[4-years experience with quality control of decentralized reflectometry blood glucose measurement in the Vienna-Lainz hospital]. / 4 Jahre Erfahrung mit der Qualitätskontrolle der dezentralen reflektometrischen Blutzuckermessung im Krankenhaus der Stadt Wien-Lainz.

Since 1987 a quality control programme for ward-based blood glucose assays has been established in Lainz Hospital, Vienna. In 1991 following a decision to standardise the type of reflectometer used in the ward, 62 Reflolux IIS reflectance meters (Boehringer Mannheim) were assessed in a quality control consisting of 4 ring trials a year (blood glucose determination in two "unknown" samples) and in daily measurements of control solutions of known glucose concentrations. Experience with this quality control procedure is reported in this presentation of the relevant results of the ring trials. The most frequent errors in performing the test are discussed and the importance of instructing and training the nursing staff in the proper use and maintenance of the meters is pointed out.

[ExacTech--a new measuring system for personal control of blood glucose]. / ExacTech--ein neues Messsystem zur Blutzuckerselbstkontrolle.

ExacTech is a pen-sized glucose meter that uses an amperometric principle for blood glucose determination. Accuracy was assessed in 94 capillary blood samples by comparing the ExacTech values to the hexokinase method. Correlation between the methods was 0.983. 76% of ExacTech measurements were within +/- 10% of the reference method. Coefficients of variation for within run precision determined in two different blood glucose levels were 3.2% (81 mg/dl) and 4.2% (222 mg/dl) resp. 12 diabetic patients compared ExacTech to their reflectance meters. The ExacTech readings when correlated with the hexokinase method gave slightly better results than those obtained with common glucose meters. Patients acceptability of this novel measuring system was excellent.

[Comparison of the accuracy and precision of 7 reflectometers in self-control of blood glucose]. / Vergleich von Richtigkeit und Präzision bei 7 Reflektometern zur Blutzuckerselbstkontrolle.

7 types of reflectance meters (Hypocount GA and MXB, Glucometer II and M, Petita B and B II, Reflolux II) were tested for accuracy and for within-run precision. To test the accuracy blood sugar was measured in 30 venous blood samples in the blood glucose ranges from 30 to 70, 71 to 180 and 181 to 300 mg/dl resp. on 4 instruments of each meter-type and by the hexokinase method as a reference method. With Hypocount MXB and Glucometer II great differences between correlation coefficients within the 4 instruments occurred. In the low blood glucose range all meters correlated best with the hexokinase method whereas poorer results were obtained in the low and the high glucose range. As regards the mean percental deviation, Reflolux II correlated closely with the reference method in the blood glucose range from 30 to 70 mg/dl, Hypocount MXB in the range from 71 to 180 mg/dl and Petita B in the range from 181-300 mg/dl. The greatest differences were found with both types of Hypocount- and Petita-meters in low blood sugar levels. With none of the tested meters a linear correlation with the hexokinase method was observed over the whole blood glucose range. Coefficients of variation for within-run precision ranged from 1.9% (Reflolux II) to 8.1% (Hypocount GA) depending on blood glucose concentration.

No sign of amyloidosis in pump-treated diabetics.

Serum concentrations of amyloid A (SAA) and C-reactive protein (CRP) were measured in 122 diabetic patients treated by continuous insulin infusion, 40 patients receiving conventional injection therapy and in 28 healthy controls. Of the patients on pump therapy, 63 had an implanted, constant basal rate device (36 i.p., 27 i.v.) and 59 extracorporal, portable programmable pumps (8 i.p., 3 i.v., 48 s.c.). SAA and CRP-values did not significantly differ between the diabetics, irrespective of the method of insulin substitution used, and the healthy controls. Elevated SAA-levels were either associated with raised CRP, indicating a non-specific acute phase reaction, or were markedly diminished or normalized in a six-month follow-up, in spite ongoing pump therapy. Increased SAA-concentrations did not correlate with sex or age of patients, diabetes duration, diabetes type, duration of pump treatment, route of insulin, insulin preparation, catheter material and pump model, indicating that pump treatment does not stimulate a specific amyloidogenic reaction.

[New instrument for blood glucose determination. Results of a clinical trial of the Reflocheck]. / Neues Gerät zur Blutglucosebestimmung. Ergebnisse der klinischen Erprobung von Reflocheck.

Reflocheck, a new microprocessor-regulated apparatus determining blood sugar levels was tested in six laboratories. In the range of 20-450 mg/dl the apparatus gave precise results (co-efficient of variance 0.8%-6.4%), in good agreement with results by the hexokinase method. Reflocheck is an accurate and reliable instrument for the measuring of blood glucose levels.

Lipid-lowering effect of the new drugs eniclobrate and beclobrate in patients with hyperlipidemia type II a and type II b.

First clinical results are presented for two newly developed drugs. Both are diphenylmethane derivatives named ethyl-(+/-)-2-([alpha-(p-chlorophenyl)-p-tolyl]-oxy)-2-methylbutyrate (beclobrate, B) and (+/-)-2-(4-[(4-chlorophenyl)methyl]phenoxy)-2-methyl-butanacid-3-pyridinylmethylester (eniclobrate, E). These drugs were given in a doubleblind crossover trial with placebo periods before, in between and afterwards to 6 patients with type IIb and 13 patients with type IIa hyperlipidemia. Beclobrate was given in a dosage of 100 mg twice daily and eniclobrate in a dosage of 130 mg twice daily. Besides effectively reducing LDL-cholesterol in type IIa there was a remarkable increase in HDL-cholesterol in both types of hyperlipidemia especially for beclobrate.

[Comparison of glibenclamide, gliquidone, glisoxepide and placebo in maturity onset diabetics of differing degrees of severity (author's transl)]. / Vergleich von Glibenclamid, Gliquidon, Glisoxepid und Plazebo an Erwachsenendiabetikern mit unterschiedlichem Schweregrad des Diabetes.

The purpose of the study was to investigate whether the potency of effect on the beta cell differs with type of sulfonylurea (SU) and with degree of severity of diabetes. 12 maturity onset diabetics were classed according to fasting blood glucose (FBG) in three groups of 4 patients each. Each patient served as his own control. Glibenclamide, Gliquidone, Glusoxepide and placebo were administered in random order with degree dosage adjusted according to degree of severity of diabetes. All patients were given a standardized diet with 150 g carbohydrates per day. Fullday profiles of blood glucose, insulin, C-peptide and sulfonylurea level in serum were made on the third day under each preparation. Results showed that with proper nutrition and sufficient weight reduction, patients in group I (FBG 80--130 mg/dl) needed no oral medication and in fact showed a tendency towards hypoglycaemic episodes under oral therapy. In group II (FBG 130--200 mg/dl) the effect of nutrients on beta cell secretion appeared to be both enhanced and accelerated by SU administration. Satisfactory metabolic control was achieved with SU, but not with placebo. This group seems to represent the type of patient most likely to benefit from SU therapy. In spite of high dosage levels, satisfactory control was not achieved with SU in any patient in group III (FBG greater than 200 mg/dl). Depending on individual factors such as ketosis-proneness, vascular complications, age and psycho-social aspects, insulin administration should be considered for these patients. There were not differences between the individual SU preparations in the parameters studied. There was insufficient evidence for a pharmacokinetic differential diagnosis.

[Blood sugar self-profiles. Improvement in diabetes control in outpatients (author's transl)]. / Blutzuckerselbstabnahme. Verbesserung der Diabeteseinstellung durch ambulante Tagesprofile.

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.

Treament of biguanide-induced lactic acidosis with dichloroacetate. 3 case histories.

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.

[Biguanide-induced and - associated lactic acidosis: serum and tissue biguanide levels in hyperlactaemia and lactic acidosis (author's transl)]. / Biguanid-induzierte und Biguanid-assoziierte Laktazidose. Serum- und Gewebsspiegel der Biguanide bei Hyperlaktämie und Laktazidose.

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.

[The risk of lacticate acidosis: a comparison of the 3 biguanides in treatment of diabetics (authors' transl)]. / Risiko zur Laktazidose? (Vergleich der 3 Biguanide an Diabetikern).

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 cases of fatal lactic acidosis during biguanide therapy (author's transl)]. / Vier tödliche Laktazidosen unter Biguanidtherapie.

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.

[Suppressive effect of somatostatin on secretin-CCK-PZ-stimulated endocrine and exocrine pancreatic function in man (author's transl)]. / Suppression der endokrinen und exokrinen Pankreasfunktion durch Somatostatin beim Menschen unter Stimulation durch Sekretin und Cholezystokinin-Pankreozymin.

With a view toward the therapeutic use of somatostatin in the treatment of acute pancreatitis, a preliminary investigation was conducted with 6 healthy volunteers, in which the suppressive effect of somatostatin on endocrine and exocrine pancreatic function was observed. A 30-minute baseline measurement period was followed by the administration of cyclic somatostatin (100 microgram by i.v. injection plus a 90-minute infusion at a rate of 200 microgram/hr). After the first 45 minutes of this infusion secretion was submaximally stimulated by the infusion of secretin-cholecystokinin-pancreozymin (CCK-PZ) (75 U each), over two hours. No decrease was observed in basal bicarbonate or enzyme concentration under somatostatin administration alone. However, secretion did not show the usual steep rise after the commencement of stimulation. After the somatostatin infusion was stopped, i.e. under secretin-CCK-PZ alone, a significant increase occurred in the values of secretin-induced volume, bicarbonate concentration and total bicarbonate contents of the duodenal aspirate, as well as in CCK-PZ-induced enzyme secretion. The release of insulin, both basal and stimulated, was also significantly decreased by somatostatin.