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Biomedical subjects

T Deckert

Publications and source records attributed to T Deckert.

At least 109 records · Page 6Linked to original sources

Absorption of isophane (NPH) insulin and its clinical implications.

Absorption of 125I-NPH insulin (125I-isophane insulin) (40 IU/ml) was studied in eight diabetics given 50% and 150% of their normal daily dose of insulin. Insulin absorption correlated with plasma insulin (r = 0.97, p less than 0.001) and blood glucose (r = -0.87, p less than 0.01) concentrations. Absorption was slower at higher doses, so that trebling the insulin dose only doubled the amount absorbed over the first 24 hours. The plasma elimination half time (t12) of insulin was about five minutes. Thus, the disappearance of radiolabelled insulin is a reliable and quantitative index of insulin absorption; subcutaneous degradation, if present, is minimal and constant. Changes in dise of intermediate-acting insulin further increases the large variation in insulin absorption. This implies that minor adjustments of intermediate insulin dosage are probably futile.

Absorption↗

Diet versus average Danish food in insulin-dependent diabetes mellitus. An evaluation during treatment with an artificial betacell.

Ten randomly selected insulin-dependent diabetics with minimal betacell function were studied during treatment with an artificial betacell during two consecutive 24-hour periods. Patients were randomly served diabetic diet for one 24-hour period and average Danish food during the other 24-hour period. No significant (P greater than 0.05) difference was found between the mean blood glucose concentrations, nor insulin requirements on average Danish food compared to diet. However, the mean amplitude of glucose excursions was significantly higher on average Danish food than on diabetic diet (median 3.6 versus 2.7 mmol/l, P less than 0.05). Thus insulin-dependent patients not following their diabetes diet will show increased blood glucose fluctuations.

Adolescent↗

Absorption of NPH-insulin from subcutaneous tissue: a methodological study in pigs.

To elucidate the validity of the indirect method of following insulin absorption from the subcutaneous tissue, i.e. external counting of injected 125-I insulin, the disappearance of 125-I NPH insulin from subcutaneous tissue was measured by a biotelemetric method (external measurement of radioactivity) and by direct determination of radioactivity and insulin in subcutaneous tissue extracted one to 300 min. after injection of 8 units 125-I NPH porcine insulin, 5 mm beneath the surface of the skin in 6 anaesthesized pigs. Furthermore, the appearance of insulin in arterial plasma was measured after inhibiting the endogenous insulin secretion of the pigs by epinephrine and propanolol. The disappearance of radioactivity measured continuously for 5 hours was of first order kinetics with t1/2=462+/-36 min. (mean+/-S.E.M.). The half-life of the injected depot of radioactivity (t1/2) demonstrated a large intra- as well as interindividual variation as seen in diabetics. In tissue extracts a highly significant (2P less than 0.001) correlation was found between radioactivity and insulin (r=0.93), indicating the radioactivity to be representative of insulin. During gel chromatography on Sephadex G 50 M only one peak of radioactivity was seen in all tissue extracts. 300 min. after NPH-insulin injection, however, the specific radioactivity of insulin was significantly higher (2P less than 0.05) than in tissue extracts sampled one min. after NPH insulin injection, indicating a slight accumulation of non-immunoreactive insulin degradation products. A fair correlation (r=0.75, 2 P less than 0.05) was seen between the disappearance of externally measured radioactivity or insulin from tissue extracts and the appearance of insulin in plasma. It is concluded that the insulin absorption coefficient is a relevant and biologically sensible expression of insulin absorption.

Absorption↗

Diurnal pattern of insulin requirements in insulin-dependent diabetics.

A total of 35 experiments in which insulin-dependent diabetics were connected to an artificial beta cell (Biostator) for feedback control of blood glucose during at least 24 h, were evaluated. Only 14 experiments, however, were available for analysis, since interruptions of more than 45 min/24 h in feedback control due to clots in analyser tubing occurred in those remaining. In these 14 experiments the 24-h insulin-infusion pattern was analysed. Basal insulin requirements (BIR), (between 01.00 and 04.00 hours) was found to be 0.178 +/- 0.044 (SD) mU/kg X min. Insulin requirements increased in the early morning (04.00-07.00 hours) to 0.231 +/- 0.084 mU/kg X min (P less than 0.01). A significant correlation between BIR and 24-h insulin requirement was found (r = 0.53, P less than 0.05). Insulin requirements per kJ following breakfast were higher than after lunch, 0.57 +/- 0.20 muU/kg X min X kJ versus 0.41 +/- 0.29 muU/kg X min X kJ (P less than 0.05).

Adult↗

[The prognosis of insulin-dependent diabetes mellitus].

The prognosis of juvenile-dependent diabetics is characterized by an overmortality of 600 per cent. The quality of life is reduced, too, since about 15 per cent of the patients with a diabetes onset before the age of 31 will become blind, 10-15 per cent will become amputated on calf or thigh and 20-30 per cent will develop uraemia. A highly significant increased survival was seen in patients, who were controlled 4 to 5 times a year at the diabetic out-patient clinic. Death from ketoacidosis, hypoglycaemia, and suicide was significantly higher in the group not referred for out-patient control, and death by uraemia occurred earlier in this group. Juvenile diabetics with long-standing diabetes and persisting and endogenic insulin secretion had significantly less severe retinopathy and nephropathy than comparable patients without endogenous insulin secretion, and survival of juvenile diabetics with clinical indications of persisting endogenous insulin secretion seems not to be different from non-diabetics. It is concluded that more should be done to motivate patients for self-care and to preserve remaining insulin producing cells in insulin-dependent diabetics.

Adolescent↗

Diabetic nephropathy: fault or destiny?

Twenty-one young onset Type 1 (insulin dependent) diabetics who developed severe diabetic nephropathy after 14.5 +/- 3.3 years (mean +/- SD) and 21 age and sex matched Type 1 diabetics without evidence of nephropathy after more than 32 years of disease were compared with particular reference to body build, insulin requirements, stability of diabetes, heart rate and blood pressure before the development of nephropathy. Attempts were made to evaluate the quality of metabolic control during the first 20 years of diabetes from more than 1,600 out-patient measurements of blood and urinary glucose in each group. The renal tubular reabsorption capacity for glucose was calculated in both groups. No differences between the two groups were found for any of the parameters examined, except that the frequency of ketoacidosis was higher in the patients who developed nephropathy. It is concluded that many Type 1 diabetics seem to be protected against the deleterious effect of diabetes on the kidney. The nature of the protecting factors is unknown.

Adolescent↗

Stimulatory effect of serum from diabetic patients on insulin release from mouse pancreatic islets maintained in tissue culture.

Islets of Langerhans from NMRI-mice were kept for one week in tissue culture in medium supplemented with human serum obtained from either normal healthy subjects or newly diagnosed juvenile diabetic patients before insulin treatment. Islets cultured in diabetic serum released more insulin than islets cultured in normal serum, whether tissue culture medium 199 with 5.5-8.3 mmol/l glucose and 10% serum, or culture medium RPMI 1640 with 11 mmol/l glucose and 0.5% serum were used. Islets kept for one week in culture with diabetic serum did not show any decrease in DNA content or glucose induced insulin secretion and biosynthesis. It is concluded that serum from newly diagnosed insulin-dependent diabetic patients stimulates insulin release from isolated mouse islets kept in tissue culture. The underlying mechanism is unknown.

Animals↗

Comparison of 24-hour insulin requirements in IDDM patients during control by an artificial betacell and during conventional therapy.

Insulin requirements were measured over 24 hours during feed-back control by an artificial betacell (Biostator) in 25 lean insulin-dependent diabetics with no endogenous insulin secretion. The set of constants selected for the algorithms was that which resulted in the minimum insulin infusion consistent with normal glucose tolerance during an OGTT. The results were compared with the daily dose of insulin chosen, using standard clinical criteria, by physicians with no knowledge of the experimental results. Plasma IRI remained within the normal range during Biostator control, and the insulin dose given over 24 hours was almost identical - 101 +/- 9% with that selected on clinical grounds. The reproducibility of insulin requirements established with the Biostator was tested over two consecutive days in nine patients; all required an increased amount of insulin (mean + 6.9%, range + 0.5 to + 12.2%) on the second day.

Adolescent↗

An artificial betacell: assessment of the glucose analyser, infusion system and optimization of constants for the algorithms.

The glucose analyser and insulin infusion modules of the Biostator were tested. The infusion system was reliable since more than 99% of the computed volume of insulin solution was delivered by the infusion pump at infusion rates above 1/100 of maximum, and no insulin was adsorbed onto infusion bags or tubing. Blood glucose results from the Biostator were compared with routine laboratory methods during long-term feedback control. Both slope (0.73) and scatter (r=0.87) around the regression line were unsatisfactory when the recommended calibration procedure was used. Tests in fasting non-diabetic subjects showed a significant correlation between the variation in Biostator glucose read-out and the plasma protein concentration in the detector outflow. In diabetics the ratio between Biostator glucose read-out and laboratory glucose determinations declined significantly with time. These observations led to the introduction of a standardization procedure based on externally determined blood glucose concentrations. During long-term feedback experiments in diabetics this procedure resulted in a significant increase in slope (0.84) but no improvement in scatter around the regression line. Repeated OGTTs revealed a set of constants for the algorithms, which enabled normal glucose tolerance to be achieved with smaller amounts of insulin.

Adolescent↗

24-hour blood glucose profiles in insulin-dependent diabetics treated with intravenous insulin infusion systems. A comparison between closed- and open-loop systems.

The aim of this study was to compare the 24-hour blood glucose profiles of insulin-dependent diabetics during treatment with preprogramed insulin delivery systems with those of patients on treatment with the artificial beta cell (Biostator). Mean blood glucose (MGB) was 4.4 +/- 0.5 mmol/l for 15 controls, 5.8 +/- 1.0 for 53 patients on open-loop and 6.0 +/- 0.6 for 20 patients on closed-loop treatment. MBG was significantly higher in diabetics than in non-diabetic, but the difference between the two diabetic populations was not significant. Mean amplitude of blood glucose excursion was 1.8 +/- 0.6, 4.3 +/- 1.3 and 3.5 +/- 0.8 mmol/l respectively, the difference between the diabetic groups being significant. No hypoglycemia was seen in patients during closed-loop treatment, whereas this was the case in 10 of 53 patients on treatment with open-loop systems. Physical exercise resulted in small but normal decreases in blood glucose without hypoglycemia. Plasma insulin was within the normal range during both regimes. It is concluded that blood glucose control during treatment with closed-loop system is superior to that during treatment with open-loop systems. However, under standard conditions i.v. insulin infusion with preprogramed pump devices resulted in blood glucose fluctuations comparable with those during Biostator treatment.

Adolescent↗

Comparison of intraperitoneal, intraportal and intravenous insulin infusion.

In order to avoid complications induced by long-term infusion of insulin into the portal vein, we examined the effect of intraperitoneal (ip) insulin infusion on arterial plasma insulin and glucose concentrations in 6 pigs, made diabetic by a constant intravenous (iv) infusion of glucose, epinephrine and propranolol. Insulin was infused by an electromechanical programmable mini-pump (Pharmaject Micro Infusion System, Pharmacia Electronics) as a booster injection of 46 mU highly purified porcine insulin Leo/kg body weight, followed by 3 infusion periods of 30 min each with stepwise decreasing rates of 1.6--0.8 and 0.2 mU/kg/min in a total volume of 192 microliters. Insulin was infused in a peripheral vein, a portal vein and into the peritoneal cavity. A steep rise of arterial plasma insulin was demonstrated followed by a slow and identical decline in the peripheral and portal experiments, whereas only a small increase of plasma insulin was seen in the ip experiment, indicating insufficient absorption of insulin from the peritoneal cavity. The decrease of plasma glucose was identical in the peripheral and portal vein experiments, indicating that insulin infused in the portal vein does not seem to have a higher hypoglycaemic effect, than insulin infused in a peripheral vein. Intraperitoneal insulin infusion seems not to be a practical substitute for iv insulin infusion.

Animals↗

The influence of supervision and endogenous insulin secretion on the course of insulin-dependent diabetes mellitus.

In order to study the importance of out-patients' supervision on survival, a prospective study of 1061 juvenile diabetics was performed. After the first hospitalization at the Steno Memorial Hospital 5.3 +/- 4.5 years after the onset of diabetes, this population of diabetics was divided into two comparable groups by their own practitioners. One group (n = 525) was referred for further out-patient supervision to the out-patient clinic, the other group (n = 536) was not. 96.7% of the patients were followed at least 25 years. A highly significant increased survival was seen in patients seen in 4-5 times a year at the diabetic out-patient clinic. Death from ketoacidosis, hypoglycemia, and suicide was significantly higher in the group not referred for further out-patient control, and death in uremia occured earlier in this group. Juvenile diabetics with long-standing diabetes and persisting endogenous insulin secretion evaluated on the basis of C-peptide examination had significantly less severe retinopathy and nephropathy than comparable patients without endogenous insulin secretion, and survival of juvenile diabetics with clinical indications of persisting endogenous insulin secretion seems not to be different from non-diabetics.

Adolescent↗