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Biomedical subjects

A M Albisser

Publications and source records attributed to A M Albisser.

At least 19 recordsLinked to original sources
PubMed1990

The effect of a time delay on the characteristics of the canine glucoregulatory system.

In order to elucidate the effect of a relative time delay on glucose regulation, we performed experiments with differently timed infusions of insulin and glucose in a canine model. When portal insulin infusion (0.03 U/kg over 5 minutes) preceded portal glucose infusion (0.05 g/kg over 5 minutes) by 1 minute, glycemia increased to a maximum value of 104 +/- 4 mg/dL at 6 minutes, whereas insulinemia peaked at 3 minutes at a level of 130 +/- 4 microU/mL (baseline, 21 +/- 7 microU/mL). C-peptide levels increased from 200 +/- 50 to 270 +/- 30 pmol/L. Glycemia then decreased to a minimum level of 61 +/- 4 mg/dL, significantly lower (P less than .02) than the corresponding values in control experiments when insulin was infused alone. With a reversed timing sequence of infusions with glucose infusion preceding insulin infusion by 1 minute, glycemia increased similarly, but decreased to a minimum level of only 84 +/- 4 mg/dL, which was significantly higher (P less than .01) than in the above experiment. Insulinemia peaked similarly at 126 +/- 7 microU/mL, and C-peptide increased from 210 +/- 50 to 280 +/- 50 pmol/L. These experiments demonstrated an unexpected effect: adding glucose to an insulin infusion almost doubled the biological activity of the exogenous insulin as measured by its hypoglycemic action. They also indicated that small perturbations of glycemia and insulinemia in the portal circulation have a profound effect on metabolism, and that even short relative time delays in elevating either insulinemia or glycemia can cause significantly different metabolic outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Controlled study in diabetic children comparing insulin-dosage adjustment by manual and computer algorithms.

A controlled trial of a new microprocessor device for insulin-dosage adjustment was undertaken in two matched groups of a priori well-controlled diabetic children. A prospective study design with three equal 8-wk periods was used. In the first period, both groups used manual methods for insulin-dosage adjustment after manual criteria. In the second period, one group of children adjusted insulin dosage by computer algorithms, whereas the other continued to use manual methods. In the third period, both groups again adjusted insulin by traditional methods. Mean premeal glycemia and glycosylated hemoglobin levels did not change in either group throughout the study. During the second period, episodes of hypoglycemia were more frequent in children without the computer than in those who used the device. In keeping with the latter outcome, the group that used the microprocessor device was given less insulin in the second period than the first (0.88 +/- 0.02 vs. 0.94 +/- 0.02 U.kg-1.day-1, P less than 0.0001) and in comparison to the control group of patients who concurrently were given an increased insulin dose in the second period compared with the first. This study showed that insulin treatment through specific computer-mediated dosage-adjusting algorithms was safe and minimized hypoglycemia by effectively accommodating seasonally changing insulin requirements. We recommend the device to help diabetic children and their families in the care of insulin-dependent diabetes.

Algorithms↗
PubMed1990

Blood or urine glucose-based insulin therapy and control of glycemia. Computer-simulation study.

Adjustment algorithms for conventional insulin therapy must be tested for safety and efficacy before clinical implementation. We did this by computer simulation. Accordingly, a computer simulator of human intermediary metabolism created 10 randomly chosen diabetic subjects for study. All were well defined with respect to compliance (i.e., medication and diet) and life-style (i.e., physical and emotional stress). Insulin-adjustment algorithms that were tested calculated daily insulin dosages for these computer-simulated patients based on either blood or urine glucose concentrations self-measured 4 times/day before breakfast, lunch, dinner, and bedtime snack. The twofold purpose of the simulation study was to determine the ability of the adjustment algorithms to improve initially poor metabolic control and to compare the outcomes when either blood or urine glucose measurements were the basis on which glycemic control was implemented. A significant improvement in metabolic control could be achieved with either blood or urine glucose measurements as input to the algorithms. Detailed comparisons between blood and urine glucose-based treatments showed no significant advantage of blood glucose-based algorithms at breakfast (122 +/- 21 vs. 131 +/- 16 mg/dl) and dinner (117 +/- 27 vs. 130 +/- 23 mg/dl), whereas mean glycemia at lunch (122 +/- 24 vs. 164 +/- 21 mg/dl) and bedtime (117 +/- 25 vs. 150 +/- 21 mg/dl) after 120 days of simulation did differ significantly (P less than 0.01). Hypoglycemia was not provoked by either treatment. Total daily insulin doses evolved by blood glucose-based algorithms were significantly (P less than 0.05) higher than the doses used by urine glucose-based algorithms (53 vs. 47 U).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Six generations of the insulin dosage computer: a new clinical device for diabetes self-management through specialized centres.

Modern technology and dedicated micro-processors in particular, are revolutionizing the treatment of diabetes. Through specialized centres and a select group of new medical experts, conventional diabetes management is gradually being replaced by a system of technology assisted self-care. The present paper outlines the characteristics of six consecutive generations of a new device called an insulin dosage computer. It facilitates self-care by calculating insulin dosages each day at each meal based on glucose measurements made by the patients themselves. The device was initially developed in 1982 and is now extended to over 1200 patients each of whom has acquired expert skills for self-management and thereby achieved improved metabolic control with freedom both from hypoglycemia and from the psychological dependencies usually accompanying this disorder.

Diabetes Mellitus, Type 1↗
PubMed1989

Intelligent instrumentation in diabetic management.

This presentation describes the problem of insulin-dependent diabetes mellitus and the various approaches to creating intelligent instrumentation for management of this type of diabetes. The article traces closed-loop diabetes control from 1974 to the present. Development and implementation of a microprocessor device aimed at achieving this in a practical sense are described. Accordingly, a chronological description of the earliest devices and their shortcomings is given, focusing on the use of blood glucose sensors and vascular access devices. A description of open-loop diabetes control and alternative systems is presented, highlighting the fundamental limitations of subcutaneously injected or infused insulins. A practical system for optimizing conventional therapy is described, together with its design criteria and the creation of a clinical closed-loop that includes the patient. The system has to deal with the effects of diet and exercise while fulfilling the need for adjusting insulin dosages according to expert intervention. Algorithms for this purpose and a computerized approach based on a portable microprocessor expert system are highlighted.

Algorithms↗
PubMed1989

Continuous flow peritoneal dialysis in pigs, using a silicone rubber double lumen catheter.

Continuous flow (CFPD) and intermittent (IPD) peritoneal dialysis were compared in pigs, using a double lumen silicone rubber peritoneal dialysis catheter. For CFPD, after instillation of 30 ml/kg into the peritoneal cavity, dialysate was continually infused and drained at approximately 25 ml/kg/h. A dwell volume of 30 ml/kg was also used for IPD. Similar length cycles of each technique were compared in Experiment 1. In Experiment 2 total solute clearance and ultrafiltration achieved over two consecutive IPD cycles were compared with CFPD of a similar duration. The catheter functioned well with few complications. In Experiment 1, CFPD produced greater ultrafiltration and significantly improved the clearance of urea, potassium and phosphate compared to IPD. No significant difference between the techniques was observed in Experiment 2. Our data suggest that for CFPD to retain its advantage over IPD intermittent complete drainage of the peritoneal cavity may be necessary.

Animals↗
PubMed1988

Compliance in microcomputer-assisted conventional insulin therapy: computer simulation study results.

Compliance in diabetes self-management is a complex issue. It involves the interdependent daily actions of self-measurement of blood glucose and adherence to a prescribed schedule of daily activities. This impacts strongly on lifestyle because it necessitates precise meal timing as well as control of size and carbohydrate content. We sought to identify how strongly relaxing the lifestyle constraints per se would impact the ability to achieve improved metabolic control. To isolate these effects from those that result from poor measurement compliance, we used a computer simulator called OMNI et al. Furthermore, to standardize the "clinical" therapy, a second microprocessor device called an "Insulin Dosage Computer" was used to adjust insulin doses based on the usual clinical practice of four times a day precibal blood glucose measurements. Ten type 1 diabetic patients were stimulated and each followed for 120 simulated days. In each such subject, the simulation was repeated three times to include three different levels of lifestyle compliance ranging from excellent to poor. In all three protocols, starting from a level of poor control of diabetes, mean blood glucose values were significantly improved without significant differences after 120 days of computer-simulated treatment. Only the standard deviations, expressing the fluctuations of blood glucose and hence its stability, increased with decreasing lifestyle compliance. This computer simulation predicts that consistent self-monitoring of four blood glucose values per day is the cornerstone of diabetic self-control and that the use of these data according to a standardized therapeutic algorithm for insulin adjustment may successfully stabilize even patients with poor lifestyle compliance. Clinical studies must follow.

Blood Glucose↗
PubMed1988

Counterregulatory hormone responses preserved after long-term intravenous insulin infusion compared to continuous subcutaneous insulin infusion.

The counterregulatory hormone responses of cortisol, growth hormone, glucagon, epinephrine, norepinephrine, and dopamine to a fixed hypoglycemic stimulus (50 mg/dl for 1 h) were studied in five type I (insulin-dependent) diabetic subjects during conventional insulin therapy (CT), after 3 mo of continuous subcutaneous insulin infusion (SC), and after 3 mo of continuous intravenous insulin infusion (IV). During the two infusion periods, the overall mean levels of preprandial blood glucose (116 +/- 6 SC vs. 114 +/- 5 mg/dl IV) and glycosylated hemoglobin (6.1 +/- 2 SC vs. 5.9 +/- 2% IV) were virtually identical, but there were more hypoglycemic episodes and greater variability of preprandial blood glucose levels during SC than with IV. During the last 30 min of the hypoglycemic clamps, the mean levels of epinephrine and cortisol were significantly lower after 3 mo of SC (epinephrine, 268 +/- 80 pg/ml; cortisol, 14 +/- 1 microgram/dl) than with both CT (epinephrine 485 +/- 80 pg/ml; cortisol, 20 +/- 2 micrograms/dl) and IV (epinephrine, 443 +/- 62 pg/ml; cortisol, 19 +/- 2 micrograms/dl)(P less than .05). The mean growth hormone level was significantly (P less than .05) lower after SC (37 +/- 9 ng/ml) than after IV (79 +/- 12 ng/ml), but it did not reach statistical significance compared with CT (66 +/- 12 ng/ml). The mean glucagon, dopamine, and norepinephrine levels during the same period of hypoglycemia were not different when all treatment regimens were compared. We conclude that intensified insulin therapy with SC leads to significant blunting of the counterregulatory hormone response to hypoglycemia, whereas IV does not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Selective in situ pancreatic perfusion via chronic in vivo celiac artery catheterization.

A new technique to catheterize the celiac artery has been developed. This has opened the possibility for direct in vivo, in situ study of pancreatic endocrine cell function in a conscious experimental animal. The catheter is small, soft and placed without arterial ligation so that celiac artery, hepatic, splenic, and pancreatic blood flows were essentially not compromised. Arterial vessel integrity, absence of inflammation, and thrombosis as well as catheter patency were achieved for periods exceeding eight months. Metabolically and hormonally, the presence of the catheter had no effect on the fasting status. However, we found somewhat lower glucose levels and higher insulin levels in the response to oral glucose challenges after catheterization, but these differences were statistically not significant. Glucose loads of 50 mg/kg (0.75 g) administered directly to the pancreas via the celiac artery produced peak insulin levels similar to peripheral glucose loads some tenfold larger. We suggest that this technique may be useful to selectively study the first-pass pancreatic response to a variety of hormones, drugs or metabolic substrates.

Administration, Oral↗
PubMed1987

Physiological relationships between growth hormone level, glycemia and metabolic control in dogs.

This study was undertaken to explore the physiological relationships between fasting glycemia, antecedent glycemic control and fasting growth hormone levels in pancreatectomized dogs. In contrast to other studies, we used continuous intravenous infusions of insulin in an attempt not only to normalize fasting plasma glycemia but also to eliminate the characteristic fluctuations of diabetes usually encountered in the postprandial and postabsorptive periods. For comparison, a similar group of healthy animals served as normal controls. In the healthy dogs, fasting growth hormone (GH) levels were stable and well within normal limits for this species, demonstrating an overall mean +/- SD of 2.50 +/- 0.46 ng/ml. In the pancreatectomized group as a whole, the fasting GH levels were significantly elevated (4.63 +/- 2.42 ng/ml, P less than 0.01) and significantly (P less than 0.001) more variable than in the controls. Multiple regression and analysis of variance confirmed the expected significant positive correlation between fasting GH and fasting plasma glucose levels, but also elucidated a heretofore unknown direct relationship between fasting GH levels and the preceding instability of glycemic control.

Animals↗
PubMed1986

The metabolic and hormonal adaptations of normal dogs to long-term exogenous sulfated insulin infusions.

Hyperinsulinism frequently accompanies glucose normalization in type I diabetes but the long-term consequences of this exaggerated hormonal state are not known. To study this condition, normal dogs received constant exogenous sulfated insulin infusions for prolonged periods up to 43 weeks. During the interval and inspite of prevailing postabsorptive and fasting hypoglycemia, overt resistance to the infused insulin or loss of sensitivity did not occur. In counterring the imposed fasting hyperinsulinemia and the resulting hypoglycemia, fasting pancreatic glucagon levels rose while the fasting levels of several glucogenic precursors (lactate, pyruvate, and alanine) decreased. Fasting free fatty acid (FFA) levels were suppressed, but beta-hydroxybutyrate (beta-OHB) levels were unchanged. Body weight did not change. Most remarkably, all changes measured in the fasting levels of the hormones and metabolites reverted to normal following the cessation of exogenous sulfated insulin infusion. In addition to the hormonal and metabolite adaptations invoked by chronic exogenous hyperinsulinism in the fasting state of these normal dogs, there were interesting responses to their usual mixed meals. Of particular interest in this regard were the plasma glucose, insulin, and FFA diurnal profiles. First of all, a definite and unusual postprandial glycemic excursion occurred. Second, insulin levels were elevated some sixfold, and rather unresponsive to the meal in general. Inspite of the depressed fasting FFA levels and the absence of a postprandial rise in insulinemia, FFA showed a distinct fall after the meal. Whether the sulfated insulins infused were of the bovine or porcine species of origin made no discernible difference.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1986

Intermediary metabolism in diabetic dogs treated with pancreatic autotransplants and insulin pumps.

Diurnal metabolite profiles were studied in pancreatectomized dogs who had received grafts of their own pancreas. The results were compared to similarly diabetic animals who received exogenous insulin pumped intravenously either peripherally or portally. All animals were studied at least 52 weeks after pancreatectomy. Nondiabetic animals were similarly studied as normal controls. Interestingly, all of the diabetic animals were in excellent metabolic control but significant differences from normal in one or more of the metabolic variables existed in each group. Thus, none of the methods of insulin replacement entirely restored to normal the metabolic state of the pancreatectomized dogs. For example, in the autotransplanted animals, the profiles of glucose, lactate, pyruvate, and alanine manifested either abnormal levels and/or abnormal postprandial excursions. The grafts delivered insulin into the peripheral rather than portal circulations. In the peripherally infused animals, the profiles of pyruvate, alanine, and free fatty acids were also somewhat abnormal. In the portally infused animals the profiles only of pyruvate and alanine showed minor abnormalities without clear statistical significance in some respects as well. The other differences observed were statistically significant (P less than 0.05-0.01). These results suggest that the portal route of insulin delivery may be the route of choice if intermediary metabolism is to approximate normal most closely whether exogenous intravenous insulin is replaced by implanted pumps or endogenous insulin is replaced by pancreatic transplants and that none of these futuristic methods of insulin replacement entirely restore to normal the metabolic state of pancreatectomized dogs.

3-Hydroxybutyric Acid↗
PubMed1986

Metabolic control in diabetic dogs treated with pancreatic autotransplants and insulin pumps.

Fasting metabolite and hormonal levels were studied prospectively in pancreatectomized dogs who had received grafts of their own pancreas. The results were compared with similarly diabetic animals who received exogenous insulin pumped intravenously either peripherally or portally. All animals were studied for 48-91 wk after pancreatectomy. In the autotransplanted animals, the fasting levels of glucose, lactate, pyruvate, alanine, pancreatic glucagon, insulin, gastric inhibitory peptide, and pancreatic polypeptide were all abnormal. In the peripherally infused animals, the fasting levels of glucose, pyruvate, alanine, free fatty acids, and insulin were also abnormal. In the portally infused animals, pyruvate, alanine, gastric inhibitory peptide, gastrin, and pancreatic polypeptide were abnormal. These results suggest that the portal route of insulin delivery may be necessary if fasting metabolite and hormonal levels are to approximate normal most closely whether exogenous intravenous insulin is replaced by implanted pumps or endogenous insulin is replaced by pancreatic transplants.

Animals↗
PubMed1986

Pumped intravenous insulin in experimental diabetes.

We infused experimentally diabetic animals continuously with exogenous insulin for periods of up to 324 days. Direct intravenous infusions from a prototype of an implantable device were used to explore whether this route can achieve repetitive control of fasting glycaemia within normal limits, here defined as being between 60 and 120 mg/dl. Fasting plasma glucose levels were controlled by simply adjusting the rate of exogenous insulin delivery when the observed level was outside the range of 100-120 mg/dl. An analysis of the results obtained indicated that 73% (427/591) of the fasting plasma glucose levels were within these normal limits. Remarkably, only 1% (6/591) of them were below 60 mg/dl, the lowest being 42 mg/dl. Hyperglycaemia above 150 mg/dl was seen in 11% (67/591) of the observations. However, all (6/6) of the hypoglycaemic episodes and most, 87% (58/67), of the hyperglycaemic episodes were of an accountable nature secondary to mechanical failures, electrical failures, methodologic or other problems encountered episodically during the long course of these studies. Two parallel control groups of experimentally diabetic animals received the same diet and were treated prospectively by daily subcutaneous injections for periods up to 224 days. The goal of this treatment was to attain metabolic control by either "conventional" or "intensified" injection methods. To these ends, fasting plasma glucose levels were measured on a daily basis (5 days/week) in both groups, and also at intervals postprandially in the intensively controlled group. These data were used to adjust insulin dosages. An analysis of the results indicated that only 24% (148/617) of the fasting plasma glucose levels were within the normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Biological effects of sulphated insulin in adipocytes and hepatocytes.

The binding affinity of sulphated insulin compared with unmodified, neutral insulin has been reported to be approximately four times lower in human and rat adipocytes but over twenty times lower in rat hepatocytes. In the present study the biological action of sulphated insulin was assessed in rat hepatocytes and human and rat adipocytes. To achieve half-maximal stimulation of fatty acid synthesis in rat hepatocytes about twenty one times higher concentrations of sulphated than neutral insulin were required (15.07 +/- 5.50 vs 0.71 +/- 0.34 nmol/l), this ratio being similar to the ratio of binding affinity in rat hepatocytes. In human adipocytes, half-maximal stimulation of initial rates of glucose uptake was observed at 11.6 +/- 5.1 vs 2.9 +/- 1.3 pmol/l for sulphated and neutral insulin respectively, and half-maximal inhibition of lipolysis at 31.0 +/- 13.5 vs 7.3 +/- 2.5 pmol/l respectively. These data are consistent with the four-fold lower binding affinity of sulphated insulin to human adipocytes. However, in rat adipocytes the biological potency of sulphated insulin was found to be much lower than anticipated from the binding data, half-maximal stimulation of initial rates of glucose uptake being observed at 757 +/- 299 vs 35 +/- 13 pmol/l respectively and half-maximal inhibition of lipolysis at 35.9 +/- 12.1 vs 1.5 +/- 0.5 pmol/l respectively. Thus, in rat adipocytes, approximately 22 times the concentration of sulphated insulin was required to achieve equivalent biological effect. A discrepancy between binding affinity and biological action with respect to sulphated insulin was identified in rat adipocytes but not human adipocytes nor rat hepatocytes suggesting differences in the binding-action linkage in these cells.

Adipose Tissue↗
PubMed1985

How laboratory dogs accommodate meals of different size but similar composition.

Healthy laboratory dogs appear to absorb a mixed meal from the gut at a constant rate. This rate is apparently not affected by meal size. If this is the case, then duration of absorption should depend on total or integrated meal size, whereas metabolite and hormonal levels would be independent of the number of feedings. To explore these hypotheses further, we compared the metabolite and hormonal responses with a single mixed meal and one divided in two halves, provided in two feedings 4 h apart. We detected no effect of the second meal in the metabolic response levels of glucose, lactate, pyruvate, alanine, free fatty acids, or 3-hydroxybutyrate or the hormonal responses of insulin, pancretic glucagon, gastrin, or secretin. Only minor differences were detectable in the hormonal response levels of pancreatic polypeptide, gastric inhibitory peptide, and enteroglucagon, consistent with a response to a second meal. We conclude that the observed change in circulating metabolite or hormone concentration is independent of the size of meal eaten, but the duration of the excursion depends on meal size. Thus, during the bulk phase of nutrient uptake, the absorption mechanism of the laboratory dog appears to be saturated.

Amino Acids↗
PubMed1985

Changes in blood amino acids account for the insulin and glucagon responses to mixed meals in dogs.

The relationships between changes in the plasma levels of immunoreactive insulin (IRI) and glucagon (IRG) in response to the postprandial increments of circulating amino acids were studied under normal physiological conditions in healthy dogs. In the presence of a unique postprandial physiological euglycemic "glucose clamp" which occurs in these dogs, plasma IRG rose to an earlier peak than IRI and both remained elevated for 16-19 hr. Amino acid (AA) profiles also showed postprandial incremental responses for up to 16 hr. Multiple correlation analyses indicated that only branched chain AAs were significantly correlated with IRI profiles and were devoid of a relationship to IRG. Similarly, only ornithine, lysine and glycine were significantly correlated with IRG profiles and devoid of a relationship to IRI. The significance of individual IRG stimulating effects of alanine and arginine were masked by other amino acid interactions, as significant intercorrelation was found among all 13 amino acids. Two equations were derived from the multiple regression analysis accounting for the postprandial time course of changes in IRI and IRG levels with only 5 amino acid concentrations: (1) (delta IRI) = 0.37 (delta Leu) -0.45(delta His), and (2) (delta IRG) = 0.55(delta Orn) + 0.37(delta Gly) -0.69 (delta Ser). These observations confirm the physiologic role in islet hormone secretion of the postprandial increments in circulating amino acids in the absence of glycemic change.

Amino Acids↗