is 35–40% with the same duration.4 After fifteen years duration of diabetes, 60–70% of patients will have retinopathy.3–5 The true prevalence of diabetic retinopathy remains unknown, however, and statistical data are complicated by a variety of factors. Most studies focus on juvenile-onset diabetes, or of diabetes of long duration, and do not include the large numbers of elderly patients with mild diabetes without retinopathy. Studies have usually been done in referral centers for either diabetes or eye disease. Thus, the prevalence of the disease is probably more common than appreciated by most physicians, but not as common as thought by most ophthalmologists who are biased by the type of diabetic patients referred for ophthalmic care.
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 2 of this translation will appear in the July–August issue of DIABETES CARE.
Having Fun and Being Physically Active
Authors: Travis Luther B , Speegle Debbie
Published: December 2014

The general goal of this series is to provide meaningful information to young people who have diabetes mellitus so that they can enjoy a better life. Specific objectives are to present a piece of information aimed at a single subject and to provide this information at a time when it is most appropriate. The series is multiauthored, with each segment reflecting the tenets of that author. Thus, the philosophies expressed from one segment to the other may not be concordant. The physician or diabetes educator choosing to photocopy and distribute these articles to young persons with diabetes should exercise discretion in selection so that they are in general agreement with the patient's overall management plan. Suggestions for improvement of the format or for new additional topics should be directed to the Committee on Youth Education, % DIABETES CARE. The Committee is also seeking volunteers for development of subjects.
Diabetes Mellitus in the Internal Medicine Literature
Authors: Shuman Charles R
Published: December 2014

The format of Mini-Reviews is the presentation of abstracts of selected articles, with commentary on the topics raised by these articles. Previous Mini-Reviews in DIABETES CARE examined the literature on Psychosocial Issues in Diabetes, and Diabetes in the Pediatric Literature. All summaries in this Mini-Review of Diabetes Mellitus in the Internal Medicine Literature are verbatim.
What Geriatricians Should Know About Diabetes Mellitus
Authors: Porte Daniel , Kahn Steven E
Published: December 2014

Aging is associated with a progressive decline in glucose tolerance to the extent that most elderly people have abnormal carbohydrate metabolism and an increasing proportion have type II (non-insulin-dependent) diabetes mellitus. This review focuses on the pathophysiology, evaluation, and treatment of this process and emphasizes that although normal glucose tolerance and diabetes mellitus are strictly defined, there is a large subset of elderly individuals who, although nondiabetic, fall into the carbohydrateintolerant zone. This diminished carbohydrate tolerance is the result of a decrease in insulin sensitivity and an impairment of pancreatic β-cell function, which both may result, in part, from changes in sensitivity to dietary carbohydrate associated with aging. Similar defects in insulin action and insulin secretion are also present in type II diabetes. Although the macro- and microvascular complications of diabetes mellitus occur in older individuals with hyperglycemia, carbohydrate intolerance does not appear to be associated with microvascular events. Thus, therapeutic decisions must be based on an understanding of the degree of impairment in carbohydrate tolerance and the risk of acute and chronic complications associated with this abnormality. This is of even more importance when managing a group of subjects whose life expectancy is reduced and who may be less amenable to interventions that could include diet, oral sulfonylureas, or insulin. Furthermore, although all these interventions may result in a decline in glucose level and improved health, they are also associated with risks, some of which may be life threatening in this population.
Biguanides and Sulfonylureas as Combination Therapy in NIDDM
Authors: Hermann Leif S
Published: December 2014

Oral combination therapy with biguanides (metformin) and sulfonylureas is discussed. The rationale for the use of this combination is based on the different sites of action of the two kinds of drugs and the possibility for obtaining additive or potentiating effects and reduced side effects. The clinical usefulness of chlorpropamide and glyburide in combination with metformin has been demonstrated in some clinical trials. The combination may provide satisfactory glycemic control for several years, and possibly insulin therapy can be postponed or even avoided. No special safety problems are encountered with the use of the combination other than those attributed to the use of metformin or sulfonylurea alone, i.e., lactic acidosis and hypoglycemia, respectively. The lethality risks of these associated conditions are comparable. It is concluded that more data are needed to evaluate the full clinical potential and the mechanism of action of oral combination therapy.
Relationship Between Insulin Resistance and Hypertension
Authors: Reaven Gerald M
Published: December 2014

Patients with hypertension have been shown to be resistant to insulin-stimulated glucose uptake and to be both hyperinsulinemic and hypertriglyceridemic compared with matched normotensive control groups. These abnormalities are present before the institution of antihypertensive therapy and do not necessarily improve when blood pressure is effectively lowered. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and high blood pressure can be produced in fructose-fed Sprague-Dawley rats, but the development of these changes is inhibited by exercise training or somatostatin infusion. Furthermore, insulin-stimulated glucose uptake is lower in spontaneously hypertensive rats (SHRs) than Wistar-Kyoto rats, and this is associated with higher plasma triglyceride concentrations and blood pressure. In addition, a defect in insulin-stimulated glucose uptake can be shown in adipocytes isolated from SHRs, and the greater the degree of in vitro insulin resistance, the higher the plasma insulin concentration and blood pressure. These data strongly support the view that abnormalities of insulin and lipid metabolism are associated with high blood pressure in both patients and rodent models of experimental hypertension. In the latter context, endogenous hyperinsulinemia and hypertriglyceridemia are risk factors for coronary heart disease. The fact that antihypertensive treatment has not focused on correcting these metabolic abnormalities may explain why it has been difficult to show that lowering blood pressure decreases the risk of coronary heart disease. It can be argued that abnormalities of carbohydrate and lipoprotein metabolism play a role in both the etiology of hypertension and the clinical course of hypertensive patients.
Epidemiology of Hypertension in Diabetic Patients and Implications for Treatment
Authors: Fuller John H , Stevens Lynda K
Published: December 2014

We review the epidemiology of hypertension in diabetic patients and discuss the implications for treatment. The relationship between coronary heart disease (CHD) mortality and blood pressure (BP) in the World Health Organization Multinational Study of Vascular Disease in Diabetics (WHO MSVDD) is evaluated. One thousand two hundred seventy-seven patients with insulin-dependent diabetes mellitus (IDDM) and 3463 patients with non-insulin-dependent diabetes mellitus (NIDDM), aged 35–55 yr at baseline, from 10 centers throughout the world were evaluated. CHD mortality after a follow-up of 6–7 yr was measured. Estimates of usual diastolic BP were made with data from the Framingham study. The relative risk (RR) of CHD death was plotted against usual diastolic BP for IDDM and NIDDM, and the shapes of the relationship were compared with a metaanalysis of nine prospective studies in nondiabetic populations. For the NIDDM group, the CHD RRs were significantly >1.0 only for the uppermost diastolic BP category (RR 2.23, 95% confidence interval 1.14–4.40). For the IDDM group, the shape of the diastolic BP-CHD relationship was difficult to assess in view of the small number of events. In neither diabetic group was the evidence for a J-shaped relationship. Elevated BP is associated with increased cardiovascular/renal mortality in both types of diabetes. However, the efficacy of antihypertensive therapy in the prevention of these outcomes remains unclear. Prospective data from the WHO MSVDD do not provide clear evidence of benefit from treating diastolic BP <95–100 mmHg in NIDDM patients. The cost-benefit implications of aggressive BP treatment in IDDM must be more clearly defined before such treatment policies are accepted.
Need to Assess Readability off Written Materials for Diabetes Education Curricula
Authors: Siminerio Linda M , Frith Michael
Published: December 2014

Diabetes is a chronic illness that requires the active participation of patients in daily self-care for them to maintain control over their metabolism. Education about diabetes has become accepted as an integral part of care for the person with diabetes (1). Several groups (2–5) demonstrated the positive effects of diabetes education by documenting reduced hospitalizations for acute complications of diabetes or improvement in measures of metabolic control, for example, fasting blood glucose, GHb, and blood pressure. Although these reports demonstrate the benefits of some diabetes education programs, many other diabetes education programs have not achieved such favorable results. For instance, Miller et al. (6) found that 45% of patients who had attended diabetes education programs failed all aspects of an evaluation; of those without any training, 67% failed. Whitehouse et al. (7) reviewed medical records of 178 patients who attended an outpatient follow-up program. These patients did not experience a lower incidence of ketoacidosis, foot infections, or hypoglycemia—conditions usually considered closely related to poor self-care. Korhonen et al. (8) found a highly significant improvement of metabolic control in IDDM patients immediately after intensive education; however, a similar change also occurred in the control group. In a more recent study by Bloomgarden et al. (9) in 1987, patient education improved knowledge, but did not appear to offer a benefit in overall glycemic control.
Insulin Therapy in Type II Diabetes
Authors: Koivisto Veikko A
Published: December 2014

Administration of exogenous insulin can ameliorate metabolic abnormalities in type II diabetes: It compensates for reduced endogenous insulin secretion, reduces excessive hepatic glucose production, and stimulates glucose uptake, enhancing both glucose oxidation and storage in the muscle tissue. In addition, insulin therapy has anti-atherogenic effects on serum lipid profile. The main concerns of insulin therapy are weight gain, hyperinsulinemia, hypoglycemia, and possibly sodium and fluid retention. Although studies in vitro and in experimental animals suggest that hyperinsulinemia may accelerate atherosclerosis, these data are not substantiated in patients with type II diabetes. Insulin therapy in type II diabetes patients can be used either temporarily when insulin requirements are increased (e.g., surgery, infection, pregnancy), or in the long-term when endogenous insulin secretion is vanishing or hyperglycemia does not respond to other therapy. Whether insulin should be used as a primary therapy in addition to diet and exercise in some patients has not been examined. The decision regarding the beginning of insulin therapy and targets should be established individually, taking into account factors such as age, other diseases, or life expectancy. Various regimens can be used, including evening insulin alone or in combination with oral agents, multiple injections, use of premixed insulins (shortplus intermediate-acting insulin in various combinations). Continuous subcutaneous insulin infusion also has been used. Comparative data between the regimens are scant, but a few studies suggest that no major differences occur between the regimens, with regard to glycemic control or hypoglycemic complications. In the future, insulin therapy in type II diabetes may become more common, particularly among patients with the autoimmune type of the disease.
Hypoglycemia Unawareness in IDDM
Authors: Cryer Philip E
Published: December 2014

Hypoglycemia unawareness—loss of the neurogenic (autonomic) warning symptoms of developing hypoglycemia—is one of three hypoglycemia-associated clinical syndromes that exemplify hypoglycemia-associated autonomic failure in IDDM. Reduced awareness of developing hypoglycemia (an elevated glycemic threshold for symptoms) is a feature not only of hypoglycemia unawareness but also of the syndromes of defective glucose counterregulation, elevated glycemic thresholds for symptoms, and activation of glucose counterregulatory systems during effective intensive therapy. These syndromes are major risk factors for severe iatrogenic hypoglycemia in individuals with IDDM. Their pathogenesis is unknown and likely multifactorial. Recent antecedent iatrogenic hypoglycemia may be one factor, perhaps a major factor, that, by reducing both the symptoms of and defenses against developing hypoglycemia, results in recurrent iatrogenic hypoglycemia, thus creating a vicious cycle. On the other hand, treatment with human compared with animal insulin does not appear to be an important factor.
Carbohydrate and Dietary Management of Individuals With Insulin-Requiring Diabetes
Authors: Nuttall Frank Q
Published: December 2014

Diet has always been considered a major component in the treatment of diabetes mellitus. However, it has been and continues to be one of the most difficult aspects of the treatment regimen for both the patient and healthcare professionals.
Assessment of Peripheral Vascular Disease in Diabetes: Report and Recommendations of an International Workshop Sponsored by the American Heart Association and the American Diabetes Association
Authors: Orchard Trevor J , Strandness D Eugene
Published: December 2014

Recognizing the considerable excess burden of both cerebrovascular disease and LEAD suffered by individuals with IDDM or NIDDM (1,2), a workshop was convened to 1) provide a current review of the knowledge pertaining to the prevalence, incidence, and risk factor associations of cerebrovascular disease and PVD in diabetes, and 2) review and make recommendations about the methodology for identifying and quantifying LEAD in both clinical and research settings.
Hypoglycemia
Authors: Cryer Philip E , Fisher Joseph N , Shamoon Harry
Published: December 2014

Iatrogenic hypoglycemia causes recurrent physical and recurrent or even persistent psychosocial morbidity, and some mortality, in patients with insulindependent diabetes mellitus (IDDM), and in some patients with non-insulin-dependent diabetes mellitus (NIDDM) (1,2). There is now compelling evidence, from the Diabetes Control and Complications Trial (DCCT), that metabolic control delays the development and progression of retinopathy, nephropathy and neuropathy in IDDM, albeit at the expense of an increased frequency of treatment-induced hypoglycemia (3). These findings will almost assuredly provide further impetus to patients and health care providers to attempt to maintain plasma glucose levels as close to the nondiabetic range as possible. If so, hypoglycemia will become an even more common problem for patients with diabetes in the near future.
The DCCT and Medical Care for Diabetes in the U. S.
Authors: Harris Maureen I , Eastman Richard C , Siebert Carolyn
Published: December 2014

The Diabetes Control and Complications Trial (DCCT) has convincingly established that intensive treatment of insulin-dependent diabetes mellitus (IDDM) can substantially reduce the incidence and progression of retinopathy, nephropathy, and neuropathy (1). Development of retinopathy in those without retinopathy at baseline was reduced by 76%, and progression of retinopathy in those with early retinal disease at baseline was reduced by 54%. Intensive therapy was associated with a 39% reduction in the occurrence of microalbuminuria (≥40 mg of urine albumin per 24 h) and a 54% reduction in the incidence of albuminuria (≥300 mg of urine albumin per 24 h). Development of clinical neuropathy was reduced by 60%. A reduction also occurred in macrovascular disease events (41%), although this did not reach statistical significance.
The Penile Prosthesis and Diabetic Impotence: Some Caveats
Authors: Sotile Wayne M
Published: December 2014

Literature published as of January 1978 contains reports of 103 diabetic men who have undergone implantation of a penile prosthesis as treatment for sexual impotence. Two forms of prosthesis have been used. One procedure involves the use of semi-rigid silicone rods. The other procedure uses inflatable silicone rubber cylinders. Both devices have yielded very high success rates within diabetic populations. Prospective recipients of a penile prosthesis should undergo extensive evaluation geared toward discrimination of organic versus psychogenic factors contributing to the sexual dysfunction. Before recommending prosthesis implantation, the physician should assess the expectations of the patient and his regular sex partner regarding the effects of the procedure. The stability of the patient's relationship with his regular sex partner should be considered an important determinant of response to implantation. Controlled investigations regarding the short- and long-term effects of this procedure are still needed.
Subcutaneous Glucagon-Like Peptide I Combined With Insulin Normalizes Postcibal Glycemic Excursions in IDDM
Authors: Dupré John , Behme Margaret T , Hramiak Irene M , Mcdonald Thomas J
Published: December 2014

OBJECTIVE

To determine whether a subcutaneous injection of truncated glucagon-like peptide 1 (tGLP-I)(7–36) amide that delays gastric emptying transiently can prevent postcibal hyperglycemia in IDDM without causing hypoglycemia when administered with insulin.

RESEARCH DESIGN AND METHODS

The postcibal increase in plasma human pancreatic polypeptide (HPP) was used as a presumptive indicator of arrival of nutrient in the small intestine. Studies in seven normal human volunteers established the dose of tGLP-I that delayed the postcibal rise in HPP by 30 min. This dose was tested in six patients with IDDM with a range of residual endogenous insulin secretion. The patients received a standard liquid test meal with or without subcutaneous tGLP-I and their usual dose of regular insulin before the meal. Blood samples collected at timed intervals were assayed for plasma concentrations of glucose, C-peptide (CP), immunoreactive insulin (IR1), HPP, and glucagon (GLN).

RESULTS

In normal subjects after administration of tGLP-I, postcibal plasma glucose concentration at 20 min fell below fasting levels in a dose-dependent manner. At 10 and 20 min, transient increments in plasma CP and IRI, and decrements in GLN, occurred. Subsequently, through 60 min, the excursions of plasma HPP, CP, and IRI were negatively correlated to the dose of tGLP-I. In subjects with IDDM, the selected dose of tGLP-I given with insulin before the meal delayed the plasma HPP response for 30 min and confined excursions of plasma glucose within the range observed in normal subjects receiving saline injections, whereas administration of insulin with saline injections in IDDM was followed by supranormal increases of plasma glucose. In IDDM, this dose of subcutaneous tGLP-I had no effect on plasma CP, IRI, or GLN.

CONCLUSIONS

In normal subjects, transient hypoglycemia after injections of tGLP-I with a meal was associated with transient stimulation of insulin secretion and inhibition of glucagon secretion. These actions together with delayed gastric emptying may account for the hypoglycemia, but other unidentified mechanisms cannot be excluded. In the subjects with IDDM, the selected relatively low dose of tGLP-I delayed excursions of plasma HPP as in normal subjects, but did not reduce the plasma glucose below the fasting level and had no effect on plasma CP, IRI, or GLN. However, injection of tGLP-I reduced the postcibal glycemic excursion and confined it within the normal range. Thus, in IDDM, a pharmacological dose of subcutaneous tGLP-I that presumably delays gastric emptying by ∼30 min can normalize glycemic excursions after a meal when given in combination with insulin. Because this cannot be achieved with regular insulin alone without risk of hypoglycemia, this combination of glucoregulatory peptides has therapeutic potential in insulin-requiring diabetes.
Relation of Glycemic Control to Diabetic Complications and Health Outcomes
Authors: Klein Ronald , Klein Barbara EK
Published: December 2014

Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) demonstrated that the incidence of diabetic complications is directly related to glycemic control. The results of the Diabetes Control and Complications Trial and Stockholm Study showed that intensive insulin therapy and improved glycemic control reduced diabetic complications in people with type 1 diabetes. Results of the U.K. Prospective Diabetes Study Group and the Kumamoto trial also support the relationship between glycemic control and diabetic complications in individuals with type 2 diabetes. Preliminary WESDR health outcomes data suggest that higher levels of glycemia are related to a decreasing quality of life. This study and others showing that higher levels of glycemia are associated with an increased incidence of complications suggest that it is the complications of diabetes that contribute to a decrease in quality of life. Despite evidence of the benefits of improved glycemic control, a large percentage of people with diabetes maintain poor glucose control in part because of the limitations of the therapies available for diabetes management.
A Portable System for Continuous Intravenous Insulin Delivery: Characteristics and Results in Diabetic Patients
Authors: Hanna Amir K , Mlnuk Howard L , Albisser A Michael , Marliss Errol B , Leibel Bernard S , Zinman Bernard
Published: December 2014

A portable insulin delivery system for clinical use has been developed, with the aim of improving glycemic control for prolonged periods for individuals with insulin-dependent diabetes. It weighs 1.5 kg and measures 8 × 11 × 20 cm. A plastic case contains two insulin reservoirs, two peristaltic pumps (flow variability ± 3%), a battery pack, and voltage regulator. Silastic tubes connect the reservoirs to an indwelling intravenous catheter inserted into the arm. The system is carried by a strap over the shoulder. One pump operates continuously, giving insulin at a “basal” rate, and the other is activated during meals to give a preprogrammed waveform of insulin, the latter controlled by a small bedside unit.

Twelve insulin-dependent diabetic patients were infused with insulin by this system for 4–60 days (mean 18 days), for a total of 199 patient days. Insulin delivery rates were modified according to data obtained by intermittent glycemic monitoring, and on one and in some cases two days glycemia was continuously monitored (N = 10). With a basal infusion rate of 18 ± 2 mU/min (mean ± SEM), fasting glycemia was 99 ± 7 mg/dl.

The mean insulin delivered with meals was 12 ± 2 U for breakfast, 9 ± 2 U for lunch, and 11 ± 2 U for dinner. Mean glycemia before lunch and supper was 102 ± 6 and 121 ± 11 mg/dl, respectively. The lowest mean glycemia occurred after lunch (88 ± 7 mg/dl) and the mean peak postprandial glycemia was 136 ± 8 mg/dl (2 h after supper). The range from lowest to highest observed value was 47–189 mg/dl. This system is capable of maintaining glycemia within the normal range for periods up to 60 days. Further refinement of the waveforms of insulin delivery may allow for total glycemic normalization. The future refinement of such a system will allow for longer-term studies addressing the relationship between glycemic control and complications.
The Peritoneum — A Potential Insulin Delivery Route for a Mechanical Pancreas
Authors: Schade David S , Eaton Philip
Published: December 2014

The potential advantages of the peritoneum as an insulin delivery site for an implanted mechanical pancreas are reviewed. During embryogenesis in humans, the development of the pancreas and liver are closely related such that, in the adult, all endogenous insulin secreted by the pancreas passes directly to the liver before entering the peripheral circulation. This anatomic relationship permits the direct modulation of absorbed nutrients from the gut by both the liver and pancreatic hormones. Preliminary studies in the dog indicate that at least a portion of insulin infused into the peritoneal space enters the hepatic portal vein before entering the peripheral circulation, thereby simulating normal pancreatic insulin secretion.

Infusion of insulin directly into the peritoneum in humans has demonstrated that (1) insulin absorption is rapid (within minutes), (2) it results in appropriate meal-related peaks in peripheral insulin concentration, and (3) the insulin has biologic activity in suppressing meal-induced hyperglycemia. Furthermore, analysis of the absorbed insulin pattern indicates that approximately 50% of the delivered insulin is removed before entering the peripheral circulation, compatible with hepatic insulin removal. In addition, insulin delivered into the peritoneum in diabetic individuals may result in a reduction in meal-related glycemic excursions, compared with a similar quantity of NPH insulin delivered subcutaneously. Thus, the peritoneum may be a rational alternative to both the intravenous and subcutaneous delivery sites for an implanted insulin delivery system,
Treatment of Juvenile-onset Diabetes by Subcutaneous Infusion of Insulin with a Portable Pump
Authors: Sherwin Robert S , Tamborlane William V , Genel Myron , Felig Philip
Published: December 2014

We have evaluated the efficacy of an insulin infusion system in the treatment of juvenile-onset diabetic patients that delivers insulin via the subcutaneous route with a portable pump at constant basal rates with pulse dose increments before meals. Studies in the hospital in 15 diabetic patients for 2–14 days indicated rapid restoration of normal glucose homeostasis. Mean plasma glucose levels on pump therapy averaged 85–90 mg/dl, maximal fluctuations in plasma glucose fell by 50–75%, and glycosuria was eliminated. Minimal plasma glucose values varied between 45 and 67 mg/dl. Cholesterol, triglycerides, and free fatty acids as well as fasting and postprandial branched chain amino acid levels were elevated on conventional treatment but fell to normal after 7 days of pump therapy. Pump treatment also restored to normal increased basal growth hormone levels and excessive exercise-induced rises in growth hormone and catecholamines. Normalization of body fuel metabolism occurred, although the total dose of insulin administered by the pump was no greater than the usual insulin dose given by conventional means. We have treated seven insulin-dependent diabetic patients (aged 13–32 yr) for 3–8 mo outside of the hospital. Patients pursued their usual work or school activities. Mean blood glucose (237 ± 28 mg/dl during conventional therapy) fell to 105 ± 5 mg/dl after 4 wk of pump treatment and was maintained between 80 and 104 mg/dl beyond 8 wk. Total glycosylated hemoglobulin was normalized in all patients within 8 wk, as were cholesterol and triglyceride levels. Symptoms of hypoglycemia and overinsulinization and underinsulinization due to human error was relatively uncommon. No episode of mechanical pump failure occurred in 1110 patient-days of use. We conclude that normalization or near normalization of blood glucose levels and correction of abnormal lipid and amino acid metabolism can be achieved with a portable subcutaneous insulin infusion system when continuously used to treat juvenile-onset diabetic patients. Long-term use of this system may provide a feasible means for determining whether metabolic changes resulting from insulin lack cause the complications of diabetes.
Prolonged Peritoneal Insulin Infusion in a Diabetic Man
Authors: Schade David S , Eaton R Philip , Friedman Neal M , Spencer William
Published: December 2014

This study examines the feasibility of prolonged (5-day) peritoneal insulin administration in an insulindependent diabetic subject. Regular insulin was delivered through a 22-gauge polyethylene catheter into the peritoneal space by a portable, rotary solenoid pump at a concentration of 60 ∪/ml. The protocol permitted normal daily activities and attendance at work. At night, the diabetic subject slept in the Clinical Research Center, which allowed frequent monitoring of plasma glucose concentration. Blood samples were obtained every 2 h throughout the 5-day period for glucose, insulin, and C-peptide assay. The results of this study were compared with a control, subcutaneous insulin injection study completed during an additional 5-day period. The results suggest that 5-day intraperitoneal insulin infusion is superior to a comparative 5-day period of subcutaneous insulin injection. Not only were large swings in plasma glucose concentration prevented by intraperitoneal insulin delivery but also mean blood glucose concentration was reduced significantly. Furthermore, intraperitoneal insulin administration resulted in acute meal-related increases in plasma free insulin concentration, suggestive of a normal plasma insulin profile. Thus, intraperitoneal insulin may be a rational insulin delivery site for long-term insulin delivery by a mechanical insulin delivery device.
Closing the Loop: Practical and Theoretical
Authors: Peterson Charles M , Jovanovic Lois B , Brownlee Michael , Jones Robert L , Cerami Anthony
Published: December 2014

Using presently available technologies, a closed-loop system can be devised that employs patient-monitored glucose determinations and self-adjusted insulin administration. Improved glucose control has been documented in type I diabetes and in pregnant women with insulin-dependent diabetes mellitus. In pregnancy, self-administered insulin may achieve levels of carbohydrate control that are superior to those achieved using a self-contained glucose-controlled insulin infusion system, programmed by existing algorithms. Improved closed-loop systems are necessary in order to achieve carbohydrate “control” that will surpass that which can be attained using presently available means. A potential approach might employ a lectin glucose-controlled insulin delivery system,
Perinatal Islet Function in Gestational Diabetes: Assessment by Cord Plasma C-Peptide and Amniotic Fluid Insulin
Authors: Ogata Edward S , Freinkel Norbert , Metzger Boyd E , Phelps Richard L , Depp Richard , Boehm John J , Dooley Sharon L
Published: December 2014

We have attempted to use perinatal islet performance as an index of the impact of maternal fuels during fetal development. Accordingly, we analyzed cord plasma for C-peptide and amniotic fluid (secured several weeks before delivery) for immunoreactive insulin in infants of mothers with normal metabolism (NM), gestational diabetes (GDM), and tightly regulated White Class B or Class C insulin-dependent diabetes mellitus (IDDM). We tried to subdivide mothers with GDM on the basis of severity by distinguishing between those with fasting plasma glucose within the normal range for pregnancy (i.e., less than 105 mg/dl and those with fasting plasma glucose of 105 mg/dl or greater). Most of the latter were treated with insulin whereas the former received diet alone. We found that cord plasma levels of C-peptide in infants of mothers with GDM < 105, GDM ≥ 105, and IDDM did not differ significantly from one another; all were approximately twofold greater than in infants from mothers with NM. Values for insulin and ratios of insulin/glucose in amniotic fluid were also increased and to a similar degree in all three diabetic groups; all exceeded the findings in the NM group. Our results indicate that islet function is enhanced at birth in the offspring of mothers with even the mildest forms of untreated gestational diabetes (i.e., GDM < 105) to a degree that is not appreciably different than in more severe forms of diabetes receiving tightly regulated insulin therapy. The augmented B-cell secretion cannot be ascribed to intrapartum events, since similar changes were also found in amniotic fluid secured several weeks before delivery. We conclude that neonatal insulin secretion may constitute an exquisitely sensitive index of the effects of ambient fuels during intrauterine life. Neonatal B-cell function thereby may provide a useful yardstick for the retrospective evaluation of maternal glucoregulation during late gestation.