Biomedical subjects
Publications and source records attributed to H Kritz.
Portable insulin infusion pumps with simple or complex systems for controlling the insulin dose profile have provided new ways of treating diabetes. This paper described 2 1/2 years of experience with these so-called
This is a report of the implantation and first 100-day operation using a remote-controlled programmable insulin infusion device in an insulin-dependent diabetic. To prevent insulin aggregation, a special surface-active polymer developed by Hoechst AG, Frankfurt, was used as an additive. Implantation was completed on April 8, 1981, and good metabolic control was reached immediately and has continued to date (July 1981), with this unit providing the only source of insulin. There have been no hypoglycemic attacks. Patient acceptance is very good. The Siemens unit, PFA 01 (external) and DFA 01 (implanted) has proved reliable and precise.
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15 insulin-dependent diabetics who had been hospitalised for evaluation and modification of their treatment regimen were trained to take their own blood samples with 10 microliter glass capillaries. Blood sugar self-profiles were analysed from each patient twice in hospital and afterwards at home. Urine samples were also self-tested for sugar. The profiles were carried out reliably and seem to cause a minimum of trouble to the patient. This method of feedback, with comparison of blood and urine sugar values, increased the patient's understanding and ability to vary his own insulin dosis. The analysis of 3 daily profiles for each patient showed increasing improvement in metabolic control. This also increased motivation to keep to a regimen in which insulin dosage, physical activity, and nutrition are in balance. For the first time daily profiles were introduced which could be carried out under the normal conditions of the patient's daily life.
An investigation was carried out on 30 diabetic patients in an attempt to clarify the relationship between serum biguanide levels and raised lactate. No consistent relationship was demonstrable between the serum biguanide level, administered dosage and time of administration. There was also no correlation between biguanide and lactate increase. It is not justifiable to quote a specific serum level of biguanides in defining lactic acidosis. A causal association between biguanide medication and lactic acidosis seems to be possible only by determination of serum and tissue levels. Determination of biguanide levels was carried out in the serum and tissue of a patient who had died as a result of lactic acidosis after phenformin administration. While the serum levels were only slightly higher than the therapeutic range, both liver and kidney tissue showed highly toxic levels. Furthermore, the amount of biguanides in the body was calculated in another patient successfully treated for lactic acidosis after buformin therapy. A differentiation should be made between biguanide-induced and biguanide-associated lactic acidosis. In both forms serum levels can be within relatively low ranges. In the former condition, the biguanides alone are responsible for the development of lactic acidosis by blocking the respiratory chain. In the latter condition they aggravate an already existing pathological condition, and can, therefore, represent a lethal factor.
A portable insulin dosage-regulating apparatus (PIDRA) was used with five volunteer diabetic subjects for periods ranging from 1 wk to more than 3 months to explore the possibilities of achieving near normoglycemic control over long time periods with such an apparatus. PIDRA consists of a matchbox size pump with insulin reservoir and a pocket size electronic control box. It can infuse a preprogrammed basal rate of insulin plus externally manipulated supplementary doses in rectangular profiles. The quality of blood glucose control was monitored with the Miles Biostator and through self-testing by the patient in the outpatient phases. Under inpatient conditions, the relatively simple PIDRA insulin administration profile was almost as effective in achieving normoglycemia as the Biostator, and good control could be maintained over long periods of time. The apparatus allows considerably greater ease in variation of insulin dosage with less risk of hypoglycemic epidoses as compared with conventional subcutaneous injections. Several technical problems remain to be solved, but it is concluded that PIDRA represents a viable alternative as a means of achieving tight control, at least as a step toward the goal of an implanted glucose-contingent insulin infusion system.
A glucose-controlled insulin infusion system (Biostator) was used to determine patient insulin requirement for clinical evaluation of a portable pump system (technical development by Siemens AG). Results from 6 insulin-dependent diabetics with respect to quality of control, carbohydrate/insulin ratio, and insulin requirement are shown. Preprogrammed insulin infusion with the portable system was carried out for up to 117 days.
The use of an artificial pancreas for blood glucose monitoring and feedback correction for evaluation and improvement of subcutaneous insulin therapy facilitates the process of finding an optimal therapy regime for the individual patient. The frequency of hypoglycemic episodes can be reduced while maintaining good control, and hospital stays can be considerably shortened. This procedure is particularly useful in achieving tight control in pregnant diabetics.
The administration of dichloroacetate (DCA) in cases of biguanide-induced lactic acidosis (LA) improves pyruvate oxidation and therefore increases energy production from glucose. Preliminary results of treatment of LA in humans are reported. A continuous fall in pyruvate was observed in all 3 cases after administration of at least 20 g of DCA (4 g i.v. bolus, then continuously 12 g/h). In Case 1, in which no supplementary measures for controlling the acidosis were applied, the acidosis did not improve and the patient died. In Case 2, despite administration of tris-buffer and dialysis, pH-values could not be raised sufficiently. The production of hydrogen ions persisted and lactate continued to rise. This patient also died. Case 3 was admitted in the beginning stages of a phenformin-induced LA, and in this case therapy was successful. The decline in pyruvate was accompanied by a slow fall in lactate, and a further fall in pH was averted. The clinical condition of the patient improved markedly after i.v. administration of a total of 34 g of DCA.
A portable insulin infusion pump was used to achieve diabetic control over a period of 7 weeks in a juvenile onset-type diabetic. Insulin was infused at a basal rate and further doses could be triggered externally by the patient. Insulin requirement had been previously determined by means of an artifical beta-cell (Glucose Controlled Insulin Infusion System). This method of insulin administration resulted in a clear improvement in diabetic control. Some problems did arise in connection with materials from which the instrument and catheter were constructed. However, it was shown that a portable insulin pump can be used with out-clinic patients for a number of weeks and is also justified for at least certain cases.
Hyperlactaemia was induced by means of a standard exercise test in 10 diabetics receiving normal treatment with biguanides (either buformin, metformin, or phenformin) in combination with either a sulfonylurea or insulin. The treatment regimen was then continued without biguanides for 3 weeks and the exercise test was repeated at the end of this period. All 3 biguanide preparations induce hyperlactaemia in diabetics. Physical stress leads to an additional increase in lactate, which reaches pathological proportions. Discontinuation of biguanide treatment leads to a significant decrease in resting and stress values. In a comparison of the 3 biguanide products, phenformin induced significantly higher lactate values in response to exercise than buformin. Of the biguanides, phenformin appears to carry the greatest risk of causing hyperlactaemia in susceptible patients, induced by concurrent circumstances, with progression to severe lacticate acidosis. The special pharmacokinetic properties of phenformin and the 8-fold higher incidence of lacticate acidosis than under buformin or metformin therapy support this observation.
Four case reports of lactic acidosis occurring during biguanide treatment (2 with phenormin, 2 with buformin) are analysed. Three of the patients died in a toxic state of lactic acidosis, whilst the fourth patient survived lactic acidosis, but died 11 days later due to myocardial infarction. In spite of serum biguanide levels within the therapeutic range, one patient had highly toxic hepatic levels of phenformin (13,500 ng/g tissue). Two factors are essential for the treatment of lactic acidosis: 1. rapid diagnosis: history of biguanide intake; clinical symptoms; acid-base imbalance; rapid lactate determination to establish the diagnosis. 2. therapy: correction of acidosis, insulin and glucose; shock treatment; forced diuresis and/or haemodialysis. From the high numbers of biguanide-treated diabetics and the incidence of lactic acidosis in other countries it can be assumed that this toxic side effect of biguanide treatment occurs relatively frequently in Austria too, but remains largely undetected.
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The effect of guar mini-tablets (5 g t.i.d.) on carbohydrate and lipid metabolism of outpatients with overt diabetes mellitus with glycosuria (is greater than 5 g/24 h) was determined in an open-controlled, randomized, multicenter, crossover study. A 4-wk pretreatment period was followed by a 6-wk treatment period. The treatment period consisted of a 2-wk guar period (treatment period II), which was followed by the wash-out period. The other half of the patients received treatment in the reverse order. Out of 93 patient records, 79 (41 sulfonylurea [SU] and 38 insulin-treated) were suitable for statistical analysis. No relevant weight-reducing effect of guar could be found in both 2-wk treatment periods. At the end of treatment period II, the lowering of the 1-h postprandial values of blood glucose (SU 12%, insulin 10%), cholesterol (SU and insulin 25%) was significant after 2-wk of guar treatment compared with the wash-out period. No clinically relevant changes in the safety laboratory parameters were observed during guar treatment. Side effects were observed in 40 of the 93 patients included in the trial. Treatment had to be discontinued in 11% of the patients due to gastrointestinal side effects. On the basis of our results,guar treatment in combination with sulfonylurea and insulin can be recommended for the improvement of carbohydrate and lipid metabolism.