[Inpatient rehabilitation of diabetic patients--immediate metabolic effects]. / Stationäre Rehabilitation diabetischer Patienten--unmittelbare metabolische Effekte.

In 1981 the Rehabilitation Centre Laab (A-2381 Laab im Walde, Austria) had admitted a total of 1149 patients. These included 968 patients with diabetes mellitus (431 male, 537 female), of whom 428 (44.21 percent) had been insulin-dependent (IDDM) and 540 (55.79 percent) non-insulin-dependent (NIDDM). The mean blood glucose (MBG) levels present at the time of admission indicated that glycemic control was better in patients with IDDM than those with NIDDM. The poorest glycemic control was encountered in NIDDM of (A) age 31-40 (MBG = 187 mg/dl) and (B) over age 70 (MBG = 194 mg/dl); it had been possible in these patients to lower MBG to (A) 138 mg/dl and (B) 147 mg/dl. Juvenile IDDM patients (under age 30) had poorer glycemic control (MBG = 190 mg/dl) than the older IDDM patients (MBG = 181 mg/dl), and therapeutic success was greater in the latter group. Concluding from the glycohaemoglobin changes found, improvements in glycemic control were achieved in 35.32 percent (IDDM: 15.39 percent; NIDDM: 19.93 percent); in 62.08 percent (IDDM: 26.65 percent; NIDDM: 35.43 percent) it had remained unchanged, and had deteriorated in 2.16 percent (IDDM: 1.75 percent; NIDDM: 0.41 percent). For 13 patients treated so far by diet alone, oral medication had to be started; 2 patients (0.2 percent) required immediate introduction of insulin. In 126 patients (12.9 percent) on oral medication, insulin therapy had to be initiated, whereas in 32 cases (3.3 percent) oral medication was discontinued in favour of purely dietetic control.

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.

[Comparative double-blind investigation of bezafibrate and clofibrate in patients with primary hyperlipoproteinaemia]. / Vergleichende Doppelblinduntersuchung von Bezafibrat und Clofibrat bei Patienten mit rimärer Hyperlipoproteinämie.

The lipid-reducing effects of bezafibrate and clofibrate were investigated in a double-blind crossover trial. 3 x 200 mg/d bezafibrate and 3 x 500 mg/d clofibrate were administered for periods of 8 weeks each to 22 patients with primary hyperlipoproteinaemia (9 Type IIb, 13 Type IV). Placebo periods preceded and followed the periods of medication. Compliance was checked by determination of the serum concentrations of bezafibrate and clofibrate. As compared with the pre-therapy value under placebo, cholesterol was reduced by 14% with bezafibrate and 7% with clofibrate in the group as a whole. In Type IIb patients cholesterol was reduced by 16% with bezafibrate as against 10% with clofibrate, and in Type IV patients by 12% with bezafibrate and 6% with clofibrate. A similar response was found in triglyceride reduction: 36% vs. 18% for the group as a whole; 47% vs. 31% for Type IIb; and 29% vs. 9% for Type IV. The difference in triglyceride reduction for the group as a whole was significant at the p less than 0.05 level. Body weight, pulse rate, and blood pressure showed no changes during the entire period of investigation. Fasting blood glucose was somewhat lower under both substances than under the subsequent placebo period while urea-N and creatinine was increased for both as compared with both pre- and post-therapy placebo periods. Under bezafibrate there was an increase in CPK as compared with the second placebo phase. There were no changes in GOT and GPT. Reductions in gamma-GT, alkaline phosphatase, and bilirubin were observed under both bezafibrate and clofibrate, as were slight decreases in haemoglobin, erythrocytes, and leucocytes, and a small increase in thrombocytes. No changes in urinary excretion of protein or glucose were observed. No subjective side effects were reported, either for bezafibrate or for clofibrate.

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.

[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.

[No free water in the treatment of "hyperosmolar diabetic coma": treatment control by comparing serum and CSF (author's transl)]. / Kein freies Wasser bei der Therapie des "Coma diabeticum hyperosmolare"! Therapiekontrolle durch Vergleich von Serum und Liquor.

Some serum and CSF concentrations were measured in five patients with severe hyperosmolar coma (mean blood sugar = 58.9 mmol/l; osmolarity = 406 mosmol/l). A gradual decrease of serum osmolarity prevented the development of an osmotic gradient between CSF and extracellular space. Insulin treatment (1-20 IU/h) with a motor infusion pump and infusion of hypertonic solutions decreased serum osmolarity by 2-4 mosmol/l X h. The faster fall of glucose in the extracellular space was compensated by hypertonic saline infusions (up to 365 mosmol/l). All patients survived.

[Changes in glucose tolerance, serum insulin and blood lipids during contraceptive medication (oestrogen-gestagen) in metabolically-healthy women (author's transl)]. / Glukosetoleranz, Insulin und Blutlipide unter einem Ovulationshemmer bei stoffwechselgesunder Frauen

A low-dosage combination type of contraceptive (oestrogen-gestagen) was given to 19 metabolically- healthy women of normal weight over a period of 6 months. Glucose tolerance, serum insulin and serum lipids were measured 1 month before, during and 2 months after medication. There was a slight decrease in the basal insulin values and an opposite trend in the basal blood glucose values, not exceeding 10 mg% in comparison to pretreatment values. The oral glucose tolerance test with a load of 100 g oligosaccharides did not show any statiscally significant changes during the 9 month observation period. The serum insulin curve, however, showed a delayed increase with a tendency to return to original values after medication had stopped. A slight degree of insulin resistance without change in glucose tolerance can, therefore, be assumed. There was a tendency for triglyceride values to increase over the observation period. A trend towards decreased cholesterol, on the other hand, was statistically insignificant. The observed changes were all within the normal range in all cases.

[Investigations of the effect of midodrine on carbohydrate and fat metabolism with particular reference to the diabetic metabolic state (author's transl)]. / Untersuchungen über den Einfluss von Midodrin auf Kohlenhydrat-und Fettstoffwechsel mit besonderer Berücksichtigung der diabetischen Stoffwechselsituation

Midodrine, which is used in the treatment of hypotensive circulatory distrubances was investigated with respect to possible effects on carbohydrate and fat metabolism in 5 healthy subjects and 7 patients with disturbed glocuse tolerance. An i.v. glucose tolerance test was carried out on both groups and was repeated a few days subsequently with simultaneous administration of midodrine (5mg i.v.). Midodrine had no significant effect on glucose tolerance in either group, nor was there any significant effect of midodrine on FFA, serum insulin, triglyceride or cholesterol levels. 15 diabetic patients controlled by different therapeutic regimens (5 by diet only, 5 by oral preparations and 5 by insulin treatment) were given 3x5mg midodrine orally over a 5-day period and the effects on diabetic control and metabolic parameters compared with a 5-day pretreatment period without midodrine. Midodrine did not cause any change in the quality of diabetic control nor any significant alteration in serum lipid or uric acid levels.

Carbohydrate metabolism and hormonal replacement therapy: problems and clinical results.

Substitution treatment with a biphasic hormone combination (Cyclacur) was administered to twenty women in menopause. Nine of these had undergone hysterectomy and/or ovarectomy. The experimental cycle consisted of a daily dose of 2 mg estradiol valerianate as estrogen for 11 days, the identical dose of estrogen plus 0.5 mg dl-norgestrel as gestagen for 10 days, and a 7-day medication-free period. An initial placebo cycle was administered, followed by 7 experimental cycles and one final placebo cycle. Laboratory tests were carried out regularly. There were no significant changes during the investigation in serum lipids, blood sugar values, or serum enzyme tests used as parameters of hepatic function. Of the hematological parameters a moderate rise in hematocrit was observed. There was no change in serum protein-bound iodine.

Reduction of serum lipids by means of etiroxate (Liponorm).

Ten out-patients with primary Type IIa hyperlipoproteinemia and a further 10 with Types IIb, IV, and V were administered with DL-alpha-methyl-thyroxine ethyl ester (etiroxate) (20 mg twice daily) for an average of 308 days. The aim of the study was to determine the effects of the drug on the cholesterol and triglyceride levels, tolerance and side-effects, particularly in coronary patients. The T4 values rose in all but one patient and fell again when the drug was discontinued. In Type IIa patients cholesterol fell by an average of 75.5 mg/100 ml (20.6%) as compared with the period before treatment and normal triglyceride levels dropped by 17 mg/100 ml (12.6%). In Type IIb, IV and V patients cholesterol levels decreased by 69.1 mg/100 ml (21%) during treatment. Serum triglycerides, which in some patients were extremely high before treatment were only slightly affected, falling by an average of 165.3 mg/100 ml (22.8%). For the whole group of patients the fall in cholesterol during treatment was highly significant in comparison with the period before and after therapy, whereas the changes in the triglycerides were not significant. Only one patient had an increase in the frequency of angina pectoris attacks; another showed temporary restlessness and slies, were not observed. Red and white cell counts, differential blood count, thrombocytes, the transaminases SGOT, SGPT, alkaline phosphatase, bilirubin, urinalysis and erythrocyte sedimentation rate did not change during treatment. There was no lasting increase in pulse rate in any patient and no significant changes in systolic-diastolic blood pressure. ECG showed no rhythm disorders nor any other changes which were not present before treatment was initiated.

[Gynecological, hematological and metabolic studies during therapy with an estrogen-gestagen combination preparation]. / Gynäkologische, hämatologische und Stoffwechseluntersuchungen unter der Therapie mit einem Ostrogen-Gestagen-Kombinationspräparat

Twenty women after menopause were submitted to substitution treatment with a biphasic hormone combination (Cyclacur¿). Nine of these had undergone hysterectomy + ovarectomy. Through 11 days each of the women was administered a daily dose of 2 mg estradiol-valerianate as estrogen. Subsequently, for another 10 days each was given the identical dose of estrogen plus 0.5 mg DL-norgestrel as gestagen. Upon this followed an intermission of 7 days without any medication. After 1 cycle of placebo, 7 cycles of medication were followed by 1 cycle of placebo again with regular controls. Climacteric signs and symptoms were eliminated entirely. In those women without hysterectomy withdrawal-menorrhagia occurred promptly 2--3 days after discontinuing medication. During the entire period of investigation there was no significant change in serum lipids, blood sugar values, or serum enzyme tests used as parameter of hepatic function. As far as hematology is concerned there was a moderate rise of hematocrit. No change of serum protein-bound iodine was observed.