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Biomedical subjects

C D Saudek

Publications and source records attributed to C D Saudek.

At least 19 recordsLinked to original sources
PubMed1992

Long-term intraperitoneal insulin delivery.

Over the past 5 years, 21 patients with insulin-dependent diabetes mellitus have been managed at the Johns Hopkins Medical Institutions with variable rate, remotely controlled implanted insulin pumps. To date, nearly 70 patient-years of experience has been gained with intraperitoneal delivery of a new U-400 insulin with a surfactant. All 21 patients are alive after a mean of 39.3 months (range, 10 to 65 months) after insulin pump implantation. Nineteen of the 21 patients remain on intraperitoneal insulin, for a 5-year actuarial system survival of 90%. Glucose control was improved, especially during the first 16 months after pump implantation, without an increased incidence of severe hypoglycemia. Catheter blockage has been a significant problem, occurring in nine of the 21 patients (43%). Catheter occlusion has been successfully managed, however, with laparoscopic repair in seven of 10 attempts or with catheter change in four of five patients. Nevertheless, quality of life and patient acceptance remain excellent. Moreover, pre-existing nephropathy, neuropathy, and retinopathy have been surprisingly stable. With an aggressive policy of catheter change or laparoscopic clearance of catheter blockage, long-term intraperitoneal insulin delivery is now a safe and effective treatment for type I diabetics.

Adult↗
PubMed1992

Why intraperitoneal delivery of insulin with implantable pumps in NIDDM?

In the normal state, pancreatic secretion of insulin results in a portal/peripheral gradient with the highest concentrations of insulin in the liver. In diabetic patients with absent or insufficient pancreatic insulin secretion who require exogenous insulin, this normal gradient is lost, resulting in numerous abnormalities. This consideration led to interest in the intraperitoneal delivery of insulin, hoping to produce a therapeutic state more closely resembling normal physiology. The development of implantable insulin pumps, which can deliver insulin intraperitoneally, led to numerous studies on insulin-dependent diabetes mellitus (IDDM) patients, demonstrating that insulin delivered intraperitoneally is rapidly and predictably absorbed with most of it going into the portal system, resulting in hepatic delivery of insulin. Studies in IDDM patients have demonstrated that good glucose control can be achieved with intraperitoneal delivery of insulin from implantable pumps with lesser glycemic fluctuations and, therefore, fewer episodes of hypoglycemia. Furthermore, intraperitoneal insulin results in carbohydrate and particularly lipid metabolism that more closely mimics the normal physiological state than produced by injections of insulin. Thus, implantable insulin pumps are being studied for use in IDDM. Many non-insulin-dependent diabetes mellitus (NIDDM) patients have insufficient pancreatic secretion and require exogenous insulin. Because of alterations in hepatic sensitivity to insulin, increments in insulin delivery to the liver may be even more important in NIDDM than IDDM. Furthermore, insulin resistance, which is an integral part of NIDDM, results in higher physiological levels of insulin, which are required for glucose control, and thus significant peripheral hyperinsulinemia occurs in patients receiving exogenous insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Normalization of composition of triglyceride-rich lipoprotein subfractions in diabetic subjects during insulin infusion with programmable implantable medication system.

OBJECTIVE: To investigate whether long-term improved glycemic control by intraperitoneal insulin infusion normalizes the compositional abnormalities of triglyceride (TG)-rich lipoproteins in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Seven subjects were studied before and 12-14 mo after initiation of treatment with the programmable implantable medication system (PIMS). Plasma TG levels were measured, and the composition of three TG-rich lipoprotein subfractions (Svedberg flotation [Sf] greater than 400, 100-400, and 20-100) were analyzed before and every 1.5 for 7.5 h after ingestion of corn oil. RESULTS: PIMS significantly improved glycemic control, as measured by mean blood glucose (P less than 0.02), and HbA1 (P less than 0.001, paired t test) levels. Weight loss was also observed during PIMS treatment. Significant changes occurred in the composition of TG-rich lipoprotein subfractions during PIMS treatment in both the fasting (P less than 0.002) and the postprandial (P less than 0.0001) state. Most changes were in the direction of nondiabetic values. PIMS treatment reduced the total cholesterol enrichment in IDDM subjects in all three subfractions in the postprandial state and the very-low-density lipoprotein subfractions (Sf 100-400 and 20-100) in the fasting state. Multivariate analysis showed that the compositional changes were affected by improved glycemic control, as assessed by both mean blood glucose and HbA1, whereas the very-low-density lipoprotein compositional changes were by both the improved glycemic control and body weight. CONCLUSIONS: In IDDM subjects during PIMS treatment, there was normalization of most abnormalities in the composition of fasting and postprandial TG-rich lipoproteins, including enrichment in total cholesterol, which is considered atherogenic.

Adult↗
PubMed1991

Differential effect of diabetes education on self-regulation and life-style behaviors.

OBJECTIVE: To examine the effect of diabetes education on self-regulation and life-style behaviors. RESEARCH DESIGN AND METHODS: Participants in an outpatient diabetes education program completed a protocol measuring several self-care behaviors and glycemic control at entry (n = 165) and 6 (n = 124) and 12 (n = 89) mo after the program. RESULTS: Improvement was noted at 6 mo for most self-care behaviors and glycemic control. At 12 mo, lower glycosylated hemoglobin levels were maintained (P less than 0.001) without increases in perceived hypoglycemia. Improvement was not maintained for those self-care behaviors that require change in life-style, i.e., diet and exercise. However, self-care behaviors that allow patients to self-regulate their glycemic control--self-monitoring of blood glucose and insulin dose self-adjustment--were improved at 12 mo over preprogram levels (P less than 0.001). Frequency of insulin self-adjustment continued to increase during the period between follow-ups. CONCLUSIONS: The findings suggest that diabetes education is effective in promoting self-regulation behaviors, although it has less effect on traditional regimen behaviors such as diet and exercise.

Activities of Daily Living↗
PubMed1990

The programmable implantable medication system (PIMS): design features and pre-clinical trials.

This report describes the clinically significant design features of a variable rate implantable insulin infusion pump, the Programmable Implantable Medication System (PIMS), and its function in pre-clinical trials. PIMS has a number of unique features, including a solenoid, pulsatile pump design requiring minimal power (less than 15 microwatts) and a less-than-atmospheric pressure reservoir. Two-way communication is accomplished by radiotelemetry. The implanted device stores programs, and records its own hourly history of insulin delivery. Limits are set on total insulin delivery over time. Basal rates are adjustable, and patterned prandial insulin delivery curves can be programmed. Initial trials (3.1 dog-years) identified four problems which were corrected prior to final pre-clinical trials: microcracks in the diaphragm, a valve-seating leak, electronic failure of prototype microchips, and insulin aggregation. Sixteen dog-years of final pre-clinical trials with a single system design demonstrated that 5 pumps were still working continuously after up to 3.75 years (mean 3.3 years) without mechanical or electronic pump failure. The longest interval between reservoir refills was 5 months. Remaining potential causes of flow stoppage, however, include blockage of the peritoneal catheter by omentum (which occurred once), and air lock (which occurred two times).

Animals↗
PubMed1990

Cerebrovascular and metabolic responses to hypoxia during hypoglycemia in dogs.

The effects of insulin-induced hypoglycemia on the response of cerebral blood flow (CBF-microspheres), electroencephalogram (EEG), and cerebral uptake/production of oxygen (CMRO2), glucose (CMRglu), lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate to isocapnic hypoxic hypoxia were studied in pentobarbital-anesthetized, mechanically ventilated dogs. Hypoglycemia [1.3 +/- 0.2 mumol/ml, (+/-SE); n = 9] did not produce an isoelectric EEG and did not affect base-line CBF or CMRO2. When arterial O2 content was reduced from 17.4 +/- 0.6 to 7.5 +/- 0.5 and 5.1 +/- 0.2 vol% during hypoglycemia, CBF increased from 25 +/- 3 to 54 +/- 6 and 84 +/- 8 ml.100 g-1.min-1, respectively. This response was not different from that during normoglycemia (3.5 +/- 0.3 mumol/ml; n = 12). During normoglycemia, hypoxia increased CMRglu from 17.0 +/- 1.2 to 32.2 +/- 4.7 and 49.9 +/- 6.6 mumol.100 g-1.min-1, respectively. Hypoglycemia did not affect CMRglu during normoxia, but the hypoxia-induced increase in CMRglu was abolished. CMRO2 during hypoxia was unaffected by hypoglycemia. We conclude that levels of hypoglycemia that do not produce an isoelectric EEG may impair the normal increase in CMRglu during hypoxia but do not alter the global CBF response to hypoxia.

Animals↗
PubMed1990

Hypoglycemia and cerebral autoregulation in anesthetized dogs.

We examined the effects of moderate hypoglycemia with near-normal cerebral glucose consumption on cerebral autoregulation during graded hemorrhagic hypotension in anesthetized dogs. Four groups of animals (n = 8 each) were studied: normoglycemia, insulin-induced hypoglycemia (1.1 mM), normoglycemia plus alpha- and beta-adrenergic blockade [propranolol (1 mg/kg loading dose + 1 mg.kg-1.h-1 infusion) plus phentolamine (2 mg/kg loading dose + 2 mg/min infusion)], and hypoglycemia plus alpha- and beta-adrenergic blockade. As cerebral perfusion pressure was reduced to 40-50 mmHg, cerebral blood flow and O2 consumption increased in the hypoglycemic group. These increases were not observed after adrenergic blockade or in the normoglycemic groups. The perfusion pressure at which cerebrovascular resistance was minimal was higher during hypoglycemia (40 mmHg) and hypoglycemia plus blockade (50 mmHg) than in either of the normoglycemic groups (30 mmHg). This study demonstrates that hypoglycemia increases the lower limit of cerebral autoregulation during hypotension. Furthermore, adrenergic mechanisms acting during combined hypoglycemia and hemorrhagic hypotension increase cerebral blood flow and O2 consumption and attenuate the hypoglycemia-induced increase in the lower limit of autoregulation.

Anesthesia↗
PubMed1989

A preliminary trial of the programmable implantable medication system for insulin delivery.

We undertook a trial to determine whether an implanted insulin-delivery system, the programmable implantable medication system (PIMS), could be used to treat patients with insulin-dependent diabetes. PIMS is a pulsatile, programmable pump with a battery life expectancy of five years. The reservoir is refilled transcutaneously every two months with a surfactant-stabilized human insulin preparation containing 400 U of insulin per milliliter. Eighteen patients received PIMS-delivered insulin for 4 to 25 months (mean, 18). The total PIMS-implantation experience comprised 28 patient-years. Good glycemic control was established and sustained during treatment (mean plasma glucose level, 7.3 mmol per liter; mean glycohemoglobin level, 8 percent [upper limit of normal, 7.5 percent]), with significantly reduced glycemic fluctuations. The total mean daily insulin dose did not change. Insulin solutions withdrawn from the pump reservoirs contained 92 percent native insulin and preserved biologic activity. There were no surgical or skin complications, severe hypoglycemic episodes, or instances of diabetic ketoacidosis. One pump was replaced because of a manufacturing defect, and four patients had catheter blockages due to omental-tissue encapsulation; two withdrew from the study and two had devices that were repaired successfully. The actuarial rate of survival of catheter function was 78 percent at 1.5 years. We conclude from this pilot study that insulin treatment with an implanted, variable-rate, programmable pump is feasible for periods up to two years.

Adult↗
PubMed1989

Data source automation: new technology for the management of patient-generated test results.

Self-monitoring of blood glucose is widely accepted by patients today, but its usefulness to clinicians has been seriously limited by our inability to interpret the patient-generated data. It is difficult or impossible to make optimal use of hand-kept diaries, no matter how compulsively kept. Patterns elude us, summaries are inaccurate, and large blocks of data are almost entirely ignored. To remedy these problems, data source automation--the automatic recording of data at their site of origin--is being applied to diabetes. Meters will measure blood glucose and memorize the result, date, and time of day. One system even allows the patient to record insulin dosage, exercise, and diet. The advantage of these systems lies in their potential for data management. Recognition of patterns of blood glucose concentration, easy longitudinal comparison of data, and aggregation of large data bases are all facilitated by computerized manipulation of the stored data. In-hospital use of glucose meters can have better documented quality control. It is possible to communicate data to physicians by telephone modem. Effective use of these systems, though, requires convenient software; and their acceptance in actual clinical practice must be demonstrated. But data management capabilities, as they are refined and brought into common use, could significantly improve diabetic management.

Autoanalysis↗
PubMed1989

Effect of hypoglycemia on cerebral metabolism and carbon dioxide responsivity.

This study examined the effects of hypoglycemia (HG) on cerebral metabolism and cerebrovascular reactivity to carbon dioxide. Cerebral blood flow (CBF) was determined using radiolabeled microspheres in pentobarbital-anesthetized dogs. Cerebral oxygen, glucose, lactate, pyruvate, acetoacetate, and beta-hydroxybutyrate uptakes were calculated using the respective concentrations measured in arterial and sagittal sinus blood samples. EEG was recorded throughout each experiment. HG was induced with insulin to obtain a blood glucose less than 30 mg/100 ml. Hypercapnia was studied in 10 animals (3 control, 7 HG) by increasing arterial carbon dioxide tension (PaCO2) from control (35 +/- 4; mean +/- SE) to 54 +/- 2 Torr during normoglycemia (NG) and HG. Hypocapnia was studied in 11 animals (3 control, 8 HG) by decreasing PaCO2 from control (39 +/- 1) to 14 +/- 1 Torr in NG and HG. Measurements were taken after reaching steady-state PaCO2 in both groups at each control and altered PaCO2 state. In the hypercapnic group, glucose decreased from 71 +/- 3 to 28 +/- 3 mg/100 ml. CBF increased with hypercapnia to 175% of control in both NG and HG. Cerebral metabolic rate of oxygen and electroencephalogram (EEG) did not change in the hypercapnic group. In the hypocapnic group glucose decreased from 71 +/- 3 to 19 +/- 2 mg/100 ml. CBF decreased with hypocapnia to 62 +/- 5% of control in NG but remained at control in HG. This was not accompanied by changes in cerebral oxygen consumption; however, a flat EEG occurred in all HG hypocapnic animals. No change occurred in uptake of the other cerebral metabolites measured in any group. This study shows that the CBF hypercapnic response remains intact during HG; however, hypocapnia causes severe EEG disturbances and impairs the cerebral vasoconstriction response.

Animals↗
PubMed1988

Pancreatectomized swine as a model of diabetes mellitus.

The development of a model of diabetes mellitus using swine offers the potential for new investigations in the study of human diabetic complications. In particular, animal models for the study of accelerated atherosclerosis associated with diabetes are important and presently lacking. Swine were selected because they have a natural susceptibility to atherosclerosis and have plasma lipoprotein patterns which are close to those of humans. Diabetes mellitus was induced in nine miniature swine by total pancreatectomy. Following surgery, they were maintained on porcine derived insulin at doses predicated on blood glucose levels. Pancreatic enzymes were replaced by dietary supplementation. Eight of the nine pigs were pancreatectomized successfully and stabilized with insulin. After initial weight loss, the pancreatectomized pigs maintained growth rates comparable to controls. Hypoglycemia and bacterial infections were the major problems experienced. Post-operative survival ranged from 50 days to 455 days. Our study shows that swine can be pancreatectomized successfully and maintained as insulin dependent animals, presenting a realistic model for research on the complications of diabetes.

Animals↗
PubMed1987

Stable insulin preparation for implanted insulin pumps. Laboratory and animal trials.

The stability and longevity of the polyethylene-polypropylene glycol-stabilized insulin have been tested in vitro and in vivo in an implanted insulin-infusion device, the programmable implantable medication system (PIMS). In vitro tests demonstrated long-term compatibility with refill cycles of up to 3 mo, with a preparation of 400 U/ml. Total test period in vitro was 3.2 device-yr (combined time of device use). Insulin retained 88-93% native structure. A major modification, which was biologically active and nonimmunogenic, was identified and partially characterized. Examination of one device by scanning electron microscopy and X-ray microanalysis after 1 yr of insulin infusion revealed surfaces clean of insulin precipitate or other material along the entire insulin-delivery pathway. Surface analysis of the silicone-lined polyethylene catheters after 6 mo of infusion also showed no evidence of major insulin precipitate. In vivo stability trials were accomplished with PIMS implanted in diabetic dogs with an intraperitoneal delivery site. There has been no insulin blockage of the catheter of active pumps after 5.1 dog-yr (combined time of trials) of trials (up to 5 mo between refills in a single dog). Structural stability of insulin was analyzed by high-performance liquid chromatography. On average, 90.8% of the insulin sampled from the reservoir in vivo was native insulin, with an average of 96.2% retention of active forms.

Animals↗