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Biomedical subjects

D L Horwitz

Publications and source records attributed to D L Horwitz.

At least 19 recordsLinked to original sources
PubMed1979

Use of a glucose controlled insulin infusion system (artificial beta cell) to control diabetes during surgery.

An artificial beta cell has been used to achieve and maintain a preset plasma glucose concentration in five diabetic patients undergoing surgery. These subjects were compared to control groups of normal subjects receiving either saline or glucose, and diabetics receiving glucose intraoperatively. Hyperglycaemia during surgery was seen in normals (mean plasma glucose +/- SEM: 185 +/- 16 mg/dl) and, to a greater degree, diabetics (247 +/- 36 mg/dl) receiving glucose. Insulin and C-peptide levels did not increase during 2 hours of operation in any of the control groups, suggesting beta cell suppression during surgery. As C-peptide levels declined similarly in normal subjects whether they received saline or glucose, the hyperglycaemia seems to be due to an inability to use exogenous glucose. This is confirmed by a correlation of maximal plasma glucose to glucose infusion rate (r = 0.78, p less than 0.01). The artificial beta cell was able to achieve the same plasma glucose after 2 hours of operation (128 +/- 21 mg/dl) as normal subjects receiving saline (110 +/- 7 mg/dl). The artificial beta cell proved to be a safe, convenient and effective way of monitoring and controlling the hyperglycaemia seen in diabetic patients undergoing surgery.

Blood Glucose↗
PubMed1979

Evaluation of insulin secretory capacity in diabetes mellitus.

The capacity of the pancreatic beta cells to secrete insulin can be evaluated in vivo by measurement either of circulating immunoreactive insulin or of C peptide, a by-product of insulin synthesis. Evaluation of serum levels is complicated, however, by the variable degradation rates and distribution spaces of these peptides. Also, interpretation of peripheral vein concentrations of insulin, and perhaps C peptide, is more difficult because of hepatic catabolism. Quantitation of these peptides in the urine may provide an integrated measure of insulin secretion. In insulin treated diabetic patients who develop circulating insulin antibodies, beta cell secretory capacity may be assessed by C peptide measurement, or by techniques that allow separate determinations of "free" and "total" insulin. A variety of stimulatory tests may be used to investigate insulin secretory capacity.

Adult↗
PubMed1979

An 'artificial beta cell' for control of diabetes mellitus: effect on plasma glucagon levels.

We have investigated the use of a glucose-controlled insulin infusion system, or artificial beta cell. On the feedback day, mean plasma glucose was significantly effect of improved control on plasma glucagon levels. Five insulin-requiring diabetic subjects in stable control were hospitalized for two 24 h periods. During one, they were given their usual dose(s) of subcutaneous insulin. In the other, the 'feedback' day, insulin administration was under feedback control by the artificial beta cell. One the feedback day, mean plasma glucose was significantly-lower in all subjects. Variability in plasma glucose throughout the day was also significantly less on the feedback day. All five subjects showed a significant fall in serum immunoreactive glucagon levels on the feedback day, suggesting that the glucagon abnormalities of diabetes may be secondary to the insulin deficiency, rather than a second primary defect of diabetes.

Adult↗
PubMed1979

Continuous monitoring and control of plasma glucose during operation for removal of insulinomas.

A glucose-controlled insulin and glucose infusion system (Biostator system, Miles Laboratories Inc., Elkhart, Ind.) was used during operation for removal of four suspected insulinomas. In two patients the Biostator system continuously monitored plasma glucose levels and, through a computer-controlled feedback mechanism, automatically infused insulin or glucose as needed. In this way plasma glucose could be kept at approximately 110 mg/dl throughout the procedure. In one patient a rise in insulin infusion rate and a fall in glucose infusion rate followed removal of the tumor. In the other, absence of these findings was consistent with the clinical suspicion that the source of hypoglycemia had not been removed. In two other patients the Biostator system continuously monitored the patient's plasma glucose, without feedback-controlled administration of insulin or glucose. This demonstrated that, in these patients, tumor manipulation and removal did not lead to severe hypoglycemia, and thus eliminated any need to prophylactically infuse large amounts of glucose. Successful tumor removal was followed by a rise in blood glucose levels in both of these individuals. The glucose-controlled insulin and glucose infusion system appears to be a useful instrument for intraoperative management of patients with suspected insulinomas.

Adenoma, Islet Cell↗
PubMed1979

Use of an artificial beta cell in surgery.

Using a Biostator glucose-controlled insulin infusion system to monitor blood glucose during surgery, we have shown that both nondiabetic and diabetic patients have a tendency towards hyperglycemia during surgery. This appears to be due to suppression of endogenous insulin secretion as measured by serum C-peptide levels. Some diabetic patients maintained relatively normal glucose values during surgery when infused with saline alone and not given glucose or insulin, but 2 of 5 were not well controlled by this means. Hyperglycemia in both diabetic and non-diabetic patients was related to the rate of infusion of exogenous glucose. The biostator glucose-controlled insulin infusion system could be used in feedback mode as an apparently safe and effective means of controlling blood glucose during surgery on diabetic patients.

Artificial Organs↗
PubMed1979

Insulin responses to mixed meals: comparison of an artificial beta cell and normal beta cells.

The peripheral glucose and free insulin levels seen following a mixed meal in six insulin-dependent diabetic patients whose insulin was administered by a glucose-controlled insulin infusion system (GCIIS) were compared to those of normal subjects who received the same mixed meal or who were given separately carbohydrate, protein, or fat in amounts equivalent to those contained in the mixed meal. Patients treated with the GCIIS achieved nearly normal glucose levels immediately after the mixed meal, but this was accompanied by marked hyperinsulinemia. In the period from 120 to 240 minutes after the start of the mixed meal, the GCIIS duplicates the insulin levels produced by the normal pancreas after a glucose meal and, with appropriate algorithm constants, closely approximates those seen after a mixed meal.

Artificial Organs↗
PubMed1979

Salt.

Explore the source record for details and available documents.

Diet, Sodium-Restricted↗
PubMed1978

Proinsulin and C-peptide in diabetes.

The availability of C-peptide measurement continues to provide new and useful information about the state of beta cell secretory function and the natural history of diabetes. Measurement of proinsulin is of value in the diagnosis of insulin-secreting tumors.

C-Peptide↗
PubMed1978

Kinetics of human connecting peptide in normal and diabetic subjects.

The metabolic clearance rate (MCR) of synthetic human connecting peptide (C-peptide) was measured with a single-dose injection technique in six normal and seven diabetic subjects and with a constant infusion technique in one normal subject. The MCR of C-peptide did not differ in normal subjects (4.4 ml/min per kg; range, 3.7-4.9) and in diabetic subjects (4.7 ml/min per kg; range, 3.7-5.8). Employment of both techniques in one subject gave similar MCR. The average half-life of C-peptide in plasma calculated from the last 1-h period of the single-dose injection studies was longer in the insulin-dependent diabetics (42.5 min; range, 39.4-48.5) than in the normal subjects (33.5 min; range, 24.9-45.3). These results indicate that the beta-cell secretory capacity of normal and insulin-dependent diabetic subjects can be compared by measuring the C-peptide concentration in peripheral venous plasma. The difference in the half-life of C-peptide in plasma between diabetics and normals suggests an altered kinetics of the disappearance of the peptide, while the overall metabolism, as expressed by the MCR, is similar.

Adult↗
PubMed1978

Characterization of seven C-peptide antisera.

The plasma C-peptide immunoreactivity (CPR) in 10 normal subjects varied considerably when measured with different antisera in parallel assays. The CPR level correlated with the blank "CPR" value measured in plasma devoid of C-peptide and to a lesser degree with the sensitivity of the standard curves obtained with the individual antisera. Storage of plasma samples at different temperatures and for different lengths of time before the analyses were carried out resulted in further variation in the CPR results. This was caused by a time- and temperature-dependent fall in CPR, which was more pronounced with some antisera than with others. This sensitivity to storage of plasma did not correlate with the antigenic characteristics of the antisera as determined by their reactivity with 11 specific fragments of the C-peptide molecule. The contribution of human proinsulin to the CPR concentration relative in normal subjects was considered to be negligible even though the relative immunoreactivity of human proinsulin and C-peptide ranged from 11 to 143 per cent among these antisera. These results suggest that differences in C-peptide antisera are a major reason for the variation in the concentration of circulating CPR as measured in different C-peptide immunoassays.

Animals↗
PubMed1978

Heterogeneity of circulating human C-peptide.

Values reported for serum C-peptide immunoreactivity in healthy individuals vary considerably. To assess factors that contribute to this finding, three human C-peptide assay systems were developed utilizing three distinct antisera that react differently with various C-peptide fragments. Preparations of natural pancreatic and synthetic human C-peptide standards were compared immunologically in these systems. The curves of the natural C-peptide and the synthetic preparations were not identical. The relative immunoreactivity of each standard varied, depending on the particular antiserum used. Serum C-peptide concentrations varied when measured in the different assay systems. Furthermore, the results of dilution and recovery tests and stability of the C-peptide during storage showed differences among the three assays. Gel filtration of serum indicated heterogeneity within the major C-peptide peak, and in addition, a smaller peak of lower molecular weight material was present in some samples. Although degradation of serum C-peptide may occur during storage, fragments of C-peptide may also be secreted or arise during in-vivo metabolism. Thus, the present studies indicate the need for careful standardization and checking of each particular assay system before its use in clinical studies.

C-Peptide↗
PubMed1978

C-peptide in conditions other than diabetes mellitus.

Measurement of serum and urinary C-peptide has been shown to be of value in several conditions other than diabetes mellitus. It is particularly useful because it can distinguish endogenous beta cell secretion from exogenously administered insulin and because circulating insulin-binding antibodies do not interfere with its measurement. Because the liver removes little, if any, C-peptide, peripheral blood values may more accurately reflect beta cell secretion than do peripheral insulin levels. Clinically, serum C-peptide has been most useful in diagnosing hypoglycemic disorders. Diagnosis of insulinomas is facilitated in both diabetic and nondiabetic patients, and surreptitious insulin injection is readily detected. In studies of insulin regulation, circulating C-peptide has been used to demonstrate suppression of endogenous insulin secretion by exogenous insulin. Peripheral insulin and C-peptide levels have been compared in studies of the role of the liver in states of altered insulin homeostasis. Because of its higher urinary clearance, determination of urinary C-peptide is preferable to urinary insulin measurement in situations where frequent blood sampling is impossible or difficult to accomplish.

Blood Glucose↗
PubMed1978

High-fiber diets in the treatment of diabetes mellitus.

Eight patients with insulin-requiring diabetes were given, in random order, a diet containing 3 g and one containing 20 g of crude fiber. Each diet was maintained for 10 days and was the same in calories, carbohydrate, fat, and protein. Insulin dose was kept constant. Mean plasma glucose on the low-fiber diet was 169.4 +/- 11.7 mg/dl, significantly higher (P less than 0.001) than the value of 120.8 +/- 10.1 on the high-fiber diet. Hypoglycemic reactions were more common on the high-fiber diet. Weight remained essentially constant on both diets. Mean serum glucagon level on the high-fiber diet was significantly lower (P less than 0.001) than on the low-fiber diet, while serum free insulin levels were unchanged. These data indicate that substantial changes in fiber content of the diabetic diet may lead to marked changes in diabetic control and that increasing dietary fiber may be a useful means of lowering plasma glucose in some diabetic patients.

Adult↗