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  • 1
    ISSN: 1432-5233
    Schlagwort(e): Hypertension ; Non-insulin-dependent diabetes ; Microalbuminuria ; Lisinopril ; Nifedipine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of the angiotensin-converting enzyme lisinopril were compared with those of the calcium antagonist nifedipine in 162 non-insulin-dependent diabetic hypertensive patients for a 24-week period. In 83 and 79 patients, respectively, lisinopril and slow-release nifedipine produced similar reductions in blood pressure (systolic/diastolic: −16/−13 mmHg supine and −14/−11 mmHg standing after lisinopril; −15/−12 mmHg supine and −14/−11 mmHg standing after nifedipine). Fasting and post-prandial plasma glucose, glycosylated haemoglobin and plasma lipids appeared to be unaffected by either agent. Also, 28% of the patients on lisinopril and 30% of those on nifedipine presented microalbuminuria. Both drugs induced a reduction in the albumin excretion rate (AER). The geometric meanxx: tolerance factor of the reduction in AER among the 23 microalbuminuric patients on lisinopril (−10.0xx:1.3 μg/min) was greater, though not significantly so, than that observed in the 26 on nifedipine (−0.9x:1.2 μg/min). Moreover, lisinopril appeared to be better tolerated than nifedipine in our study population. Microalbuminuria is an important risk factor for cardiovascular mortality in non-insulin-dependent diabetic patients as well as in the general population. To what extent a reduction in the AER could ameliorate the cardiovascular prognosis in non-insulin-dependent diabetic patients is, at present, unknown. Finally, both lisinopril and nifedipine showed a similar antihypertensive effect in these patients which was not associated with significant differences in plasma glucose, insulin or lipid concentrations. The clinical consequences of the insignificant differences in AER remain unclear.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Acta diabetologica 29 (1992), S. 278-279 
    ISSN: 1432-5233
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-5233
    Schlagwort(e): Leucine clearance ; Leucine concentration ; Hyperinsulinaemia ; Type 1 diabetes mellitus ; Isotopic methods
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In a series of studies in normal and type 1 diabetic subjects, we analysed the relationship between isotope-calculated leucine clearance and plasma leucine concentration. All studies were performed under euglycaemic conditions. Plasma leucine concentrations were either experimentally decreased by means of insulin infusion, or increased by means of exogenous amino acid infusion in the presence of hyperinsulinaemia. Leucine clearance rates were compared in normal and diabetic subjects at similar plasma insulin levels. The effect of hyperinsulinaemia was examined by measuring clearance rates in normal subjects at comparable leucine levels but different insulin concentrations. Our data show that leucine clearance is inversely related to leucine concentration, and that it is not independently stimulated by hyperinsulinaemia. Type 1 diabetes is not associated with decreased leucine clearance. A general equation relating leucine concentration and clearance is proposed. These data support the view that peripheral leucine utilization is not decreased in type 1 diabetes mellitus.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-5233
    Schlagwort(e): Key words Non-insulin-dependent diabetes mellitus ; Triglycerides ; Insulin secretion ; Metabolic control
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We assessed the efficacy of gemfibrozil therapy on lipid profile and glucose metabolism in a large cohort of (type 2) non-insulin-dependent diabetic patients. We enrolled 217 type 2 diabetic patients with plasma triglyceride concentrations equal to or above 2 mmol/l: 110 were randomized to gemfibrozil (600 mg twice daily) and 107 to placebo treatment in a double blind fashion. Each treatment was followed for 20 weeks. To assess postprandial glucose metabolism and insulin secretion, at time 0 and 20 weeks, a standard meal containing 12.5 g of proteins, 40.1 g of carbohydrate, 10 g of lipids was given. No differences in demographic characteristics were observed between patients randomized either to gemfibrozil or to placebo therapy. No differences were observed in total cholesterol and LDL-cholesterol concentration changes between the baseline observations and week 20 of both treatments. At variance, both treatments significantly increased HDL cholesterol. Gemfibrozil treatment significantly decreased plasma triglyceride concentration from 316±84 to 214±82 mg/dl (P 〈 0.001), whereas with placebo triglyceride levels increased from 318 + 93 to 380 + 217 mg/dl. No changes were observed in non-esterified fatty acid concentrations or in fasting plasma glucose concentrations, in HbA1C values, insulin and C-peptide concentrations. Gemfibrozil treatment: 1) significantly reduces circulating triglyceride concentration; 2) does not significantly affect cholesterol concentration; 3) does not worsen glucose metabolism.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-5233
    Schlagwort(e): Key words Sulfonylurea ; Gliclazide ; Endogenous glucose production ; Insulin secretion ; Glucose tolerance ; Glucose kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract An extrapancreatic effect of sulfonylureas has been postulated. However, in vivo results have been disputed because the amelioration of insulin action that follows sulfonylurea may represent the relief from glucose toxicity rather than a direct effect of the drug. Therefore, we studied the hypoglycemic action of gliclazide acutely and after 2 months of therapy in seven type 2 diabetic patients. All patients received a 240-minute IV glucose infusion with [3-3H]glucose. In a random order, 160 mg gliclazide (study 1) or placebo (study2) was given orally before glucose infusion. Finally, the effect of 160 mg gliclazide was reassessed after a two-month treatment with the same sulfonylurea (80 mg t. i. d.). Basal plasma glucose, insulin, C-peptide and endogenous glucose production (EGP) were similar before the two initial studies. During glucose infusion, EGP was more suppressed after gliclazide in spite of comparable increase in plasma insulin and C-peptide. After the two-month therapy, basal plasma glucose levels and HbA1c were lower while plasma insulin and C-peptide were higher with respect to baseline (p 〈 0.05). Gliclazide further reduced plasma glucose, the incremental area above baseline, and EGP during glucose infusion, while plasma insulin and C-peptide achieved higher plateaus (p 〈 0.05). When data were pooled, plasma glucose concentration and EGP correlated both in the basal state (r = 0.71) and during the last hour of glucose infusion (r = 0.84; both p 〈 0.05). These data suggest that gliclazide enhances the suppression of EGP induced by insulin and that this effect is greater with chronic treatment because of concomitant improvement of insulin secretion.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-0428
    Schlagwort(e): Glucagon ; A cell ; pancreatectomy ; diabetes ; arginine ; somatostatin ; pancreatitis ; glucose ; big plasma glucagon
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Plasma immunoreactive glucagon, C-peptide and substrates (glucose, lactate, and alanine) were measured in 21 pancreatectomized patients and 28 patients with chronic calcifying pancreatitis during arginine infusion. Results were compared with those obtained in control and in insulin-dependent diabetic subjects, and in pancreatectomized subjects receiving a combined infusion of glucagon and arginine or somatostatin and arginine. Plasma immunoreactive glucagon in the pancreatectomized patients was 230±26 pg/ml (control subjects 100±13 pg/ml, p〈0.001), but was unchanged following arginine or somatostatin. Following ethanol extraction of plasma it became undetectable. Similar results were obtained in patients with chronic pancreatitis. In contrast to the insulin-dependent diabetic subjects, no changes in blood glucose, lactate, and alanine concentrations were found during arginine infusion in the pancreatectomized or pancreatitis patients. Addition of glucagon restored the metabolic response to arginine in the pancreatectomized patients. Our results confirm previous smaller studies that in pancreatectomized patients, A cell function is absent or insignificant.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-0428
    Schlagwort(e): Diabetes ; autoimmunity and diabetes ; islet cell antibodies ; insulin and glucagon secretion ; glucose and arginine infusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Thirty-nine patients (14 non-diabetics, 8 chemical diabetics, and 17 overt diabetics) with circulating islet cell antibodies (ICA) were studied. Insulin and glucagon secretion after oral (100 g) and intravenous glucose loading (200 mg/kg bolus injection followed by an infusion of 20 mg/min over 60 min) and arginine infusion (25 g over 30 minutes) were evaluated in these patients and in non diabetic and diabetic ICA-negative controls. In the non-diabetic groups with or without ICA, insulin and glucagon responses to glucose were similar. Moreover, in ICA positive patients the response of these hormones to arginine infusion was reduced. Similar alterations in insulin and glucagon secretion were observed in the ICA positive and negative patients with chemical or overt diabetes. In particular, fasting hyperglucagonaemia and glucagon hyperresponse to arginine are associated with a lack of insulin secretion in the patients with overt diabetes. Hormonal differences between diabetics with and without ICA could not be detected.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-0428
    Schlagwort(e): pancreatogenic diabetes ; pancreatectomy ; glucagon ; alanine ; lactate ; pyruvate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary High levels of gluconeogenic precursors have been reported in patients with long-term diabetes secondary to total pancreatectomy. In the present study, blood concentrations of alanine, lactate and pyruvate were measured in six patients undergoing total pancreatectomy and in nine control subjects undergoing major abdominal surgery. To exclude the simple effect of lack of insulin and hyperglycaemia in the development of hyperalaninaemia following total pancreatectomy, three pancreatectomized patients and five control subjects underwent surgical operation while connected to an artificial pancreas. Blood concentration of alanine was constant in the control subjects during surgery (182±20 and 243±31 μmol/l with and without the artificial pancreas, respectively). In pancreatectomized patients basal blood alanine levels were similar to those in control subjects. Blood alanine level rose quickly after removal of the pancreas from 182±24 to 285±15 μmol/l (p〈0.05) in the patients connected to the artificial pancreas, and from 198±17 to 395±47 μmol/l (p〈0.05) in patients undergoing total pancreatectomy without artificial pancreas. These values were higher than those observed in the control subjects at the end of the operation (192±22 and 230±45 μmol/l with and without artificial pancreas, respectively.) Basal and intraoperative blood concentrations of lactate and pyruvate were similar in pancreatectomized patients and control subjects.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-0428
    Schlagwort(e): Pancreatogenic diabetes ; total pancreatectomy ; partial pancreatectomy ; glucagon ; free insulin ; gluconeogenesis ; intermediary metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Patients with diabetes due to pancreatectomy have metabolic features different from Type 1 (insulin-dependent) diabetes after insulin withdrawal. Whether or not glucagon by itself or combined glucagon-insulin absence are responsible for this metabolic behaviour is unknown. This study was carried out to evaluate the ability of insulin replacement to abolish differences between patients with Type 1 diabetes and patients with diabetes due to pancreatectomy. We studied the diurnal patterns of intermediary metabolites, free insulin, and glucagon using the Biostator (glucose-controlled insulin infusion system) and intensive subcutaneous insulin therapy in five patients after total pancreatectomy, five after partial pancreatectomy and seven patients with Type 1 diabetes. All were studied for 24 h after an overnight period of normoglycaemia. Insulin requirement was lower in the patients with total pancreatectomy than in patients with partial pancreatectomy or Type 1 diabetes during both types of insulin treatment (p〈 0.05). Blood glucose and free insulin were similar in all the groups in both conditions. Immunoreactive glucagon was higher in the patients with diabetes secondary to pancreatectomy than in Type 1 diabetic patients. However, glucagon levels did not increase after arginine infusion in the patients with total pancreatectomy, and column chromatography of blood samples from two totally pancreatectomized patients showed no significant levels of immunoreactive pancreatic glucagon. Non-esterified fatty acids and ketone bodies were similar during Biostator and intensive subcutaneous insulin therapy. By contrast, gluconeogenic precursors (lactate, pyruvate, alanine and glycerol) were higher in patients with total pancreatectomy than in patients with partial pancreatectomy and Type 1 diabetes. In particular, alanine was significantly higher in the patients with total pancreatectomy (400±50 μmol/l during Biostator; 437±62 μmol/l during intensive subcutaneous insulin therapy) than in patients with partial pancreatectomy (207±13 μmol/l, p〈0.005 and 226±14 μmol/l, p〈0.005) and in Type 1 diabetic patients (191±11 μmol/l, p〈0.005 and 216±10 μmol/l, p〈0.005). Our data show that the high levels of gluconeogenic precursors, already reported in patients with diabetes due to total pancreatectomy after insulin withdrawal, do not become normal even in the presence of insulin. This finding shows that gluconeogenesis is primarily dependent on pancreatic glucagon and confirms the role of glucagon in the development of diabetic hyperglycaemia.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 10
    ISSN: 1432-0428
    Schlagwort(e): insulin ; sulfonylurea ; combined therapy ; insulin action ; insulin secretion ; metabolic control
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Metabolic control, insulin secretion and insulin action were evaluated in seven Type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral antidiabetic agents before and after two months of combined therapy with supper-time insulin (Ultratard: 0.4 U/kg body weight/day) plus premeal glibenclamide (15 mg/day). Metabolic control was assessed by 24 h plasma glucose, NEFA, and substrate (lactate, alanine, glycerol, ketone bodies) profile. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, hyperglycaemic clamp (+7 mmol/l) and 24 h free-insulin and C-peptide profiles. The repeat studies, after two months of combined therapy, were performed at least 72 h after supper-time insulin withdrawal. Combining insulin and sulfonylurea agents resulted in a reduction in fasting plasma glucose (12.9±7 vs 10.4±1.2 mmol/l; p〈0.05) and hepaic glucose production (13.9±1.1 vs 11.1±1.1 μmol·kgc-min−1; p〈0.05). Mean 24 h plasma glucose was also lower (13.7±1.2 vs 11.1±1.4 mmol/l; p〈0.05). Decrements in fasting plasma glucose and mean 24 h profile were correlated (r=0.90; p〈0.01). HbA1c also improved (11.8±0.8 vs 8.9±0.5%; p〈0.05). Twenty-four hour profile for NEFA, glycerol, and ketone bodies was lower after teatment, while no difference occurred in the blood lactate and alanine profile. Insulin secretion in response to glucagon (C-peptide =+0.53±0.07 vs +0.43±0.07 pmol/ml) and hyperglycaemia (freeinsulin = 13.1±2.0 vs 12.3±2.2 mU/l) did not change. On the contrary, mean 24 h plasma freeinsulin (13.2±2.6 vs 17.5±2.2 mU/l; p〈0.01) and C-peptide (0.76±0.10 vs 0.98±0.13 pmol/l; p〈0.02) as well as the area under the curve (19.1±4.1 vs 23.6±3.1 U/24 h;p〈0.01 and 1.16±0.14 vs 1.38±0.18 μmol/24 h; p〈0.02 respectively) were significantly increased. The ratio between glucose infusion (M) and plasma insulin concentration (I) during the hyperglycaemic clamp studies (M/I, an index of insulin sensitivity), was not statistically different (1.40±0.25 vs 1.81±0.40 μmol·kg−1· min−1/mU·l−1). These data suggest that, in Type 2 diabetic patients with secondary failure to oral antidiabetic agents, the combination of supper-time longacting insulin and premeal sulfonylurea agents can improve metabolic control. This positive effect is possibly mediated through an increased secretion of insulin in response to physiologic stimuli.
    Materialart: Digitale Medien
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