Biomedical subjects
M Eggstein
Publications and source records attributed to M Eggstein.
Hormonal counterregulation, symptom awareness, and neurophysiological function in type 1 diabetes during insulin-induced hypoglycaemia.
To evaluate a putative differential impact of human (HI) and porcine (PI) insulin on human brain function we examined 10 Type 1 (insulin-dependent) diabetic patients without any signs of sensory or autonomic neuropathy. The glucose clamp technique was applied to achieve stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol l-1 on two occasions with randomized and blinded allocation of either HI or PI. At each of the plateaus, symptom awareness, hormonal counterregulation, and neurophysiological functions (primary sensory information processing of the auditory and somatosensory system) were recorded. The effect of both types of insulin on glucose metabolism and counterregulatory hormone response was almost identical. Catecholamines increased (adrenaline p less than 0.05; noradrenaline p less than 0.02) during hypoglycaemia, independent of the type of insulin being used. Symptom awareness increased significantly during the fall of blood glucose concentration. This effect was more pronounced (total symptom score 26 vs 2, p less than 0.05) with PI, but only during developing hypoglycaemia (3.3 mmol l-1-plateau). For brainstem auditory evoked potentials and somatosensory evoked potentials, all individual and averaged latencies and corresponding amplitudes were within the normal range. No effect of insulin type or blood glucose concentration on neurophysiological measures could be detected. Our results suggest a differential impact of HI and PI on human brain function with regard to symptom awareness, but not hormonal counterregulation. This direct effect of insulin on central nervous function does not involve the afferent transmission in the auditory and somatosensory system.
Cognitive and psychomotor function during severe insulin-induced hypoglycaemia in insulin-dependent diabetic patients.
Cognitive and psychomotor function, hormonal counterregulation and symptom awareness during severe insulin-induced hypoglycaemia were evaluated in 10 insulin-dependent diabetic patients. The glucose-clamp technique (Biostator) was applied to achieve a stable hypoglycaemic (39 +/- 2 mg/dl) plateau. A battery of 7 neuropsychological tests and a standardized questionnaire assessing hypoglycaemia symptoms were administered during euglycaemia and hypoglycaemia. There was a significant increase in counterregulatory hormone response (cortisol, growth hormone, p less than 0.05). Every patient experienced symptoms during severe hypoglycaemia. Four patients, however, were not aware of this threatening metabolic state. There was a significant performance decrement in all but two neuropsychological tests (Aiming Center I, Aiming Center II, Line Tracing Errors, Reaction Time, p less than 0.01; Digit Symbol, p less than 0.05). Performance of simple motor tasks as well as cognitive tasks requiring complex discrimination deteriorated similarly. Furthermore, the patients' general well-being (subjective condition) worsened considerably. In conclusion, a significant impairment of neuropsychological functions emerged during severe hypoglycaemia in insulin-dependent diabetes mellitus, even in the face of adequate hormonal counterregulation, and did not always coincide with an appropriate patient awareness of the actual metabolic state.
Catecholamine response during human and pork insulin-induced hypoglycemia in IDDM patients.
OBJECTIVE: To evaluate the catecholamine response during human and pork insulin-induced hypoglycemia. RESEARCH DESIGN AND METHODS: Ten insulin-dependent diabetes mellitus (IDDM) patients without any signs of autonomic neuropathy received either human or pork insulin in a randomized crossover fashion on 2 nonconsecutive days. The glucose clamp technique was applied to achieve stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM. RESULTS: The effect of both types of insulin on glucose metabolism and circulating catecholamines was almost identical. There was a sharp rise of both epinephrine (P less than 0.05) and norepinephrine (P less than 0.02) during hypoglycemia, which did not depend on the type of insulin applicated. Symptom awareness increased significantly during the decrease of blood glucose concentration. Only during developing hypoglycemia (3.3-mM plateau), was this effect more pronounced (cumulative symptom score 2 vs. 26, P less than 0.05) with pork insulin. CONCLUSIONS: AN attenuated catecholamine secretion seems not to be the putative mechanism of a reduced awareness of human insulin-induced hypoglycemia.
Simple computer-assisted diagnosis of acute myocardial infarction in patients with acute thoracic pain.
In order to minimize the initial diagnostic uncertainty in patients suspected of having acute myocardial infarction, we prospectively extracted predictive variables from previous history, ECG, and clinical chemical parameters of 87 patients, who were admitted for acute thoracic pain. The variables thus extracted were: Thoracic pain in previous history, duration of pain, white blood cell count, blood glucose, creatine-kinase, and S-T elevation in the ECG. These parameters were used for formulating a mathematical model based upon univariate and multivariate statistical methods. The sensitivity of the model in the study population was 95% and the specificity 77%. Correct classification was achieved in 89% of cases. In a second phase, the prognostic index was prospectively evaluated in a second set of 122 consecutive patients. In this test population, the sensitivity was 89% and the specificity 86%. 87% of patients were classified correctly.
Increase in glucose consumption by acetylcysteine during hyperglycemic clamp. A study with healthy volunteers.
Thiols have been shown to be related to insulin secretion and to uptake of glucose into tissues. In the present study the effects of i.v. administration of acetylcysteine (N-acetylcysteine, NAC, CAS 616-91-1) on glucose consumption and plasma free thiols were studied in young healthy volunteers during hyperglycemic clamp. NAC (0.5-2.0 mg/kg) significantly increased glucose consumption. This effect was not obvious at higher doses of NAC. Plasma free NAC depended on the dose of NAC injected. The t1/2 of NAC was 11 min. NAC produced significant increases of plasma cysteine concentrations, and a slight but insignificantly increase of plasma glutathione. These data suggest that a moderate increase in plasma thiols augments glucose consumption during hyperglycemic clamp.
Selected ion monitoring gas chromatography/mass spectrometry using uniformly labelled (13C)glucose for determination of glucose turnover in man.
An optimized method is described for the mass fragmentographic determination of uniformly labelled (13C)glucose in human plasma using a butylboronic acid acetate derivative, and capillary gas chromatography. The advantages of the method are the ease and speed of the derivatization procedure, the small sample size, high precision (interassay coefficient of variation 5.7%), and applicability of a relatively low-cost mass spectrometer. This method allows glucose tracer experiments to be performed in man using the bolus injection technique, necessitating analysis of many samples. The results on glucose turnover obtained in a clinical experiment were in full agreement with previously published data.
Application of a new LDL apheresis system using two dextran sulfate cellulose columns in combination with an automatic column-regenerating unit and a blood cell separator.
Extracorporeal procedures for selective removal of low-density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column-regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous-flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57-year-old male with drug-resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4-5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A-I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug-resistant familial hypercholesterolemia without or with concomitant hypertriglyceridemia.
Different awareness of hypoglycaemia induced by human or purified pork insulin in type I diabetic patients.
Recently, there have been reports on a diminished awareness of hypoglycaemia after a switch from purified pork insulin (PPI) to human insulin (HI) in insulin-dependent diabetes mellitus (IDDM). To clarify this phenomenon we investigated nine IDDM patients without signs of autonomic neuropathy. After an overnight euglycaemic clamp, blood glucose was lowered to hypoglycaemic levels by means of an artificial pancreas (Biostator) on 2 days. Insulin was used in a double-blind, randomized, cross-over fashion, either PPI or HI. The symptomatology and the hormonal counterregulation of developing hypoglycaemia was recorded. Venous concentrations of free insulin, cortisol, glucagon, growth hormone and the prevailing blood glucose were similar under both insulins. Eight out of nine IDDM patients felt more symptoms and at a higher blood glucose concentration under PPI than under HI. The first symptom of developing hypoglycaemia appeared at a mean blood glucose concentration of 61.1 +/- 5.4 mg.dl-1 under PPI and 44.4 +/- 5.3 mg.dl-1 under HI respectively (P less than 0.05). We conclude that HI may cause symptoms of hypoglycaemia to appear later and with a lesser number in comparison to PPI.
Influence of breakfasts with different nutrient contents on glucose, C peptide, insulin, glucagon, triglycerides, and GIP in non-insulin-dependent diabetics.
To examine the influence of coingestion of fat and protein in a mixed meal on carbohydrate metabolism, subjects with non-insulin-dependent diabetes mellitus (NIDDM) received three different breakfasts varying in the amount of fat and protein (group 1) or only in the amount of fat (group 2). Compared with the changes after a standard breakfast, insulin increased after the protein-rich meal and decreased after the fat-rich meal in group 1. Glucose and gastric inhibitory polypeptide (GIP) remained constant. In contrast, only GIP showed a significant increase after a high-fat meal in group 2. Thus, in NIDDM subjects, glucose and insulin responses to different mixed meals do not appear to be exclusively mediated by GIP. Protein was confirmed as a potent stimulator of insulin secretion. Other factors, such as an altered beta-cell response in diabetics to GIP or other incretions, must be considered to explain the reported results.
Symptoms of hypoglycemia--a comparison between porcine and human insulin.
For more than 2 years now it has been controversially debated whether awareness of hypoglycemia is reduced when type I diabetic patients are switched from porcine to human insulin. In order to address this question, we studied nine C-peptide negative diabetics (age 27.6 years, Broca index 106%, duration of diabetes 5.7 years, HbA1, 8.8%) in comparison with eight healthy volunteers (age 22.4 years, Broca index 104%). Following euglycemic monitoring overnight, a controlled hypoglycemia was induced by altering the algorithms of the Biostator. This was done in a double-blind, cross-over fashion using porcine or human insulin on 2 nonconsecutive days. There were no differences between the results obtained with respect to the time course of the study, blood glucose, amount of insulin infused, and concentration of venous free insulin achieved. Of the nine diabetics, eight were aware of hypoglycemia at a higher blood glucose level under porcine insulin. The first symptom of hypoglycemia was perceived at a mean blood glucose level of 61.1 +/- 5.4 mg/dl under porcine insulin and of 44.4 +/- 5.3 mg/dl under human insulin (P less than or equal to 0.05). Thirty symptoms were noted under porcine insulin exclusively or preferentially as opposed to only eight which were observed exclusively or preferentially under human insulin. The healthy volunteers evidenced fewer symptoms at lower blood glucose concentrations than the diabetics. The clear difference between human and porcine insulin could not unequivocally be reproduced in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Urinary excretion patterns of endogenously produced alcohols in type 1 (IDDM) and type 2 (NIDDM) diabetes mellitus compared with healthy control subjects.
Urinary excretion patterns of various endogenously produced alcohols, such as ethanol, propanol, isobutanol, butanol, and isopentanol, were evaluated in 17 type 1 (IDDM) and 15 type 2 (NIDDM) diabetic patients, and in two different groups of healthy control subjects (n = 12, n = 8, respectively) matched for sex, age and weight. In addition to the urinary alcohol excretion determined by gas-chromatography and mass-spectrometry, four cardiovascular reflex tests were performed, and the motor and sensory conduction velocities of three different peripheral nerves were measured. In the type 1 diabetic patients, urinary excretions of ethanol and propanol were significantly higher than in the control subjects (P less than 0.0001, P less than 0.00001, respectively), whereas the control subjects exhibited significantly higher urinary excretion rates of the other three alcohols (P less than 0.007, P less than 0.02 and P less than 0.002, respectively) compared with the type 1 diabetic patients. In the type 2 diabetic patients, only the urinary excretion of propanol was significantly elevated (P less than 0.002) compared with the control subjects, while the urinary excretion rates of butanol and isopentanol were significantly lower (P less than 0.02, P less than 0.05, respectively) than in the controls. Urinary alcohol excretions were not related to diabetic peripheral neuropathy in both groups studied. The clinical meaning of the urinary excretion patterns of different endogenously produced alcohols in diabetes mellitus has to be further evaluated.
Insulin pens in elderly diabetic patients.
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Exercise and insulin requirements.
In order to facilitate the management of sports and work for insulin injecting diabetic patients we analyzed 6 different situations: 1) In the morning before injecting insulin stepwise increasing bicycle ergometry until exhaustion with a duration of less than one half hour may be performed without previous reduction of insulin or additional oral carbohydrates. Maximal work load can thus be determined with ECG monitoring. After insulin injection we advise our patients to estimate their reaction by calculating with exercise units. One exercise unit equals 20 minutes of half maximal exercise or one hour of 30% maximal exercise. 2) Performing one exercise unit the diabetic will have to anticipate a blood glucose reduction of -60 mg/dl. In order to maintain normal blood glucose levels he will have to reduce the regular insulin bolus 3) in the morning by -3,3 IU or 4) by -1.7 IU in the evening or he should 5) take +12 g of oral glucose (quickly absorbable carbohydrates). 6) A reduction of basal rate (CSII) or NPH insulin (ICT) is not advisable for exercise up to 3 hours. On the basis of these mean values every diabetic patient has to monitor blood glucose during exercise and adapt the measures to his individual reactions.
Gallbladder emptying in diabetic patients and control subjects assessed by real-time ultrasonography and cholescintigraphy: a methodological comparison.
Gallbladder motor function was studied in nine diabetic patients and nine control subjects matched for sex, age, and weight. None of the subjects had gallstones. Two different techniques were employed: real-time ultrasonography and cholescintigraphy using 99mTc-HIDA as imaging agent. Gallbladder volumes were determined sonographically by using three dimensions: length, lateral, and anterior-posterior diameters. Gallbladder emptying was stimulated by a standard test drink (Biloptin). Ejection fraction was computed and the results obtained by both techniques were compared. Fasting and residual gallbladder volumes after contraction were significantly larger in the diabetic patients than in the control subjects (15.9 +/- 7.6 cm3 vs. 2.3 +/- 1.3 cm3, p less than .0007; and 9.2 +/- 9.8 cm3 vs. 0.7 +/- 0.7 cm3, p less than .0007). Ejection fractions (ultrasonography/cholescintigraphy) were lower in the diabetic patients compared with the control subjects (59.9 +/- 26.6% and 63.1 +/- 23.2% vs. 73.2 +/- 23.8% and 75.3 +/- 24.8%), however, this difference was not statistically significant. Sonographically and scintigraphically determined ejection fractions were closely correlated (r = 0.90, p less than .00005).
Reduction by orbital radiation of cumulative doses of glucocorticoids in patients with Graves'-Basedow ophthalmopathy.
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[Dipeptidyl aminopeptidase IV in hospitalized patients and in galactosamine hepatitis of the rat: Activity and lectin affinity chromatography in serum and hepatic plasma membranes].
The activity of dipeptidyl aminopeptidase IV was studied in the sera of 378 hospitalized patients. The mean activity of dipeptidyl aminopeptidase IV was elevated significantly in patients with neoplasmata and hepatitis, but not in patients with liver cirrhosis. Significant correlations (p less than 0.001) existed with gamma-glutamyl transferase, glutamate dehydrogenase, alkaline phosphatase and leucine aminopeptidase. A significant correlation with lactate dehydrogenase existed only in patients with neoplasmata. Principal component analysis, performed with aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, leucine aminopeptidase, lactate dehydrogenase and dipeptidyl aminopeptidase IV, revealed correlations between the activities of aspartate aminotransferase and alanine aminotransferase, and between alkaline phosphatase and leucine aminopeptidase, but neither dipeptidyl aminopeptidase IV nor lactate dehydrogenase showed any correlation with either of these two groups. In lectin affinity chromatography with concanavalin A and wheat germ lectin sepharose, serum dipeptidyl aminopeptidase IV from liver cirrhosis patients showed the same binding pattern as that from healthy subjects. The activity and glycosylation of dipeptidyl aminopeptidase IV in serum and hepatic plasma membranes was investigated in rats, following the induction of hepatitis with galactosamine. In the serum, dipeptidyl aminopeptidase IV activity was elevated as early as 6 h after galactosamine injection, and the elevated activity persisted until the 7th day. At the same time dipeptidyl aminopeptidase IV activity was also elevated in the hepatic plasma membrane. Ninety eight percent of hepatic dipeptidyl aminopeptidase IV bound to concanavalin A as well as to wheat germ lectin and this value was unchanged during hepatitis. In the serum of control rats, 90% of dipeptidyl aminopeptidase IV bound to concanavalin A but only 39% to wheat germ lectin.(ABSTRACT TRUNCATED AT 250 WORDS)
[What is assured in therapy with HMG-CoA reductase inhibitors (cholesterol synthesis inhibitors)?].
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