Treatment Of Insulin-dependent Diabetes Mellitus Research Articles

Experimental validation of a glucose-insulin control model to simulate patterns in glucose turnover

To verify a structured model of the glucose-insulin system, metabolic measurements were compared with model-based simulations in insulin-dependent diabetic dogs which had been previously identified in terms of model parameters. Glycaemia, glucosuria, plasma insulin, and the rates of appearance R a and disappearance R d of glucose (kinetics of double-labelled glucose, evaluated according to Steele's equation in its non-steady-state version) were observed under the following conditions, starting from normoglycaemia during glucose-controlled insulin infusion (GCII): (I) insulin withdrawal, (II) insulin withdrawal and glucose infusion, (III) constant i.v. infusion of glucose and insulin, (IV) glucose infusion during GCII. After fitting the patterns of glycaemia, simulations of the other state variables were accomplished, employing the individual model parameters, the preset experimental inputs, and the GCII control constants (test IV only). Under nearly all conditions, correspondence was excellent between measured and simulated data. There were, however, the following exceptions: incomplete representation by the model of kinetics in glucose utilisation after interruption of insulin supply, overestimation of glucosuria by the model in the presence of insulin. It is concluded that the model provides a reasonable representation of metabolic processes which are of importance in the treatment of insulin-dependent diabetes mellitus and that it might thus appropriately simulate the outcome of metabolic regimens.

Penetration of pefloxacin into human allograft pancreatic juice

The penetration of pefloxacin (400 mg) into pancreatic juice, following a single oral dose, was investigated in five patients subjected to pancreatic transplantation as treatment for insulin-dependent diabetes mellitus. The pancreatic juice was temporarily diverted to the exterior by means of a pancreatic duct catheter. Studies on pure human pancreatic juice were thus made possible. Simultaneous blood and pure pancreatic juice samples were collected at regular intervals for up to 24 h after drug intake. The antibiotic concentrations were determined by bioassay. The average concentration of pefloxacin in pancreatic juice was 100% of that in serum. The mean peak concentration in pancreatic juice was 4.6 +/- 0.9 mg/l (+/- S.E.) and occurred at 2.5 h after drug intake. The decrease in concentration with time was parallel to the serum concentration curve. The concentrations of pefloxacin in pancreatic juice exceeded the MICs of many bacteria associated with pancreatic infections for several hours after administration of a single oral dose.

The Role of Islet Transplantation in the Treatment of Insulin-dependent Diabetes Mellitus

Allograft immunity and disease recurrence both represent immune-mediated responses that result in islet destruction by distinct cellular pathways. A comparison of the salient features of these two processes is summarized in Table 7. Support for an inflammatory mechanism of islet destruction in diabetic pathology is indicated by the findings that the disease is not MHC-restricted by the islet tissue, is CD4 T-cell-dependent, and can be controlled by agents that inhibit inflammatory damage. As such, the pathogenesis of diabetes bears a striking similarity to the pathology of experimental allergic encephalomyelitis. Studies of the latter have shown that the pathology is not MHC-restricted by the target tissue,32 that adoptive transfer of disease is CD4 T-cell-dependent,13 and that disease can be inhibited by desferrioxamine.12 Results emerging from experimental islet transplantation show that the two differing immune-mediated processes that inflict islet damage, allograft immunity and disease pathology, can be inhibited by tissue pretreatment and control of inflammatory damage, respectively. These findings suggest that the clinical application of islet transplantation may indeed be possible without the requirement for prolonged immunosuppression, which we believe is the ultimate goal of islet transplantation.

ASSOCIATION OF INCLUSION OF THE DONOR SPLEEN IN PANCREATICODUODENAL TRANSPLANTATION WITH REJECTION

Clinical pancreas transplantation (txp) using a pancreaticoduodenal allograft (pda) and the donor spleen has been applied as treatment for insulin-dependent diabetes mellitus. Inclusion of the spleen in the pda is purported to protect against thrombosis and may be of possible immunological benefit. In pancreatectomized pigs, we compared the results of pda txp with (n = 8) and without (n = 10) the donor spleen. Animals were maintained on cyclosporine (6 mg/kg/day i.v.) and prednisolone (1.5 mg/kg/day i.v. tapered over 7 days to a maintenance dose of 0.5 mg/kg/day i.v.). Pancreatic exocrine enzyme replacement was administered daily. In 10 recipients of the technically successful pda without the spleen, rejection (blood glucose greater than 150 mg/dl) was not seen in the 28 days after txp. Mean daily blood glucose was 95 +/- 8 mg/dl during this period. In contrast, 5 of 8 recipients of the technically successful pda with the donor spleen rejected their grafts an average of 13 days (range 7-16) after txp (P less than 0.01). Mean daily blood glucose was 88 +/- 21 mg/dl prior to the declaration of rejection and increased to 275 +/- 59 mg/dl after rejection (P less than 0.0001). Rejection was histologically confirmed in all cases. None of the recipients of the pda with the donor spleen developed signs of graft-versus-host disease. Glucose tolerance testing carried out 28 days after transplantation in normoglycemic pigs from both experimental groups demonstrated no difference between the groups. In the porcine pda model used in this study, the inclusion of the spleen in the pda was associated with rejection of the transplant.

THE USE OF ACTIVITIES EM THE APPROACH TO NON-COMPLIANCE IN THE TREATMENT OF JUVENILE DIABETES

Article THE USE OF ACTIVITIES EM THE APPROACH TO NON-COMPLIANCE IN THE TREATMENT OF JUVENILE DIABETES was published on July 1, 1985 in the journal International Journal of Adolescent Medicine and Health (volume 1, issue 3-4).

Therapy in Childhood Diabetes

The treatment of insulin-dependent diabetes mellitus is rapidly changing with the introduction of portable insulin infusion pumps, multiple injections of insulin daily, determination of glycosylated hemoglobin (GHb) values, and self-monitoring of blood glucose levels. Although some diabetologists believe that the development of long-term complications of diabetes can be prevented or delayed by normalization of blood glucose levels, others are of the opinion that the relationship of normoglycemia and diabetes complications has not been fully established. To complicate matters, there is controversy among diabetes experts as to whether or not the possible benefits of intensive therapy are worth the added potential risk of hypoglycemia and psychological problems. Elsewhere in this issue (p 2913), Geffner and colleagues show that children with diabetes are willing to accept modifications in therapy, including changing from one injection to multiple injections of insulin daily, and changing from urine glucose monitoring to blood glucose monitoring. In my

Plasmapheresis in the initial treatment of insulin-dependent diabetes mellitus in children.

Several factors indicate that autoimmune mechanisms may play a part in the aetiology of insulin-dependent diabetes mellitus. At the onset of the disease in 10 children (aged 11-16 years) plasmapheresis was performed four times over one to two weeks. Seventeen age-matched children with the same clinical features served as controls. The C-peptide concentrations at onset were the same in the two groups, but after one month the children treated with plasmapheresis had significantly higher values. This difference became even more pronounced after three, nine, and 18 months, both during fasting and at the maximum response to a standardised meal. The study group also had a significantly more stable metabolism, longer partial remission, and no higher insulin requirement. Of the 10 treated children islet-cell cytoplasmic antibodies were present in seven before plasmapheresis and in nine during treatment. The antibodies remained detectable in five and six out of nine patients at one and six months respectively after plasmapheresis. Although the mechanisms are obscure, plasmapheresis performed at the onset of insulin-dependent diabetes mellitus may help to preserve beta-cell function.

Diabetics in school. Knowledge and attitudes of school staff in relation to juvenile diabetics.

The purpose of this study was to assess whether the schools satisfy the special requirements of diabetic pupils. Both school staff and parents were of the opinion that diabetic pupils need special consideration at school. However, the results reveal an inadequate knowledge of the basic facts about diabetes and its treatment--a situation which could have dangerous consequences for the child and complicate its schooling in a number of ways. The treatment of juvenile diabetes may also become difficult to manage. Most school staff seemed to lack any source of information about diabetes. The contact between parents and school was not always sufficient and information from the hospital was seldom adequate. At present the school cannot be expected to participate in the treatment of diabetes in the way that could be desired. Improved information of school staff on the subject is recommended, as well as early and repeated contacts between hospital and school. These conclusions are drawn from an investigation in which 308 school staff members and the parents of 61 diabetic pupils answered questiomaires.

EFFECTS OF SOMATOSTATIN ON PLASMA INSULIN, GROWTH HORMONE AND GLUCAGON LEVELS IN OBESE AND DIABETIC CHILDREN AND ADOLESCENTS

Somatostatin (GHRIH) could be helpful in the treatment of diabetes mellitus when high levels of growth hormone and glucagon interfere with the metabolic control. In obese children the i.v. injection of 3 ug/kg of ideal body weight of GHRIH before i.v. glucose tolerance test lowered significantly the glucose disappearance rate, the plasma insulin levels, and delayed the peak value. In diabetic children the i.v. administration of 3 μg/kg of GHRIH over two min, followed by a 60 min infusion of 7 μg/kg in saline solution induced a significant decrease of blood sugar, growth hormone and glucagon levels; the administration of 3 μg/kg of CHRIH immediately before a standardized physical exertion significantly reduced the rise of growth hormone levels. GHRIH can open new possibilities in the treatment of juvenile diabetes, at least after puberty.

Management of Juvenile Diabetes Mellitus

Doctors Traisman and Newcomb cover the usual subjects of the cause, diagnosis and treatment of juvenile diabetes, leaving about one-third of the text for a detailed description of diet therapy. The book is designed as a how-to-do-it guide, and should be judged accordingly. In these modest terms, it is a reasonably useful book. A few omissions, however, are worthy of note. For example: the four-page discussion of differential diagnosis omits postconvulsive and acute febrile glycosuria—two well-known though uncommon entities.

Observations on the treatment of young diabetics with an oral drug (phenethyl-biguanide).

ABSTRACT A brief comparison of phenethyl-biguanide (D. B. I.) with other oral hypoglycaemic drugs is made. A series of 31 juvenile diabetics treated with D. B. I. is described, and the reasons for partial success or failure are considered. The advantages and dangers of the drug are discussed. It is concluded that the unique action of this drug may give it a place in the treatment of juvenile diabetes.

Diabetic Care in Pietures

Rosenthal, B.S., and Joseph Rosenthal, M.D. Price, $4.50. Pp. 237, with 137 illustrations (12 color plates). J. B. Lippincott Company, E. Washington Sq., Philadelphia 5, 1960. This excellent manual offers valuable aid to physicians, nurses, and others who have the duty of teaching diabetic management to patients and to parents of diabetic children for their self-management at home, although it is mainly intended for adult patients. The nature of diabetes, its incidence and heredity, signs and symptoms, and principles that guide treatment, are explained in admirably simple language. The visual aids comprise 135 black-and-white figures and 12 color plates, all well selected and presented. Diet for diabetes is discussed in detail and food exchange lists are presented with abundant illustrations. Insulin preparations in current use are featured together with equipment for the injection; also, reagents and equipment for simplified tests for detecting the presence of sugar, acetone, and diacetic acid in the urine. In the case of the color Plate 8 (for Clinitest) there should have been included a warning that concentrations of sugar in urine much above the 2% illustrated (++++ orange) often give a dirty green color resembling the color (+ or 1+) illustrated as indicating only Vi%. Chapter 5 includes a good discussion of the with a clear statement that the action of these drugs is different from that of insulin and therefore none is to be regarded as a substitute for insulin. This statement might be amplified to indicate that investigators are practically unanimous in agreeing that the oral drugs have not yet proved to be of much value in the treatment of juvenile diabetes. The section on care of the feet, anticipating late complications of peripheral vascular disease, may seem redundant for pediatrie practice, but even so may be useful for warning older children to be alert for possible late complications of the disease as they grow older. GEORGE M. GUEST, M.D.

Observations on the management and treatment of juvenile diabetes

Observations on the management and treatment of juvenile diabetes