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  • 1
    ISSN: 1432-0428
    Keywords: Glucose dependent insulinotropic polypeptide ; Type 2 (non-insulin-dependent) diabetes mellitus ; normal subjects ; glucose ; insulin ; C-peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Considerable disagreement exists regarding the levels of immunoreactive glucose dependent insulinotropic polypeptide in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Glucose dependent insulinotropic polypeptide levels were therefore studied during oral glucose and mixed meal tolerance tests in normal subjects (n=31) and newly presenting previously untreated patients with Type 2 diabetes mellitus (n=68). The tests were performed in random order after overnight fasts and blood samples were taken at 30 min intervals for 4 h. During the oral glucose tolerance test plasma glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a fasting value of 20±3 pmol/l to a peak of 68±5 pmol/l at 30 min and in the Type 2 diabetic patients from a similar fasting level of 27±3 pmol/l to a higher peak value of 104±6 pmol/l at 30 min (p〈0.001). Glucose dependent insulinotropic polypeptide levels were significantly higher in the diabetic patients compared with the normal subjects from 30–90 min (p〈0.01–0.001) following oral glucose. During the meal tolerance test glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a pre-prandial value of 22±4 pmol/l to a peak of 93±6 pmol/l at 90 min and in the Type 2 diabetic patients from a similar basal level of 25±2 pmol/l to a higher peak of 133±7 pmol/l at 60 min. Glucose dependent insulinotropic polypeptide concentrations were significantly higher in Type 2 diabetic patients compared with the normal subjects at 30 min (p〈0.001), 60 min (p〈0.01) and from 210–240 min (p〈0.05) during the meal tolerance test. The groups were subdivided on the basis of degree of obesity and glucose dependent insulinotropic polypeptide concentrations were still higher in the diabetic subgroups compared with the normal subjects matched for weight. Type 2 diabetes mellitus is associated with an exaggerated glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals which is independent of any effect of obesity.
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  • 2
    ISSN: 1432-0428
    Keywords: Glucokinase gene ; microsatellite ; polymorphism ; linkage disequilibrium ; haplotypes ; Type 2 (non-insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to evaluate the role of potential glucokinase defects contributing to susceptibility to Type 2 (non-insulin-dependent) diabetes mellitus in Welsh Caucasians. For this analysis, two microsatellite repeat polymorphisms flanking opposite ends of the gene were employed. For a recently described microsatellite (GCK2), located 6 kilobases upstream of islet exon 1, six different sized alleles were observed, with heterozygosity of 0.50 and polymorphism information content 0.44. Combined heterozygosity with another microsatellite repeat (GCK1) was 0.72. Significant linkage disequilibrium was noted between GCK2 and GCK1, suggesting that haplotypes may be a better predictor of Type 2 diabetes than analysis with either microsatellite alone. Using these two markers, the association with Type 2 diabetes was examined. The frequencies of alleles and genotypes at GCK1 did not differ between the patients with Type 2 diabetes (n=157) and control subjects (n=73). Similarly no differences were observed in GCK2 alleles or genotypes. The frequencies of haplotypes, derived from the two markers, also did not differ between the two groups. To investigate the possibility of minor metabolic effects of glucokinase defects, we also studied the association between the GCK alleles or haplotypes and the response profiles to meal tolerance tests. No association was observed between plasma glucose or insulin responses to meal tolerance tests with GCK haplotypes or alleles. These results suggest that glucokinase mutations in Welsh Caucasians are not major determinants of susceptibility to the common type of Type 2 diabetes.
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  • 3
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; renal haemodynamics ; improved glycaemic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The impact of improved glycaemic control on renal function in newly-presenting Type 2 (non-insulin-dependent) diabetic patients has not been adequately researched. Consequently, glomerular filtration rate and effective renal plasma flow and urinary albumin excretion rates were determined in 76 subjects (age (mean (SD)): 54 (9.5) years; 50 male) of an original cohort of 110 newly-presenting normotensive non-proteinuric Type 2 diabetic patients following 6 months treatment with diet alone (n=42) or with oral hypoglycaemic agents (n=34). Significant reductions were observed in (presentation vs 6 months): body mass index (p〈0.01); fasting plasma glucose (p〈0.001); glycated haemoglobin (HbA1) (p〈0.001); systolic blood pressure (p〈0.01); and diastolic blood pressure (p〈0.001). Glomerular filtration rate declined from 117 (22) to 112 (21) ml·min−1 (p〈0.01), with unchanged effective renal plasma flow (534 (123) vs 523 (113) ml·min−1) and filtration fraction (22.4 (3.0) vs 21.8 (3.4)%). Albumin excretion rate (median (range)) declined from 1.1 (0.1–34.7) to 0.5 (0.1–29.9) μg·min−1 (p〈0.01). Changes in glomerular filtration rate (Δ values) were inversely correlated with presentation values (p〈0.001), and positive relationships were observed with Δ effective renal plasma flow (p〈0.01), and Δ glycated haemoglobin (p〈0.05). Type 2 diabetic patients with glomerular filtration rate values at presentation over 120 ml·min−1 demonstrated significant reduction in glomerular filtration rate (n=31; p〈0.001), whilst those with original values less than 120 ml·min−1 remained unchanged (n=45). Glomerular filtration rate, effective renal plasma flow and filtration fraction for the Type 2 diabetic patients remained elevated compared with age-controlled normal subjects (p〈0.01-0.001). Albumin excretion rate at presentation and 6 months were positively correlated with fasting plasma glucose levels (p〈0.05) but not renal haemodynamics. Thus, glomerular filtration rate and albumin excretion rate in newly-presenting Type 2 diabetic patients are influenced by metabolic control. Improved glycaemia for 6 months produces a reduction in glomerular filtration rate, mainly in the younger patients with values greater than 120 ml·min−1 at diagnosis of diabetes. Despite these changes, renal haemodynamic parameters remain elevated compared with age-matched normal subjects.
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  • 4
    ISSN: 1432-0428
    Keywords: Human insulin ; insulin activity ; insulin pharmacokinetics ; glucose clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of semi-synthetic human insulin has been compared with porcine insulin in normal man using an euglycaemic glucose clamp at two different insulin infusion rates. In a two hour infusion insulin levels plateaued for both types of insulin at 44–48 mU/l (infusion rate 0.05 U kg body weight-1 h-1) and 22–24 mU/l (0.02 U kg-1 h-1), giving identical metabolic clearance rates. The glucose delivery required to maintain euglycaemia in the second hour of insulin infusion was 13.9±2.1 g (mean±SEM) and 14.7±1.5 g (NS) at the lower dose for porcine and human insulins respectively, and 27.1±2.5 and 28.0±2.9 g (NS) at the higher dose. The potency ratio for human, compared with porcine, insulin was 1.06 ±0.12. No differences were seen in the time of onset of action of the insulins, serum half-life or distribution space. The responses of blood lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were identical. No untoward reactions occurred. The activity and disposal of this semi-synthetic human insulin are indistinguishable from porcine insulin in normal euglycaemic man.
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  • 5
    ISSN: 1432-0428
    Keywords: Porcine NPH insulin ; semi-synthetic and biosynthetic human NPH insulin ; pharmacokinetics ; pharmacodynamics ; normal subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma glucose, C-peptide and insulin responses to subcutaneously administered highly purified porcine, ‘semi-synthetic’ and ‘biosynthetic’ human isophane (NPH) insulin and diluting medium as control in normal male subjects were evaluated. Porcine and semi-synthetic human NPH insulins were administered at two dose levels of 0.15 and 0.30 U/kg body weight and biosynthetic human NPH at 0.15 U/kg body weight only. At the low dose level the three insulin preparations resulted in a similar maximal hypoglycaemic effect within 3–5 h after administration. However, over the remainder of the 11 h post-injection period, the plasma glucose level was lower after semi-synthetic human insulin. In contrast, at the 0.30 U/kg dose level, there was no difference in the early or late hypoglycaemic response between porcine and semi-synthetic human NPH insulins of equivalent pharmaceutical formulation. The clinical relevance of these findings needs further evaluation. The data suggest that for the ‘intermediate-acting’ NPH insulin preparations, both the species of insulin, nature and quantity of the retarding protein and their subsequent interaction may determine their time-action characteristics.
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  • 6
    ISSN: 1432-0428
    Keywords: Glucose ; insulin ; C-peptide ; glucose dependent insulinotropic polypeptide ; normal subjects ; Type 2 diabetic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of porcine glucose-dependent insulinotropic polypeptide given by continuous intravenous infusion in normal subjects (n=6) and Type 2 (non-insulin-dependent) diabetic patients (n=6) have been investigated. The subjects were studied on 2 separate days after overnight fasts. On each day 25 g of glucose was infused from 0–30 min plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (0.75 pmol·kg−1·min−1) or control solution. During the glucose-dependent insulinotropic polypeptide infusion plasma glucose values were reduced in normal subjects from 30–60 min (p〈0.01) and in Type 2 diabetic patients at 45 and 60 min (p〈0.05). In the normal subjects insulin concentrations were greater from 10–35 min (p〈0.01) following glucose-dependent insulinotropic polypeptide infusion and peak values were increased by 123%. In the Type 2 diabetic patients following glucose-dependent insulinotropic polypeptide infusion insulin levels were increased from 4–40 min (p〈0.01) but peak values were only increased by 27%. In the normal subjects C-peptide values were greater from 25–45 min (p〈0.01) following glucose-dependent insulinotropic polypeptide infusion and peak C-peptide levels were increased by 82%. In the Type 2 diabetic patients following the glucose-dependent insulinotropic polypeptide infusion C-peptide levels were increased from 6–55 min (p〈0.01) and peak values were increased by 20%. Plasma glucose-dependent insulinotropic polypeptide levels were within the physiological post prandial range during the glucose-dependent insulinotropic polypeptide infusion. Glucose-dependent insulinotropic polypeptide is insulinotropic in normal subjects and Type 2 diabetic patients at physiological concentrations and results in improved glucose tolerance. This insulinotropic effect is less marked in the diabetic patients and may represent insensitivity of the B cell to glucose-dependent insulinotropic polypeptide.
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Diabetic retinopathy ; screening ; ophthalmoscopy ; photography ; general practitioner ; optometrist.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Welsh Community Diabetic Retinopathy Study was designed to assess the effectiveness of the Field Guide Book for screening for diabetic retinopathy in Europe. A community-based sample (prevalence 2 %) of diabetic patients was recruited from four general practices. Standardised training and equipment were provided. All patients were invited to attend practice-based screening sessions on two occasions over 3 years (phases 1 and 2). After mydriasis, clinical ophthalmoscopy was performed by a study optometrist and general practitioners (GPs). 2 × 45 ° field 35 mm retinal slides were obtained according to EURODIAB protocol. Anonymised slides were assessed by GPs, diabetologists and the optometrist. All the findings were graded externally (reference standard). In phase 2 community optometrists also performed ophthalmoscopy and assessed photographs. For detecting sight threatening diabetic retinopathy using ophthalmoscopy, GPs achieved a sensitivity of 65.7 %, specificity 93.8 % and positive predictive value (PPV) 65.7 %. Community optometrists achieved a sensitivity of 82.2 % with a PPV of 50.7 %; the study optometrist 79.2 and 55.9 %, respectively. The use of 35 mm slides improved sensitivity for the detection of sight threatening retinopathy to 87.3, 91.1 and 97.2 % for GPs, community optometrists and the study optometrist, respectively. PPV fell to 51.2 % for GPs, 40.6 % for community optometrists, but increased to 58.8 % for the study optometrist. Diabetologists achieved a sensitivity of 88.7 % and a PPV of 65.6 %. It is concluded that the European field guide is an effective tool for screening for retinopathy in clinical practice. [Diabetologia (1998) 41: 59–64]
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 192 (1961), S. 1067-1068 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A column was prepared from two lengths of copper tubing each 10-ft. long by 3/16 in. bore, filling them with Molecular Sieve 5A of particle size 30-44 B.S.S. mesh and then activating the sieve by heating to 350 C. in vacuo. Each section was coiled into a helix of 4 in. diameter and they were joined ...
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 201 (1964), S. 901-902 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE adsorption isotherms of highly reactive fluorine -containing gases cannot be measured with certainty by conventional methods based on the pressure changes observed when successive volumes of adsorbate are admitted to a vessel containing adsorbent, since reaction of the gas with the vessel or ...
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