Preserved GLP-1 effects in a diabetic patient with Cushing's disease.

CONTEXT: A patient with diabetes mellitus, who participated in a study with intravenous administration of GLP-1, was later found to have Cushing's disease (markedly elevated 24 h urinary cortisol excretion and inadequate suppression of fasting cortisol with 2 mg dexamethasone). His diabetic state disappeared (2 h plasma glucose after 75 g oral glucose 159 mg/dl=IGT) after successful pituitary surgery (normal 24 h urinary cortisol excretion and adequate cortisol suppression with 2 mg dexamethasone). OBJECTIVE: The present analysis was undertaken to compare GLP-1 actions on fasting glycemia in diabetes mellitus due to Cushing's disease with GLP-1 actions in typical type 2 diabetes. DESIGN AND METHODS: GLP-1 (1.2 pmol/kg/min) and placebo had been infused into ten patients with diabetes mellitus over 4 h in the fasting state. The results from the patient with Cushing's disease (C) were compared to the data from the remaining nine patients with type 2 diabetes (D). RESULTS: Within 4 h glucose decreased from basal (C: 12.9; D: 12.9+/-0.7 mmol/l) to normal fasting values (C: 5.0; D: 4.9+/-0.4 mmol/l). The stimulation of insulin secretion and suppression of glucagon secretion was similar in the patient with Cushing's disease compared to those with type 2 diabetes. CONCLUSIONS: The insulinotropic, glucagonostatic and glucose-lowering actions of GLP-1 in a patient with diabetes mellitus due to cortisol excess were similar to actions in typical type 2 diabetes. Therefore incretin mimetics might be a novel therapeutic strategy for the treatment of glucocorticoid-induced diabetes mellitus.

Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients.

OBJECTIVE: Glucagon-like peptide I(7-36) amide (GLP-1) is a physiological incretin hormone that, in slightly supraphysiological doses, stimulates insulin secretion, lowers glucagon concentrations, and thereby normalizes elevated fasting plasma glucose concentrations in type II diabetic patients. It is not known whether GLP-1 has effects also in fasting type I diabetic patients. RESEARCH DESIGN AND METHODS: In 11 type I diabetic patients (HbA1c 9.1 +/- 2.1%; normal, 4.2-6.3%), fasting hyperglycemia was provoked by halving their usual evening NPH insulin dose. In random order on two occasions, 1.2 pmol . kg-1 . min-1 GLP-1 or placebo was infused intravenously in the morning (plasma glucose 13.7 +/- 0.9 mmol/l; plasma insulin 26 +/- 4 pmol/l). Glucose (glucose oxidase method), insulin, C-peptide, glucagon, GLP-1, cortisol, growth hormone (immunoassays), triglycerides, cholesterol, and nonesterified fatty acids (enzymatic tests) were measured. RESULTS: Glucagon was reduced from approximately 8 to 4 pmol/l, and plasma glucose was lowered from 13.4 +/- 1.0 to 10.0 +/- 1.2 mmol/l with GLP-1 administration (plasma concentrations approximately 100 pmol, P < 0.0001), but not with placebo (14.2 +/- 0.7 to 13.2 +/- 1.0). Transiently, C-peptide was stimulated from basal 0.09 +/- 0.02 to 0.19 +/- 0.06 nmol/l by GLP-1 (P < 0.0001), but not by placebo (0.07 +/- 0.02 to 0.07 +/- 0.02). There was no significant effect on nonesterified fatty acids (P = 0.34), triglycerides (P = 0.57), cholesterol (P = 0.64), cortisol (P = 0.40), or growth hormone (P = 0.53). CONCLUSIONS: Therefore, exogenous GLP-1 is able to lower fasting glycemia also in type I diabetic patients, mainly by reducing glucagon concentrations. However, this alone is not sufficient to normalize fasting plasma glucose concentrations, as was previously observed in type II diabetic patients, in whom insulin secretion (C-peptide response) was stimulated 20-fold.

Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients.

Glucagon-like peptide 1 (GLP-1) (7-36 amide) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations. Previous work has shown that even in Type 2 (non-insulin-dependent) diabetic patients GLP-1 (7-36 amide) retains much of its insulinotropic action. However, it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control. Therefore, in 10 Type 2 diabetic patients with unsatisfactory metabolic control (HbA1c 11.6 +/- 1.7%) on diet and sulphonylurea therapy (in some patients supplemented by metformin or acarbose), 1.2 pmol x kg-1 x min-1 GLP-1 (7-36 amide) or placebo was infused intravenously in the fasting state (plasma glucose 13.1 +/- 0.6 mmol/l). In all patients, insulin (by 17.4 +/- 4.7 nmol x 1-1 x min; p = 0.0157) and C-peptide (by 228.0 +/- 39.1 nmol x 1-1 x min; p = 0.0019) increased significantly over basal levels, glucagon was reduced (by -1418 +/- 308 pmol x 1-1 x min) and plasma glucose reached normal fasting concentrations (4.9 +/- 0.3 mmol/l) within 4 h of GLP-1 (7-36 amide) administration, but not with placebo. When normal fasting plasma glucose concentrations were reached insulin returned towards basal levels and plasma glucose concentrations remained stable despite the ongoing infusion of GLP-1 (7-36 amide). Therefore, exogenous GLP-1 (7-36 amide) is an effective means of normalizing fasting plasma glucose concentrations in poorly-controlled Type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

About the possibilities of registration of drug influence by means of radiocardiographic function analysis.

Changes in cardiac dynamics were analyzed by means of radiocardiographic function analysis under an infusion of epinephrine using the method of RAB. Typical changes in heart rate, stroke volume and blood pressure were observed after the application of epinephrine. Compared to examinations under physical exercise in case of healthy control subjects there was no typical decrease of enddiastolic volume dependent on the heart rate. Ejection time and ejection velocity was placed within the variation compared to values of a control group under physical exercise but there was a steeper increase of the curve under the effect of epinephrine. Under the influence of Solcoseryl no significant change could be observed in this series of tests compared to the basic values. The effect of epinephrine was changed by Solcoseryl in the way of an essentially smaller rise in heart rate and of a definite prolongation in diastolic time. A change in ejection time under the influence of epinephrine after the application of Solcoseryl could not be found. This allows the conclusion, that under the influence of Solcoseryl and after the administration of epinephrine better conditions for the metabolic restitution of heart muscle are given and consequently a direct effect of Solcoseryl on the heart muscle can be assumed.

Estimation of cardiac function by means of radiocardiographic function analysis.

The radiocardiographic function analysis represents a relatively simple procedure for the clinician to collect information concerning the changes of cardiac dynamics. The advantage of this method is to register non-invasively changes in cardiac dynamics at rest and during exercise such as those of enddiastolic volume, stroke volume, endsystolic volume, ejection time and filling time, and to permit the calculation of mean ejection velocity, etc. After insertion of a cardiac catheter, it is possible to record the corresponding pressure pulse in the right ventricle or in the pulmonary vessels simultaneously.

[The influence of the plasmaexpander hydroxyethyl starch on the serological blood grouping tests as compared to dextran 60 and whole blood (author's transl)]. / Der Einfluss des Plasmaexpanders Hydroxyäthylstärke auf die die blutgruppenserologischen Bestimmungen im Vergleich zu Dextran 60 und Vollblut

The influence of HES on serological blood grouping (ABO. Rh. crossmatch) was tested in comparison with dextran. It was shown out that a previous volume substitution up to 20% did not influence the reading of blood grouping determination. Higher dilutions of blood led to rouleaux formation which however could be easily distinguished from agglutination by addition of isotonic saline solution. Crossmatching brings difficulties, as weak antibodies might be missed even using the AHG test due to too high a degree of dilution of the patient's serum by plasma expanders. Increasing the sensitivity be enzyme technics (Papain, Eldon) is not advisable as irreversible non-specific reactions can be found already at low degrees of volume substitution.