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Biomedical subjects

R Prager

Publications and source records attributed to R Prager.

At least 91 records · Page 5Linked to original sources
PubMed1992

Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of beta-cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure. SUBJECTS: We studied 16 patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these patients were re-evaluated one year after surgery. The control group consisted of 18 healthy volunteers. DESIGN AND MEASUREMENTS: All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual. RESULTS: The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs 9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 +/- 4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either. CONCLUSIONS: Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially ameliorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.

C-Peptide↗
PubMed1992

[24-hour blood pressure changes in elderly people with isolated systolic hypertension, essential hypertension and normotension].

In order to evaluate circadian blood-pressure (BP) profile characteristics typical of old age, we compared circadian BP profile in elderly subjects with isolated systolic hypertension (ISH; greater than 160/less than 90 mmHg), essential hypertension (EH; diastolic BP greater than or equal to 95 mmHg), and normotension (N; less than 140/less than 90 mmHg). Each group consisted of 18 subjects, approximately matched in age and sex, (age range 60-82 years; mean age 67.5 years). Ambulatory 24-h BP-monitoring was carried out using a SpaceLabs 90202 with measurements made every 30 min. In ISH, causal systolic BP is higher and circadian systolic BP is lower than in EH (n.s.). Circadian diastolic BP is lower than in EH and higher than in N; both are statistically highly significant (p less than 0.001, u-test, Wilcoxon). The decrease during the resting period is 6 mmHg in EH and 17 mmHg in ISH. In ISH there is a considerable difference of 39 mmHg between casual BP and circadian 24-h BP, in contrast to N and to EH, and this is due to a particular hyperreactivity. This discrepancy is typical of old age and holds the danger of over-treatment, if only causal BP is taken into consideration.

Aged↗
PubMed1991

Basal and stimulated plasma levels of pancreatic amylin indicate its co-secretion with insulin in humans.

Amylin is a 37-amino acid pancreatic polypeptide, probably involved in the pathophysiology of Type 2 (non-insulin-dependent) diabetes mellitus. We have determined amylin in human plasma by extraction-based radioimmunoassay (Sep-Pak C18). Of 23 healthy control subjects plasma amylin was determined as 11.9 +/- 3.5 ng/l. Of 27 patients with Type 2 diabetes receiving insulin the amylin levels were lower, and in 16 patients with Type 2 diabetes on oral medication they were higher than in the control subjects; 8.2 +/- 4.4 ng/l (p less than 0.01) vs 18.8 +/- 9.9 ng/l (p less than 0.05). In 14 Type 1 (insulin-dependent) diabetic patients we found extremely low mean amounts of amylin: 2.9 +/- 1.9 ng/l (p less than 0.002). Thus, basal amylin appears to be associated with the capacity to release insulin. An oral glucose load stimulated the release of amylin, this was more pronounced in patients with Type 2 diabetes than in healthy subjects. An excellent correlation of mean amylin with mean insulin concentrations was obtained (r = 0.949). In patients with Type 2 diabetes amylin was reduced congruent to decreases in C-peptide during a hyperinsulinaemic, euglycaemic glucose clamp experiment (r = 0.971 for linear correlation between C-peptide levels and amylin). We conclude, that amylin and insulin are co-secreted in humans, and that the amylin release is under feedback-control by insulin.

Adult↗
PubMed1991

Metabolic effects of isradipine versus hydrochlorothiazide in diabetes mellitus.

Most antihypertensive drugs have negative effects on metabolic control in diabetic patients. Calcium antagonists have been widely used in antihypertensive treatment of diabetics, although a possible influence on glucose tolerance, insulin secretion, and insulin action is unknown. Therefore, the effect of the calcium antagonist isradipine on glucose tolerance and insulin secretion (75 g oral glucose tolerance test) and on peripheral and hepatic insulin action (euglycemic clamp) was evaluated in 11 type II diabetic patients. All patients were treated with placebo or isradipine for 8 weeks (double-blind, crossover design). A second group of six diabetic patients received a thiazide diuretic, hydrochlorothiazide, according to the same protocol. Systolic blood pressure was significantly lowered after isradipine and hydrochlorothiazide compared with placebo (127 +/- 3 versus 139 +/- 6 mm Hg and 129 +/- 4 versus 142 +/- 4, respectively; p less than 0.05). Fasting blood glucose (190 +/- 21 versus 152 +/- 15 mg/dl; p less than 0.01), glucose levels, basal and glucose-stimulated insulin levels were significantly higher after hydrochlorothiazide compared with placebo but remained unchanged after calcium antagonist treatment. Basal hepatic glucose production and peripheral insulin resistance were significantly elevated after hydrochlorothiazide compared with placebo or calcium antagonist therapy. These data indicate that the calcium antagonist isradipine has no effect on glucose tolerance, insulin secretion, and insulin action in type II diabetic patients and might therefore be a useful drug for antihypertensive treatment in diabetes mellitus. However, diuretic treatment can lead to impairment of metabolic control and reduction of insulin action in type II diabetes mellitus.

Adult↗
PubMed1991

Contribution of postprandial insulin and glucose to glucose disposal in normal and insulin-resistant obese subjects.

We recently found that postprandial hyperinsulinemia does not compensate for the insulin resistance of obese subjects and proposed that postprandial hyperglycemia might be more important in promoting glucose disposal via the mass action effect of glucose. To test this idea we perform oral glucose tolerance tests (OGTT) in six lean and eight obese subjects, measuring glucose and insulin levels. Afterward two insulin infusion studies were performed. During infusion study I, insulin was infused in a dynamic square wave fashion to mimic the individual post-OGTT insulin levels at content euglycemic glucose levels. During study II, glucose and insulin infusions were varied to mimic post-OGTT levels in each subject. Overall glucose turnover was measured isotopically by infusion of [3-3H] glucose. During the OGTT the obese subjects exhibited significantly higher insulin (P less than 0.005) and glucose levels (P less than 0.002). Insulin-stimulated glucose disposal rates and total incremental glucose disposal (IGD) over 4 h during study I at euglycemia were significantly lower in obese compared to lean subjects (area under the curve, 824 +/- 166 vs. 1222 +/- 161 mmol/L.m2; P less than 0.01) despite higher post-OGTT insulin levels in obese subjects. When insulin plus glucose levels were matched to the individual OGTT levels, IGD was not significantly different between obese and control subjects (1712 +/- 253 vs. 1617 +/- 444 mmol/L.m2; P = NS). A significant inverse correlation (r = -0.73; P less than 0.05) existed between the degree of glucose intolerance (OGTT) and the decrease in IGD during the phasic hyperinsulinemic euglycemic study (infusion study I). These data suggest that with increasing insulin resistance, hyperinsulinemia is less effective in compensating for this decrease in insulin action, and hyperglycemia becomes more important in augmenting overall glucose disposal values.

Adult↗
PubMed1991

Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes.

Amylin, a 37-amino acid polypeptide, has been identified as the major protein component of pancreatic amyloid deposits in patients with non-insulin-dependent (type II) diabetes mellitus. Amylin is stored and released together with insulin and has been proposed to play a major role in the pathogenesis of type II diabetes. To compare amylin release and its proportion to insulin secretion under different metabolic conditions, oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in healthy, lean control subjects, obese patients with normal and impaired glucose tolerance (NGT and IGT, respectively), and obese type II diabetic patients. Compared with control subjects, basal and stimulated amylin secretion during OGTT was significantly higher in obese patients with NGT and IGT but not in type II diabetic patients. The integrated amylin response was significantly higher in obese patients with NGT than lean control subjects and type II diabetic patients matched for degree of obesity. The amylin-insulin ratio decreased slightly in obese subjects with NGT and IGT and significantly in type II diabetic patients. Amylin secretion was significantly stimulated during IVGTT in control subjects and obese patients with NGT and IGT but not in type II diabetic patients. These findings suggest that amylin is physiologically released by pancreatic beta-cells in a constant ratio to insulin in nondiabetic subjects. Glucose-stimulated amylin secretion is increased in obese subjects with NGT and IGT. In type II diabetes mellitus, amylin secretion relative to that of insulin is decreased, and amylin is not stimulated by IVGTT.

Adult↗
PubMed1991

The effects of ramipril on glucose tolerance, insulin secretion, and insulin sensitivity in patients with hypertension.

To evaluate a possible influence of the angiotensin-converting enzyme inhibitor ramipril on glucose tolerance and insulin sensitivity, an oral glucose tolerance test (oGTT) and an euglycemic clamp were performed in 10 nonobese, nondiabetic patients with mild hypertension before and after treatment with ramipril for 14 days. Following ramipril treatment, systolic and diastolic blood pressures were significantly lower (152.5 +/- 10.6/97.5 +/- 4.3 vs. 136.5 +/- 18.9/79.5 +/- 16.4 mm Hg). Therapy with ramipril showed no influence on glucose tolerance (serum glucose of 106.8 +/- 32.8 vs. 109.1 +/- 33.9 mg/dl at 120 min during the oGTT), insulin secretion (53.0 +/- 45.7 vs. 41.1 +/- 10.6 microU/ml at 120 min), and insulin sensitivity (glucose infusion rate of 180.8 +/- 60.7 vs. 199.8 +/- 77.5 mg/m2/min after 3 h of clamp). In conclusion, short-term treatment of hypertension with ramipril has no influence on glucose metabolism in nondiabetic patients.

Aged↗
PubMed1991

123I-tyrosine-(A14)-insulin: preparation and preliminary clinical studies.

Insulin was radioiodinated with 123I (123I-tyrosine-(A14)-insulin) to a specific activity of 1 micrograms/mCi, corresponding to 0.025 I.U. of insulin/mCi. This preparation was used for in vitro binding experiments with adipose tissue, showing active binding to the two subunits of the known insulin receptor. In a preliminary clinical investigation, 5 adipose patients with (n = 2) and without (n = 3) diabetes mellitus Type II, were subject to in vivo injection of the same radiolabeled product using 3 mCi/patient. During the first minutes of dynamic imaging, the liver was the major organ of tracer uptake in all patients. Furthermore, the pancreas, and in one patient the kidneys, were visualised. Further studies on insulin in vivo kinetics and quantification are under way.

Diabetes Mellitus↗
PubMed1991

[Glycosylated hemoglobin and diabetes--self monitoring (compliance) in depressed and non-depressed type I diabetic patients].

128 type I diabetics were examined in view of connections between psychosocial factors and metabolic control. Indications of a direct interaction between depressivity, incidence of complaints and the level of hyperglycemia were found. The prevalence of manifest depression ranges at a total of 25 percent. The results further show connections between coping with the disease and behavior. High recording frequency, frequent measurements and medical consultations are found in active coping. Changes in relations to close persons and frequent change of job are psychosocial effects of the disease manifesting themselves in poorer metabolic control. In conclusion, high-risk groups of depressive diabetes patients and those under particular stress are defined.

Adaptation, Psychological↗
PubMed1991

[Role of amylin in the pathogenesis of type II diabetes mellitus].

Amylin, a peptide, which was isolated from the islet amyloid of type II diabetics, might play a potential role in the pathogenesis of type II diabetes mellitus. In in vitro and in vivo studies it has been shown that amylin has an effect on insulin secretion as well as on insulin sensitivity. From measurements of plasma amylin levels it is known that amylin is cosecreted with insulin and patients with hyperinsulinemia have also elevated amylin levels. In patients with impaired glucose tolerance and type II diabetes amylin levels are decreased compared to insulin. A secretory defect of amylin and its local accumulation in the islets of type II diabetics might be a cause for the insulin secretory defect in type II diabetes. Additionally, amylin can induce peripheral insulin resistance, which might also be a cause for type II diabetes mellitus. Amylin is a new pancreatic peptide, which might play an important role in the pathogenesis of diabetes mellitus.

Amyloid↗
PubMed1990

The actions of 2-hydroxy-saclofen at presynaptic GABAB receptors in the rat hippocampus.

The actions of 2-hydroxy-saclofen (2-OH-S), a recently developed analog of baclofen, were studied at presynaptic GABAB receptors in the rat hippocampal slice. Baclofen (0.5-20 microM) reduces the amplitude of excitatory postsynaptic potentials (EPSPs) recorded from hippocampal CA1 pyramidal neurons. In the presence of 200-500 microM 2-OH-S, the synaptic depressant action of baclofen is significantly reduced. These data show that 2-OH-S is an effective antagonist at presynaptic GABAB receptors on excitatory terminals in the hippocampus.

Animals↗
PubMed1990

Evaluation of glucose tolerance, insulin secretion, and insulin action in patients with primary hyperparathyroidism before and after surgery.

Glucose tolerance, insulin secretion, and insulin sensitivity were evaluated in 8 asymptomatic patients with primary hyperparathyroidism (PHPT) before and at least 8 weeks after surgical correction of PHPT by means of the hyperglycemic clamp technique. In addition, 15 sex- and age-matched control subjects were investigated for comparative reasons by the same technique. Glucose metabolized (M) during the hyperglycemic clamp was not significantly (NS) different between patients with PHPT and controls (7.9 +/- 2.3 vs. 6.3 +/- 1.9 mg/kg/min). However, insulin secretion (I) was significantly elevated in patients with PHPT compared to controls (87 +/- 17 vs. 45 +/- 12 microU/ml, P less than 0.05). The calculated insulin sensitivity index (M/I) was significantly reduced in PHPT compared to controls (11.0 +/- 2.1 vs. 15.2 +/- 1.4 mg/kg/min per microU/ml x 100, P less than 0.05). Comparing patients with PHPT before and after surgery, the M value, which is a measure of glucose tolerance, was not significantly different (7.9 +/- 2.3 vs. 7.8 +/- 1.5 mg/kg/min). However, insulin secretion was significantly lower after surgical correction of PHPT compared to the preoperative situation (48 +/- 9 microU/ml vs. 87 +/- 17 microU/7 ml, P less than 0.01). The calculated M/I rose significantly after surgery compared to the preoperative value (11 +/- 2.1 vs. 17.6 +/- 2.7 mg/kg/min per microU/ml x 100, P less than 0.001). We conclude that disturbed carbohydrate metabolism, such as insulin hypersecretion and insulin resistance, in patients with PHPT is an early finding in this disease and that these early disturbances in glucose metabolism are, however, fully reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Decreased peripheral insulin sensitivity in acromegalic patients.

In 13 nondiabetic acromegalic patients glucose homeostasis was studied by use of the hyperglycaemic clamp technique and compared to a group of sex and age matched and a group of sex, age and weight matched controls. When compared to a control group of normal weight glucose stimulated insulin release (I) was significantly increased and tissue sensitivity to insulin (M/I) significantly decreased. However, no significant differences were observed when the parameters were compared with a weight matched group. Glucose stimulated insulin release correlated positively with growth hormone (GH) and somatomedin-C levels, whereas no such a correlation could be obtained for M/I. Thus, chronic growth hormone excess seems to induce hyperinsulinaemia which in turn leads to obesity and metabolic changes comparable to those of obesity.

Acromegaly↗
PubMed1990

Platelet aggregation and metabolic control are not affected by calcium antagonist treatment in type II diabetes mellitus.

Calcium antagonists have become widely used as antihypertensive treatment in diabetic patients, although data concerning a possible influence on glucose tolerance, insulin secretion, and platelet aggregation during long-term, placebo-controlled studies are lacking. Therefore, the effects of isradipine, a new calcium antagonist, on glucose tolerance and insulin secretion during a 75-g oral glucose tolerance test (OGTT) and on ADP- and collagen-induced maximum first-wave platelet aggregation (Tmax%) were studied in 11 type II diabetic patients with borderline hypertension. After a 2-week washout period, patients were treated with placebo or isradipine for 8 weeks in a double-blind, crossover study. Systolic blood pressure was lowered significantly after isradipine therapy compared to placebo (127 +/- 3 vs. 139 +/- 6 mm Hg; p less than 0.05). Fasting blood glucose (153 +/- 14 vs. 157 +/- 16 mg/dl; NS), glucose levels, and basal (17 +/- 4 vs. 17 +/- 2 mU/ml; NS) and stimulated insulin during the OGTT remained unchanged after either treatment. Platelet aggregation after stimulation with different concentrations of ADP and collagen showed no significant differences. These data indicate that calcium antagonists have no adverse effects on glucose tolerance, insulin secretion, and platelet aggregation in type II diabetes mellitus, and are therefore useful in the treatment of hypertension in diabetic patients.

Blood Glucose↗
PubMed1990

[The value of fructosamine in hemodialysis patients].

Fructosamine is thought to be an alternative diabetic long term parameter to HbAlc. A possible advantage of fructosamine is the shorter half life of this parameter. Therefore changes in the metabolic control of diabetes can be evaluated faster. However, daily variations of protein concentrations limit the clinical usefulness of fructosamine, especially in patients on hemodialysis, where we see variations in total protein- and albumin concentration during dialysis. Due to these limitations we studied the clinical usefulness of a new fructosamine assay in 38 patients with chronic renal failure. Fructosamine values, total protein, albumin, blood glucose and creatinine were measured before and after three hours hemodialysis treatment as well as glycosylated hemoglobin. Before dialysis HbA1c correlated with HbA1c after dialysis (r = 0.99), which documents the usefulness of glycosylated hemoglobin in patients on hemodialysis. Fructosamine before dialysis shows a correlation with fructosamine values after dialysis of r = 0.77. After correction with total protein the correlation was r = 0.95, also after correction with albumin. Fructosamine values before and after dialysis correlated excellently (r = 0.95). Fructosamine values before and after dialysis can only be compared after correction with total protein or with albumin.

Blood Glucose↗